Paediatric Forensic Medicine and Pathology

PAEDIATRIC FORENSIC MEDICINE AND PATHOLOGY : dited by Anthony Busuttil Em eritus Regius Professor of Forensic Medicin...

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PAEDIATRIC FORENSIC MEDICINE AND PATHOLOGY

: dited by

Anthony Busuttil Em eritus Regius Professor of Forensic Medicine, University of Edinburgh; and Medical Director, Fo rensic Medical Services, NHS Lothian, Edinburgh, UK

Jean W Keeling _::ormerly Consultant Paediatric Pathologist, Royal Hospital for Sick Children, ::diilburgh, UK

i, ARNOLD HODDER ?ART OF HACHETTE LIVRE UK

I

CONTENTS

I

Contributors

xiii

Preface

xiv

Acknowledgements

xv

ist of abbreviations used

1

Clinical assessment in suspected child abuse

xvi

1

Helen Hammond

2

Introduction Alerting signs Types of abuse The need for comprehensive assessment Significant harm The interagency context (flow chart of process) Joint working and the complementalY skills of paediatricians and forensic specialists

Legislation Consent and confidentiality The process - joint paediatric/forensic examination Documentation and report writing Interpretation of the findings Formulating an opinion Ongoing health care Involvement in ongoing legal and child -care processes References

17

21

21

22

22

Investigation of suspected sexual abuse

24

Jacqueline YQ Mok

Introduction The colposcope in the medical examination Forensic evidence Skills and experience required Consistent vocabulalY Normal female genital anatomy Perianal findings Acute, healing and healed anogenital trauma Female genital findings in sexual abuse Signs of anal abuse Conditions that mimic abuse Screening for sexually transmitted infections Interpretation of clinical and laboratOlY findings SummalY References

1

2

3

4

4

5

6

7

8

8

16

24

27

27

28

29

29

36

37

38

39

40

41

42

43

44

vi I

Contents

3

Radiology of child abuse Maeve McPhillips

Role of the radiologist Radiological investigations

Skeletal injuries

Head injury Visceral injuries Soft-tissue injury Differential diagnosis Conclusion References

47

Haematological abnormalities that can simulate abuse

76

4

47

48 51

60

68 69 69 73 73

Angela Thomas

Introduction

Primary haemostasis Secondary haemostasis

Laboratory tests

Measurements of primary haemostasis Evaluation of a bleeding patient Patterns of abnormal results

Normal coagulation screen with a normal platelet count Abnormalities of platelet number or morphology Coagulation defects The neonate

Drugs associated with bleeding Bone marrow failure syndromes Systemic disease associated with a bleeding tendency Activation of coagulation Conclusion References

5

Biochemical investigations on post-mortem specimens

76 78

79 81

82

82

86

90

94

96

97

98

99

100

101

101

102

106

Denis R Benjamin

Introduction General evaluation Hypoxia Inflammation

Anaphylaxis Infection

Dehydration and electrolytes Time of death (post-mortem interval) Endocrine disorders

Genetic metabolic disorders presenting as sudden unexpected death Technical considerations at the time of autopsy References

6

106 107 109 109 109

110

110

111

112

114

117

120

125

Ocular involvement in non-accidental injury Harry Willshaw

125 125

Introduction

Scope of ocular and adnexal injury

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Contents I

Fundus haemorrhages References

vii

128

134

7 The death scene following the sudden death of a child Anthony Busuttil Introduction Scene management The crime scene manager Sequence of events at the death scene Unclothing the body A good look around Sudden infant death syndrome or non-sudden infant death syndrome External petechiae Bruising Abandoned neonates Deaths from trauma Dyadic and multiple deaths Sudden deaths of older children Sensitivity and stress of the investigation Inquests and inquiries References

137

8 Post-mortem examination in babies and children Jean W Keeling

Introduction Death scene investigation Rectal temperature Medical and family history Other important information Radiological examination Photography Microbiological samples Toxicological investigations Biochemical and metabolic investigations Weights and measurements External examination Estimating blood loss Dissection (infants and older children) Examination of the brain, spinal cord and eye Examination of the newly born Histological samples Retention of organs Exchange of information and multidisciplinary review References

145

9

166

Pathology of neurological abnormality in early life Waney Squier Introduction Clinical manifestations of early brain damage: cerebral palsy Timing of injuries by histology

137

137

138

139

139

139

140

140

140

140

141

141

142

142

143

143

145

145

146

146

146

146

147

148

149

149

150

150

152

152

156

158

162

163

163

164

166

167

167

viii I Contents

Acquired intra-uterine damage Birth-related injury Stroke in the developing brain Metabolic disorders Infections References

169

173

]76

177

177

178

10 Fetal and perinatal death

180

Jean W Keeling

Introduction Definitions The law Background information Concealed pregnancy Unattended delivery Was the baby born alive? Is the baby of sufficient maturity to survive? Is there evidence of prolonged or difficult labour? Are there any significant injuries? Fetal death foJlowing maternal injury Is there a natural cause for death? Can I give a cause of death? Should the intrapartum still birth be a medicolegal autopsy? References

180

180

181

182

182

182

183

187

187

]88

190

193

193

194

195

11 Sudden unexpected death in infancy: sudden infant death

198

syndrome or something else?

Jean W Keeling

Introduction The definition of SIDS Epidemiology Sleeping environment Pathological findings in sum Death certification References

198

199

201

203

205

2]8

219

12 Sudden natural death in infants and children

225

Dick Variend

Introduction Cardiovascular causes of sudden death X-linked hypohidrotic (anhidrotic) ectodermal dysplasia Intracranial haemorrhage, neoplasms and malformations Gastrointestinal causes Fatal anaphylaxis Sickle cell disease Haemorrhage as a cause of sudden death Respiratory causes of sudden death Epilepsy and sudden death Deaths from acute asthma

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225

226

235

236

239

239

240

240

240

242

243

.... .

Contents I

Diabetes mellitus

Genetic metabolic disorders

Other bacterial infections

Deaths related to obstetric events and premature birth

Miscellaneous causes of sudden natural death

Sudden unexplained death in older children

Sudden natural death in the early neonatal period

Sudden death associated with 'intermediate' pathology

References

13 Recent advances in paediatric toxicology

ix

243 244 247 248 248 249 249 249 250 256

Patrice Mangin and Christian Giroud

Scope of the problem Specificity of paediatric toxicology Techniques used in drug testing Special techniques for analysis of volatile substances Alternative specimens for drug testing Pitfalls and limitations of drug screens Specific applications The importance of paediatric toxicology in specific cases Conclusions and future considerations in forensic paediatric toxicology References

256 258 259 262 262 267 271 274 274

275

14 Head and neck injuries Robert A Minns and TY Milly Lo Definition

Epidemiology

Non-accidental head injury

Traumatic birth injury

Primary mechanisms of injury to the brain

Secondary mechanisms of brain injury

Injury to the cervical spinal cord

Genetic influence on recovery from traumatic brain injury

References

282

15 Heat-induced injury or death

318

282 283 294 300 302 307 311

312 313

Anthony Busuttil

Introduction

House fire deaths

The pathologist's role

References

318 318 319 327

16 Asphyxial deaths in children

329

Anthony Busuttil

Petechiae

Scene of death

Traumatic asphyxia in children

Entrapment asphyxia

Foreign body inhalation

329 330 330 330 330

xI

17

Contents

Plastic bag asphyxia Overlaying and wedging Strangulation Hanging by a ligature Drowning and near drowning Imposed airways obstruction Abuse of inhalants (solvent abuse) Reverse suspension Chemical asphyxia Prevention References

331

331

331

332

332

332

333

333

333

333

334

Accidental injuries in children

336

Anthony Busuttil

18

Overview of paediatric trauma Bicycle helmets Falls Playground injuries Sports injuries on snow and ice Riding injuries Agricultural injuries Prevention Older children and substance abuse Accidental poisoning Hypersensitivity References

336

338

339

340

340

341

341

341

341

342

342

342

Drowning and near drowning

345

John Pearn

19

Introduction The causes of childhood drowning: a perspective The drowning medium The pathophysiology of drowning Forensic immersion syndromes References

345

345

346

349

351

359

Sudden death of children in hospital

362

Jem Berry

Introduction Definition and frequency Deaths due to natural disease Deaths due to failure to monitor Therapeutic misadventures Deaths due to dmg treatment Deaths due to medical devices and procedures Deaths in the dental chair Sudden death in newborn babies Accidents Suicide Filicide and homicide in hospital

362

362

363

365

366

366

368

371

371

372

373

373

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Contents I

Investigation of sudden unexpected death of children in hospital References 20 Road traffic accidents in children

xi

375

377

385

Anthony Busuttil

Road traffic fatalities Investigation of a fatal road traffic collision Vehicular collisions Other supervening problems in collisions Pedestrian injuries Child cyclists Diffuse axonal injury Whiplash injuries Injuries to children in utero Other vehicular accidents References

385

387

390

391

392

392

393

393

393

393

394

21 Forensic DNA profiling in cases involving children Alex M Graham and David J Harrison

Introduction Inheritance of genetic material Forensic DNA analysis: history and techniques Sample collection and processing DNA evidence and child sexual offence Y chromosome short tandem repeat typing Mixed samples Additional sample problems and solutions Mitochondrial DNA Paternity testing Identification of body remains and missing persons Identification of the 'abandoned baby' or fetal material and avenues for identifying the source of an unknown profile

DNA databases References

395

22 The dentist's role in child abuse and neglect

420

395

395

398

402

403

405

406

407

407

408

411

413

414

414

David Whittaker

Introduction Dental neglect Facial and oral pathology The dentist accused of child abuse Bite marks References 23 Paediatric dental identification

G Howard Moody

Introduction Comparison Facial reconstruction and dental profiling

420

422

422

425

425

432

435

435

435

440

xii I

Contents

24

Age estimation References

441

444

The expert witness and expert testimony

447

Anthony Busuttil

447

448

449

449

450

450

450

452

452

453

453

454

454

454

454

455

Introduction Mission statement of the expert Claim to expertise Professional witnesses Opinions Yes or no? Admissibility of expert evidence Communications from the expert witness Declaration by the expert in the report In the witness stand or box Pre-trial communication Conflict of interest Rules of evidence Conclusion Recent developments References

457

471

485

Appendix A: Child protection examination forms Appendix B: Tables of standard measurements Index

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CONTRIBUTORS

I

Denis R Benja min Department of Laboratories Cook Children's Medica l Cen ter Fo rt Worth, TX, USA

Maeve McPhillips

Department of Rad iology

Royal Hospital for Sick Children

Edinburgh, UK

Jem Berry Formerly Professor in Paediatric Pathology Directorate of Pathol ogy St Michael's Hospital Bristol, UK

Robert A Minns Professor of Paed iatric Neurol ogy Dep artment of Child Life and Hea lth The University of Edinburgh Edinburgh, UK

Anthony Busutt il Formerly Emeritus Regius Professo r of Forensic Medicin e Un iversity of Edinburgh; and Med ical Director forens ic Medical Services 0i HS Lo thian Edin burgh, UK

Jacqueline YQ Mok Consultant Paed iatrician Department of Community Child Health Roya l Hospi tal for Sick Children Edinburgh, UK

Christian Giraud Institut Universitaire de Medicin e Legale La usann e, Switzerland .-\lex M Graham Division of Pathology (Fore nsic Medicine) University of Edinb urgh Ed inbu rgh, UK Helen Hammond Consultant Paedia tri can (Community) Department of Community Child Hea lth St John's Hospital Livingston, UK David J Harrison Professor of Pathology Division of Pathol ogy (Forensic Medicine) The University of Edinburgh Edin burgh, UK Jean W Keeling fo rmerly Consultant Pa ediatric Pathologist ~oy al Hospital for Sick Children :::din burgh, UK :y Milly Lo

Cl inical Research Fellow )epartment of Ch ild Life and Health - e University of Edinburgh ~ inburgh, UK ~at rice

Ma ngin :nsritut Universitaire de Medici ne Legale _ausanne, Switzerl and

G Howard Moody Consultant in Oral Pathology Edinburgh Denta l Institute Edinburgh, UK John Pearn Professor of Paediatrics and Child Health The University of Queensland Royal Children'S Hospita l Herston, Queensland. Australia Waney Squier Consul tant Neuropathologist Radcliffe Infirmary Oxford, UK Angela Thom as Consultant Paediatric HaematoJogist Roya l Hospi ta l for Sick Children Edinburgh, UK Dick Variend Consultant Paediatric Pathologist (retd) The Children'S Hospital Sheffield, UK David Whittaker Emeritus Professor in Forensic Dentistry University of Wales Cardiff, UK Harry Willshaw Consultant Paediatri c Ophthalmologist Th e Birmingham Child ren's Hospital Birmingham, UK

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I

PREFACE

The possibility that a child may have been injured, abused, neglected or otherwise ill treated rightly raises the indigna tion and anxiety of the caring professions and involves law enforcement agencies. However, in the interests ofjustice a nd fairness, a person accused of such injury or negl ect is entitled to appropriate legal representatio n at any hearing and is deemed to be innocent until proven guilty. Quite frequently, dubiety and uncertainty linger about whether or not, in any specific situation, observations made, clinically or pathologi cally, can be interpreted solely as a manifestation of inflicted injury or neglect, or whether there is a possibility that the observed findings could have come about in other, non criminal, circumstances. These matters necessitate advice from those with expelience and expertise in this field. The aim of this book is to furnish an authoritative, com prehensive tex t to assist practitioners of medicine and the law dealing with such cases in the approp ri ate interpreta tion of these matters and to enable clinical and pathological findings to be presented in an unbiased and dispassio nate manner so that the co urts are able to better evaluate the specialist evidence put before them. The investigation and interpretation of findin gs of alleged ill treatment of infants and children requires a multidisciplinary app roach , centred on the child, his or her well-being in both the short term and longer term, as well as that of any siblings within the same environment. All of the avai lable information about any in cident must be care full y collected, collated and evalu ated. Laboratol), data, both clinical and forensic, the results of radiological investigatio ns and information from the examinat.ion of the scene where any incident took place sho uld be carefully sought and evaluated against the clinical findings. A team approach is essential, with close collaboration of famil y physicians, paediatricians involved in both community and hospital practice, the clinical fo rensic medical examiner and specialist pa tho logists, together with police and social welfare serv ices. No incident should be looked at in isola tion but rather in the context of the child's development and interaction with his or her family, environment and peer group. The survivors of inflicted injul)' or neglect in childhood must be carefully followed up, protected and their family unit supported.

In this book, some of the top ics covered here are rele vant specifically to maltreatment in ea rly life, beginning with the examination of an infant or child for whom ab use is suspected, incorporating the family environment and set against criteria for normal deve lopment. The difficult prob lem of suspected sexual abuse of children is considered separately. The extensive clinical experience of the authors of the opening chapters is readily apparent, highlighting, as they do, the pitfalls of incomplete investigation and iIl considered interpretation. The ap propri ate level of investi gation of specific findings, interpretation of investigations and consideration of differential diagnoses are addressed in chapters contributed by a paediatric radiologist, a haema tolo gist and a clinical pathologist, respectively. Those areas requiring specialist clinical expertise and experience - the eyes, mouth a nd central nervous system - are considered by specialists in those fields with ex tensive paedi atric experience. The examination of the scene of death or injury is discussed as a backg round to post-mortem examination of the very yo ung. The interpretation of cerebral pathology in the newborn, the investigation of sudden or suspicious perinatal death and sudden death in both infa nts and older children are addressed by experienced practitioners. Sepa rate consideration is given to sudden or suspicious deaths that occur in hospital. In subsequent chapters, more general areas of forensic pathology, including asphyxia and thermal injury, drown ing, injury to road users and oth er accidents are add ressed from a paediatric viewpoint. A similar approach is evident in the chapters covering toxicological investigation, DNA profiling and dental identification. The book concludes with consideration of the role of th e expert witness in criminal judicial cases and the provision of reports in the civil medicolegal context. Although the majority of contributors to this te xt are UK based , the subject matter is presented, as far as possible, wit hout national or geographic bias, so that the contents have in te rnation al releva nce. Anthony Busuttil Jean W Keelin g January 2008

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ACKNOWLEDGEMENTS

We would like to thank our contributing authors for their hard work and for their patience and ready responses in the li g ht of requests for updates and answers to specific quelies. Colleagues in Edinburgh and elsewhere in the UK have read the Editors' contribu tions and made useful sug ges tions. JWK thanks Dr Roger Malcomson for his assistance

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and expertise in the preparation of the illustrations for her chapters. We would like to thank the many staff at Hodder Arnold with whom we have been involved fo r their expert ise and encouragement ; in particular, Philip Shaw and our Project Editor Amy Mulick for their most helpful sugges tions in the late stages of manuscript completion.

I

LIST OF ABBREVIATIONS USED

AIDS ALTE APOE aPTT ARDS ARVD ATP AV AvD0 2

amino acid accident and emergency alternating current a cid-citra te-de xtrose adrenocorticotrop hic hormone antidiuretic hormon e adenosine diphosph ate autosoma l dominant polycystic kidney disease acquired immune deficiency syn drome appa rent life-threatening events apolipoprotein E activated partial thromboplastin time adu lt respiratory distress synd rome arrthythmogenic right ventricular dyspla sia adenosine triphosphate atrioventricular arteriovenous ditTerence of oxygen

0APP BPA BPNA BUN

beta amyloid precursor protein British Paediatric Association British Paediatric Neurology Association blood urea nitrogen

CACTO CAP CAPMI CASK CBF CD CESDI SUDI

carn itine acyJcarnitine translocase deficiency common approach pathway computer-assisted post-mortem identification ca rer-associated serial kill ing cerebral blood flow compac t disc Confidential Enquiry into Stillbirth and Deaths in Infancy Sudden Unexpected Death in In fancy ce rebra l function analys in g monitor cystic fibro sis transmembrane conductance regulator congenital heart disease Canadian Hospital Injury Reporting and Prevention Program confidence interval cytokeratin I cerebral metabolic rate for oxygen cytomega lovirus central nelVOUS syste m copy number variation ca rboxyhaemoglobin Combined DNA Index System combined paternity index

AA ARE AC ACD ACTH ADH ADP ADPKD

CFAM CFIR CHD CHIRPP CI CKI CMR0 2 CMV CNS CNV COHB CaDIS CPI

CSF CSM CT CVP CVR CZE

cerebral perfusion pressure cardiopulmonary resuscitation cumulative pressure-time index carnitine palmitoyltransferase type " carnitine palmitoyltransferase type 1 deficiency carnitine plamitoyltransferase type 2 deficiency cerebrospinal fluid crime scene manager computerized tomography central venous pressure cerebrovascular resistance cap illary zone electrophoresis

DAB DAI DAVlD DC DIC DMF DNA DRVvr DVD

DNA Advisory Board diffuse axonal injury disaster and victim identification direct current disseminated in travascular coagulation decayed , missing and filled teeth deoxyribonucleic acid dilute Russell's viper venom time digital versatile disc

ECF ECG EDH EDTA EEG EFE ELISA EM EMIT EPP EPS EPU ERG ESR EVG

extracelluar fluid electrocardiogram extradural haemorrhage ethylenediamine tetra acetic acid electroencephalography endocardial fibroelastosis enzyme- linked immunosorbent assay electron microscopy enzyme-multiplied immunoassay technique polypropylene expanded polystyrene expanded polyurethane electro retinograp hy erythrocyte sedimentation rate elastic van Geison stain

FAa FBI FOP FHM FIl FLAIR FPIA

fatty acid oxidation Federal Bureau of Investigation fibrinogen degradation product familial hemipl.egic migraine fabricated or induced illness fluid-attenuated inversion recovery fluoresce nt polarization immunoassay

CPP CPR CPT CPT 11 CPTlD CPT2D

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List of abbreviations used I

FPP

fitness to practice panel

GAS GC-MS GCS GDP GI GMC GMD GOS GSD

group A streptococcal infection gas chromatography-mass spectrometry Glasgow Com a Scale general dental practitioner gastroin tes tin a I General Medical Council genetic metabolic disorder Glasgow Outcome Score glycogen storage disease

HbF HCM HDN HE HELLP

fetal haemoglobin hypertrophic cardiomyopathy haemorrhagic disease of the newbo rn haematoxylin and eosin (e.g. HE stain) haemolysis, elevated liver enzymes, low platelets hypoxic-ischaemic encephalopathy hypoxic-ischaemic injury human immunod eficiency virus haemophagocytic Iymphohistiocytosis hi gh-molecular-weight kininogens high-performance liquid chroma tography human papillomavirus herp es simplex virus

HIE Hll HIV HL H HMWKS HPLC HPV HSV ICD JCH ICP ICU lDDM IgA IgE IPH ISS ITP lTU

IUGR IVF rVB

LCAD LCN LCHAD LQTS LM LoC LSD \-1A DD \,IlAP .\1 CA \ilCAD

International C1a ssificatiol1 oj Diseases intracrania l haemorrhage intracra nial pressure intensive care unit insulin-dependent diabetes mellitus immunoglobulin A immunoglobulin E idiop athic pulmonary haemosiderosis inUlY severity score idiopathic thrombocytopenic purpura intensive therapy unit intrau terine growth restriction in vitro Ferti Iization intraventricu lar haemorrhage

long-ch ain acyl-CoA deficiency low copy num ber long-chain 3-hydroxyacyl-CoA dehydrogenase long QT syndrome laser microdissec tion loss of consciousness lysergic acid diethylamide multipl e acyl-CoA dehydrogenase deficiency mean arterial pressure middle cerebral artery medium chain acyl CoA dehydrogenase deficiency

MDA MDMA MECC MELAS MERRF MfV MPS MRI mtDNA MS/MS MSUD MVC MVF NAAT NAHI NAI NAIT NEC NEQAS NICHD NKH NSPCC

OECD OJ

OR OTS OXPHOS

Pac0 2

xvii

3,4-methylenedioxyamph etamine 3,4-methylenedioxymethamphetamine micellar electrokinetic capillary chromatograp hy mitochondrial encephalomyopathy myoclonic epilepsy with ragged red fibres mean flow volume mucopolysaccharide magnetic resonance imaging mitochondrial DNA tandem mass spectrometry maple syrup urine disease motor vehicle collision mean flow volume nucleic acid amp lification test non-accidental head injury non-accidental injury neonatal alloimmune thrombocytopenia necrotizing enterocolitis National External Quality Assessment Scheme National Institute of Child Health and Development non-ketotic hyperglycinaemia National Society for the Preven tion of Cruelty to Children Organisation for Economic Co-operation and Development osteogenesis imperfecta odds ratio ornithine transcarba milase oxidat ive phosphorylation

PSA PT PTA

partial pressure of arterial carbon dioxide plasminogen activator inhibitor-I Perls ' Prussian blue reactio n polym erase chain reaction pyruvate dehydrogenase posit ron emission tomography posterior inferior cerebellar alielY paediatric intensive care unit prekallikrein phospho lipid post-m ortem examination plasma membrane carnitine transpolier deficiency phosph ate-specific antigen prothrombin time post-traumat ic amnesia

RBC RIA RCPCH RFLP

red blood cell radioimmunoassay Royal College of Paediatrics and Child Health restriction fragment length polymorphism

PAI-I PBR PCR PDH PET PICA PICU PK PL PM PMCTD

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CHAPTER 2

INVESTIGATION OF SUSPECTED

SEXUAL ABUSE Jacqueline YQ Mok

Introduction The colposcope in the medical examination Forensic evidence Skills and experience required Consistent vocabulary Normal female genital anatomy Perianal findings Acute, healing and healed anogenital trauma

24 27 27 28 29 29 36 37

INTRODUCTION

Sexual abuse has been defined as the involvement of depend ent, developmentally immature children and adolescents in sexual activity that they do not fully comprehend and to which they are unable to give informed consent or that vio late the social taboos of family roles. l In this situation, there is an imbalance of power between abuser and abused, and an element of control of the child by a trusted adult. Sexual abuse ranges from violent assault to gentle seduction. The activities include all forms of digital-genital , oral-genital, genital-genital contact between abuser and child, as well as non-contact abuse such as exhibitionism and use of the child in the production of pornographic material. A diagnosis of sexual abuse has both civil and criminal implications. The medical profession 's early involvement with child sexual abuse was limited to psychiatrists, who were interested in the behavioural manifestations following sexual abuse. The subject received scant paediatric recogni tion until publications by Jaffe 2 and Kempe3 changed the willingness and ability of paediatricians to recognize and deal with the problem. Paediatricians must have a high index of suspicion and be willing to consider sexual abuse as a dif ferential diagnosis when a child presents with behavioural problems or somatic symptoms that suggest that sexual abuse might have occurred. All physician s should act accord ing to their local child protection procedures, with the welfare and protection of the child as paramount considerations.

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Female genital findings in sexual abuse Signs of anal abuse Conditions that mimic abuse Screening for sexually transmitted infections Interpretation of clinical and laboratory findings Summary References

38 39 40 41 42 43 44

The widespread occurrence of child sexual abuse has been known for many years, although the exact prevalence is diffi cult to define. Prevalence studies have been canied out by interviewing adults about childhood events. In a summary of 19 studies conducted in the USA or Canada between J 980 and 1994, Finkelhor4 found that the rate of sexual abuse reported by women varied from 2 per cent to 62 per cent, with an approximate prevalence of 20 per cent. The ra tes reported by men varied from 3 per cent to J 6 per cent, with a reasonable estimate of approximately 10 per cent. However, studies based on interviews of adults provide limited information owing to differences in study design, the response rate, methods of data collection, definition of sexual abuse, definition of a child, and the accuracy of recall of events that might be traumatizing. Data from studies of reported incidences of abuse pro vide information about the number of children recognized annually, usually at individual centres. It does appear that increasing numbers of children are referred because of suspicions of sexual abuse, owing to either a t ru e increase in the occurrence or better recognition of the problem. In the USA it is estimated that between 120 and 150 per 10000 children have been subjected to sex ual abuse. More recently, Jones et a1 5 identified a significant reduction in the incidence of substan tiated child sexual abuse in the USA, and a population-based study in Australia has also provided evidence of a decline in the underlying rate of child sexual abuse.6 Such findings may indicate the effect iveness of personal safety progra mmes for young children.

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Introduction I

An earlier paper from one city in the UK 7 described 51 children in 1985 who presented after they disclosed abuse, a number that rose to 79 in the subsequent year. Thirty eight per cent of the children were aged less than 5 years of age at diagnosis and the mean age was 8 years. Of the alleged abusers, 60 per cent were related to the child, and one-half of these were natural fathers. Because the vast majority of children are abused by someone they know and trust, force and restraint are not commonly used when abusers engage children in sexually inappropriate activities. There is usually little intent to harm the child, and bribes or threats are often used to prevent the child from reporting the abuse. Children are ideal victims for sexual exploitation and abuse, as they are vulnerable and see adults as trusted and powerful. The 'child sexual abuse accommodation syn drome's describes the stages of traumatic sexualization, feelings of betrayal, powerlessness and entrapment that lead to the child's accommodation of the abuse. As a result, very few children disclose abuse immediately following the event, making the retrospective interpretation of healed trauma a great diagnostic challenge.

The Medical Evaluation Child sexual abuse should rarely, if ever, be diagnosed on the basis of physical signs alone. A clear statement from the child is the single most important factor towards mak ing a diagnosis. The medical evaluation of children sus pected to have been sexually abused should be part of a multidisciplinary process that spans the investigative, diagnostic and therapeutic needs of the child and family. The medical examination should be a comprehensive health assessment that should aim to: • establish any need for immediate treatment; • provide background information that mayor may not support the diagnosis; • provide information or evidence to sustain criminal proceedings and/or care plans; • plan or coordinate ongoing care; • reassure the child and family. A minimum of physical examinations should be con ducted as is necessary, and if several medical specialists are to be involved it is desirable that they should examine the child together. Joint examinations can be performed by a paediatrician and a forensic medical examiner (police sur geon) to encompass, in a single examination, the child's medical needs with the legal requirements for evidence. 9 Although a carefully structured approach to the examin ation is required for legal purposes, the medical assessment should be compassionate and thorough, resulting in a thera peutic experience for the child and family.lO.11 The examin ers must be both familiar and comfortable with normal childhood behaviour and development, genital and anal anatomy, as well as physical findings of abuse. Core skills

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and case-dependent skills for any paediatrician or forensic medical examiner who undertakes such examinations have been defined by the Royal College of Paediatrics and Child Health and the Faculty of Forensic and Legal Medicine (October 2007).12 Core skills include: the ability to commu nicate with children and their carers about sensitive issues; an understanding of the child's developmental, social and emotional needs; a knowledge of consent and confidential ity issues as they relate to children; an understanding of the range of normal genital and anal anatomy for the age and gender of the child to be examined; an ability to docu ment and interpret the clinical findings; competence in the production of a report; a willingness to communicate and co-operate with other agencies; and the aptitude to present the evidence and be cross-examined in civil and criminal proceedings.

History As with all medical consultations, the starting point is in the history, taking care to avoid asking leading questions. Investigative interviews are usually conducted by desig nated agencies (police and social services) to avoid repeti tive questioning of the child. This should not preclude physicians asking relevant questions that are essential to the medical examination. In eliciting the history, the clin ician should approach the child in the same manner as he or she would in any other paediatric condition. Details should be obtained about the child's birth and development, past medical history, and family and social background. The systematic enquiry should cover symptoms and signs relat ing to the genitourinary and gastrointestinal systems. Specific questions should be directed to the presence of pain, itch, rash, discharge or inflammation 'down below', episodes of bleeding (on pants or on toilet paper), and fre quency and consistency of bowel movement. When appro priate, girls should be asked the menstrual history, type of sanitary protection used, sexual history and previous gynaecological examinations. The child's terminology for the various body parts should be documented, and any statement made by the child recorded verbatim. 13 The importance of the psychological aspects of sexual abuse, both in the short and long term, has been high lighted. 14 ,15 Emotional difficulties include anxiety, sadness, anger, behaviour problems, school refusal, sleeplessness, withdrawal and sexualized behaviour. Somatic complaints that have been reported include: eating disorders, abdom inal pain and headaches, as well as loss of bladder and bowel control. The medical evaluation should include an enquiry into the child's emotional status and general well-being, as the carers may not associate behavioural difficulties with a past history of abuse. The carers may even be unaware that sexual abuse has occurred. Child sexual abuse is a diagno sis that, like other paediatric diagnoses, requires a consider ation of the history, physical examination and supportive

26 I


laboratory tests when appropriate. 16 Although the medical history qualifies as 'hearsay evidence', many states in the USA permit an exception to the hearsay rule, for medical histories obtained by physici ans,u

Technique of the Examination Th e exa mination should be carried out in the presence of a trusted adult, usually the child's mother. The whole child should be examined, and this includes measuremen t of hei ght and weight, assessment of the general appearance, developmental milestones, demeanour and behaviour. As part of the physical examination, general signs associ ated with trauma should be sought, such as distribution a nd pattern of bruises, grip marks, ' love bites', teeth marks and scratches, as well as injuries within the mouth. In most situ ations, the disclosure involves past abuse and th e exam in at ion can be planned to suit the child and family. Delay should be minimized in the following circumstances, when: • the a buse has occurred within the previous 72 hours; • there is a history of acute trauma; • there is a possibility of pregnancy resulting from the abuse, so that post-coital contraception can be prescribed. Considerable reassurance will be required and to avoid further distress no force or restraint should be used, no mat ter how well intentioned. An explanation ofwhat the exam ination entails should be given, with clear emphasis on 'a health check' and 'taking a look'. Wi th calm reassurance and an unhurried approach, most children can be examined without the use of any sedation. The recommended position for the female genital examination is the supine 'frog legged' position, with the hips flex ed and abducted, the soles of the feet touching. Very young children can be examined on their mothers' laps. Sometimes the adult can assist by sitting astride the examining couch, cradling the child as she leans back against the adult's body. In the supine 'frog-legged' position , the external geni talia should be inspected for signs of injury. Gentle lateral parting of the labia majora with the examiner's middle and index fingers (labial separation) allows visualization of the posterior fourchette, vestibule, perihymen al regions and urethra; the hymen may be visible at this stage. In order to visualize th e ma rgins, configuration and size of the hymenal openin g, labial traction is applied . This involves grasping the posterior ends of the labia majora between thumb and index finger and pulling gently up an d out wards. The vaginal walls may be demonstrated by this pro cedure; however, digital examination of the vagina is rarely indicated in the prepubertal child. Any sign observed should be described and documented, using the clock face to denote the location of the finding; in the anatomical position, 12 o'clock is anterior while 6 o'clock denotes the posterior position .

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Sometimes the hymen can be difficult to visualize because of sticky or redundant folds. If labial traction does not cause the hymen to open, douching with warm water will result in 'floating of the hymen', Further definition of the anatomy can be obtained with the use of a cotton bud, applied behind the hymen to 'tease out' the folds, This technique should not be used in prepubertal children, in whom the hymen is extremely sensitive, unless preceded by the gentle application of a local anaesthetic gel. In ado lescent girls, the hymenal edge can also be examined using the Foley cath eter stretch technique,18 A 14-gauge Foley catheter is inserted through the hymenal orifice into the vaginal vault, and infl ated with 40 mL of air. Gentle pulling toward the hymen results in stretching and displaying of hymenal tissue over the surface of the balloon,19,20 The toluidine blue dye test was deve loped by Lauber and Souma 21 to help detect lacerations in adult rape victims. Toluidine blue is a nuclear stain that will bind to nuclei in the deeper dermis when exposed by lacerations in the skin. In a study of girls "vho alleged sexual abuse, the applica tion of a I per cent aqueous solution of toluidine blue dye was found to increase the detection rate of posterior fourchette lacerations from 4 per cent to 28 per cent in adolescents, and from 16.5 per cent to 33 per cent in the paediatric population .22 The prone knee-chest position is recommended if there is difficulty in visualizing the posterior hymenal rim. With t he child resting on her knees and elbows, the buttocks are parted upwards and outwards, using the examiner's palms. This technique usually exposes the vestibule, perihymenal structures and hymen. Any suspicious findin gs in the pos terior hymenal rim can be clarified , as the effect of gravity causes the posterior rim to stretch out. The perianal area is traditionally examined in the left lat eral position. With use of the colposcope, some examiners prefer to continue with the examination in the supine pos ition, by asking the child to 'curl up into a little ball'. This is achieved by flexion of the child's hips and knees against the abdomen. The buttocks are gently separated using the palms of both hands, and the perianal area inspected for signs of abuse. The external anal sphincter usually relaxes during this procedure, making it easier to visualize fissures in the anal margin. Sometimes the ana l canal opens to reveal a clear view of the rectum. A digi ta l examination of the anus is rarely necessary and is unhelpful in assessing anal tone. There is also no evidence to suggest that a digital examin ation provides useful clinical information. If there are suspi cions of injuries or pathology higher up the anal canal or rectum, referral should be made to a paedi atlic surgeon for an examination under anaesthesia. Most units have a dedicated suite of rooms where chil dren can be examined in a child- fr iendly environment. The minimum requirement is an area that is integrated into a children's outpatient department to allow access to labora tories a nd other investigative facilities but which offers some privacy. Other important considera tio ns include the

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Forensic evidence I

specific needs of adolescents, the gender of the examiner and the availability of follow-up for sexual health coun selling and therapeutic support.

Examination of Boys The same sensitive and age-appropriate techniques should be used when examining boys. As with girls, any evidence of trauma such as bruises, swellings, scratches and bites should be sought for and documented . The genital examination should focus on the groin, penis, urethra, scrotum and testes while the ch ild is supine. The presence of discharge or warts should also be noted. "'lhen examining the pelianal region, various positions can be used, depending on the age of the boy. The young child may be examined in the supine knee-chest position, immediately after examination of the penis and scrotum. Older boys may be more comfortable in the left lateral position, with either the right knee or both knees pulled up to the chest. The anal examination usually involves inspection of the soft tissues only. An assessment of the anal to ne can be made, with the buttocks parted. Find ings should be documented either by line drawings or photo graphs. The colposcope can be used as a source of light and magnification, as well as photographic documentation.

THE COLPOSCOPE IN THE MEDICAL EXAMINATION The medical examination of children reporting sexual abuse evolved from a search for ways to improve lighting and visualization of the young child's genitalia. Methods for recording observations were also important, to assist in the interpretation of findings. In the early 1980s when physicians began to examine the genitalia of children, instruments such as a hand-held magnifying glass and an auriscope were used to enhance visualization. In 1925, the colposcope was invented by Hinselman , to assist in exam ination of the female cervix. Teixeira 23 used the colposcope to examine victims of alleged sexua l assault. Five years later, Woodling and Heger24 promoted the use of the colpo scope in the assessment of chi ldren who alleged sexual ab use. The colposcope is a no n- invasive magnifying instrument with a built-in light source, which allows mag nification of the external genitalia from 2 to 25 times. It contains a binocular system of lenses of varying strengths, co upl ed to an integral light source. The instrument can either be mounted on the wall, the examination couch, or on a caster system to enable mobility. Light intensity can be varied to cope with changes in magnification, and most instruments incorporate a green filter to improve the visu alization of abnormal vasculature or scars. Tei xei ra reported that an additional 11.8 per cent of sus pected cases were corroborated than would have been when conventional examination techniques were used. In

27

the prospective study by Muram and Elias,25 130 prepubertal girls (mean age 5.5 years) were evaluated bo th by an unaided examination and by colposcopy. Overall, 92 girls were found to have abnormal findings, the majority of which (96 per cent) were observed during the unaided examination. Of the four patients in whom findings were detected initially by colposcopy, these were observed dur ing the repeat unaided examination. In only one patient were the findings observed only by colposcopic examin ation alone. The authors concluded therefore that una id ed examination by an experienced cl ini cian is adequate for the evaluation of most victims of sexual abuse. The most obvious advantage of the colposcope is the integral photographic facility. Documentation of all visible findings in abuse is increasingly expected as the standard of good practice. Images produced by the colposcope can be converted into slides or photographs using a single-lens reflex camera or a Polaroid camera. Modern video technol ogy allows the image to be recorded onto a videotape, compact disc (CD) or digital versatile disc (DVD) for imme diate viewing, and has the advantage over still photog raphy as it shows the dynamic variability of anogenital anatomy as the examination proceeds. The colposcope is now standard and acceptab le equip ment in the examination of sexua l abuse. With photo doc umentation, the most obvious benefit to the child is that there is no need for repeated examinations. Many examin ers do not position their eyes in the binocular lenses of the colposcope; rather they view the image produced on the monitor at a more comf0l1able position and distance from the ch ild . The child is also able to observe the examination on the monitor, and this helps to achi eve a sense of control and participation in the examination. The instrument is usually in trod uced to the child to gain cooperation, and many enjoy playing with it prior to the examination. The use of high technology is both accepted and expected in the modern health care system, and is preferable to attempting to peer between a ch ild's legs wit h an auriscope. The ability to capture images, either as slides, photographs, videotapes, CDs or DVDs enhances undergraduate and postgraduate physician training. 26 - 3o

FORENSIC EVIDENCE Verba l consent is usually adequate for both the examin ation and photo-documentation. This should be obtained from the person with parental responsibility and from the child of sufficient maturity to understand the nature and consequences of the examination. If the child is the subject of legal proceedings, the consent of the court is required. The person obtainin g consent must record the procedure in the case notes. Written consent for each component of the examination can be documented on a standard form and on appropriate forms.

28 I


Correct procedures must be followed for the collection of forensic sampJes and evidential material, recognizing the principle of the unbroken chain of evidence. This legal concept requires that the origin and history of any exhibit to be presented in a court of law must be clearly demon strated to have followed an unbroken chain from its source, through its examination and to the court. A note of the persons handling the sample, time, date and place where the sample was obtained, along with the places and condi tions of storage must be documented. In an acute assault (within 72 hours), the clothing worn during the assault should be coI1ected individually in paper bags and handed to the investigating police officer. The skin should be inspected for a ny stains, and swabs taken to examine for saliva, lubricant or semen. If judged appropriate, a sample of blood should be taken for DNA analysis. Stains on cloth ing are best preserved by drying and storing at cool room temperature. Blood or semen collected on swabs is best preserved by frozen storage. The presence of lubricant or spermatozoa can be sought from swabs in and around the mouth (taking care to swab in the labial-gingival sulci) and from saliva. Young children will tolerate external and internal anal a nd vaginal swabs, if the a ppropriate size of swabs is used, moistened with water. Spermatozoa can be detected for up to 14 hours in saliva J I 3 days in anal sam ples J 2 and 6 days in vaginal samples. JJ The time limits for detection of seminal fluid are 3 hours in the anus and J 2- J 8 hours in the vagina. Improved DNA diagnostic tech niques allow detection of useful evidence from unwashed or partially washed clothing, bedding and other items used during the assault. General guidelines for the collection of forensic evidence in cases of acute sexual assault a re not well suited for prepubertal children. In a review of 273 child victims of sexual assault aged less than 10 years, the majority (64 per cent) of forensic evidence was found on linen or clothing. Over 90 per cent of children with positive forensic evidence were seen within 24 hours of the assault. After 24 hours, all evidence, with the exception of one pubic hair on a child, was recovered from clothing or linens. The authors suggested that any collection of foren sic evidence from a prepubertal child 's body may not be necessary more than 2 days after the assault. J4 In cases of chronic abuse, when the last episode of contact was more than a week previously, collection of evidence consists of a careful histolY, thorough examination and screening for sexually transmitted infections (STls) . Although a highJy trained and experienced examiner is not likely to miss any abnormalities during an unaided examin ation, the colposcope allows a review of photographs and video recordings when findings thought to be suspicious during the examination might be interpreted on review as normal or non-specific. Permanent documentation of visible findings protects the examining practitioner by providing objective evidence, thus only the interpretation of the find ings can be challenged. Still photographs, videotapes or CDs of the injuries often provide key information for assessment

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and evidence for prosecution in child abuse cases. Tradi tional systems for photographing abused children using a single-lens reflex camera still provides the highest quality image. The use of Hi-8 and Super VHS video cameras offers significant improvements in image quality and resolution over the traditional videotapes. More recent developments in computer imaging technology have resulted in greater ease in transforming analogue images to a digital format for computer storage and conversion into slides or prints. [mages can also be converted into a computer file, which assures preservation without degradation of the initial image. A video capture card, a scanner and/or a digital cam era, allow a computerized database to be developed. With appropriate software products, images can be transmitted over the Internet, enabling a second opinion to be sought and thereby brings telemedicine into remote areas. J 5,J6 Photographs, video, CD and DVD recordings must be properly verified and relevant, they must bear the patient identifier, date and time of recording, and must be signed by both medical and forensic examiners. Images are neces sary to explain or illustrate adequately the complexity of the injuries, and are therefore relevant for courtroom pro duction. However, the production of sensitive images and photographs of children's genitalia in the courtroom is not common practice and should be discouraged. An alterna tive line diagram can always be used to illustrate the injuries. All recorded material should be available to any medical expert instructed by defence solicitors.

SKILLS AND EXPERIENCE REQUIRED Although medical findings are not necessary for the legal conclusion of sexual abuse, health-care professionals who examine children for signs of sexual abuse are often asked to render an opinion as to whether their examination was nor mal, non-specific, suggestive or indicative of abuse. Despite this important role, the literature contains little information regarding examiner competence in assessing children's geni talia. Undergraduate and postgraduate training on the subject of child sexual abuse is woefully inadequate. The medical investigation of children in whom abuse and neglect is suspected has become a complex and technical specialty. A new group of physicians has emerged, who are specialists in the wide ramifications of child abuse and neglect. A sound knowledge is expected in general, behavioural and developmental paediatrics, as well as in . gynaecology and infectious diseases. The child abuse specialist also needs to be familiar with forensic examinations, civil and criminal laws, child advocacy and public policy, and must be comfortable when testifying in court. For these reasons, structured train ing programmes must be developed to improve the quality of care delivered to abuse children and their families.37 Brayden et al J8 evaluated the interobserver reliability of clinicians rating colposcopic photographs, and examined

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Normal female genital anatomy I

correlates of reliable interpretations. Seventy-one physici ans and two nurse practitioners were asked to assess blindly six photographs of prepubertal female genitalia, five of which were taken from children who had given histories of sexual abuse. Experts in the field of child sexual abuse assessment made significantly more accurate assessments than paedia tricians, paediatric and family practice residents, and trainee physicians. In another study, Adams and Wells 39 sought to determine how well medical examiners agreed on the significance of certain anogenital findings in children, by showing colposcopic photographs of 16 patients to 170 med ical examiners who were blinded to the history of each patient. The agreement between the participants and the experts on the abnormal cases (mean 81 per cent) was signif icantly higher than on the normal cases (mean 71 per cent, p = < 0.001). There was also higher agreement on genital findings (78 per cent) than on anal findings (63 per cent, p = 0.000). In the participants, higher experience level and use of a colposcope were associated with higher overall agreement with the experts (74 per cent versus 44 per cent, p = < 0.0001). The history was also found to influence physicians' interpretation of girls' genital findings. Paradise et al 40 conducted a questionnaire survey of 1387 randomly selected fellows of the American Academy of Pediatrics and all 802 members of child abuse professional groups, using seven simulated cases, in 6 of which the histories were changed at a second mailing 4 months later. The proportion of changed or reversed opinions varied from 0 per cent to 5.6 per cent amongst experienced examiners; 1.6-19.8 per cent amongst moderately experienced examiners and 3.6-27.2 per cent where the examiners were inexperienced. The like lihood of an interpretation being changed was influenced by a diagnostic expectation (change in history) and ambiguity of the photographs.

CONSISTENT VOCABULARY Medical examiners are often asked to determine whether a child has been sexually abused and whether penetration has occurred, as well as how often a child has been abused. More often than not, the physical appearances will be nor mal or non-specific. In preparing the medical report, care must be taken to avoid terms that can be misinterpreted and lead to confusion. Subjective descriptions such as a 'lax' sphincter or a 'gaping' hymen are unhelpful unless sup ported by measurements. It is important that clinicians are aware of the recommended terminology used to describe the genitalia, as well as interpretation of anogenital findings, so that those who examine children for alleged sex ual abuse can understand each other's descriptions. 41 - 43 Practice guidelines are now available and should be widely dissemi nated. 44 - 47 In an excellent review of hymenal morphology and non-specific findings in girls selected for non-abuse,

Heger et al 48 called for a thorough understanding of normal

29

studies and a consistent application of established terminol ogy that can prevent the misinterpretation of non-specific or congenital findings as post-traumatic changes.

NORMAL FEMALE GENITAL ANATOMY Figure 2.1 is a diagrammatic representation of the prepu bertal female genitalia, with the parts labelled using recom mended terminology. The most consistent landmark is the clitoris, which is usually prominent in young girls because of the lack of subcutaneous fat in the surrounding tissues. The vestibule is the area enclosed within the labia minora, and includes the urethral opening which can be pinpoint or patulous. Bilateral lines (Hart's lines) drawn medially from the posterior ends of the labia minora converge at the pos terior fourchette. The introitus refers to the hymen and hymenal opening or orifice. Sometimes the vaginal walls can be seen through the hymenal opening. The area between the posterior fourchette and inferior edge of the hymen is referred to as the fossa navicularis. Between the posterior fourchette and the anus, deep within subcuta neous tissues, is the perineal body. In order to identify the signs of sexual abuse, the clinician must have a sound knowledge of normal anogenital anatomy and its variants. Contemporary textbooks provide little insight into the characteristics of hymenal anatomy or the changes of the hymen in response to oestrogen levels during the childhood years. The appearances vary considerably according to the age of the child. In the newborn, the effects

Labium-

majorum

Clitoris - - - - H - t -

Labium - - i - t ' minorum

(}L-1--\;\---\---'.-- Ure th ra I

opening

Hy menal}2 orifice Hymen .E

'e

-.....;:::7'--+-7--.1----

--tt

Fossa ----'' 15 mm in size and reproducible. When seen in association with a history of anal abuse, especially in the presence of other signs such as fissures, it supports the diagnosis. In the abse nce of a dis closure from the child, follow-up is justifi ed. A summary of the perianal signs of abuse is shown in Tab le 2. 5. These signs, from the 1997 publication by the Royal College of Physicians, have been replaced by an evidence-based review of physical signs of child sexual abuse .47

CONDITIONS THAT IVIIIVIIC ABUSE General paediatlicians are often asked to see children because a physical finding may raise concerns of sexual abuse. A lack

Figure 2.1 9 'Tyre' sign, showing thickened anal folds with venous congestion.

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Table 2. 5

Perianal signs af abuse'

Non-spe cific acute changes

Erythema Oedema Fi ssures Venou s co ngestion Bru isi ng Signs supportive of abuse

Anal laxity without other explanation Reproducib le reflex anal dilatation> 15 mm Chronic changes, i.e., thickening of anal skin verge, increased elasticity and reduced anal sphincter tone Bite marks Signs diagnostic of blunt force penetrating trauma

Fresh lace ration Healed sca r extending beyond anal margin on to perianal sk in in the absence of a reasonable alternative explanation -Ada pted from ref. 46.

of fa miliarity with the normal female genital anatomy, as well as the manifestation of infection, common childhood conditions and accidental trauma, will cause physicians to misdiagnose sexual abuse. In the atopic individual the vulval skin can be moist and inflamed, as a result of contact derma titis from use of cosmetics or washing material (bubble bath, biological soap powders). Vulvovaginitis is the most common gynaecological complaint in childhood, and major causes include poor hygiene, threadworms and infec tion with Candida or group A beta-haemolytic streptococcus.8486 Soreness and itch lead to scratching or rubbing, and bleeding may be a presenting complaint. A prolonged history of 'vulvovaginitis' may be a pre sentation of lichen sclerosus, often misd iagnosed as recur rent thrush. This is a disease of unknown aetio logy and with an unpredictable course. Affected areas include the external genitalia and perianal skin. In boys, th e prepuce and glans penis may be more variably involved. The child may present with bleeding associated with pain and itch, and on exa mination the perineal skin is thin and friable, with white shiny macules. There may be vascula r or pur puric areas, sup erfici al abrasions, haemorrhagic bullae, erosion and ulceration . Usua lly the affected skin is sharply demarcated from the surrounding normal skin, rarely extendin g beyo nd a figure-of-eight distribution around the labia and anus. Lichen scl erosis has been mistaken for sex ual abuse 87-89 Submucosa l haemorrhages in lichen sclero sus are seen in Fig. 2.20. Physicians in the children's emerge ncy department are sometimes asked to see children who present with perineal injuries, and the question of sexual abuse may arise. Unin tentional injuries to the perineum in children are usually accompanied by a witnessed account of the event and are usually superficial. Hymenal injuries are rarely the result of

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Screening for sexually transmitted infections

Figure 2.20 Lichen sclerosis. Cutaneous and submucosal haemorrhages seen in the posterior fourchette and vestibule. The patient was a 6-year-old girl who presented with pain and bleeding 'down below:

accidental injury, when the labium minomm is the most frequent structure involved. Deeper injuries tend to be anterior or lateral to the hymen. In a multicentre study of 56 prepubertal girls who sustained unintentional perineal injuries, the hymen was involved in only one child who fell in a park with her legs abducted. A pinpoint abraded area was found on the hymen at the 3 o'clock position. 9o Congenital abnormalities such as haemangiomas and failure of fusion of the median raphe raise concerns of abuse when they first present. The raphe is a flesh-coloured. slightly raised, linear structure in the perineum, and when failure of fusion occurs the opposing edges may split and appear like a traumatic lesion, with bleeding. Midline avas cular areas in the posterior part of the vestibule or posterior fourchette may be seen as a white line (linea vestibularis) or a white spot (partial linea vestibularis), and is easily mis taken for scar tissue. They have been observed in 25 per cent of newborn girls,91 and can vary in size as well as con figuration in the first year of life. 92 In contrast with scar tis sue the linea vestibularis is generally in the midline, without accompanying disturbance in vascularization. Normal vari ants such as bumps and notches between 3 and 9 o'clock on the hymen can be mistaken as residua of sexual abuse. Urethral prolapse is a circular eversion of the mucosa that usually occurs at the urethral meatus without accompanying symptoms. Some bleeding may occur following straining, and assumed by carers to have come from the vagina. 9 ] Care ful examination reveals an oedematous area anterior to the hymen, through which the urethral opening may be identi fied (Fig. 2.21). Crohn's disease can involve any part of the alimentary system, and one presentation consists of extra intestinal manifestations. There may be perianal and vulval ulceration with oedema, suggesting trauma. 94 ,9 5 Clinicians may also have to sort through histories given by adults who have misinterpreted nomlal childhood masturbation or

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~ Figure 2.21 A 10-year-old girl with a 4-year history of 'vaginal bleeding'. An oedematous and erythematous 'polyp' is seen anterior to the hymenal opening. The appearances suggest a prolapse of the urethra.

sexual play between children, and by parents engaged in custody disputes. The normal, age-appropriate sexual exploitative behaviour must be differentiated from disturbed behaviour arising from child abuse.96.97

SCREENING FOR SEXUALLY TRANSMITIED INFECTIONS Debate continues as to whether the screening for STls should be routine in the evaluation of sexual abuse. The presence of a sexually acquired organism can indicate prior sexual contact in a child, and when accompanied by other indicators of sexual abuse supports the diagnosis. Non-sex ual transmission of STls is rarely an issue in adults, but when the same diseases are found in children, there is a tendency to attribute them to an asexual mode of transmis sion. 98 The immature anogenital tract is more vulnerable to infection, especially if there is a breach of the mucosal lin ing following traumatic abuse. The low numbers of children reported to have acquired STIs from sexual abuse may rep resent the lack of systematic screening, or the non-recogni tion by clinicians that children can be infected through sexual abuse. However, other routes of transmission that must be considered, although difficult to exclude are: • perinatal acquisition from an infected mother who may be asymptomatic (Chlamydia trachoma tis, Neisseria gonorrhoeae, Trichomonas vagina/is, herpes simplex vims, human papillomavirus [HPV], human immunodeficiency virus [HNJ); • non-sexual adult to child contact (HPV, herpes simplex vims); • auto-inoculation (HPV, herpes simplex virus). The risk of a child or young person acquiring an STI depends on the prevalence of STis within the local population: maternal STI during pregnancy that might lead to vertical

42 I


transmission; the type of sexual contact during abuse ; injuries to the genital tract; the sexual maturity of the victim; and whether a condom was used during abuse. Transmission from mother to child is welJ documented for most STIs and the organism can lie dormant for up to 2 years (and possibly 3 years). In dealing with a child who is less than 3 years old, it is therefore important to establish if the parents are infected and to screen them if possible. Sexual abuse should be sus pected when an infection is diagnosed after infancy and before sexual activity occurs in the older child. Under these circumstances, gonorrhoea and syphilis would be diagnostic of sexual abuse, whereas infection with Chlamydia, Tri chomonas, herpes simplex virus and HPV would be suggestive of sexual abuse. 12,44,99,100 A prospective study of 1538 children who were examined for possible sexual abuse found the overall prevalence of STIs to be 6 per cent. The diagnosis of a STI was highly cor related with a history of sex ual contact (alleged by 49 per cent of the children) and the presence of a discharge. l01 The authors had attempted to exclude perinatal acquisition as a source of infection by selecting verbal children who could understand questions regarding sexual contact. Although the prevalence of STIs was only 3.7 per cent in a cohort of 159 girls who had been sexuaJly abused, Robinson et al 102 also found a significant association of sexually transmitted organisms with the presence of a vaginal discharge. The authors recommended that the presence of vaginal discharge in sexuaJly abused girls was an indication for STI screening. The use of an algorithm to assess the risk of gonococcal and chlamydial infections was found to reduce the cost and trauma of unnecessary sampling. Major factors in the risk assessment were genital-genital or genital-anal contact or penetration, suspicious anogenital findings, genital dis charge and suspicion of an STI in the perpetrator, although vaginitis and referral for suspected abuse in a sibling were designated minor factors. Restricting testing to children with at least one major or two minor factors in their study population of 3040, 45 per cent would have been tested and all known cases of gonorrhoea or chlamydia infection would have been identified. Testing would have been avoided in 51 per cent of girls and 72 per cent of boys. 103 More recently, the Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Disease in the UK produced guidelines for the management of sus pected STls in children and young people. The recommen dations included the need for sta Ff worki ng in genitourinary medicine to be: alert to the possibility of child abuse and neglect ; aware of local guidelines; and trained in child pro tection procedures and protocols. Screening should be con sidered in all young people who may have been sexually abused or who have been found to have an STI. 104 Human papillomavirus infection is one of the most common STIs, and is estimated to affect 10 per cent of the adult population. Subclinical infection is common, and the increasing incidence of condyloma in children probably reflects the increased prevalence of HPV disease in the

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adult population. Results from studies of children with anogenital warts suggest that the majority of children do not acquire these sexually. Vertical transmission is an important source of infection in young children, and household members of children with anogenital warts should be routinely screened for the presence of non-geni tal as well as anogenital warts. 105.106 At present, there is no reliable method to determine the mode of acquisition in a child with HPV infection. Children who disclose sexual abuse should be screened for STIs under the following circumstances: • presence of symptoms and signs at the time of assault or subsequently (bleeding, discha rge, dysuria); • suspicious anogenital findings; • history of genital-genital or genital-anal contact or penetration; • alleged abuser known to have, or at high risk of acquiring, STI; • STI prevalent in the community; • request from child or young person. The forensic science laboratory will not examine samples obtained for screening of STls. For each organism, sampling techniques and transport media should be individually tai lored and must meet the criteria for maintaining the chain of evidence. Swabs must be taken by a doctor with appropriate training and experience. lt is therefore important to establish good liaison with the diagnostic laboratories, as well as physicians in genitourinary medicine. Fine, wire-mounted urethral swabs can be passed through the hymen, even in young children, to enable cultures for STls. 107 A vaginal wash procedure, using stelile saline introduced through tubing from a butterfly needle, has also been found to be acceptable as a diagnostic test for STIs in prepubertal girls.!08 Testing for infection with HlV involves a blood test for HlV antibody, obtained at the time of the initial examination and at follow up. Newer, more sophisticated tests for HfV-RNA or proviral DNA need only be done in a young child to exclude vertical transmission. 109 Serological testing for infection with Tre ponema pallidum, hepatitis B or hepatitis C virus should be considered on an individual basis. The child or young person may require active and passive immunization against hepati tis B infection as well as antiretroviral therapy. Expert opin ion should be sought from an infectious diseases specialist. In general, there have been relatively few studies where children with a particular STI have been evaluated for the possibility of child sexual abuse. This has resulted in a lim ited evidence base to determine whether a particular STI is a marker for sexual abuse 47

INTERPRETATION OF CLINICAL AND LABORATORY FINDINGS Many changes have occurred in the medica l evaluation of children suspected of having been sexually abused, and

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Summary I

how physical findings are interpreted. A comprehensive list of the clinical and laboratory findings seen in abused and non-abused children was first drawn up by Adams et al. 43 Sometimes known as the Adams Classification System, it has been developed over the years and the latest revision 45 is the result of examining published data and consensus amongst 18 experienced physicians. The classification sys tem can be summarized as: • findings documented in newborns, or commonly seen in non-abused children: - normal variants; - findings commonly caused by other medical conditions. • indeterminate findings (owing to insufficient or conflicting data): - physical examination fmdings, for example deep notches or clefts in the hymen; smooth, uninterrupted rim of hymen of < 1 mm wide; immediate dilatation of the anus> 2 cm; - Lesions with indeterminate specificity for sexual transmission: for example, anogenital condyloma accuminata, anogenital herpes. • fi ndings diagnostic of trauma and/or sexual contact: - acute trauma to external genital/anal tissues, for example fresh laceration or extensive bruising; - residual (healing) injuries, for example perianal scar; - injuries indicative of blunt force penetrating trauma: for example acute laceration, extensive bruising, healed hymenal transection; - presence of infection that confirms sexual

contact, for exam pIe gonorrhoea;

- diagnostic of sexual contact: for example, pregnancy or sperm identified in specimens taken directly from the child's body. Until a better evidence base is available, this system provides a useful tool that both assists physicians in inter preting clinical findings and helps to achieve some consist ency in terminology.

SUMMARY Whenever abuse of a child is suspected the clinician must refer to local multi-agency child protection procedures for appropriate action. Siblings and close friends of the victim must also be interviewed and examined if appropriate, as it is likely that they may also have been exposed to the alleged perpetrator. 110 There may be an association between different types of abuse, and following a diagnosis of any form of abuse a medical assessment for sexual abuse should also be considered. In the investigation of sexual abuse of children, clinicians should remember that the medical examination is only a part of the jigsaw. Physical evidence is neither essential for, nor

43

predictive of, conviction. The child's history is the single most important factor in the accurate diagnosis of most cases of sexual abuse. III ,11 2 In a review of child sexual abuse criminal court cases, those involving the youngest victims were found to have a significantly lower conviction rate. Successful prosecution, particularly in the youngest chil dren, depended on the quality of the verbal evidence and the effectiveness of the child's testimony. II ) The literature reports a marked variability of medical findings in children examined for sexual abuse and the diagnosis of sexual abuse cannot be made on the basis of physical findings alone. It has been suggested that a model could be developed for the prediction of anatomic findings, based on an inventory of variables that would include the age of the child, type of contact, whether penetration occurred, and a history of pain or b1eeding.1l4 Expert medical testimony may help to interpret the presence or absence of physical signs, but the overall effect on the legal outcome is unknown. Increased communica tion between prosecutors and paediatricians may improve the outcome, especially if the paediatrician is told whether she is a witness to fact, or an expert witness. The distinc tion is important to allow adequate preparation and to avoid an injustice to the child. A medical expelt should be able to demonstrate relevant training or experience in child abuse cases that are similar to ones in which he or she has been called on to provide expert testimony. Irresponsible medical testimony must be avoided; this includes use of unique theories of causation, unusual interpretations of medical findings, alleging non-existent physical signs, deliberate omission of pertinent facts or knowledge and misquoting of medical literature H5 Medical , social and legal professionals have relied too heavily on the medical examination in diagnosing sexual abuse. Normal findings are consistent with abuse, and the examiner must document all signs, positive or negative, whenever any child is examined. There is now a consensus on terminology and interpretation of findings in child sex ual abuse, 12,44,45,47,48,56 but these guidelines are only helpful if examiners are meticulous in documenting their findings. There needs to be an agreement on the minimum standards for the training of medical professionals who perform sex ual abuse examinations. 9 ,37,116,117 Medical care for children and young people who disclose abuse has evolved into a complex and technical specialty. Expert medical testimony can be crucial to the legal outcome of a case of alleged sex ual abuse. The evaluation of child sexual abuse is not rou tinely taught in undergraduate or postgraduate training programmes. Specialized training programmes must be developed to ensure better research as well as the dissemin ation of knowledge and expertise.37, 11 8 In September 2006, the American Academy of Pediatrics recognized child abuse as a new pediatric subspecialty. It is hoped that the accred itation of trained specialists will benefit child victims of sexual abuse, families, health-care professionals and those in social services and law enforcement.

44 I

Investigation of s us pected sexual abu s e

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Woo dling BA, Heger A. The use of the colpos cope in the diag nos is o f sex ua l a bu se in th e pedi a tri c age group. Child A buse Et Neglect 1986 ; 10: J11 - 14. Mura m D, Eli as S. Ch ild sex ual abus e: geni ta l tra ct findin gs in prep ubertal girls . n. Comp arison of colp oscopi c and unaided examinati ons. Am J Obste tr Gy J1 ecol 1989; 160 :3 33 - 5. Ada ms JA, Phillips P, Ahm ad M. The usefulness o f coJ pos copic pho to graph s in the evaluat io n o f suspected child sexual abuse. Adolesc Pedia tr Gyneco /1 990; 3:75-8 2. Mura m D, J ones CE oTh e use o f vid eo- colposcopy in the gynecologic exa minati o n of infa nts, children, and yo ung adolescents. Ado lesc Pediatr Gym'col 1993 ; 6: 154-6. McCann Jl. The colposcop ic ge nita l exa min atio n o f the sex ua lly abu sed prep ub erta l fe male. Adolesc Pedi atr GYl1 ecol 1993 ; 6:123 - 8. Hobb s C, Wy nn e J. Use of the colpo scope in examin ation for sex ual abuse. Arch iues of Diseas e in Childhood 1996 ; 75 :53 9- 42. Heger AH. Twe nty years in the ev aluati on of the sex ually a bused child : h as medi cin e helped or hUlt th e child a nd the fa mily? Child Abuse Et Neglect 1996; 20:893 -7. Will ott GM, Cross MA. Th e de tec tion o f sperm a tozo a in the mo uth. J Fo rel/sic Sci Soc 1986 ; 26 :12 5-8. Willot t GM, All ard JE. Sp erma tozo a - their persi sten ce a Fter sex ual in terco urse. ForeJ1 sic Sci Int 1982; 19:13 3-5 4. Davi es A, Wilson EM . Th e persi sten ce of se minal constitu ents in the hum a n vagina. Forensic Sc ience 1974; 3 :45-55. Christ ian CW, Lavelle JM, De Jong AR et al. Fore nsi c ev id ence fi ndi ngs in prepub erta l v ictims of sex ual assault. Ped iatrics 2000 ; 106 : 100-4. Fin kel MA , Ricci LR. Docum enta ti on and prese rva ti o n o f visua l evid ence in ch ild a buse. Ch ild Ma ltreatment 1997; 2 :322-30. Finkel !VIA. Techni cal condu ct of the CSA medic al exa min at ion. Child Abuse & Neglect 1998 ; 22 :555-66. Bl ock RW, Palusci V1. Ch ild Abuse Pedia trics: A new pedi atri c subs peci alty. J Pediatr 2006 ; 148:711- 12. Brayden RM, Altemeier WA IJ], Yeager T, Muram D. Interp reta tio ns o f coJposcopi c photogra ph s: Evidence fo r com peten ce in assess ing sex ua l a buse. Child Abuse Et Neglect 1991 ;15:69-7 6. Adam s J A, Well s R. Normal versus a bno rma l gen ital findings in ch ildren: how well do exa min ers agree? Child Abuse & Neglect 1993 ; 17:663-7 5. Paradi se l E, Win ter MP, Finkel IVIA et al. Influ ence of hi story on physici ans ' interp ret ation of girls ' genit al finding s. Pediatrics J999 ; 10 3 :980- 6. Bu tle r-Sloss E. Report of the inqui ry il1 to child abuse ill Clellelan d 19 87. London: HMSO. Adams JA. Gra nd round s : medica l iss ues and case s tudi es. Sign ifican ce of medi cal findin gs in s uspec ted sex ual a buse: mo vin g towards con sensus. J Child Sex Abuse 1992 ; 1 :9 1-9. Ada ms J A, Ha rper K, Kn ud son S. A proposed syste m for the cla ss ifi cati on of anogenital findings in children with susp ected sex ual abus e. Adolesc Pediatr Gy neco l199 2; 5:73-5. Ameri can Aca demy of Pediatrics Committee on Child Abuse a nd Neg lect. Gonorrhea in prepu berta l children. Pedia trics 1998; 101: 13 4- 5. Ada ms J A. App ro ach to the in terpreta ti on of medica l and labora tory findings in sus pected child sex ual abu se: a 2005 revisio n. Th e APSAC Advisor 200 5; Summer:7-1 3. Royal College of Physi Cia ns of Lond on. Physical Sig ns of Se.rual A bus e in Child re n. Lond on: Lav enham Press , 1997. Ro yal College o f Paediatrics a nd Child He alth. Th e physical

signs of child sexu al abuse. A n elJ ide nce-based relJ iew and gu idance fo r best pra ctice. Lo nd on, RCPCH.

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48 Heger AH, Ticson L, Guerra L et al. Appearance of the genitalia in girls selected for non-abuse: review of hymenal morphology and non-specific findings. ] Pediatr Adolesc

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Berenson AB. A longitudinal study of hymenal morphology in

the first 3 years of life. Pediatrics 1995; 95:490-6. Yordan EE, Yordan RA. The hymen and Tanner staging of the breast. Adolesc Pediair Gynecol1992; 5:76-9. McCann J, Wells R, Simon M, Voris J. Genital findings in prepubel1al girls selected for nonabuse: a descriptive study. Pediatrics 1990; 86:428-39. Berenson AB, Heger, AH, Hayes, JM et al. Appearance of the hymen in prepubertal girls. Pediatrics 1992; 89:387-94. McCann J, Voris J, Simon M, Wells R. Comparison of genital examination techniques in prepubertal girls. Pediatrics 1990; 85:182-7. Gardner JJ. Descriptive study of genital variation in healthy, nonabused premenarchal girls.] Pediatr 1992; 12:251-7. Berenson AB, Chacko MR, Wiemann CM et al. A case-control study of anatomic changes resulting from sexual abuse. Am ] Obstet Gynecol 2000; 182:820-34. Berenson A, Heger, A, Andrews, S. Appearance of the hymen in newborns. Pediatrics 1991; 87:458-65. Emans SJ, Woods ER, Flagg NT, Freeman A. Genital findings in sexually abused, symptomatic and asymptomatic girls. Pediatrics 1987: 79 :778-85. Heppenstall-Heger A, McConnell G, Ticson L et al. Healing patterns in anogenital injuries: a longitudinal study of injuries associated with sexual abuse, accidental injuries, or genital surgery in the preadolescent child. Pediatrics 2003; 112:829-37. Kerns DL, Ritter ML, Thomas RG. Concave hymenal variations in suspected child sexual abuse victims. Pediatrics 1992; 90:265-72. Hobbs CJ, Wynne JM, Thomas AJ. Colposcopic genital findings in prepubertal girls assessed for sexual abuse. Arch Dis Child 1995; 73:465-9. Cantwell H. Vaginal inspection as it relates to child sexual abuse in girls uncler thirteen. Ch ild Abuse Et Neglect 1983; 7:171-6. White ST, Ingram DL, Lyna PRo Vaginal introital diameter in the evaluation of sexual abuse. Child Abuse Et Neglect 1989; 13:217-24. Kerns DL. Cool science for a hot topic. Child Abuse Et Neglect 1989; 13:177-8. Paradise JE. Predictive accuracy and the diagnosis of sexual abuse: a big issue about a little tissue. Child Abuse Et Neglect 1989; 13:169-76. Heger A, Emans SJ. Introital diameter as the criterion for sexual abuse. Pediatrics 1990; 85:222-3. Hobbs CJ, Wynne JM. Buggery in childhood: a common syndrome of child abuse. Lancet 1986; ii:792-6. McCann J, Voris J, Simon M, Wells R. Perianal findings in prepubeltal children se.iected for nonabuse: a descriptive study. Child Abuse Et Neglect 1989; 13:179-93. Priestley B. Reflex anal dilatation and abuse. Lancet 1987; ii:1396. Stanton A, Sunderland R. Prevalence of reflex anal dilatation in 200 children. EM] 1989; 298:802-3. Clayden G. Reflex anal dilatation associated with severe chronic constipation in children. Arch Dis Childh 1988; 63 :832-6. Agnarsson U, Warde C, McCarthy G, Evans N. Perianal appearances in childhood constipation. Arch Dis Childh 1990; 65:1231-4.

45

73 Hobbs CJ, Wynne JM. Sexual abuse of English boys and girls: the importance of anal examination. Child Abuse Et Neglect 1989; 13:195-210. 74 Berenson AB, Somma-Garcia, A, Barnett, S. Perianal findings in infants 18 months of age and younger. Pediatrics 1993; 91 :838-40. 75 Finkel MA. Anogenital trauma in sexually abused children. Pediatrics 1989; 84:317-22. 76 McCann J, Voris J, Simon M. Genital injuries resulting from sexual abuse: a longitudinal study. Pediatrics 1992; 89:307-17. 77 McCann J, Voris J. Perianal injuries resulting from sexual abuse: a longitudinal study. Pediatrics 1993; 91:390-3. 78 Muram D. Child sexual abuse: Relationship between sexual acts and genital findings. Child Abuse Et Neglect 1989; 13:211-16. 79 Adams J, Harper K, Knudson S, Revilla J. Examination findings in legally confirmed child sexual abuse: it's normal to be normal. Pediatrics 1994; 94:310-17. 80 Adams JA, Knudson, S. Genital findings in adolescent girls referred for suspected sexual abuse. Arch Pediatr Adolesc Med 1996; 150:850-7. 81 Heger A, Ticson L, Valesquez 0, Bernier R. Children referred for possible sexual abuse: medical findings in 2384 children. Child Abuse Et Neglect 2002; 26:645-59. 82 Slaughter L, Brown CRV, Crowley S, Peck R. Patterns of genital injuIY in female sexual assault victims. Am ] Obstetr Gynecol 1997; 176: 609-16. 83 Kellogg ND, Menard SW, Santos. A. Genital anatomy in pregnant adolescents: 'Normal' does not mean 'Nothing happened'. Pediatrics 2004; 113 :e67-9. 84 Paradise JE, Campos JM, Friedman HM, Frishmuth G. Vulvovaginitis in premenarchal girls: clinical features and diagnostic evaluation. Pediatrics 1999; 70:193-8. 85 Straumanis JP, Bocchini JA. Group A beta-hemolytic streptococcal vulvovaginitis in prepubertal girls: a case report and review of the past twenty years. Pediatric Inject Dis] 1990; 9:845-8. 86 Pierce AM, Hart CA. Vulvovaginitis: causes and management. Arch Dis Childh 1992; 67:509-12. 87 Jenny C, Kirby P, Fuquay D. Genital lichen sclerosus mistaken for child sexual abuse. Pediatrics 1981; 83:597. 88 Handfield-Jones SE, Hinde FR, Kennedy CT. Lichen sclerosus et atrophicus in children misdiagnosed as sexual abuse. EM] 1987; 294: 1404-5. 89 Muhlendahl KE. Suspected sexual abuse in a 1O-year-old girl. Lancet 1996; 348:30. 90 Bond GR, Dowd MD, Landsman I, Rimsza M. Unintentional perineal injury in prepubescent girls: A multicenter, prospective report of 56 girls. Pediatrics 1995; 95:628-31. 91 Kellogg ND, Parra JM. Linea vestibularis: a previously undescribed normal genital structure in female neonates. Pediatrics 1991; 87 :926-9. 92 Kellogg ND, Parra JM. Linea vestibularis: follow-up of a normal genital structure. Pediatrics 1993; 92:453-6. 93 Johnson CF. Prolapse of the urethra: Confusion of clinical and anatomic characteristics with sexual abuse. Pediatrics 1991; 87 :722-5. 94 Wallis SM, Walker-Smith J. Case report: an unusual case of Crohn's disease in a West Indian child. Acta Paediatr Scand 1976; 65:749-51. 95 Sellman SPB, Hupertz VF, Reece RM. Crohn's disease presenting as suspected abuse. Pediairics 1996; 97:272-4. 96 Friedrich WN, Grambsch P, Broughton D et al. Normative sexual behavior in children. Pediatrics 1991; 88:456-64. 97 Friedrich WN, Fisher J, Broughton D et al. Nonnative sexual behavior in children: a contemporary sample. Pediatrics 101 :e9.

46 I


98 Neinstein LS, Goldenring J, Carpenter S. Nonsexual transmission of sexually transmitted infections: an infrequent occurrence. Pediatrics 1984; 74 :2 17-25. 99 American Academy of Pediatrics. Sexually tra nsmitted diseases. In Pickering LK (ed .) Rep ort oj th e Co mmittee on InJectious Diseases, 26th ed n. Elk Grove Village, lL: Ballinger, 2003, pp. 157-67. 100 Am erica n Aca demy of Pediatrics Co mmi ttee on Child Abuse and Neglect. The eva luation of sexua l abuse of children. Pediatrics 2005; 11 6:506-12. 101 In gra m DL, Everet t D, Lyna PR et al. Epidemi ology of adult sexually transmitted disease agents in children being evaluated for sexual abuse. Pediatr Inject Dis J 1992 ; 11 :9 45-50. 102 Robinson AJ , Watkeys JEM, Ridgway GI. Sexually tra nsmitted organisms in sexually abused ch ildren. Arch Dis Childh 199 8 ; 79: 356-8. 103 In gram DM, Miller WC, Schoenbach VJ et al. Risk assessment for gono co cca l an d ch lamy dial infec tions in young children underg oing evalua tion for sexua l ab use. Pediatrics 2001: 107 :e73-80. 104 Th o mas A, Forster G, Robinson A, Rogsta d K for the Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study o f Venereal Diseases). Nation al guideline for th e management of suspected sexu ally transmitted infections in children a nd yo ung people. Sex TrailS Inject 2002; 78:324-31 . 105 Handl ey J, Dinsmore W, Maw R et aJ. Anogenital warts in children; sexual abuse or not? Int J STl ft AIDS 1993 ; 4:271-9. 106 Si eg fri ed E, Rasnick-Conley J, Co ok S et al. Human pap ill o mavirus screening in pediatric victims of sexual abuse. Ped iatrics 1998 ; 101 :43- 7. 107 Steele AM , de Sa n Lazaro C. Transhymenal cultures for sexually transmissible organisms. Arch Dis Childh 1994; 71 :423-7.

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108 Embree JE, Lindsay D, William s T et al. M. Acceptability a nd use fulness of vaginal washes in premenarch eal girls as a diagnostic procedure for sexua lly transmitted infections. Pediatr Inject Dis J 1996; 15 :651-66. 109 Mok JYQ. Routine Hrv testing after child sexual abuse? Child Abuse ReI! 1998; 7:6 3-9. 110 Muram D, Spe ck PM, Gold SS. Genital abnorma lities in female siblings and friends of child victims of sexual abuse. Child Abuse ft Neglect 1991 ; 15: 105-10. III Bays J, Ch adwic k, D. Med ical diagnosis of the sexually ab used child. Ch ild Abuse ft Neglect 199 3; 17:9 1-11 0. 112 Muram D. Child sex ual ab use. Curl' Opin Obstetr GYllecol 1993 ; 5:784-90. 11 3 De Jong AR, Rose M. Legal proof of child sex ual abuse in the absence of physical evidence. Pediatrics 199 1; 88:506-11. 114 Kerns DL. Triage and referral s for child sexual a buse medical examinations: Which children are likely to have positive medical findings? Ch ild Abuse ft Neglect 1998 ; 22:515-18. 115 Chadwick DL, Krous HF. Irresp ons ibl e testimony by medical ex perts in cases involv ing th e physica l abuse and neglect of ch ildren. Child Maltreatment 1997; 2: 313 -21. 116 Adams JA. Th e role of photo do cu mentati on of genital findings in medical evaluations of suspected child sexual abuse. Child Maltreatment 1997; 2:341-7. 117 Mok JYQ, Busu ttil A. Medical exa minati ons for Child Sex ual Abuse in Scotla nd: good enough practice? Child Abuse Revi ew 2004; 2004; 13:324-37. 118 Jen ny C. Pediatric fellowships in child abuse and neglect: the development o f a new subspecialty. Child Maltreatment 1997; 2:356-61. 119 Emans SJ, Woods ER, Allred EN, Grace E. Hymena l findings in adolescent wo men: impact of tampon use an d consensual sexual activity. J Pedlatr 199 4; 125: 153-60.

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CHAPTER 3

I

RADIOLOGY OF CHILD ABUSE Maeve McPhillips

Role of the radiologist Radiological investigations Skeletal injuries Head injury Visceral injuries

47 48 51 60 68

Child abuse has been a concem of paediatric radiologists since Caffey's description of multiple fractures in children with a subdural haematoma in 1946. He describes fractures of the long bones as a 'common complication of infantile subdural haemato ma' and, although suggesting that there is a trau matic origin, states that 'the causal mechanism remains obscure'.! In 1971 , Guthkelch, a British neurosurgeon, first proposed shaking as a cause of infantile subdural haematoma, and the following year Caffey published his paper 'On the theory and practice of shaking infants'. 2,J Since then, non accidental injury has been a subject of great importance to those who have responsibility for the care, diagnosis and investigation of children who may have been victims of abuse. Teams of clinicians work closely together, aware that only when they are in possession of all the information available about the child can the correct diagnosis be reached.

ROLE OF THE RADIOLOGIST Paediatric radiologists have expertise in the interpretation of imaging of in fants and children and a familiarity with the appearances of the normal brain and ske leton. The appeara nces of the skeleton and brain followin g accidental trauma will be well known to them, and they will have an understanding of possible mechanisms of injury, and so be able to judge whether the given history is appropriate for the injury. The first role of the radiolo gist is to be alert for injuries that, in the light of the history supplied, may not have

Soft-tissue injury Differential diagnosis Conclusion References

69 69 73 73

occurred accidentally, or have been identified as incidental findings on a radiograph performed for another purpose. Such cases w ill need to be discussed with the referring clinician . When referred a case of possible non-accidental injury, the radiologist should review the presenting injury, and discuss the patient with the clinician. A knowledge of nor mal skeletal development and variations in ossification can prevent unn ecessary investigation. 4 - 7 There shou ld be a recognized departme ntal protocol for a skeletal survey for suspected non - accidental injury and all im ages should be reviewed by the radiologist before the child leaves the department. Th is is to ensure high-quality images and to allow for any necessary supplementary views. An assess ment should be made of the age of any injuries. The possi bility of an underlying bone disease or other condition, together w it h the need for appropriate im aging, should be considered at this stage. The report should be commun icated verb ally to the responsible clin ician as soon as is practicable and a formal written report issued promptly. If there is doubt as to the presence or significance of a lesion, this should be clearly stated together w ith a plan of investigation to clarify the findings. The need for further imaging, in particular neuro imaging, should be discussed with the clinician at th is stage. The radiologist should be available for any discus sions with clinicia ns and members of the chi ld protection team, including the police. Because of the possibility of child protection or other legal proceedings, all images and reports should be retain ed in a secure place.

48 I

Radiology of child abuse

RADIOLOGICAL INVESTIGATIONS

A separate exposure should be obtained of each anatomical area to optimize image quality, reduce geomet ric distortion and allow for the detection of subtle abnor malities. At least two views of the skull should be obtained. Both oblique views of the ribs should be obtained routinely. Two perpendicular views should be obtained of any focal injury. Coned views of the metaphyses, in anteroposterior (AP) and lateral projections, may be helpful to confirm or exclude classic metaphyseal lesions. The skeletal survey is not an emergency investigation and should be performed during the standard working day. It requires two radiographers and a lo t of time. It should be performed in the radiology department unless the child is critically ill , in which case it may be performed using mobile radiography equipment in the paediatric intensive care unit. Image quali ty may be compromised in this situation. Most radiol ogy departments no longer use hard-copy radiographs for reporting. Soft-copy reporting has been shown to be superior to hard copy owing to its abil ity to vary the grey -scale settings and to magnify sections of the image selectively. 13

Skeletal Survey The radiographic skeletal survey is the mainstay of investi gation of non-acc idental injury in yo ung children and infants. There has been much variability in the quality of exa minations 8,9 a nd national stand ards have been intro duced by the American Academy of Paediatrics, JO the American College of Radiology,l1 the Royal College of Radiology and the Royal College of Paediatrics and Child Health. 12 Table 3.1 shows a suggested protocol. A ' babygram' of the whole body with a si ngle exposure or coverage of the whole body using th ree or four films is inadequate. High-quality radiographs must be obtained with optimum exposure factors and good coning. High resolution cassettes should be used with no grid. The patient name, side marker, and date and time of the examina tio n must be clearly visib le on the radiograph . The names of the radiographers must be recorded: they should wo rk in pairs. Not only does this allow for increased efficiency in what can be a prolonged investigation, but it provides legal safe guards for both the patient and the ra diographers. The radiograp hers should obtain positive identifi cation of the patient from the accompanying staff or carer and the identity should be checked on the na me band. It is impor tant that the responsible clinician has discussed the need for the skeletal survey with the parents or caregivers, as they should be allowed to accompany the child during the investigation. It may also be appropriate that a member of the nursing staff is in attendance.

Table 3.1

Follow-up Skeletal Survey If there is ongoing clinical concern, the skeletal survey should be repeated in 10-14 days, apart from the skull radiographs. This is particularly relevant if the presentation has been with head injury and the initial skeletal survey has been normal. If there are areas of radiological concern, repeat radiographs should be obtained of these areas, also at lO-14 days (Fig. 3.1). For patients in whom there is no particular diagnostic unceltainty, it is still important to obtain repeat chest radio graphs, including obliques, and views of the id entified bony abnormalities. It has been shown that repeat skeletal surveys can identify a greater number of fractures, particularly of ribs, and can confirm suspected fra ctures. 14-16 Lack of change over time can confirm a normal valiant. Radio grap hs taken on two separate occasions can also help more accurate dating of injury and show evidence of different ages of injuries.

Suggested protocol for initial skeletal survey

Skull

Spine Chest

Abdomen Limbs

Supplementary

AP and lateral views Towne's view if occipital injury suggested clinically Lateral views of cervical, thoracic and lumbosacra l sp ine AP to include clavicles Lateral Oblique views of both ribs - each to include whole chest AP whole abdomen, to include pelvis and hips AP both upper arms AP both forearms PA both hands AP both femora AP both lower legs AP both feet Additional views of any questionable areas AP and la tera l coned vie ws of metaphyses

Post-mortem Skeletal Survey The same high standards should be applied to the examina tion of the deceased child as to the live child. A 'ba bygram' should not be performed . Individual exposures of each anatomical area should be obtained, with particular atten tion paid to the presence of COITect identifiers on each image. The skeletal survey must be obtained prior to the autopsy (Fig. 3.2). If necessary, the autopsy should be delayed to allow this. The reporting radiologist should co mmunicate his or her findings to the pathologist as soon as possible. A verbal report will suffice, as long as it is documented in the notes and in the final radiological report. Detailed radiography of removed specimens of bone can be very

AP, anteroposterior; PA, posteroanterior.

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Radiological investigations I

49

helpful (Figs 3.3 and 8.1, p. 147). Perpendicular views shou ld be obtained of all bones. For the ribs this mean s that the additional view is an axial , or supero-inferior image. 17, 18

Ultrasound Ul trasound is not used routinely in the assessment of non accidental musculoskeletal injury, mainly because of its

Figure 3.2 Skeletal survey following a post- mortem showing bowel in the chest. Known rib fra ctures are obscured by bowe l.

Figure 3.1 (a) Admission film. Healing fracture s of the necks of the seventh , eighth, ninth and tenth ribs can be seen on the left as we ll as a mid-shaft fra cture of the clavicle. (b) Follo w-up fi lm 12 days later. Now visible are healing fra ctures of the left clavicle and of the necks of the fifth to eighth ri bs on the left and of the sixth to ninth ribs on ri ght. The left tenth rib has compl etely remodelled in the 12-day interval and the ninth rib is identifiable only by minimal irregul arity.

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Figure 3.3 Subtle metaphysea l fra cture identified on post mortem skeletal survey prior to autopsy. High-definition specimen radiograph following stripping of soft tissues. The irregu larity in the distal femoral metaphysis was co nfirmed by histo logy to be a fracture. It was not palpable.

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Figure 3.4

Transfontanellar high-resolution ultrasound image.

Cystic cavities (arrows) at the junction of the grey and white matter are tears caused by shearing.

dynamic, operator-dependent nature. Positive findin gs will need to be documented using a nother imaging modality. Ultrasound can be used, particularly in the very young child, to assess cartilaginous epiphyseal fracture-separation, which may be underdiagnosed radiographically. 19,20 Its use has also been described in the detection of rib fractures. 21 The use of transfontanelJar ultrasound is more esta blished although it is still a subjective examination and not useful i~ a legal setting, as experts find it difficult to review another operator's images. It is easily performed in the clitically ill infant at the bedside and has a definite role in the manage ment of an infant with head injUly, to monitor extra-axial collections, ventricular dilatation and intracranial blood flow. High-resolution ultrasound using high-frequency probes (10 MHz) can differentiate subarachnoid from subdural fluid, particularly when colour-flow imaging is used, Con tusional tears at the grey-white matter junction can be demonstrated elegantly and may not be visualized on com puted tomography (CT) (Fig. 3.4). Fresh tears may contain a clot and older tears appear cystic; these cysts may later col lapse. 22 Collapsed tears may be overlooked at autopsy unless specifically targeted. Fluid is well visualized by ultrasound as free intraperi toneal or pleural fluid. The liver, spleen and kidneys are easily assessed by ultrasound, with an accuracy of 94 per cent,23 but CT is more widely used in th e assessment of blunt abdominal trauma. 24

Computed Tomography Prior to the development of CT for neuroimaging, subdural haemorrhage was identified indirectly by cranial angiography

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or air encep halography, or at post-mortem examination. In accidental and inflicted head injury, CT shows different patterns of injury.25.26 It is the imaging modality of choice for suspected brain injury. lt is recommended as part of the investigation of all suspected non-accidental injuries in children less than 1 year of age. 12 There is some controversy about this, particularly in a child with no neuroloo'ical '" abnormality, regarding the radiation burden. If neuroimag ing is not performed, the rea son should be documented in the patient's notes. After presentation of a non-accidental injury, CT scan ning should be performed as soon as possible, without intravenous contrast. This method of imaging is widely available, easily performed, and fast. With newe r scanners the need for sedation or general anaesthesia in the restless child is less. Standard brain and bone windows should be provided. Acute haemorrhage is readily visualized, even in the subarachnoid space. Lesions requiring neurosurgical intervention are reliably seen. Changes of brain oedema can be subtle and may be missed. Known fractures, visible on skull radiography, may not be visible on CT images, as they may lie in the plane of the imageY Three-dimensional (3D) volume rendering may be helpful in identifying frac tures or, indeed, in differentiating normal variants, such as parietal fissures, accessory sutures and synchondroses, from suspected fractures. 28 This imaging modality can be used to assess the bony integrity of th e cervical spine and fractures of the facial bones. 28 Suspected visceral trauma may also be investigated using contrast-enhanced CT. Although not used routinely, post-mortem CT scanning may be useful, particularly as the normal limitations to dose no longer apply and a high-resolution volumetric scan can be obtained in a very short tim e. Owing to the amount of data produced, reporting such an investigation will be time consuming for th e radiologist but may give considerable further information about metaphyseal and rib fractures.

Magnetic Resonance Imaging Magnetic resonance imaging (l'v1RI) is complementary to CT scanning. Although l'v1RI is less sensitive for acute haemor rhage, especially in the subarachnoid space, it elegantly demonstrates subacute subdural haemorrhage, contusions and oedema (Fig. 3.5). Images should be obtained in transverse, coronal and sagittal planes. The recommended sequences are T1-weighted, T2-weighted, FLAIR (fluid-attenuated inversion recovery), gradient echo, which is sensitive to blood products and detects small areas of haemorrhage, and diffusion weighted imaging/apparent diffusion coefficient (OWl/AD C), which demonstra tes areas of evolving brain injury, in parti cular areas of hypoxia-ischaemia. After presentation, an l'v1RI should be ca rried out as soon as possible. Because the signal from the damaged tissue normalizes after 7 days, OWl is most useful in the first week. 29 It may be appropriate to assess vas cul ar structures with mag netic resonance (MR) arteriography

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Skeletal injuries

Figure 3.5 Magnetic resonance scan, Tl-weighted image, showing a fresh small linear subdural in the right posterior parietal region and high signal as a result of fresh haemorrhage (arrows). Overlying this is a scalp haematoma. A skull fracture was not visible on magnetic resonance imaging. and venography, and to use transverse Tl-weighted fat saturated sequences to search specifically for inj ury to the major vessels in the neck. 28 Spinal cord injury is best assessed with MR, using short tau inversion recovery (STIR) sequences. Post-mortem MR scanning has been shown to be more sensitive than autopsy alone in the detection of a shearing injury, cortical haemorrhage and mastoid fluid, and to be equal to autopsy in the demonstration of cerebral oedema, focal contusions and subfalcine herniation. 3D

Scintigraphy Isotope bone scanning, using technetium-99-labelled methylenediphosphonate (99Tc-MDPl, can show bone pathology. In one series,3l 10 per cent of fractures were seen only on scintigraphy, and Mandelstam has shown that 50 per cent of rib fractures may be visible only on isotope bone scanning 32 (Fig. 3.6). The yield from radiography may have improved since the introduction of oblique views of the ribs at presentation. Many fractures also become appar ent on follow-up radiographs. Scintigraphy has a Jow sen sitivity for skull fractures. Because of the high activity in normal growth plates, metaphyseal fractures may not be apparent on isotope bone scanning, particularly if bilateral (Fig. 3.7). Fractures may show increased activity on scintigraphy for up to a year after injury. Any areas of increased activity detected using scintigraphy should

I

51

Figure 3.6 Isotope bone scan of the upper body show ing multiple areas of increased uptake in the posterior ribs, representing fractures of the posterior shafts at their necks. A spi ral fracture of the left humeral shaft is identifiable by the asymmetrical uptake in the humeri. therefore be further assessed by radiography. Bone scintig raphy is complementary to radiographic skeletal survey, and may be useful in individual patients.

SKELETAL INJURIES Fractures in child abuse are most common in infants and children under 2 years of age. It is convenient to separate fractures into two groups: (a) those that are seen fre quently, but are not very specific for non-accidental injury; and (b) those that are highly specific for inflicted injury but are less commonly seen (Tables 3.2 and 3.3).33

Periosteal New Bone Fractures repair by the laying down of subperiosteal new bone. With no obvious fracture, the presence of sub periosteal bone may be due to injury to the periosteum by rough handl ing, or by acceleration-deceleration forces during shaking. Physiological periosteal reaction is seen in normal infants as young as 8 weeks, up to about 8 months of age. It is smooth, rarely more than 2 mm in thickness and is seen along the diaphyses of the long bones. It is usu ally symmetrical, though may be more obvious on one side.

Long-bone Fractures Diaphyseal fractures of long bones are common in non accidental injury; some authors have found them to be four

52 I


(a)

PO :;. T

LT

Table 3.2

Fractures that are frequent but with low specificity for non-accidental injury

Midclavicular fractures Simple linear skull fractures Single diaphyseal fractures Reproduced with pe rmission from Cart y33

Table 3.3

Fractures considered to have a high specificity for

child abuse

Meta physeal fractures Rib fractu res Scapular fractures Fractures of the outer end of the clavicle Vertebral fractures or subluxations Finger injuries in non-ambulant children Fractures of different ages Bilateral fractures Complex skull fractures (b) Reproduced wi th permission from Carty33

Figure 3.7 Isotope bone scans of lower body. (a) Posteroanterior view shows metaphyseal fracture of the left proximal tibia (arrow). (b) Lateral view of lower limbs. The fracture cannot be seen. A posterior rib fracture is visible in the lower left chest (arrow). times more common than the more specific metaphyseal fracture. J4 It is important to correlate the appearance of the fracture with the clinical history (Fig. 3.8). Suspicion of abuse increases when there is evidence of healing, indicating a delay in seeking medical care for a child in pain. Excessive callus formation is seen owing to movement at a fracture site, causing repetitive subperiosteal bleeding (Fig. 3.9). Multiple fractures, especially in different stages of healing, without an obvious history of significant trauma, suggest at least poor parenting. In the presence of a

.

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Figure 3.8 A 6-week-old infant presented to the accident and emergency department. The mother gave a story of the child waking up and not using her arm, saying she must have caught it in the cot bars. The story is inappropriate for this fracture, which was almost certainly caused by the child being roughly lifted by this arm.

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Skeletal injuries I

53

Figure 3.10 A 14-year-old boy who died as a result of abuse. Fractures of shafts of rad ius and ulna. These are typical defensive fractures sustained when the arm is held up to ward off a blow from an assailant.

Figure 3.9 Toddler presenting with severe head injury. The radiograph shows a new buckle fracture of the distal radius and ulna and an older, untreated supracondylar humeral fracture, with resulting extensive subperiosteal reaction. fracture of high specificity, a diaphyseal fracture takes on increased significance. An isolated shaft fracture becomes more suspicious when there is other evidence of physical abuse, such as bruising. Bilateral forearm fractures in infants and toddlers are worrying beca use young children do not ex hibit the normal protective instinct to break their fall using their outstretched arms .34 There are welJ-recognized mechanisms for typical spiral, oblique and transverse fractures. The described mechanism given in the history should be assessed for each individual fracture. It should be remembered that non-accidental injury may occur when the limb is used to lift or drag the child, or if the child is thrown, or be the result of direct injury. In par ticular, transverse fractures of the forearm bones can be sus tained as defensive injuries to ward off a blow (Fig. 3.10). It should be remembered that infants who cannot yet roll over are unlikely to fall off an elevated surface and that reported falls in children who are not yet cnlising should raise suspi cion. 35 It is, therefore, important to know the degree of mobility of the individual child. The spiral fracture of the

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tibia, the 'toddler's fracture', is very commo n as children start to walk. Impaction fractures in the lower limbs appear as torus or 'buckle' fractures, and are caused by transmission of force vertically up the shaft of the bone when the child is forcibly thumped down onto a hard surface in the standing position (Fig. 3.11).

Metaphyseal Fractures Although these are highly specific for non-accidental injury in infants less than 1 year of age, they are seen in only 11-39 per cent of children surveyed. 36 .37 Their detection depends on the quality of the radiography and they may be seen as cor ner or 'chip' fractures, suggesting local avulsion, or as 'bucket-handl e' fractures depending on the projection. They are more commonly seen in the lower limb, but are also seen in the upper limb. They can be caused by shaking, but, when seen in a single limb, a twisting, pushing or pulling mecha nism may be responsible. This description is supported by the report of classic metaphyseal fractures in a group of children being treated for clubfoot, in whom the foot was pushed and twisted into forced eversion and dorsiflexion before being put into a cast. 38 Similar fractures are recognized rarely following Caesarean section,39 a breech delivery or an armling delivery. Metaphyseal corner fractures do not require any specific treatment. They are not palpable.

54 I


Figure 3.11 Healing impaction fracture of the distal femoral shaft with disruption of the normal contour anteriorly and subperiosteal new bone (arrows). The apparent defect in the anterior tibia is not a further fracture but is the site of the unossified tibial tubercle.

These classic metaphyseal lesions are planar fractures through the primary spongiosa of the metaphysis, with tra becular disruption giving rise to a disc of bone and cartilage. At the periphery, adjacent to the periosteal collar, there are more trabeculae so the fragment is denser there. The increased visibility of the peripheral bone gives rise to the radiographic appearance of a comer fracture, sometimes with a subtle metaphyseal lucency. An oblique view of the metaphysis may demonstrate the disc-like fracture fragment. Some bones, such as the tibia, are more likely to show a 'bucket-handle' appear ance, as the metaphysis is relatively straight (Fig. 3.12). The comer fracture appearance is more likely to be seen in meta physes with a more complex appearance, such as the proximal humerus or distal femur 40 (Fig. 3.13). The fracture may be

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Figure 3.12 (a) Anteroposterior and (b) lateral views of typical bucket handle metaphyseal fracture of the distal tibia (arrows).

incomplete and not pass through the whole metaphysis. Volu metric CT imaging of metaphyseal fractures may demonstrate the disc-like fragment, but would appear to be unwalTanted except in specific cases, or for research purposes. Appearances during healing are variable. The fracture may become more

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Skeletal injuries I

Figure 3.13 Typical metaphyseal corner fracture seen at the posterior aspect of the distal femur (arrow).

55

Figure 3.15 Metaphyseal fractures of the distal femur and proximal tibia with periosteal new bone along the lateral aspect of the proximal tibial metaphysis. Periostea l new bqne along the medial tibia, lateral fibula and femur is confined to the diaphysis and is probably physiological. Reproduced with permission from Carty33

Figure 3.14 Coned view of the ankle showing a healing corner fracture of the posterior tibia and a fresh corner fracture anteriorly. The healing posterior fracture shows periosteal new bone.

apparent, maximal at 10-14 days. Frequently, there is no other evidence of healing as the periosteum may not be disrupted. If it has been, there may be faint subperiosteal new bone forma tion, although more extensive new bone formation can result in thickening of the adjacent cortex and a squaring off of the metaphyseal contour40 (Figs 3.14-3.16). Healing is usually complete within 6 weeks (Fig. 3.17). Extensive periosteal

Figure 3 .16 Healed metaphyseal fracture of the right proximal humerus with subtle irregularity and sclerosis. No evidence of subper iostea l new bone formation. Healing fractures of two posterior ribs are visible (asterisks).

56 I


Figure 3.17 Close-up view of the knee. The lucent lines on the distal femur and medial half of the proximal tibia are healed metaphyseal fractures. reaction extending up the shaft of the bone can suggest local trauma, perhaps a result of forceful gripping of the bone (Figs 3.18-3.21).

Epiphyseal Plate Injury An epiphyseal plate injury may be identified using a radi ographic skeletal survey but, without a metaphyseal com ponent, when the epiphysis is un ossified they may be missed. Ultrasound or MR scanning can show displacement of the epiphysis and confirm the presence of a fracture/sep aration injury, and should be considered in a child who does not use a limb and with no obvious explanation on the skeletal survey.19

Rib Fractures In infants and young children, rib fractures are highly spe cific for non-accidental injury. They can be seen in signifi cant accidental trauma, such as motor vehicle accidents, or in infants with bone disease, such as rickets or bone disease of prematurity.41,42 They are recognized as occurring rarely as a result of birth trauma, presumably because of pressure from

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Figure 3.18 Healed metaphyseal fracture of the distal tibia, lateral view, showing squared contour and slight irregularity. There is irregular periosteal new bone extending proximally up two-thirds of the shaft of the tibia, a disproportionate reaction for a relatively minor fracture. the maternal symphysis pubis, in which case there will prob ably be a history of a large baby and a difficult deJivery.43.44 Rib fractures are splinted by adjacent soft tissue and neighbouring ribs. They may result in mild respiratory dis tress. If several ribs are fractured in more than one loca tion, this will give rise to a flail segment of chest wall, with more severe respiratory consequences. In child abuse, although ribs may be fractured by direct trauma and impact, or by compression by kneeling on the chest, the usual mechanism of injury is squeezing of the chest by the perpetrator's hands. The infant is held facing the adult, with the fingers on the back of the chest, the palms at the side and the thumbs in front. Pressure causes anteroposterior compression of the rib cage. Although fractures can be seen anywhere along the rib arc, the most characteristic fracture site involves the posterior rib, at the rib head and the costovertebral junction45 (Figs 3.1, 3.6 and 3.7, pp. 51-52). This is due to leverage of the poste rior rib on the fulcrum of the transverse process of the verte bra, with an adjacent fracture. Similar fractures have also been demonstrated in a cadaver study simulating median sternotomy with rib retraction. 46 In the same paper, a study was done comparing sternal compression and AP manual compression in rabbits. No rib fractures were seen following

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Skeletal injuries I

Figure 3.20

57

Healing metaphyseal fracture of the distal humerus

with gross periosteal new bone extending almost to the proximal meta physis.

Figure 3.19

(al Admission radiograph. Tiny metaphyseal

fractures of the distal tibia and fibula (arrows). There is soft-tissue swelling of the calf. (bl Follow-up film shows massive healing subperiosteal new bone, mainly due to healing of a subperiosteal haematoma, the extent of which was totally inappropriate for the tiny fracture. This represents very extensive trauma to the leg.

sternal compression on a firm surface and the posterior ribs showed no change in their relationship to the spine; however, fractures did occur with manual compression. Lateral rib fractures are due to the compressive force on the ribs and are

-...

.

,

-

Figure 3.21

Healing bucket handle metaphyseal fractures of the

distal tibia bilaterally with disproportionate periosteal new bone formation. Irregular periosteal new bone on the fibular diaphyses bilaterally. The appearances probably represent a direct gripping injury.

~

58 I


shown at autopsy to have distraction of their outer surface and impaction of the inner surface 47 (Figs 3.22 and 3.23). Fractures of the anterior ends of the ribs involve the costo chondral junction. These show disruption of the posterior surface, which may be a result of direct pressure from the thumbs. Rib fractures may be difficult to see unless there is some displacement. Only 36 per cent of fractures identified at autopsy were visible on the skeletal survey in Kleinman 's study.47 Lateral rib fractures may show adjacent extrapleural opacity, owing to focal haemorrhage and pleural reaction. Posterior lib fractures may also be obscured by the trans verse processes. Oblique views of the ribs are useful in detec tion of both posterior rib fractures and fractures at the costochondral junction. However, many rib fractures do not become visible until the follow-up radiograph shows callus formation. Volumetric CT scanning of the thorax may reveal rib fractures, but the radiation dose associated would pre clude its routine use for this purpose. Specimen radiography of resected ribs should be per formed in both the frontal and the axial projections. There have been studies of children which have shown no radiographic evidence of lib fractures resulting from car diopulmonary resuscitation (CPR)48.49 A recent studyS° found autopsy evidence of rib fractures in 11 per cent of 70 infants who received CPR immediately before death. The fractures were all anterolateral, linear and often bilateral. There was little, if any, associated blood and no reactive change.

Figure 3.22 Child admitted moribund. Healed fractures right sixth and seventh ribs postero'atera"y (arrows) plus fresh corner fracture proximal right humerus (white arrow). The healed left clavicular fracture could be a birth injury.

.

Spinal Trauma

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Severe spinal trauma is much less common than other frac tures in non-accidental injury. It may be underdiagnosed, but routine lateral radiographs of the whole spine (Fig. 3.24) and follow-up skeletal surveys may increase its identification. Vertebral body fractures are thought to be due to hyper flexion. This may be during a shaking episode, holding the child by the chest or the shoulders, or by slamming the child down onto a hard surface on the buttocks, transmit ting the force vertically up the spinal column. These may be anterior compression fractures, fractures extending to the superior end plate, or a combination of the two. The superior end plate fracture is thought to be similar to the classic metaphyseal fracture.5l Fractures may also occur of the spinous process, with a similar mechanism. The carti lage tip of the spinous process may be avulsed with only a small fragment of bone, which may be recognized on the lateral spine radiographs. If diagnosis is delayed, the mar gins of the avulsed fragment may be irregular, no longer matching the defect in the spinous process. This is due to further growth of the avulsed fragment. 52 Fracture disloca tion of the spine may occur, which can be associated with cord compression and long-term neurological damage. It is described at any level in the spine, including the sacrococ cygeal region. It may present as an unexplained kypho sis. 53-56 Traumatic spondylolysis of C2 , the hangman's fracture, has been described with anterior subluxation of C2 on C3. 57 Full visualization of the vertebral injury may

Figure 3.23 There are multiple healing rib fractures in both axillae with periosteal new bone around the fractures.

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Skeletal injuries I

require CT, but MRI will be necessalY to exclude a ny asso ciated cord injury.

Digital Injuries Injuries to the metacarpals, metatarsals and phal a nges are uncommon, but have a high specificity for abuse. They are usually torus fractures, and the mechanism is thou ght to be twisting, bending or hyperextension 58 (Fig. 3.25). Crush fractures may also be seen.

59

fracture healing. A radiologist whose practice involves paedi atric trauma will have co nsiderable experience in the report ing of acute and healing fractures, when the timing of the injUly is precisely known . This can then be extrapolated to the appearance of fractures for which there is an inad equate history. Despite the lack of published data, there is remark able agreement between radiologists. Approximate dating of

Other Bony Injuries Fracture of the outer end of the clavicle usuall y resu lts from a fall. A midclavicular frac ture may be as a res ult of birth trauma and an appropriate histOlY should be sought. Fractures of the acrom ion and the body of the scapula 56 ,59 (Fig. 3.2 6) have been described, as have sternal fractures. GO Pelvic fractures usually involve the superior pubic rami. 61

Dating of Injuries Precise dating is impossible. Accepted g uidelines ha ve been published (Table 3.4),62,63 but there have been few studies of Figure 3.25

Healing fractures of the bases of the proximal

phalanges, great and little toes, due to hyp erexte nsion injuries.

Figure 3.24 Lateral view of the lumbosac ral spine show in g compression fracture of L2 (arrow) with a mild lum bar kyphosis.

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Figure 3.26 Ossifying haematoma projected over scapula in a child who had been severe ly beaten. Reproduced with permission from Ca rty,s9

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Table 3.4 Dating of fractures (adapted from O'Con~or .IF, Cohen J In: Diagnostic imaging of child abuse. Baltimore: Williams and Wilkins, 1987112)

Soft-tissue resolution Early periosteal new bone Loss of fracture line definition Soft callus Hard callus Remodelling

Time

Peak

2-10 days 4-21 days 10-21 days

4-10 days 10-14 days 14-21 days

10-21 days 14-90 days 3 months to 2 years

14-21 days 21-42 days

Reproduced with permission from Carty] 3 Figure 3.27 Posterior linear parietal skull fracture in an abused child. The only indication that this was caused by abuse was the la ck of clinical history for the fracture.

fractures is always given as a range, with the limits becoming wider as time elapses from the injury. The appearance of sub periosteal new bone formation is the earliest sign of healing. It has been described as being visible as early as 4 days after injury and seen in 50 per cent within 2 weeks.63

HEAD INJURY In non-accidental injury, the infant and young child may suffer injury to the scalp, skull and face, suffer an intracra nial or brain injury, or a combination of the two. Brain injury is the leading cause of mortality and of significant neurological impairment in survivors. 64 - 67 The infant with brain injury may present acutely as encephalopathy or seizures, less acutely as irritability or vomiting, or as a relatively well child with macrocrania or failure to thrive. The initial diagnosis may be of meningitis, apnoea or collapse of unknown cause, or a search may be made for an infectious or gastrointestinal cause for vomiting. Findings suggestive of non-accidental injury may be seen on other investigations, such as incidental healing rib fractures on chest radiographs, or subdural collections on cranial ultra sound. These will then prompt further investigations.

Figure 3.28 Wide diastatic skull fracture, allegedly caused by falling off a sofa. In addition, there is a further extensive linear fracture across the lower part of the skull. bilateral fractures, complex or stellate fractures and grow ing fractures are more common in non-accidental injury74 (Figs 3.28, 3.29 and 14.6, p. 299). Bilateral fractures can be seen in accidental trauma with a fall onto the occiput or the vertex, with symmetrical transmission of force. No sku ll fracture type is characteristic, and in any individual patient the appearance of the fracture alone does not allow ajudgement as to its cause.

Skull Fractures It is important to remember that a child may sustain a skull fracture with no associated brain injury, or may have severe brain injury without a fracture.68 A sk ull fracture requires direct impact or compression. 69 There have been many stud ies of falls, including population studies/ o- 73 showing that skull fractures are unusual in low falls and that a fall from about 1 m is usually required for a skull to fracture. This is the approximate height of a fall from an adult's arms. A typical accidental skull fracture is a unilateral linear parieta l fracture, which is also the most common fracture seen in non-accidental head injury (Fig. 3.27). However

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Dating of Skull Fractures Skull fractures cannot be dated radiographically. Some indication of age may be given by the presence of adjacent

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Head injury I

Figure 3.29 Symmetrical horizontal fractures, which meet in the midline, and an additional linear parietal fracture on the left. There was no clinical history to explain how these fractures were sustained.

soft-tissue swelling, which resolves gradually according to the size of the haematoma. However, care should be taken, as a swelling may appear after some delay as a result of seepage of cerebrospinal fluid (CSF) through a fracture, or enlarge ment of a scalp haematoma during resolution. The clinician should also realize that focal scalp swelling may occur in the absence of an underlying fracture (Figs 3.30 75 and 3.31).

Extradural Haematoma Extradural haematoma is unusual in children, and rare in non-accidental head injury. Radiologically, it is a lentiform collection overlying the brain, tending to compress the underlying brain substance. There may be an associated fracture, with typical tearing of the middle meningeal artery, although venous bleeding can cause an extradural haematoma.

Subdural Haematoma Subdural haemorrhage is caused by bleeding from bridging veins crossing the subdural space, which are stretched and torn when the brain moves excessively relative to the over lying dura. A degree of trauma is required to tear these veins, though the minimum degree is not known. Mechanisms of injury in inflicted trauma are discussed in Chapter 14. Subdural haemorrhage is seen in birth trauma 76 but has been shown to be present in 8-17 per cent of asymptomatic neonates, including 6-26 per cent of spontaneous vaginal

61

deliveries. 77 ,78 Subdural blood was seen most frequently in the posterior fossa, and no interhemispheric blood was seen in either series, of 199 babies in total. Delivery by Caesarean section may still be associated with subdural haemorrhage, as there may be some difficulty in disimpact ing the engaged head. In Whitby's cohort of 111 babies, fol lowed for 2 years, the subdural haemorrhages had all cleared by 4 weeks?7 There were no recurrent bleeds. Accidental trauma can result in subdural haemorrhage, most commonly over the cerebral convexities and at a single site, localized to or opposite the impact, although occasionally, when there has been major trauma, the haemorrhage may spread over the convexity. Interhemispheric haematoma is rare, but is described, and is therefore not specific for inflicted head injury?9 Homogeneous hyperdense haematoma is seen more often in accidental injury, though this changes in the days after presentation in 25 per cent. 79 Subdural haemor rhage is, however, more common in inflicted head injUly. In a series of 100 children admitted as a result of head injury, Duhaime et al 80 identified 76 as accidental and 24 as inflicted. Only three children with accidental head injury had subdural haemorrhage, all of whom had been involved in road traffic accidents. By contrast, ) 3 of the 24 children with non accidental head injury showed subdural haemorrhage, with either no history of injury or history of a low fall (~l m) in 22 patients, and admitted assault in two. Ewing-Cobbs et al 81 studied 40 children with a head injury, 20 accidental, 20 non accidental. Subdural haemorrhages were seen in 16 of the non-accidental group, but in only nine of the accidental group, most of whom had been involved in motor vehicle accidents and none of whom had fallen. Hymel et al S2 com pared CT scans of 39 children with inflicted head injury with scans from 39 control patients with accidental head injury. Subdural haemorrhage was found in 17 in the non-accidental group, but in only four in the accidental group; interhemi spheric falx haemorrhage was seen in 17 and 2 respectively. In non-accidental head injury, subdural haemorrhage is usually bilateral, and almost always interhemispheric (Figs 3.30 and 3.32); it spreads over the cerebral convexity and may be seen in the middle cranial fossa (Fig. 3.33, p. 64). Although it is often obvious, it may be a shallow layer of blood, easily overlooked. It is uncommon for subdural haematomas at presentation to cause significant mass effect on the underlying brain (Fig. 3.30), though blood may continue to accumulate with time. S) Mixed density haematoma is more common at presentation in non accidental injury, but has been described within 2 days79 and 1 week of accidental injury.s4 Precise dating of subdural haemorrhage is difficult on both CT and MR scans, unlike the dating of intracerebral haemorrhage in adults. There seems to be considerable variation in density and intensity, which may be related to the initial volume of haemorrhage, the patient's haemoglo bin level, dilution by CSF, the oxygen tension within the CSF, and by a layering out of blood within the haemor rhage, the 'haematocrit effect' (Fig. 3.34, p. 65). Intervention,

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Figure 3.30 Magnetic resonance scans of an infant. (a) Fluid-attenuated inversion recovery [FLAIR) coronal, (b) Tl-weighted sagittal at presentation and (c) T1 sagittal 10 weeks later. High-intensity interhemispheric subdural haemorrhage is indicated by arrowheads. The low-intensity posterior fossa subdural collections [stars) are presumed to be older. Secondary herniation of the craniocervical junction (white arrows) resolved along with the subdural. An ill-defined, subependymal, high-intensity signal suggests a shearing injury [arrow). There is also a large subgaleal fluid collection [asterisk). Adapted with permission from McPh il lips.75

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such as the insertion of a pressure monitoring device or a subdural tap, will also have an effect. Appearances on sequential scans and comparison of initial CT and MR scans may be helpful.

Subarachnoid Haemorrhage Spontaneous subarachnoid bleeds can occur due to rupture of an arteriovenous malformation or an aneurysm, which is thought to be rare under 1 year of age. The distribution of blood differs from that in non-accidental injury.76 Acute subarachnoid blood is more clearly seen on CT than on MR (Fig. 3.31). In inflicted brain injury subarachnoid blood is not unusual and may result, acutely, in arterial vasospasm and later in secondary hydrocephalus.

Parenchymal Brain Injury

Figure 3.31 Computerized tomography scan shows a fresh, high-density scalp haematoma. Subarachnoid haemorrhage is visible in the sulci, mainly over the left parietal and occipita l lobes.

Focal areas of parenchymal contusion and haematoma are caused by impact of the brain against the adjacent skull or dura, such as the falx or tentorium, and are most common in the cortical grey matter of the frontal and anterior tem poral lobes. It is not clear if contusional injUly can be caused by shaking alone, or whether impact against a firm surface is required. While these injuries may be seen on CT

Figure 3.32 (a) Acute computerized tomography scan showing high-density fresh interhemispheric subdural haemorrhage poster iorly. There is some loss of the normal grey-white matter different iation due to mild cerebral oedema . (b) Follow-up scan 4 weeks later. There is mild generalized cerebral atrophy.

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Figure 3.33 (a) Fluid-attenuated inve rsion recovery (FLAIR) coronal MR image at presentation shows a thin layer of subdural blood over the convexity on the right and in the subtemporal region bilaterally (arrows). T2-weighted transverse images. (b) At presentation there is loss of grey-white matter differentiation on the right. with sl ight swelling and subtle midline shift. (e) Ten days later there is increased intensity in the right hemisphere and left frontal lobe. with prominent sulci due to early atrophy. (d) Nine months later there is extensive atrophy on the right. sparing only the basal ganglia. The left hemisphere is normal at this level. Adapted with permission from McPhillips.75

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Head injury I

scanning, MR scanning, particularly in the coronal plane, demonstrates them well, and gradient echo (GRE) images are very sensitive for blood products, which are seen as low intensity. They may be subtle at autopsy, and knowledge of the MR findings will direct attention to the appropriate areas 30 Shearing injury is unusual in head injury but, when seen in the absence of a history of a high-velocity injury, such as a road traffic accident, it is highly suggestive of non-accidental injury. The most common site for focal shearing injury is at

the grey-white matter junction in the frontal or frontopari etal lobes or in the corpus callosum (Figs 3.30 and 8.17, p. 157). At the grey-white matter junction it may actually be seen as a tear, which is readily visualized using high frequency ultrasound scanning, and is seen as a low echogenicity focus. 22 Tears may be seen on CT, but as they lie close to the vertex they are not easily characterized. On MR they may be seen as haemorrhagic (Fig. 3.34) tears initially, later becoming cystic. Follow-up imaging shows that some persist as cysts 85 (Fig. 3.35), while some show focal gliosis

Figure 3.34 Sagittal Tl-weighted magnetic resonance images. The presentation scan (al shows increased intensity posteriorly, in keeping with layering in a subdural haemorrhage (arrowheads), and a focal area of high intensity (arrow) over the frontoparietal convexity, suggestive of focal clot formation. Six days later (bl, an ill-defined, high-intensity signal can be seen in the frontoparietal subcortical white matter (arrow), representing a tear. Two months later (cl, there is residual focal atrophy (white arrows). Adapted with permission from McPhilli ps l5

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Figure 3.35 Coronal fluid-attenuated inversion recovery (FLAIR) magnetic resonance im ages at (al 3 days, (bl 3 weeks and (cl13 months after presentation. (a) III-defined, high-inten sity signal over the left convexity (arrow) and subtle irregularity inthe underlying parenchyma. (b) Cortical tear with low-intensity cyst formation (arrow) . (c) The tear now appears as a slit-like lesion (arrowl with adjacent gliosis (arrowheads) and subtle atrophy. Adapted from with permission from McPhilli ps 85

and others collapse with associated white matter loss 86 (Fig. 3.3 4) . Sometimes shearing injury may be seen as tiny focal haemorrhagic areas on MR scanning, and knowledge of these findings may direct the pathologist to a subtle lesion. 3D

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Oedema or swelling of the brain may be as a direct result of trauma, or may be a result of hypoxic-ischaemic damage or hyperaemia. Traumatic oedema is usually associated with contusion or parenchymal haemorrh age. Hypoxic-ischaemic

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Sequelae of Head Injury Some children who have suffered non-acciden ta l hea d injury will have no residu al radiological abnormality on follow-up several years later. 64 - 67 Others show mild cere bral atrophy with prominent ve ntricles and CSF spaces (Fig. 3.35). Focal injury may be seen as areas of focal infarction, while some who have had extens ive hypoxic-ischaemic injury may have widespread multicys tic encephalomalacia and severe atrop hy (Fig. 3.33). Hydrocephalus may be seen secondary to haemo rrhagic arachnoiditis. Some children with sub dural haemorrhage who have also developed cerebral atrophy may have chronic subdural collections (Figs 14.9 and 14.10, pp. 300- 30 1).

Spinal Cord Injury

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Radiological appearances of spina l inju ry in non-accidental injury are not well described. There are reports of fracture-subluxation of the vertebrae with associated cord compression.53 . 54 For eva luation of suspected injuries to the spinal cord, MR is necessary as injlllies may be present in the absence of other rad iographic abnorma lity (spinal cord injury with out radiographic abnorma lity, SCIWORA). Under lying abnormalities, such as atlan to- ax ial instability or block vertebra, which would predispose to cord injury, should also be sought. 28

Figure 3.36 CT scan showing an acu te reversal sign with low density brain, loss of normal grey-white matter differentiation and relative sparing of the thal am i an d basal ganglia, which are dense by comparison. Also visible are multiple areas of intra cerebra I petech ia I haemorrhage; bi lateraI ch ron ic subd ura I haemorrhages with fresh interhemi spheric subdural blood. There is an old linear infarct in the left occipital lobe.

Cerebrospinal Fluid Spaces

mJury is the most common radiological manifestation of non-accidental head injury and is often quite extensive. In severe cases, there is sparing only of the cerebellum and pos sibly the basal ganglia and th alami , giving rise to the 'rever sal sign' on CT scanning, in which the cerebral hemispheres are hypodense compared with these structures 87 (Fig. 3.36). Except for the occasional documented vascular dissection , the underlying causes are not well established. There are many theories abou t the seconda ry mechanisms of brain injury and cerebral oedema, wh ich are discussed further in Chapter 14. In hypoxic-ischaemic damage there is loss of clarity of the grey- white matter interface on all scanning techniques (Fig. 3.33). On CT scanning, the affected area may show abnormally low density (Fig. 3.32, p. 63), although on MR sequences the in tensity will reflect the increased water content, low on Tl-weighted sequences and high on T2 weighted sequences. Th e combination of diffusion-weighted imaging (OWl) and ap parent diffusion coefficient (ADC) mapping will show restricted diffusion, and is more sensitive than other MR sequences; however, this is not specific and may be seen in metabolic disorders, following seizures, and in encephalitis. It may be useful in predicting the prognosis.

The depth of CSF fluid spaces surrounding the brain changes in the first 2 years of life. Paediatric radiologists who scan young children are familiar with the healthy child who has widened CSF spaces and minim al, if any, ventricular dilatation. It is considered a developmental variant. Kleinman et al 88 reviewed the CT scans of 34 nor mal children, finding that the extraventricular subarach noid space is increased in children under 2 years of age, normalizing at aro und 2 years and becoming 'monoto nously uni form ' by 3 yea rs. They postulated theories for this transient increase in CSF spaces, suggesting that it was a transient alteration in CSF dynamics, perhaps associa ted with a response to the grow ing brain. 88 Kapila et al 89 stud ied CSF dynamics using nuclear cisternography a nd found no evidence of communicating hydrocephalus. Libicher and Trbger90 scanned 89 infants to determin e an upper limit of normal, based on the 95th percentile. Wilkinso n et al 91 obtained similar results, with some variation of depth with position. Fessell et al 92 reviewed cranial ultraso und scans of 38 patients with macrocrania, an occipitofrontal head circumference of 95 per cent or greater for age, who had been followed up for a mean period of 55 weeks. They showed that a CSF depth of < 10 mm had a 94-100 per cent

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negative predictive value for the development of neurolog ical abnormality. These [SF spaces should co ntain fluid with the same characteristics as the intraventricular [SF. If the density on [T images, intensity on MR images or echogenicity on ultrasound scanning is different, then this raises the possi bility of inflammation or haemorrhage, and requires fur ther investigation. Ultrasound scanning, using colour flow imaging to demonstrate subarachnoid vessels, can demon strate which comp artment is involved.

VISCERAL INJURIES Almost any organ can be injured as a result of inflicted trauma, bu t visceral injury is very unusual in child abuse, when compared with the incidence of skeletal and head injury. The typical abdominal and chest injuries result from kicking or punching the abdomen and chest, or from kneel ing or standing on the child. The child may present acutely owing to peritonitis and blood loss, or with late complica tions of injury, such as su bacute gastrointestinal obstruc tion resulting from stricture forma tion or pancreatic pseudocyst format ion. The investigation of visceral injury should be the same as for other blunt abdominal trauma.

Liver, Spleen, Kidneys and Adrenals The mechanism of abusive injury of these organs does not differ fro m accidental blunt trauma . Direct compression can cause laceration, rupture and haemorrhage. Associated rib fractures may be seen and the presence of other non accidental injury and the lack of a specific history of injury may suggest abuse. 93 95

Pancreas Pancreatic trauma can result in acute pancreatitis, often haemorrhagic. The presence of associated injuries, particu larly to nearby bowel, may suggest the traumatic aetiology. Pseudocyst formation can occur with associated mass effect. For the assessment of the degree of injury and asso ciated abnormality it may be necessary to use [T scann ing with intravenous and oral contrast. 96 -9S

Bowel Injury Duod ena l and jejunal injury can occur from direct trauma , compressing the duod en um against the spin e, but may also result from deceleration forces with shearing injury to the root of the mesentery.99 Duod enal hae matoma may be seen or transection of the j ej unum in the region of the ligament of Treitz. Ultrasound is not usually useful for ep igastric

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Figure 3.37 Barium meal in a child who presented wi th vomiting, dehydration and weight loss, showing proximal duodenal dilatation secondary to duodenal haematoma causing an apparent stricture. The jejunal mucosa is thickened secondary to haemorrhage. trauma. Upp er gastrointestinal contrast studies may be use ful if the child is not acutely ill (Fig. 3.37), bu t abdominal [T (Fig. 3.38) with intravenous and oral contrast may be most helpful. Mesenteric tears with associated vascular injury may present late with multiple strictures. 94 Gastric rupture is a rare occurrence, and is likel y to be due to com pression of a distended stom ach. 95 Pneumatosis of the gas tric wall has been described. 100 Rectal perforation is usually the result of penetrating injury, associated with sexual ab use. 94 • 10 1

Visceral Chest Trauma Injury to the lungs, heart and mediastinum is unusual, a nd likely to be a result of direct compression injury. This can result in diaphragmatic rupture, pneumothorax or pneu mopericardium. Airway obstruction may cause a pneumo mediastinum. Rib fractures may cause a haemothorax (Fig. 3.39). Secondary inflammatory change .may extend to the mediastinum from adjacent structures, most commonly being involved with pancreatitis.

Penetrating Trauma Although pharyngeal perforation is a well-recognized iatro genic injury, it is a rare manifestation of non-accidental

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Figure 3.39 Healing rib fractures in both axillae with a right haemothorax. Recent angulated fracture of right humerus. The raised right hemidiaphragm is due to liver contusion.

SOFT-TISSUE INJURY It is not unusual for soft-tissue injury to be sufficient to

Figure 3.38 Abdominal computerized tomography with intravenous contrast. (a) Fluid in dilated duodenal loop (asterisks) with denser haematoma medially. Also visible is free fluid around the liver and spleen. (b) Caudal image of the same child also shows free intraperitoneal fluid and intense enhancement of bowel wall due to 'shock bowel'.

injury, but has been described. In infants it is due to the insertion of a finger or a sharp object. IO l-1 03 In older chil dren, penetration may be related to sexual abuse. Resulting retropharyngeal abscess formation may compromise the airway and inflammation may extend into the mediastinum. Ng et al 94 described two cases of penetration by multi ple needles. In one case, the needle marks were visible and CT scanning showed one needle to lie in close proximity to the carotid artery. In another case, the needles had been inserted through the umbilicus and probably per rectum, with abscess formation in the abdomen and pelvis. Foreign bodies seen on radiographs must not be assumed to be external to the patient. 94

cause obliteration of fat planes on radiographs, and such changes can also be seen on ultrasound and MR imaging. But, in general, radiology cannot reliably detect bruiSing. Older children may be beaten, with focal haemorrhage in muscle and soft tissue. These may ossify and appear radi ographically as heterotop ic new bone formation. 104 The mechanism is similar to post-traumatic myositis ossificans. Carty has described soft-tissue calcification of a neck lace distribution in the neck. It is thought that this may represent focal fat necrosis and ischaemia. 105

DIFFERENTIAL DIAGNOSIS To miss a diagnosis of non-accidental injury and to fail to safeguard the child may result in further injury or death. To misdiagnose non-accidental injury, when there is another cause for the child's condition and radiological appear ances, is to cause heartbreak and devastation to a family. It is therefore important that all paediatric radiologists have a knowledge of the differential diagnosis of both head injuries and individual skeletal abnormalities.

Head Injury The major differential for scalp swelling and skull fracture is accidenta l injury. The history should be sufficient to explain the findings and the degree of injury. Bony skull defects with bruising or the appearance of periorbital haematoma are recognized presentations of leukaemia and metastatic neuroblastoma.

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Subdural Haematoma Even with a bleeding diathesis, some trauma is required to cause a subdural bleed, but it may be relatively minor in nature. Haematological investigation is appropriate in unexplained or suspicious cases of subdural haemorrhage. Rarely, an aneurysm or arteriovenous malformation may bleed, causing subarachnoid and subdural haemorrhage. Subdural effusions, which may be abnormal when com pared with intraventricular CSF on scanning, can be seen in meningitis. This can be confirmed clinically and by lab oratory testing. Herpes simplex encephalitis can be haem orrhagic; again clinical assessment and virological investigation should clarify this. Glutaric aciduria is uncommon, but may present with macrocrania. It can be recognized by the combination of cerebral atrophy, with particular widening of the Sylvian fissure and the CSF space a nterior to the temporal lobes, and abnormal signal in the basal ganglia and periventricular white matter. 106

Physiological Periosteal Reaction Physiological periosteal reaction is seen in normal infants between the ages of 8 weeks and about 8 months (Fig. 3.40). It is rarely more than 2 mm in thickness, smooth and seen along the diaphyses of the long bones. It does not extend to the epiphyseal plate. It is usually symmetrical, though may be more obvious on one side and, if identified on the tibia, should be visible on the femur (Fig. 3.15, p. 55).

important to be aware of the patient's stage of develop ment than their actual age, can they roll, do they stand, are they cruising? This information, together with the history, can often clarify a worrying scenario (Figs 3.41 and 3.42).

Normal Variants The paediatric radiologist should be familiar with the appearances of nutrient foramina, which may be mistaken for fractures by the unwary.107 There are numerous variants of ossification, particularly around metaphyses. These may be spurs, beaks and the 'step-off appearance, which resemble metaphyseal fracture. But close inspection, using coned views and magnification of high-quality radio graphs if necessary, will show that these structures are in continuity with normal bone and do not represent frac tures. 4 The acromion may also show irregular ossification. 6 Irregularity of the anterior cortex of the proximal tibia is also a normal variant,4 as is irregularity of the radial shaft. There are numerous sutures and synchondroses in the skull, most of which are easily recognized. The parietal fissure, or 'strip suture', is frequently misdiagnosed as a fracture. It is a short tapering lucency extending from the skull vertex into the parietal bone. They are no wider than

Accidential Injury In accidental injury, the fracture should be compatible with the mechanism described in the history. It is more

Figure 3.40

Simple physiological subperiosteal new bone seen

along the diaphysis of both femora , both medially and laterally.

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Figure 3.41

Typical innocent toddler's spiral fracture.

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2 mm, and are not assoc iated with overlying soft-tissue swelling.

described, and it should be remembered that it can be detected for up to 4 weeks following delivery.77,78

Birth Trauma

Osteomyelitis

The most common fracture sustained during delivery is of the midshaft of the clavicle. It may not be recogni zed at birth but it either presents at 2-3 weeks of age, with a palpable lump, or is seen as an incidental finding on a chest radiograph. Most h ave healed by 12 weeks and are undetectable. A few fail to unite, leaving a pseudoal1hrosis of the clavicle, which may be mistaken for a new fracture at a later date. Other diaphyseal fractures are usually recognized owing to reduced movement of the limb, humeral fractures in shoulder dystocia and femoral fractures in extended breech delivery. Rib fractures, resulting from impaction against the maternal symphysis pubis, are usually unilateral. 43 ,44 They may present as a result of crepitus or respiratOlY distress, or be seen as an incidental finding on a chest radiograph . Metaphyseal fractures may rarely be due to birth trauma, when a limb has been twisted or pulled, in the course of Caesarean section,39 an armling deliv ery or a breech delivery. The finding of subdural haematoma in a significant number of asymptomatic neonates has been

Periosteal reaction and minor metaphysea l or cortical irregularity may be see n on ultrasound or, sev era l days later, radiographically. In the absence of a histolY of trauma or clinical evidence of infection this may be ascri bed to non-accidental injury.

Metabolic Bone Disease Several conditions can present with reluctance to use a limb, in the absence of trauma. Radiographs may show a metaphyseal lucent line. Careful inspection of the radi ograph will show that this is present at every metaphys is, though more obvious at some. There is also no visible frac ture. This is a well-recognized presentation of leukae mia and neuroblastoma, and the child is likely to be systemi cally unwell. Langerhans cell histiocytosis may h ave a sim ilar presentatio n but the bone lesions are unlikely to be symmetrical and generalized. Meta physeal fractures are well recognized in scurvy, Menke syndrome and metabolic disease of the newborn. Scurvy has typical radiological appeara nces, with osteopenia, blurred metaphyses and poor trabeculation. Clinical appea r ances and biochemical investigations will clarify the diagno sis in most cases. Copper deficiency is rare, but well described. 108 Prema turity, mal nutrition, malabsorption and dietary defic iency are predisposing factors. Copper has been added to modern milk formulae and parenteral feeds to prevent its defi ciency in preterm infants. Fractures are seen in copp er defi ciency only in the presence of widespread symmetrical skeletal chan ges, showing periosteal reaction, metaphyseal spurs and cupping and fraying of the metaphyses, visible especially at the wrists, knees and costochondral junctions. Biochemical investigations will confirm this disorder. Rickets is characterized by metaphyseal fraying and cup ping, with osteopenia and poor trabeculation. Fractures may occur, but only in the presence of obvious bony abnormal ity, confirmed by biochemical abnorm alities (Fig. 3.43). Congenital syp hilis can be confirmed by clinical features and serology. Metaph yseal in'egularity is seen, but the appearances are those of undermining of the metaphysis.

Osteogenesis Imperfecta Figure 3.42 (a) Simple torus fracture of the distal tibia with slight change in the normally smooth contour of the anterior cortex. This fracture is technically metaphyseal, but this is a simple accidental injury, not non-accidental injury. (b) Healing with sclerosis at the fracture site.

Osteogenesis imperfecta is a disorder of synthesis of type I collagen, with resulting bone and connective tissue abnor malities. It is an inherited condition, with four major types described by Sillence. 109

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Figure 3.43 Immigrant child with nutritional rickets and severe osteopenia. (a) Left lower limb shows healing fractures of the tibia and fibula and a fresh corner fracture of the proximal tibia. (b) Upper limb shows a healing fracture of the radius and abnormal periosteal new bone extending to the humeral metaphysis. Typical metaphyseal fraying and cupping best seen in the distal ulna. The faint metaphyseal sclerosis is due to healing, following treatment. A diagnosis of non-accidental injury was not made because of the rickets, although there were grave concerns about the family.

• Type I is the most prevalent form, with blue sclerae, a family histolY of deafness, and sometimes abnormal dental development. Ten per cent of people with osteogenesis imperfecta show fractures at birth. This is an autosomal dominant condition but new mutations do occur. • Type II can be recognized in utero and is usually lethal in the fetal or perinatal period. It is thought to be transmitted as an autosomal recessive condition. • Type III is a rare autosomal recessive form of osteogenesis imperfecta, resulting in deformity of the limbs, spine and skull. Fractures are often present at birth. • Type IV is regarded as a rare form of osteogenesis imperfecta. The sclerae are normal in appearance. The bone disease is very variable in severity. This group may be subdivided, according to the presence of dentinogenesis imperfecta. In a mild case, particularly because of the normal sclerae, it may be difficult to

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distinguish osteogenesis type IV from non-accidental injury.

It should be remembered that children with osteogenesis imperfecta susta in fractures similar to fractures of other children from accidental trauma, just with a lesser degree of force. They w ill therefore have fractures that are similar in distribution to those in accidental trauma, and would not be expected to show metaphyseal corner fractures. Simila rly, rib fractures and skull fractures are not commonly seen in osteogenesis imperfecta. Because fractures are painful and cause the child distress, there should not be any significant delay in presentation to medical attention; therefore, previ ously unidentified fractures in various stages of healing would not be seen. Subdural haemorrhage is a rare feature of osteogenesis imperfecta, recognized in severe cases, in which the diagnosis is not in doubt. 110 Brain injury is not a feature of osteogenes is imperfecta.

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References I

There are rep orts of suspected non-accidental injury that have later been proven to be osteogenesis imperfecta . Review of the described histories would sugges t that fea tures of osteogenesis imperfecta or clinical features unusual in non- accidental injury were overlooked.IIL.112

Temporary Brittle Bone Disease There have been two hypotheses proposed for conditions that wo uld render a child more susceptible to fractures for a short period of time, with spontan eo us resolution of the abno rmali ty and with no biochemical or pathological abnormalities at the time of diagnosis. Paterson et al sug ges t tha t this is caused by a temporary copper deficiency, resulting in a temporary bony fragility w hich does not resolve until the copper levels have returned to normal. liJ His cohort included patients with rib, metaphyseal and skuJl fractures. Although metaphyseal fractures are recog nized in established copper deficiency, bone changes are acco mpanied by abnormal biochemistry and by anaemia: skull fractures are not seen. 108 A review by Chapman and Hall has co nsidered Paterson's proposed condition in detail. I14 Another group suggest that reduced bone density due to lack of fetal intrauterine movement could cause abnormally low bone density and a higher propensity to fracture. 115 The validity of this data is questioned 115 and contradicted by other authors. 117

CONCLUSION It is the du ty of the paediatric radiologist to be an advocate for the child, who should be protected fro m abuse. Natural conditions which could mimic aspects of non-accidenta l injury, or underlying conditions which could predispose to fra cture or subdural haemorrhage, must be identified where present. It must be remembered that, although rarely, such a child may also be abused. IIB.119 A mistaken diagnosis of child abuse, when the appear ances have been caused by another disorder, can be devastat ing for the child and family. However, if we fail to recognize inflicted injury, the child may be the victim of further assault, which may result in life-long disability, if not death.

REFERENCES

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Caffey J. Multiple Fractures in the long bones of infants suffering from subdural haematoma. A]R 1946; 56:163-73. Guthkelch AN. Infanti le s ubdu ra l haematoma a nd its relationship to whiplash injuries. EM] 1971; 2:430-1. Caffey J. On the theory and practice of shaking infants. Its potential residual effec ts of permanent brain damage and mental retardation. Am] Dis Child 1972; 124:161-9. Kleinman PK. Belan ger PL, KareJlas A, Spevak MR. Normal metaphyseal radiologic variants not to be confused with ftndings of inFant abuse. A]R 1991 ; 156:781-3.

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5 Kleinman PK. Schm id-like metaphyseal chondrodysplasia

Sim ul a tin g child abuse. A]R )991; 156: 576-8.

6 Kleinman PK, Spevak MR. Variations in acromial ossificatio n Simulating infant abuse in victims of sudden infant death syndro me. Radiologv 199 1; 180:185- 7. 7 Sbapiro R. Anoma lous parietal sutures and the bipartite parietal bon e. A m] Ro el1tgenol Radium Ther Nucllvled 1972; 115:569-77. 8 Omah AC, Hall CM. Observational study of skeleta l surveys in suspected non-accidental. injuly. Clinical Radiology 2003; 58: 70 2-5. 9 James SU, Halliday K, Somers J, Broderick N. A survey of

non-accidental injury im aging in England, Scotland and

Wales. Ciin Radio/2003; 58:696-701.

10 Sane SM et al for American Academy of Pediatrics. Dia gnost ic imagi ng of child abuse. Pediatrics 2000; 105:1345-8. 11 American College of Radiology. ACR Practice Guidelinefor Skeletal Surveys in Children (Res. 47, 17,35). Reston, VA: ACR Standards American College of Radiology, 2001, pp. 145-9. 12 Royal Co llege of Radiolo gists and Royal College of Paediatrics and Child He alth. Standards for Radiological hll!es tigatiolls of Su spected Non-accidental h~j!II)!. London: Royal College of Paediat rics and Child Health, 2008. 13 Omah AC, Moon L, Hall CM, Todd-Pokropek A. Diagnostic accuracy of fracture detection in suspecte d non- acc idental injury: the effect of edge enhancement and digital display on observer performance. Ciill Radiol 2006; 61: 163-73. 14 Zimm erman S, Mako roFF K, Ca re M, et al. Utility of Follow-up skeleta l surveys in suspected ch ild physical abuse evaluations. Child Abuse Et Neglecr, 2005; 29: 1075-83. 15 Kleinman PK, Nimkin K, Spevak MR, et a!. Follow-up skeletal surveys in susp ec ted child abuse. A]R 1996; 167: 893- 6. 16 Anilkumar A, Fender LJ, Broderick NJ, et a1. The role of the follow-up chest radiograph in suspected non-accidental injury. Pediatl' Radio12006; 36:216-18. 17 Kleinm an PK, Marks SC, Adams VI, Blackbourne BD. Factors affecting visualization of posterior rib fractures in abused infa nts. A]R 1988 ; 150:635-8. 18 Kleinman PK, Marks Sc. Spevak MR, Richmond JM. Fra ctures of the rib head in abused infants. Radiology 1992; 185: 119-23. 19 Nimkin K, Kleinman PK, Teeger S, Spevak MR. Distal humeral physeal injuries in chi ld abuse: MR imaging and ultrasonography findings. Pedlatr Radio/ 1995; 25:562-5. 20 Dias JJ , Lamont AC, Jones JM. Ultrasoni c diagnosis o f neonatal separatio n of th e distal humeral ep iphysis. ] BOHe ]Oil1t Surg (Er) 1988; 70-B:825-8. 21 Smeets AJ, Robb en SG, Meradji M. Sono grap hically detected costo-chondra l dislocation in an abused chi ld. Pediatr Radiol 1990; 20:566-7. 22 Jaspan T, Narborough G, Punt JAG, Lowe J. Cerebral contusional tears as a marker of child abuse - detection by cran ial sonography. Pediat,. Radiol 1992; 22:237-45. 23 Filiatrault D, Garel L. Commentary: Pediatric blunt abdominal trauma - to sound or not to so und? Pedia tr Radiol )995; 25:329 - 31. 24 Sivit CJ, Kaufman RA . Commentary: Sonography in the evaluation of children following blunt trauma: is it to be or not to be? Pediatr Radio 11995 ; 25: 326-8. 25 Ellison PH, Tsai FY, Largent JA. Computed tomography in c hild abuse and cerebra l contusion. Pediatrics 197 8; 62:151-4. 26 Zimmerman RA, Silaniuk LT, Bruce D, et al. Computed tomography of craniocerebral inju ry in the abused chi ld. Radiology J 979; 130:687 -90. 27 Saulsbury FT and Alford SA. Intracranial bleeding from child abuse: the value of skull radiographs. Perliatr Radiol 1982; 12: 175 -8.

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28 Barnes PD, Krasnokutsky M. Im aging of the central nervous system in suspected or alleged nona ccid ental injury, including the mimics. Topics MR Imaging 2007 ; 18:53-74. 29 Suh DY, Dav is PC , Hopkins KL, et a1. Nonaccidental pediatric head injUly: diffusion-weighted imaging findings. Neurosurgery 2001; 49 :309-20. 30 Hart BL, Dudley MH, Zumwalt RE. Post mortem cra nial MR T and autopsy correlation in suspected child abuse. Am )

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Foren sic NJed Patho/1996; 17: 2 17-24. 31 Sty JR, Starsh a k R1. The role of bon e sci ntigraphy in the eva luation of the sus pec ted abused child. Radiology 1983; 146:369-7 5. 32 Ma nd elstam SA, Cook D, Fitzgera ld M, Ditchfielcl MR. Complementary use of radiolog ical skel etal survey and bo ne scintigraphy in detection of bony injuri es in su spected child abuse. Arch Dis Child 2003; 88:387-90. 33 Carty HML. Fractures ca used by child abuse. ) Bo ne Joint Surg Br 1993; 75B:849-57. 34 Rao P, Carty H. Non-accidental injury: review of the radiology. Clin Radiol 1999; 54: 11-24. 35 Taitz J , Moran K, O'Mea ra M. Long bone fractures in children under 3 years o f age: is abuse being missed in emergency department presentatiolls? ) Paediatr Child Health 2004; 40:170-4. 36 Worlock P, Sto wer M, Barbor P. Pattern s of fractures in accidental and non-acc id ental injulY ill children: a comparative study. Br Med) Ciin Res Ed 1986; 293:100-2. 37 Kleinman PK, Marks Sc, Richmond 1M, Blackbo urne BD. lnflicted skeletal injury: a postmortem radiologic histopathologic study in 31 infants. AJR 1995; 165: 647-650. 38 Grayev AM, Boal DKB, Wallach DM, Segal LS. Metaphyseal fractures mimicking abuse durin g treatment for clubfoot. Pedin tr Radiol 2001; 3 1 :559-63. 39 O'Connell AM, Do noghue VB. Can classic metaphysea l lesions fol low un co mpli ca ted caesarean section? Pediarr Radiol 2007; 3 7:488-91. 40 Kleinman PK, Marks SC, Bl ackbourne B. The metaphyseal lesion in a bu sed infants: a radiologic-histopathologic study. AJR 1986 ; 146:895-905. 41 Bulloch B, Schubert CJ, Brophy PD, et a1. Cause and clinical character isti cs of rib fr ac tures in infants. Pediatrics 2000; )05:E48. 42 Cadzow SP, Armstrong KL. Rib fr ac tu res in infants: red al ert! The clini cal features, investig ations and child protection ou tco mes. ) Paediarr Child HealrlJ 2000; 36 :322-6. 43 Durani Y, DePiero AD. Images in internal medicine. An n Em erg Med 2006; 47:210-15. 44 Rizzolo PJ, Coleman PR. Neonatal rib fracture: birth trauma or ch ild abu se 7 ) Family Practice 1989; 29:561-3. 45 Kleinman PK , Marks SC, Adams VI, Blackbourne BD. Factors affecting visualization of po sterior rib fractures in abused infants. A)R 1988; 150:635-8. 46 Kleinman PK, Schlesinger AE. Mechanical fa c tors associated with posterior rib fractures: laboratolY and case studies. Pediotr Radiol 1997; 27:87-91. 47 Kleinman PK, Marks Sc, Nimkin K, et a1. Rib fra ctu res in 3 1 abused infants: postmortem radiologic-histopathologic study. Radiology 1996; 200:807-10. 48 Feldman KW, Brewer DK. Child abuse, cardiopulmonary resuscitation and rib fra ctures. Pediarrics 1984; 73:339-42. 49 Sp evak MR , Kl ei nm a n PK, Belanger PL, et a1. Cardiopulmonary resuscitation an d rib fractures in infan ts . A post- mortem radiologic-pathologic st ud y. )AMA 1994 ; 272:617-18. 50 Dolinak, D. Rib fractures in infants due to cardiopulmon ary resuscitation efforts. Am J Forensic iVied Parlwl 2007; 28:107-10.

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Kleinman PK, Marks Sc. Vertebral body fra ctures in child abuse: radiologic-histopathologic correlates. In vestigative Radiology 1992; 27:715-2 2. Kleinman PK, Zito JL. Avulsion of the s pinous processes caused by infant ab use. Radiology 1984; 151:389-91. Rooks VJ , Sisler C, Burton B. Cervical spine injury in child abuse. Report of 2 cases. Pediatr Radiol 1998; 28:193-5. Cullen Jc. Spinal lesions in battered babies. ) Bone Joint Surg Br 1975; 57B:364-6. Lonergan GJ , Baker AM, Morey MK, Boos Sc. Child abuse: radiologic-pathologic correlation. Radiograph ics 2003; 23:811-45. Kogut! MS, Swischuk LE, Fagan CJ. Patterns of injury and significance of uncommon fractures in th e battered child syndrome. Am) Roencgenol Radium Ther Nucl Med 1974; 121:143-149. Kleinman PK, Shelton YA. Hangman's fracture in an abused infant: imaging features. Pedian' Radio11997; 27:776 -7. Nimkin K, Spevak MR, Kleinman PK. Fractures of the hands a nd feet in child abuse: Imaging and pathologic features. Radiology 1997; 203 :233- 6. Carty H. Th e non-skeletal injuries of child abuse: part II the body. In The Year Book of Paediatric Radiology, Borsod County Teach ing Hosp ital, Miskolc, 1991 ; 3:25-34. Hechter S, Huyer D, Manson D. Sternal fractures as a manifestation of abusive injury in children . Pediatr Radiol 2002 ; 32 :902-6. Ablin DS, Greenspan A, Reinhart MA. Pelvic injuries in child abuse. Pediatr Radiol 1922; 22 :4 54-7. O'Connor JF, Cohen 1. In Kleinman PK (ed.) Diagnostic Im aging of Child Abuse. Baltimore: Wi lli ams and Wilkins, 1987, p. 112. Prosser I, Maguire S, Harrison SK, et al. How old is this fracture? Radiologic dating of fractures in children: a systematic review. A JR 200 5; 184: 1282 -6. Haviland J, Ross Ru sse ll RI. Outcome after severe non accidelltal head injury. Arch Dis Child 1997; 77:504-7. Jayawant S, Rawlinson A, Gibbon F, et al. Subdural haemorrhages in infants: population ba sed s tudy. BM) 1998 ; 317:1 558-61. King SJ, Boothroyd AE. Cranial trauma following bi rth in term illfa nts. Br J Radiol 1998 ; 71 :233-8. Lo TYM, McPhillips M, Minns RA, Gibson RJ. Cerebral atrophy following shaken impact syndrome and other non-accidental head injury. Pediatric Rehabilita tion 2003; 6:47-55. Lloyd DA , Carty H, Patterson M, et al. Predictive value of skull radio g raphy for intracranial injury in children with blunt head injUly. Lancet 1997; 349:821-4. Billmire ME, Myers PA. Serious head injury in infants: accident or abuse? Pediatrics 1985; 75:340- 2. Warrington SA, Wright CM , ALSPAC Study Team. Accidents and reS Ulting injuries in premobile infants: data from tb e AlSPAC stu dy. Arch Dis Child 200 1; 85: 104-7. Rob erton DM, Barbor P, Hull D. Unusual injUly? Re cent injury in normal children and children with suspected non accidenta l injury. BMJ 1982; 285:1399-401. Helfer RE, SJovis TL, Black M. Injuries resu lting when small children fallout of bed. Ped iatrics 1977;60:53 3-5. Kravitz H, Driessen G, Gomberg R and Korach A. Accid ental fa lls from eleva ted surfaces in infants from birth to o ne yea r of age. Pediatri cs 1969; 44 [Supp1.):869-76. Stoodley N. Neuroima ging in non-accidental head injury: if, when, why and how 7 Ciin Radial 2005; 60 :22-30. McPhillips M. Non-acc identa l injulY in the yOUllg infant. ln Rutherford M [ed.) MRJ of the Neonatal Bmin. London: WB Saunders, 2002 , pp. 261 -71. Newton RW. Inrra cranial haemorrhage and non-accidental injury. Arch Dis Child 19 89; 64:188-190.

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Whitby EH, Griffiths PO, Rutter S, et al. Frequency and natural history of subdural haemorrhage in babies and relation to obstetric factors. Lancet 2004; 363:846-851. Looney CB, Smith JK, Merck LH, et al. Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and relationship to obstetric and neonatal risk factors. Radiology 2007; 242:535-541. Tung GA, Kumar M, Richardson RC, et al. Comparison of accidenta l and nonaccidental traumatic head injury in children o n noncontrast computed tomography. Pediatrics 2006; 118:626 - 33. Duhaime AC, AJario AJ, Lewand er WJ, et al. Head injury in very young children: mechanisms, injury types and ophtha lmologic findings in 100 hospitalized patients younger than 2 years of age. Pediatrics 199 2; 90: 179-85. Ew ing-Cobbs L, Kramer L, Prasad M, et a l. Neuroimaging, physica l, and developmenta l findings after inflicted and noninflicted traumatic brain injury in young children. Pediatrics 1998; 102 :3 00-7. Hy mel KP, Makoroff Kl, Laskey AL, et al. Mechanisms, clinica l prese ntations, injuries, and outcomes from infli cted ve rsus noninflicted head trauma during infancy: resu lts of a prospecti ve, multicente red, co mp arative study. Pedia trics 2007; 119:922-9. Case ME, Graham MA, Handy TC, et aJ. Position paper on fata l abusive head injuries in infants and yo ung children. Am J Forens Med Path 2001 ; 22: 112 - 22. We lls RG, Vetter C, La ud P. Traumati c low attenuation subdural fluid co llec tions in chi ldren younger than 3 years. Arch Pediatr Adolesc Med 2003; 157: J005 -1 0. McPhillip s M. Initial and sequential MRI in non-accidental hea d injUiy. In Minns RA, Brown JK (eds.) Shaking and other Non-a ccidental Head Injuries ill Children. London: MacKeith Press, 2005, pp. 262-70. Ordia IJ. Strand R, Gilles F, Welch K. Computed tomography of contusional clefts in the white matter in infants. J Neurosurg 1981; 54:696-8. Han BK, Towbin RB, de Courten-Myers G, et al. Rev ersa l sign on CT: Effect of anoxic ischae mi c cereb ra l injury in ch ildren. Am J Neuroradiol 1989; 10: 1191-8. Kleinman PK, Zito lL, David so n RI, Raptopoulos V. Th e subarachnoid spaces in ch ildren: normal variations in size. Radiology 1983; 147:455-7. Kapila A, Trice J, Spies WG, et a!. Enl a rged ce reb rosp inal fluid spaces in infants with subdural hematomas. Radiology 1982; 142:669-72. Libicher M, Trager J. US meas urements of the subarac hnoid space in infants: normal values. Radiology 1992; 184:749-51. Wilkinson AG, Cooke R, Tallur KK, et al. Pericereb ra l space measurements in infants: sonographic determination. Paper presented at Hydrocephalus 2005 Internati ona l Co nsensus Meeting, Queenstown, New Zealand, August 2005. Fessell DP, Frankel DA, Wolfson WP. Sonography of extraaxial fluid in neurolo gica lly normal infants w it h head circumference greater than or equal to the 95th percentile for age. J Ultrasound !vIed 2000; 19:443-7. Nimkin K. Teeger S, Wa lla ch MT, et a!. Adrenal hemorrhage in abused children: imaging and post mortem findings. AJR 1994; 162: 661-3. Ng CS , Hall CM, Shaw DG. The ran ge of v isce ral manifestations of non-accidental injury. Arch Dis Child 1997 ; 77:167-74. Barnes PM, Norton CM , Dunstan FD , et al. Abdomina l injury due to chi ld abuse. Lancet 2005; 366:234-5. Touloukian RJ. Abdomina l visceral injuries in battered ch ildren. Pediatrics 1968 ; 42:642-6.

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97 Siovis TL, Berdon WE , Haller 10, et at. Pancreatitis and the battered child syndrome: Report of 2 cases with skeleta l involvement. Am J Roentgenol Radium Tit er Nucl iVIed 1975; 125:456-61. 98 Sivit Cl, Ingram 10, Taylor GA , et at. Post traumatic adrena l hemorrhage in children. CT findings in 34 patients. AJR 1992; 158;1299-302. 99 KJeinman PK, Brill PW, Winchester P. Resolving duodenal jejunal hematoma in abused chi ldren. Radiology 1986 ; 160:747-50. 100 Fulcher AS, Das Narla L, Brewer WH . Gastric hematoma and pneumatosis in chi ld abuse. Am J RO(,lltgenol 1990; 155: 1283-4. 101 Ablin OS, Reinhart MA. Esophagea l perforation by a tooth in ch ild abuse. Pediatr Radial 1992; 22:339-4 1. 102 McDowell HP, Fielding Ow. Traumatic perforation of the

hypopharynx: an unusual form of abuse. Arch Dis CiJild

1984; 59:888-9.

103 KJeinman PK, Spevak MR, Hansen M. Mediastinal pseudocyst ca used by pharyngeal perforation during ch ild abuse. Am J Roentgenol 1992; 158:1111-1 3. 104 Ablin OS, Greenspan A, Reinhart MA. Pelvic injuries in child abuse. Pediatr Radial 1922; 22:454-7. 105 Carty H. Case report; ch ild abuse - necklace calcification - a sign of strangulation? Br J Radio11993; 66:1186-8. 106 Twomey EL, Naughten ER, Donoghue VB, Ryan S. Neuroimaging findings in glutaric aciduria type I. Pedia tr

Radio/2003; 33:823-30. 107 108 109 110

III 112

113

114 115

116 117

118 II 9

Hartley LM, Khwaja OS, Verity CM. Glutaric aciduria type I and nonaccidental head injury. Pediatrics 2001; 107; 174-5. Shaw JCL. Copper deficiency and non-accidental injury. Arch Dis Child 1988; 63: 448-455. Sillence D. Osteogenesis imperfecta. An expanding panorama of variants. Clin Orthop 1981; 159:11-25. Pozzati E, Poppi M, Gaist G. Acute bilateral extradural hematomas in a case of osteogenesis imperfecta congenital. Neurosurgel)' 1983; 13:66-8. Gahagan S, Rimsza ME. Child abuse or osteogenesis imperfecta: how can we tell? Pediatrics 1991; 88:987-92. Wardinsky TO, Vizcarrondo FE, Cruz BK. The mistaken diagnosis of child abuse: a three-year USAF medical center analysis and literature review. Mil Med 1995; 160:15-20. Paterson CR, Burns J, f\IlcAJlion SJ. Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. Am J Med Gellet 1993; 45:J87-92. Chapman S, Hall CM. Non-accidental injury or brittle bones. Pediatr Radiol 1997; 27: 106-10. Miller MN, Hangartner TN. Temporary brittle bone disease: association with decreased fetal movement and osteopenia. Calc Tiss Int, 1999; 64:137-43. Mendels on Kl. Critical review of 'temporary brittle bone

disease'. Pediatr Radiol 2005; 35:1036-40.

Rodriguez Jl, Palacios J, Ruiz A. et al. Morphological cha nges in long bone development in fetal akinesia deformation sequ ence: An experimenta l study in curarized rat fetu ses. Teratology 1992; 45:213-21. Knight 01 , Bennet Gc. Non-accidental injury in osteogenesis imperfecta: a case report. J Pediatr Orthop '1990; 10:542-4. Dunca n AA, Chandy J. Ca se report: multiple neonatal fractures - dietary or deliberate? Ciin Radiol 1993; 48:137-9.

Further Reading Kleinman PK (ed.) Diagnostic Imaging of Child Abuse, 2nd edn.

Ba ltim ore: Mosby, 1998.

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CHAPTER 4

I

HAEMATOlOG ICAL ABNORMALITIES THAT CAN SIMULATE ABUSE Angela Thomas

Introduction Primary haemostasis Secondary haemostasis Laboratory tests Measurements of primary haemostasis Evaluation of a bleeding patient Patterns of abnormal results Normal coagulation screen with a normal platelet count Abnormalities of platelet number or morphology

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82 82 86 90 94

INTRODUCTION

Medical, nursing and other personnel who care fo r children have a responsibility to be aware of signs and symptoms that are suggestive of child abuse, including non-accidental inju ry (NAI) . .Equally, however, they must also recognize that medical and physical conditions may simu late abuse and that appro priate measures must be taken to confirm or rule out these conditions. Cutaneous lesions are by far the most common presenting manifestations of child abuse, I,2 and of the conditions that may simulate ab use haematol ogical abnormalities are manifest usually as bruising or other bleeding into the skin or mucosal mem branes. Over-reporting of natural disease as NAI will occur, especially if a full assessment of the child is not carried out. An incorrect diag nosis of ch ild abuse, a lthough at times unavoidable, can be devastating for the family a nd child 3,4 and, exceptionally, has led to parental suicide .s Another consequence of such misdiagnosis is that a condition such as haemophilia will go unrecognized and therefore untreated. This in itself may lead to morbidity and even mortality. If the child is revealed to have a genetic or serious blood diso rd er, regaining the trust of that patient and their family may be impossible. The mistaken diagnosis of child abuse has been described as a form of medical abuse. 6 However, it is important to remem ber that diagnosis of a medical condition that can simulate

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Coagulation defects The neonate Drugs associated with bleeding Bone marrow failure syndromes Systemic disease associated with a bleeding tendency Activation of coagulation Conclusion References

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98 99 100 101 101 102

abuse does not rule out abuse. 7 When the child has bruising in a recognizable pattern, such as a belt or hand, then sus pected abuse must be repo rted regardless of the results of laboratory tests. B•9 In addition, these children may be at greater risk of serious injUly secondary to bleeding/,ID as well as greater risk of bleeding secondary to an abusive injury.l1 The physi cian who evaluates the bruised child for a disorder of coagulation sh ould always assess the history and physical examination to determine whether the bruises were acqui red spontaneously, accidentally or as the result of abuse. The pattern of bruising or associated findings may yield important information. Knight and Bennett J2 describe a case of abuse in a child with osteogenesis imperfecta, which was diagnosed from the pattern of the injuries; in this case a periorbital haematoma in association with a spiral fracture of the humerus. Unusual diseases may mimic abuse - misinterpreta tion of ' usual' by the inexperienced, for example a Mongolian blue spot (see Chapter 8, Fig. 8.7, p. 152), can a lso lead to a mis diagnosis. 6 Advice from a paediatric haematologist, paediatric dermatologist, paediatrician or haematologist may be crucial in reaching the right diagnosis. Caution must be exercised when fo llowing guidance (frequently given) that abuse shou ld be suspected if there is significant bruising or bleed ing with no history of trauma or a history inconsistent with the severity of the injury.13-16 In a ch ild with a bleeding

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Introduction I

diathesis, the severity of the bruising may be disproportion ate to the injury sustained or there may be a denial of any significant injury by the parent or caregiver ; a paediatrician who is not familiar with haematological disorders may mis takenly interpret this as evidence of abuse. 17 Clinical identification of the age of a bruise compared with the age given from the history has been used to assess the credibility of the history an d to identify whom the child was with at the time the bruise occurred. However, there is an increasing amount of evidence to suggest that the age of a bruise cannot be estimated reliably.18 A bruise is caused by blood that has escaped from damaged or leaky blood vessels, usually capillaries, into the interstitia l tiss ues, but the appearance of the bruise depends on several factors. The amount of blood that escapes depend s upon the integrity of the coagulation system, the force of the injury and the integrity of the vessels. The location of the bruise also determines its characteristics; for instance, periorbital and genital bruises will appear sooner than bruises on the extremities because the tissues are loose and the vessels poorly supported. 19 The clinical ageing of bruises is most frequ ently based upon colour of the bruise when compared with an estab lished chart. 2o However, the colour of a bruise depends not only on age, but also on amount of blood present, location beneath skin, skin colour and amb ient light. 21 Stephenson and Bialas 22 conducted a study on chil dren with bruises of known ages; photographs of the bruise were taken at different time intervals and aged by a 'blind' observer. They concluded that several different colours could be present at the same time within anyon e bruise and that bruises change colour at very different rates, even when sustained at the same time in the same child. Ageing of bruises from photographs is much less precise than many textbooks imply.21 ,22 However, assessing the age of a bruise on clinical examination may be easier, as other clues such as tissue swelling or abrasion might be presentY This was not the finding in a study by Munang and col leagues, 2J in which marked variability in colour descript ion between observers of the same bruises, and thus estimation of the age of the bruise, was demonstrated; less than one third of descriptions between two observers tallied either in vivo or from clinical photographs. Wide variability in bruise development and healing urges caution in ageing bruises and therefore this should never be used as the sole criterion for child abuse;21 the pattern of distribution of the bruising is a key factor that must be linked to the child 's history and stage of development. Bruises found in atypi cal areas in toddlers, such as the trunk, hands or buttocks, are of concern, as are bruises in normal infants under 9 months who are not yet mobile. 24 Sibert and colleagues l8 ,25 have develop ed a scoring system to evaluate these factors and such tools may be useful for discriminating between abused and non-abused children.18,25 In a prospective analysis of bruising in children with a nd without an inher ited bleeding disorder it has been shown that non-mobile babies without a bleeding disorder do not bruise, but once they start to roll they develop a few bruises that increase in

77

number as they begin to crawl and walk. How ever, children with severe bleeding disorders did develop bruising when non-mobile and had larger bruises than those with mild bleeding disorders, who in turn had larger bruises than those wit h no bleeding disorder. These observations indi cate that children with severe bleeding disorders develop bruises before they are mobile and bruise more frequently than a control popul ation. 26 Although the finding of bruises of different ages coupled with an inconsistent his tory has been cited as a hallmark of child abuse,9 not only is it difficult to age a bruise accurately, but also it is impor tant to note that a child w ith a bleeding diathesis may pres ent, quite normally, with bruising of differen t ages plus an inconsistent history. Haematological investigation of a brui sed child is mandatory in all cases when the bruising is une xplained or implausible, and in cases where some explanatio n is given or found but the bleeding that results is disproportionate to the injUly sustained. In a child who may poss ibl y have been ab used, it is essential that investigations are as atrau matic as possible and yield the maximum information. In the case of a bruised or bleeding child under these circum stances, whether or not a diagnosis of NAl is enteliained, a set of screening investigations should be performed on blood taken from a single ve nepuncture, with the labora tory set up and alerted to analyse the tests with the min imum of delay, using sma ll plasma samples. Further invasive tests, such as bleeding time, should usually be avoid ed at this stage. Initial screening and investigation is aimed at the diagnosis of the commoner causes of bleeding, and exclusion or confirmation of some of the rarer causes for the safety and management of the child. Further inves tigations might be needed if no explana tion of the bleeding is found or no admission of NAJ is made. In order to be able to interpret the results of coagul ation testing, the fundamentals of primary and secondary haemostasis must be understood. Artefact can significantly distort resul ts and lead to misdiagnosis; utmost care must be exercised in the way the specimens are taken and han dled prior to processing. Haemostasis depends upon the integrity of the tissues and vasculature, the n umber and function of the platelets (pri mary haemostasisl and the formation of fibrin (secondary haemostasis). The first of these is outwith the scope of this chapter and will not be dealt with in any detail, exceptions to this being Henoch-Schbnlein purpura, which is not uncommon in children and may be mistaken for NAl, and vita min C deficiency, which will be discussed briefly. A basic scheme of the haemostatic mechanism is shown in Figure 4.1. When a vessel is injured, the subendothelial collagen is exposed, resulting in platelet adhesion, activation and aggregation forming the primary haemostatic plug. Vascular injury also leads to vasoconstriction and slowing of blood flow, aiding this process. At the same time, tissue factor is expressed on subendothelial fibroblasts and monocytes ini tiating the coagulation process, by which the inactive plasma coagulation factors are converted to their active

78 I


Coll age n exposure

1

Vasoconstriction

Platelet ....- - acti vat ion

1

Reduced blood flow

Plait pug

Ti ssue thrombop lastin

1

Blood coagulation

~ Th"~bi"

1

Clot

Figure 4.1

1

and fibronectin, which result in the spreadi ng of the platelets over the vascular surface. In areas of low flow or low shear stress, this may be sufficient to keep the platelets attached . However, in areas of high shear stress, such as those found in capillalY beds and the arterial circul ation, further interaction is required between the GpIb-lX receptor and von Willebrand factor (VWF), a large, adhesive pl asma protein. Conditions where either of these receptors is absent, for example Glan zmann's thrombasthenia (Gpllb-lIIa) or Bernard-Soulier syn drome (GpIb-lX), or where there is a lack of VWF, are characterized by abnormal bleeding of variable severity and will be discussed later in the chapter.

Platelet Activation

Fibrin

Haemostasis after injury. Activation of the

coagulation system and platelets is necessary for formation of a stable fibrin plug.

counterparts by cleavage of peptide bonds. Thrombin is generated, converting fibrino gen to fibrin , which then sta bilizes the pl atelet plug. Activation offactor XIII by thrombin allows cross-linking of the fibrin strands and further stabil ization. Thrombin also activates the protein C pathway, which is inhibitory to coagulation and profibrinolysis, allowing dissolution of the fibrin clot as healing progresses.

PRIMARY HAEMOSTASIS Platelets must be present in ad equate numbers and function normally in order for the primary haemostatic plug to form effectively. Platelets are small, disc- like cells that remain in the circulation for 7-10 days. In their quiescent state, they ex press predominantly neutral phospholipids on their outer membrane, which are haemostatically inert. However, when activated, negatively charged phospholipids, predominantly phosphatidyl serine, are exposed, providing the membrane surface required for the coagulation reactions. On the cell surface there are also specific protein receptors for platelet agonists and adhesive glycoproteins, which are essential for effective haemostasis. Storage gran ules are also contained within the platelet cytoplasm, ex granules and dense (6) granules, whose contents are released by fusion of their membrane with that of the platelet.

Platelet activation rap idly foll ows adhesion and results in a change in shape of the platelets, generation of active medi ators an d secretion of the g ranul ar conten ts. The activation process is hi g hly specific owing to the presence of platelet recepto rs that recognize appropriate ago nists, the most important of these being thrombin and ad enosine diphos phate (ADP). Thrombin binds to the platelet at several si tes, including the Gplb-IX receptor as well as a sp ecific throm bin receptor, which is the most importa nt for activation. The thrombin recepto r has been identified as a large seven domai n transmembrane protein that binds proteolytically active thrombin, which is essential for the induction of platelet activation. This results in a change in shape of the platelets, platelet aggregation and secretio n of granule contents. A second agon ist, ADP, is much weaker than thrombin in vitro but is important in vivo as both red blood cells and vascular tissues release ADP in response to damage and lead to ADP-induced platelet activation and aggregation.

Platelet Aggregation Once platelets are activated, they aggregate, linking to each other to form a haemosta tic plug. The binding of fibrino gen to the GpUb-lIla complex is essential for bridging between acUacent platelets and is crucial to platelet plug formation. Fibrin is also bound by this receptor, helping to stabilize the platelet plug.

Platelet Secretion Platelet Adhesion The initial event in haemostasis is the attachment or ad hesion of platelets to the vascula r subendothelium that is exposed after injury to the non-thrombogenic vascular endothelial lin ing. Collagen receptors on the platelets, thought most likely to be the glycoprotein (Gp)la-IJa complex, bind to the exposed subendothelial coliagenY After adhesion, the platelets undergo further interactions involving the GpIlli-llia receptor

When platelets are activated , in addition to aggregation, a release reaction occurs in which the contents of the ex gran ul es and 6 granules are secreted. The constituents so released contribute to the process of primary and second ary haem ostasis as well as wound repair and vascular remodelling. The a granules release, amongst other things, VWF (synthesi zed by the pl ate let-forming megakaryocytes) and fib rinogen (synthesized by the liver and taken up into

Secondary haemostasis the platelet). It is possible that these pro tei ns bind to the platelet surface and participate in platelet adhesion and aggregate formation. This may be particularly important in platelet-rich plugs in which th ere is limited access to plasma proteins. Factor V is also contained in the ex gran ules and is important for formation, along with factor Xa, of the prothombinase complex on the ex posed phospho lipid surface of the activated platel et.

I

79

receptor that binds fibrino gen but also VWF, facilitating aggregation. VWF is non-covalently bound to factor VIIl and protects it from protein C proteolysis. Low levels ofVWF result in correspondingly low levels of factor VIII, which, if severe, can result in defects of secondalY haemostasis.

SECONDARY HAEMOSTASIS

Initiation and Amplification of Coagulation

Platelet Enhancement of Coagulation Activated platelets accelerate coagulation several thousand fold. As well as releasing procoagul ant microparticles an d factor V, activation of the platelet revea ls anionic phospho lipid sites on the platelet surface that are required as cofac tors. Two complexes of clotting fac tors, the tenase (X ase) complex (factors lXa and VIIIa) and the prothombinase complex (factors Xa and Va) are bound to the platelet sur face, thereby increasing their effective concentration and bringing them into closer proximity. Once bound to the platelet surface, coagulation factors are protected from coagulation inhibitors such as antithrom bin and activated protein C.

Von Willebrand Factor Von Willebrand factor (VWF) is a multifunctional adhesive protein that plays an important role in primary haemostasis. It is secreted from endothelial cells and is essential for stable platelet adhesion, paliicularly at high shear rates. On release, it binds to platelet GpIb-IX, allowing adhesion and subse quent activation of the platelet. This exposes the GpIIb-I1Ia

Ex posure of tissue factor on damage to the vascular endothelium results in the binding of both factor VII and factor VIla, each of which are present in the circulation in the quiescent state. Once factor VlJ is bound to tissue factor, it is very rapidly activated by the tissu e factor-factor VIla complex. This results in the activation of both factor X to factor Xa and factor IX to fac tor IXa. Some of the factor Xa thus formed will also bind to and activate the tissue factor/factor VII complex but, once bound, is rapidly inacti vated by tiss ue fac tor pathway inhibitor (TFPI). Unbound factor Xa stays on the cell surface and activates factor V to factor Va, which, together wi th factor Xa, generates a small amount of thrombin (IJa). This thrombin burst is sufficient to activate platelets, activate fuliher factor V, activate factor VIII by cleavage from VWF and perhaps activa te plasma factor XI to factor XIa. The generation of thrombin by this pathway, however, is insufficient to sustain adequate fibrin formation because of the ina ctiva tio n of the tissue factor-factor VIla-factor Xa complex by the binding of TFPI (Fig. 4.2). Amplification of the coagulation pathway comes from the sequence of reactions following the gener ation of factor IXa and the generation of factor XIa (Fig. 4.3). Factor IXa finds its way to the surface of an activated

x

TFPl

.~

1

TF

l.I

II

.---'----,-_--,-.L---,--_,...~ _ ___,_vv_~-~a--,-r---. Xa - Va ~ Endothelial cell or monocyte

Vila

Pl ate let

i TG~\NF

XI_Xla

"\

Va IX

Villa

IXa

Activated platelet

Figure 4.2

Tissue factor (TF) is exposed after injury and binds both factor VII and activated factor VII (Vila), which both activates factor IX and genera tes a small amount of thrombin from prothrombin (II ) by activating factor X. The thrombin activates factors XI, Vand VIII by cleavage from von Willebrand factor (VWF). Platelets are also activa ted and surface phosphol ipid (PL) is exposed. Tissue factor pathway inhibitor (TFPI) binds the tissue factor-Vlla-Xa complex and inactivates it, switching off the ini tia ting pathway.

80 I


Endothelial cell or monocyte Insoluble fibrin

Vila

~

IX

XIII

• Xilia

Figure 4.4 Conversion of fibrinogen to fibrin by thrombin and thrombin activation of factor XIII forming an insoluble clot by cross- lin kage.

Figure 4.3 Amplification of the coagulation system occurs after the initial thrombin burst when factors V, VIII and XI are activated along with platelets. Activated factor VII (Vila) by binding to tissue factor (TF) has already generated a small amount of activated factor IX (lXa), which binds to the exposed phospholipid (PL) on the activated platelets along with activated factor VIII (Villa) forming the 'tenase' complex. This activates free factor X, which binds to the platelet surface, along with activated factor V, forming the 'prothrombinase' complex. This converts factor II (prothrombin) to thrombin sufficient to cause clot formation. Generation of thrombin is sustained by continued activation of factor XI by thrombin activating more factor IX in turn.

platelet. where it binds to the exposed anionic phospholipid in association with its cofactor, factor V1Ila, which, generated by the initial burst of thrombin, is already bound to the platelet surface. This 'tenase' complex converts free plasma factor X to factor Xa. Still bound to the platelet surface, fac tor Xa and factor Va, again generated by the initial burst of thrombin , form the prothrombinase complex, which con verts plasma prothrombin to thrombin in amounts suffi cient to cause clot formation. Generation of thrombin is sustained by the activation of factor XI to factor Xla by thrombin, which activates more plasma factor IX to factor IXa in addition to the factor IXa initially formed by the tis sue factor-factor V1la complex. Thrombin finally converts fibrinogen to fibrin and through the activation of factor XIlI promotes cross-linkage of the fibrin to form a stable clot (Fig. 4.4).29 Thrombin also activates a proenzyme, thrombin activatable fibrinolysis inhibitor (TAFI) , which downregu lates fibrinolysis thus slowing clot lysis.29

Classical Coagulation Pathway Until recently, the process of coagulation has been described as a biochemical cascade consisting of an extrinsic and an

-

.

-

intrinsic pathway coinciding at the activation of factor X to form the final common pathway (Fig. 4.5).30.31 The intrinsic system is predicated on the assumption that factor XI is acti vated by the contact factors factor XII , prekallikrein and high-molecular-weight kininogens (HMWKs). Factor Xla then, as described above, activates factor IX in association with its cofactor, factor V1Ila, which then activates factor X and so on. In the extrinsic system, it is assumed that the release of tissue factor and factor V11 by damaged vessels activates factor X directly. The integrity of these assumed pathways is measured in vitro using the activated partial thromboplastin time (aPTI), which is based on contact acti vation of factor XII for the intrinsic pathway and the pro thrombin time (PT) for the extrinsic pathway. This scheme sti ll works well for the diagnosis of clinical bleeding prob lems, although it is inadequate to explain what happens dur ing in vivo haemostasis. For instance, individuals with factor XII deficiency do not bleed, those with factor XI deficiency have a mild to moderate bleeding disorder, and those with factor V11I or IX defiCiency have a severe bleeding disorder. Patients with factor V11 deficiency have bleeding problems despite having an intact intrinsic system, but for the most part only if the level of FV1I is less than 0.10 U/mL. J2 These anomalies are much better explained by the revised coagu lation process depicted in Figs 4.2-4.4. It can be seen that because in vitro testing is used to elu cidate the complex in vivo system, en'ors of interpretation can occur where prolonged clotting times may not be associated with a bleeding diathesis. Examples of this are factor XII defi ciency and deficiencies of prekallikrein and HMvVKs. They are not necessary for normal haemostasis in vivo, as they are required neither for initiation nor amplification of coagula tion . The aPTT can also be prolonged if a lupus anticoagulant is present. Phospholipid is added exogenously to the in vitro coagulation reaction and can be easily inhibited by antiphos pholipid antibodies - the so-called lupus anticoagul ant. In vivo, no such inhibition occurs because the phopholipid is provided by the activated platelet and is protected from the circulating antibody.

Laboratory tests I

Intrinsic pathway

81

Extrinsic path way

XII_Xlla

1

1

XI_Xla

aPTI

IX-IXa

VII_Vila

Vllla~~

PT

Com,," p",hw",

X II -

}-:: Throm bin - - -

Fibrinogen _ Figure 4.5

1

Fibrin

The classical pathway of co agulation: it is proposed that the intrinsic system is activated by cont act with an activating

surface and the extrinsic system by tissue factor released from damaged vessels or tissue. 80th systems activate factor X which via the final common path way results in the formation of fibrin. The prothrombin time (PT) reflects the acti vity of the extrinsic and common 8ath w ays. The acti vated partia l thromboplastin time (aPTI) is most sensitive to changes in the intrinsic pathway. II, factor II (prothrombin); Va, activated factor V; Vila, activated factor VII; Villa, activated factor VIII; IXa, activated factor IX; Xa, activated factor X; XI a, activated factor XI; Xlla, activated factor XII.

LABORATORY TESTS A full blood count will yield important information regard ing platelet number, and some au tomated counters will give the mean platelet volume. However, there will be no evaluation of function, an important parameter in primary haemostasis. Haemoglobin and white cell count may also indicate an underlying haematological disorder such as leukaemia or aplastic anaemia. Examination of the blood film will reveal morphological abnormalities of platelets such as size (Wiskott-AJdrich, Bern a rd-Souli er, May Hegglin, idiopathic thrombocytopenic purpura) or abnormal granulation (Chediak-Higashi and Hermansky-Pudlak syndromes). The basic screening tests available for coagu lation are the PT, the aPIT (written also as PITK) and fibrinogen measu rement and/or thrombin time (IT) . These laboratory investigations are designed to test the integrity of both the extrinsic and intrinsic pathw ays of the classical scheme of coagulation (Fig. 4.5) and remain invaluabl e for the understanding of clot formation in vitro. The PT reflects the integrity of the extrinsic pathw ay (fac t ors V1I and X), as well as factors II (prothrombin) and V of the common pathw ay. The aPIT tests the intrinsic pathway and is prolonged by deficiencies of factors XII, XI , IX, V11I and X as well as prekaJJikrein and HMWKs. Thrombin time is a functional test of fibrinogen, by which mrombin is added to test plasma and the time to clotting is measured. It is affected by the concentration of fibrinogen and abnormalities of fibrinogen (dysfibrinogenaemia). Inhibitors of the reaction include fibrinogen- and fibrin-degradation products

(FOPs) and heparin. The clotting time and the appearance of the clot are informative. A prolonged IT is seen in hypofibrino genaemia, both congenital and acquired, as in, for example, disseminated intravascular coagulation (DIC), in which there is consumption and inhibition by FOPs and liver disease (raised FOPs) . A prolonged IT is also seen with hypoalbuminaemia. Heparin causes extreme prolongation of the IT, but a 'reptilase' time, which utilizes a thrombin-like enzyme obtained from a snake venom that is unaffected by heparin and relatively insensitive to FOPs, is normal. It is useful therefore in differen tiating contamination by heparin from fiblinogen deficiency and also in indicating if a dysfibrinogenaemia is pre-sent when it is generally more prolonged than the thrombin time. In the latter case, the nature of the clot is often abnormal , being transparent and bulky as a result of abnormal fib rin polymer ization. This can be seen in liver disease. Fibrinogen is measured in a variety of ways; some auto mated machines derive the value from the prothrombin time, which is quick and simple. However, PT-derived fibrinogen levels appear to show a false elevation in a variety of clinical settings. Conversely, if the PT is very prolonged , a fal sely low fibrinogen measurem ent can result. The Clauss fibrinogen assay is a functional assay, based on the princip al that the thrombin clotting time is inversely proportional to the fibrinogen concentration )) and is the most reliable me thod for general use in clinical laborator ies.)4 The use of diluted pl as ma and a relatively high con centration of thrombin results in little interference by FOPs or heparin, which are known to influence the technique. If a PT-derived method is used, fibrinogen levels of 6 .0 gil should be rechecked using the Clauss method. 35 The go ld standard method is measurement of clot weight but this is time-consuming and not practi ca l as a screening test. VelY lo w levels of fibrino gen «0,8 giL) wiiJ begin to prolong both the PT and t he aPTT, especially when auto mated analysers are used,

MEASUREMENTS OF PRIMARY HAEMOSTASIS In paediatrics, defects of prima ry haemostasis are more com mon than coagu]opathies. 36 Primary haemostasis is depend ent upon both number and function of platelets. Other physiolog ical variables such as temperature,37 stress,38 anaemia,39 leu copenia 40,41 and the integrity of the connective tissues and vessels also influence primary haemostasis. Many of the va ri ables that might cause abnonnal primary haemostasis such as cardiovascular or renal disease, cardiopulmonary bypass sur gery or ingestion of aspirin-like drugs, will be obvious from the history and examination of the child, or from the results of initial blood tests such as full blood count or plas ma urea level. However, platelet function and platelet-vessel wall interaction are not eluci dated by these methods. The bleeding time is an in vivo test and dependent upon both haemostatic and other physiological variables outlined above. For instance, it is prolonged in patients with the con nective tissue disease Ehlers-Danlos syndrome, generalized vasculitis and scurvy (vitamin C deficiency), patients who have a low body temperature (as can occur in prolonged sur gical procedures) and in those with leukaemia or uraemia. AJthough the bleeding time can be a useful screening test to di agnose heredita ry bleeding defects that involve platelet endothelium interaction, the test requires a highly motivated and experienced operator who und erstan ds the many vari ables influencing the result and can inform interpretation of the test. 36 The most widely used method is the Ivy bleeding time 42 using a template. The test itself is invasive; small inci sions of a standard width and depth are made in the forean}] which can cause scarring and sign ificant distress to the patient, although there are specially designed templates for children minimizing th is problem. 43-46 The norma l ranges in children of different ages vary from those in adults and older ch ildren and between bleeding devi ces. Two further methods are available to screen for platelet dysfunction: both use small volumes of whole blood, from 2 flL to 1.5 mL, a nd require special instrumentation. The first method uses flow cyto metlY and utilizes the change in expression of platelet membrane proteins as an indicator of platelet activation,47 Upon activation, P-selectin is translo cated to the platelet surface membrane due to degranulation of the a granules and there is increased expression of the GpJlb-IIIa complex. Conversely, as platelets are activated, the GpIb-IX complex is internalized and results in decreased expression. These changes in expression ca n be detected using different monoclonal antibodies both on resting

platelets and on platelets after stimulation by agonists in controlled conditions.48 Thus platelet activation and reactiv ity can be determined. The use of whole blood in the second method allows for the contribution of red and white blood cells to the haemostatic process . This method measures aggrega tion and the release reaction of pl atelets in whole blood using the PFA-lOO system 49 ,50 Using this system, whole, anticoagul ated blood is drawn under a constant vac uum into a collagen/ADP-coated or collage n/adrena line coated membrane, which has a small aperture in it. A platelet plug is formed and obstructs the fl ow through the apertu re and both the max imum velocity of flow an d closure time are recorded. The test can be performed both on resting platelets and after stimul ation by agonists in controlled con ditions. The PFA-lOO is sensitive in detecting classi ca l defects resulting in maj or platelet dysfunction, such as Glanzmann's thrombasthenia and Bernard-Soulier syn drome and also von Willebran d's disease (VWD), although a full blood count and film will demonstrate a macrothrombo cytopenia in Bernard-Soulier syndrome and abnormal val ues of VWF antigen and/or activity will be seen in VWD, if specifically tested as is recommended in investigation of NAI (see beloW). False-negative results occur with the PFA-lOO in milder platelet defects, such as storage pool disorder and release defects, which are not detectable by t he routine labor ato ry tests 50 and it is not sensitive to vascular-col lagen dis orders. Although it may be useful as a screening tool for a bleeding diathesis in children,51 its use in identifying those who have a bleeding diathesis in cases of possible NAI has not been tested. Clinicians should always perform a full range of platelet function tests when clinical susp ic ion is strong and when exclusion of a platelet defect is essenti al. If pl atelet dysfunction is suspected from the pattern of bleeding or needs to be excl uded, formal platelet function testing can be performed. This requires larger volumes of blood and arrangements need to be made with the labora tory to discuss the extent and range of tests. Screening tests would include aggregation response to the agonists ADP, adrenaline (epinephrine), ristocetin and collagen and 5-hydroxytryptamine release, indicating the secretory resp onse. If abnormal ities are fo und on screeni ng tests, fur ther testing could include t hromboxane genera tion, platelet nucleotides, t10w cytometry or electron microscopy to define t he disorder more precisely. There are, however, problems with reproducibility and the overall haemostatic condition of the patient cannot be fully assessed by this method as vessel-wall interaction is not taken into account. It ca n be difficult to determine the contributio n to bleeding made by minor abnormalities of platel et fun ction testing.

EVALUATION OF A BLEEDING PATIENT When a child presents with bruising or bleeding, the main differential diagnoses are physiological or accidental bleeding. NAI or a bleeding diathesis, The sex of the

Evaluation of a bleeding patient I

patient, age, clinical presentation, past histoty and family histoty are all important in helping distinguish these dif ferent diagnoses, directing investigations and informing interpretation of the basic screening tests. Sex is obviously important in determining the likeli hood of an X-linked disease such as haemophilia A or B. These disorders can occur in girls but, unless consanguin ity or Turner's syndrome is present, are vety rare. Extreme lyonization of X inactivation can also result in girls being affected and, although such diagnoses are unlikely, they should be tested for full evaluation. The age at presentation influences the likelihood of a particular cause of a bleeding diathesis; for instance, a neonate with a purpuric rash will have a different set of differential diagnoses from an older child. A patient with a severe congenital bleeding diathesis is unlikely to present for the first time in the adolescent years. In addition, the plasma concentration of many of the coagulation and fibrinolytic proteins is age dependent, so normal ranges of screening tests are age dependent. It is important for laboratories to establish normal ranges for age using their own reagents and methods. 52

Clinical History and Presentation The type of bleeding at presentation and the cunent history may indicate the nature of the bleeding problem. If a child has a bleeding diathesis, there is often a lack of history of trauma or the bleeding is disproportionate to the injury. For example, a boy who has bitten his tongue, which then bleeds, stops and rebleeds on a continuing basis should be investi gated for haemophilia or factor XIII deficiency if initial tests are normal. On the other hand, a child who bleeds intermit tently from the same nostril that can be easily controlled, may well have a local cause, such as a superficial vessel in Little's area. Active children, particularly as they learn to walk, often have bruises on their shins but not usually on non-exposed areas. If such bruising is associated with painful joints or reluctance to use a limb, haemophilia may be the cause. Alternatively, if the child is constitutionally unwell, the underlying disease may be malignancy, with bone mar row infiltration such as leukaemia or neuroblastoma, both of which can cause painful limbs and joints in addition to thrombocytopenia. If a child is acutely unwell and shocked with widespread petechial haemorrhages then DIC secondary to sepsis, particularly meningococcal, should be considered. Persistent mucocutaneous bleeding such as gum bleeding, epistaxis (often bilateral) or heavy menstrual bleeding indi cates a platelet disorder, either of number or function, or VWD. Drug histoty is also important, in particular whether the child is on warfarin, heparin, sodium valproate or a non steroidal anti-inflammatory drug. Past history is important in both determining whether there has been a continued bleeding problem, whether the problem is of more recent onset and whether the child has had any significant haemostatic challenges. Congenital

Figure 4.6

83

Haematoma formation 2 hours after a dose of

intramuscular vitamin K in a neonate with haemophilia.

bleeding problems such as severe haemophilia tend to pre sent early, either at birth with cephalhaematoma, intracra nial haemorrhage or after an intramuscular injection of vitamin K (Fig. 4.6) or before the first birthday as the child becomes more active and starts to crawl and toddle. Con genital thrombocytopenia presents early with bruising and petechial haemorrhages in the neonatal period, although in some conditions the initial platelet count is preserved but deteriorates with time. Significant haemostatic challenges include surgery, for example circumcision, tonsillectomy or removal of teeth. Bleeding response to injuty such as biting the tongue, sustaining a fracture or involvement in a road traffic accident can yield important information. In girls, increased menstrual loss may be an indicator of a bleeding diathesis. Concomitant disease such as hepatocellular dys function, renal disease, malabsorption or a connective tis sue disease such as Ehlers-Danlos syndrome may result in abnormal bleeding.] ·53.54 Most of the clotting proteins are synthesized by hepatocytes, and the vitamin K-dependent factors II (prothrombin), V1I, IX and X) are the most sensi tive to liver dysfunction ; however, with increasing damage other factors such as factor V and fibrinogen are affected. The vitamin K-dependent factors may also become signifi cantly depleted in malabsorption syndromes. Renal failure and associated uraemia can contribute to a bleeding diathesis as certain accumulating metabolites interfere with platelet function and accompanying anaemia results in the loss of red cells transporting centrally flowing platelets to the vessel wall, promoting adhesion to the subendothelium. 55 Paradoxically, nephrotic syndrome is associated with venous thrombosis due to an imbalance of the haemostatic system. Acute phase reactions or other mechanisms cause high VWF and fibrinogen in conjunc tion with low levels of antithrombin, an endogenous anti coagulant, secondaty to urinaty loss. Cyanotic congenital

84 I


heart disease can lead to thrombocytopenia, secondary to shortened platelet survival, and hypofibrinogenaemia, sec ondary to poor liver function, with reduced synthesis and clearance of clotting factor intermediates leading to low grade disseminated intravascular dissemination. Family history is clearly essential to detennine the like lihood of an inherited disease. Children with X-linked dis ease such as haemophilia may give a family history of affected males carried through the female line. However, the family history is not always helpful as about 30 per cent of those with haemophilia A are due to spontaneous mutations. 56 VWD is an autosomal dominant condition with variable penetrance, which often gives a positive fam ily history of bleeding but sometimes appears to skip a generation owing to VWD modifier genes that have no association with the VWF gene. 57 Autosomal recessive conditions, such as factor XIII deficiency, or conditions in which the heterozygote may only have a mild or no bleed ing tendency such as factor XI deficiency, usually do not have a positive family history unless there is consanguin ity within the family. For example, factor XI deficiency is found most frequently in those of Ashkenazi Jewish descent (in whom the carrier rate is 8 per cent) and who tend to many within a small community, resulting in a restricted gene pool. 58

Examination of the Child The general health and state of the child should be assessed. In a bruised child, particular points to look for are the distri bution, size and age of the bruises; whether they are in any recognizable pattern such as a hand or belt mark; and whether there is a haematoma indicating the extent of bleed ing. It should be noted that fingertip bruising is not infre quently found in children with a bleeding diathesis and is not pathognomonic ofNAl (Fig. 4.7). Distribution of bruising can be the key to the diagnosis of Henoch-Schonlein purpura, which is present on extensor surfaces and is due to a vasculi tis rather than a coagulopathy. Coagulation screening and a full blood count will be nonnal and thus confusion with NAl may arise (Figs 4.8 and 4.9).16.59.60 Presence or absence of petechial haemorrhages will help to differentiate disorders associated with thrombocytopenia. Such haemorrhages also occur in situations when there is raised intrathoracic pressure in the absence of a bleeding diathesis, such as a severe bout of coughing or vomiting or in strangulation. In these situ ations, the petechiae will be seen in the distribution of the superior vena cava area or around the eyes or mouth 61 (Fig. 4.10). A swollen, tender joint may indicate bleeding into the joint, as is seen in haemophilia or, much more rarely, VWD, but tender joints may also be seen in Henoch-Schonlein pur pura, acute leukaemia or neuroblastoma. Neuroblastoma may present with bilateral black eyes as a result of tumour infiltra tion; comparatively minor injury can cause the same in haemophilia (Figs 4.11 and 4.12). Systemic upset and

Figure 4.7 Fingertip bruising in a child with Glanzmann's thrombasthenia.

Figure 4.8 Symmetrical bruising on extensor surfaces seen in Henoch-Schbnlein purpura.

enlarged lymph nodes, liver or spleen usually accompany bruising and petechial haemorrhages secondary to acute leukaemia . A limp, with or without bruising, can also be seen at presentation in this disease. A rare disease, haemophago cytic Iymphohistiocytosis (HlH) presents with systemic signs and symptoms, such as pancytopenia, coagulopathy and organomegaly, but may also present with central nervous

Evaluation of a bleeding patient I

Figure 4.9

85

Buttock bruising in Henoch-Schonlein purpura . Figure 4.11 Bilateral black eyes after minor trauma in a chi ld with haemophilia.

Fig ure 4.12 Black eye and mild proptosis in a child with neuroblastoma. (Courtesy of the late Dr J. Pritchard, Edinburgh.)

Figure 4.10 Subconjunctival haemorrhage secondary to coughing in a child with no haemostatic abnormality.

Haematological Investigation system (eNS) manifestations. These can range from irritabil ity to encephalopathy and coma. Retinal and intracranial haemorrhages can be found in these circumstances and this condition has been mistaken for abuse. 62 Full examination and laboratory evaluation, however, will indicate the correct diagnosis. Disseminated intravascular coagulation with secondary bleeding is generally seen in an ill child with signs and symptoms of infection.

-

- -- - - - - -

FIRST-LINE INVESTIGATIONS

Once history-taking and examination have been done, inves tigations can proceed. The way blood is taken and processed is of paramount importance, as activation of the coagulation system by a difficult venepuncture and contamination with tissue fluids or by the presence of air bubbles will invalidate the result. Shortening of the PT or aPIT through activation of a specimen may mask a significant bleeding disorder such as

86 I


Table 4.1

Common pitfalls in specimen collection and processing

, Problem

Process

Result

Poor ve nepuncture technique

Activation of sample

Specimen taken from heparinized line Over- or underfilling specimen tube Severe polycythaemia (reduced plasma vo lume)

Heparin contamination Ratio of citrate-plasma not 1:9 Ratio of citrate-plasma> 1:9 Activation of sample Loss of factor activity

Prolongation or shortening of clotting times Thrombocytopenia Prolongation of apn

Inappropriate storage/transport

haemophilia. Conversely, if blood is taken through a cannula that has been kept patent with heparin then contamination frequently results, giving abnormal values for many of the coagulation tests. Venepuncture of children should be done by an experienced operator wherever possible, at a time when the blood can be rapidly dealt with by the laboratOly. Blood should be taken with the minimum of venous stasis and sub sequent handling. Spinning, freezing and thawing blood can cause al1efact; for example, factor XI levels may rise.6) Trans port to a laboratory some distance away, even if the specimen is transported on ice, can also cause artefact, usually a lower ing of clotting protein values. Some common pitfalls in speci men collection and processing are shown in Table 4. I. Initial tests include a coagulation screen, PT, aPIT, IT and fibrinogen as outlined above and a full blood count and film. A fa ctor VlU, factor IX level and VWF antigen and activity are recom mended in all cases of suspected NAI, as a normal or margin ally prolonged aPIT can be associated with a significant decrease in factor VIII or IX levels.64 Factor XIll may also be measured in neonates with intracranial haemonhage. If the blood is flowing well , a few millilitres extra can save a second venepuncture if an abnormality is found, for example a pro longed aPTT, and further testing is required. Bleeding time is an invasive test and although it will demonstrate the integrity of the platelet-vessel wall interaction, is usually unnecessary in the early stages of investigation. It is highly operator dependent. One of the newer tests (flow cytometry or the PFA 100) may be helpful in the future but there is no published work in this clinical setting and false-negative results may be misleading. It is sometimes helpful to investigate parents, especially if results are equivocal or subsequent testing for clarifica tion of a ny abnormality requires large volumes of blood. Identification of a child's natural parents is not always cer tain, or they may not be available or readily located, mak ing this approach impossible.

PATIERNS OF ABNORMAL RESULTS The pattern of abnormalities obtained using first-line tests along with the clinical presentation may indica te an und er lying defect/disorder. The extended testing discussed

Sho rtened or prolonged clotting times Prolonged clotting times Shortened or prolonged clotting times Prolonged clotting times

above, which includes VWF antigen and activity, and levels of factors VIII and IX , will add further information a nd minimize del ay. The results of the tests will inform the choice of fu11her tests to determine the precise diag nosis.

Isolated and Prolonged aPTI (PT Normal, TI Normal, Fibrinogen Normal, Platelets Normal) Prolongation of the aPIT is probably the commonest abnor mality found on pelforming the coagulation screen. This may be by only a second or two but can signal a significant bleed ing diathesis. Referring to the classical scheme of coagulation (Fig. 4.5, p. 81), which is a good model for in vitro coagul a tion, this indicates a defect in the intrinsic pathway. This pattern is fo und in: 1. con genital deficiency of factors VIII, IX, XI and XII, as well as prekallikrein and HMWK ; 2. VWD, as this may result in low levels of factor VIII; 3. circulating inhibitors, e.g. lupus anticoagulant; 4. mild deficiencies of factors II (prothrombin) , V and X may prolong the aPIT, whereas the PT rema ins norm al (reagent dep endent); 5. heparin, either as a contaminant or a therapeutic agent, is a common cause of a prolonged aPIT; the IT is very sensitive to heparin and will be prolonged; a reptilase time will be normal. Thus the prolongation of the aPIT is due either to a clotting factor deficiency or an inhibitor of coagulation. To differentiate between the two, a 50:50 mix of test plasma with normal plasma can be performed . If there is a deficiency there should be a correction of the clotting time to within a few seconds of normal and at least less tha n 50 per cent of the difference between the control and test plasmas. If there is no significant correction then the presence of an inhibitor is suspected. This might be heparin contamination or therapy, an acquired inhibitor of a clotting factor (velY rare, especially in children) or the lupus anticoagulant (Fig. 4.13). Therapeutic heparin administration or heparin contamin ation of the specimen can be ruled out from the history, by checking that tlle specimen was not taken from a heparinized

Patterns of abnormal results I

87

PT, aPIT, Fibrinogen, IT

... Isolated

.

I

PT

Isolated

.. I

aPIT

t Unlikely

t

t

'+

Correction

.

i

Likely

t ?

Unlikely

(I IT.

t

t

'+ Unlikely

t

t

K warfarin liver disease

111, V, X lv+vlll LA + 111

I PT, I aPn, 1 fibrinogen

Normal (including platelet count)

t

i

DIC

Severe liver

disease Afibrinogenaemia Dysfibrino genaemia

Haematological

t

Glanzmann's thrombasthenia Platelet SPD 1 XIII

1 cx,antiplasmin

1 PAI-l

Tissuelvascular

t HSP 1 vitamin C Ehler's-Danlos

? LA'

reagent

dependent:

111, V, X

HM\AlK' PK'

hw

i

aPn

t

1 XI

v\AlD 1 VIII llx

heparin Rep time N)

I

Likely

1 vit

No correction

'+

PT,

.

i

..

due to: Cong 1 VII Reagent early warfarin dependent: therapy LA' early 1 vit K early liver mild 111, V, X disease

Figure 4.13

I

50:50 plasma mix

Likely

1 VII

t

...

(I DRVVT)

t ?

factor VIII, IX or

XI inhibitor (DRVVT N)

Algorithm for initial investigation and interpretation of results in a child with a possible bleeding diathesis.

II, factor II; V, factor V; VII, factor VII; VIII, factor VIII; IX, factor IX; XI, factor XI; XII, factor XII; XIII, factor XIII; V+VIII, combined factor Vand VIII deficiency; HMWK, high molecular weight kinonogen; PK, prekallikreth; cong, congenital; LA, lupus anticoagulant; HSP, Henoch- Schbnlein purpura; SPD, storage pool disorder; DIC, disseminated intravascular coagu lation; vWD, von Willebrand Disease; PAI-l, plaminogen activator inhibitor-l ; H thrombin time; Rep, Reptilase; DRWT, dilute Russell viper venom time. 'Not associated with bleeding Table 4.2

Prolonged aPTT:differentiation of an inhibitor from a deficiency

apn

50:50 mix

DRVVT

Platelet neutralization

Reptilase time

PT

t t

Correction No correction n/a

N N N

N N N

n/a n/a No correction No correction

N N N N

N N

Inhibitor

Lupus anticoagulant Heparin Factor VIII and IX antibody

t t t

t t t

t t

Correction Correction Correction Correction

N

Deficiency

Factors VIII, IX, XI and XII VWF Factor II Factors V, X

or N sl t or N

t

N N

t t

'May be normal if deficiency mild.

aPH partial thromboplastin time; DRWT, dilute Russell's viper venom time; n/a, not applicable; N, normal; PT, prothrombin time; Willebrand Factor.

Note: Specific patterns of bleeding may be seen with specific diagnoses (Table 4.3).

line or put into a bottle containing lithium heparin before being transferred to a citra ted one. It is also possible that heparin may have been given inadvertently or with intent to cause bleeding.55 If there is uncertainty, a reptilase time can be performed, which, by activating fibrinogen directly, is nor mal in the presence of heparin. If the pattern of correction is one of an inhibitor, and heparin has been excluded, the most likely cause is a lupus anticoagulant (Table 4.2). Lupus anticoagulant is a phospholipid antibody that interferes with the phospholipid added to the in uitra test ing model. It affects the aPTT rather than the PT, as the phospholipid in the former test is more dilute and usually more sensitive than that used in the PI. FUliher tests, such

t· t
1 year

Fresh red blood cells Fresh red blood cells, polymorphon uclear leukocytes and fibrin Macrophages replace polymorphonuclear leukocytes Mixture of intact and lysed erythrocytes, siderophages present Red blood cells lysed; early angiofibroblastic proliferation Haematoma liquefies, sinusoids, 'giant capillaries' appear Vascular sinusoids are well developed Haematoma is liquefied

Fibroblast layer up to 12 cell la yers thick Fibrobla st layer is about half of the thickness of dura

Fibrin

Single layer of fibroblast cells present Fibroblast layer is a few cells thick, with an occasional capillary

Fibroblast layer is as thick as Fibrous membrane and a few capillaries see n the dura, siderophages present Fibroblast layers are hyalinized and form membranes on both surfaces, large (giant) capillaries appear early, secondary haemorrhages often develop The neomembranes fuse and contain mature fibrous tissue and scattered siderophages, after 3 months it is no longer possible to accurately date (age) the haematoma The neomembrane is a distinct fibrous connective tissue layer that closely resembles the adjacent dura mater, occasional ca lcification and/or ossification

of sum cases are detailed by Valdes Oapena et al40 and KroUS. 41 Comment will be directed paJiicularly at those organs or regions for which a different approach or empha sis is appropriate in the older paediatric age group . The task is easier when the following equipment is available: shOji

(10- to 12-cml, non-toothed forceps to mJlllmlZe tissue damage; a range of tapered, round-ended scissors (Mayos); and a variety of scalpels, rather than an autopsy knife. Reference to the need for a digital balance was made in an earlier section .

154 I

Post-mortem examination in babies and children

Forma l neck dissection to detect injUly is carried out in a sim il ar fas hion to that in adults and invo lves layer-by-Iayer examination of the anterior neck muscles. In the infant, it can be achieved following a vertical submental-symphysis pubis incision as tissues stretc h readily but is probably eas ier with a shoulder-to-shoulder appro ach. Posterior neck muscles are conveniently inspected by ensuring that th e posterior scalp refection extends to the cervica l sp ines. The thorax is best approached by serial division of costal cartilages, avoiding damage to the osteochondral junctions, some of which will be submitted for histological examina tion, a nd has the advantage of leaving the ribs intact. Fresh rib fractures may be apparent following reOection of skin and soft tissue (Fig. 8.8). Resuscitation Jib fractures are un com mon, and are usually situated at the anterior ends of lower ribs; accompanying haemorrhage is minor and there is no vital reaction on histological examination. Rib frac tures are discussed further in Chapter 11, pp. 213- 215. Relationships of orga ns are observed before disse ction commences, some abnormal relati onsh ips may suggest a syndrome diagnosis. The thymus is a prominent organ in early life, weigh ing 10 ::!: 4 g at term. It is of normal size (often described as large) in sudden death. A reduction in thymic weight below th e normal ran ge for age is a non-specific indicator of ante mortem stress, probably in excess of 12 hours' duration 42 Petechial haemorrhages v isible through the thymic capsule, particularly on its posterior aspect, a re present in about 80 per cent of SIDS 43 (see Chapter 11, p. 212). Larger, blotchy haemorrhages may be present in asphyxial death. The appearance of the lungs, noting the degree of expan sion or collapse, is recorded. The lu ngs usua lly fill the chest in SJDS but are often collapsed following attempted resuscitation

Figure 8.8

Fresh rib fractures accompanied by bruising, visible

after reflection of thoracic skin fl aps.

in hospital with a high concentration of oxygen. Fluid in the pleural and pericardial cavities is observed, measured and described. A sample of pericardium can be obtained at this stage using sterile inst ruments and placed in tissue culture Ouid for immed iate culture, if appropriate, or stored at - 280°C for future availability for investigation of putative genetic abnormality. This is followed by sampling of heart blood, lung and myocardium for microbiological purposes. External examination of the heart is conveniently canied out at this point by fully opening the pericardial sac. Cardiac abnormalities, both congenital and acqu ired, are common causes of explained SUD! (see Chapter 11, pp. 208-210) and older children (see Chapter 12, pp. 226-235). Cardiac situs is dependent on atrial morphology. The comparative size an d relationsh ip of the ascending aorta and pulmonary trunk are noted - they should be equal in size. The course ofthe an te rior descending branch of the left coronalY artery should be observed and the connection of t he vena cavae a nd pul monary veins noted. If all are normal then congenital heart disease is excluded, with the exception of septal defects and anomalous pu.lmonary venous return to the coronary sinus. The liver is relatively large in infants and protrudes below the costal margin. Colour and consistency are noted . Fatty infiltration and evidence of trauma are sought. The former requires frozen section and histochemica l staining for confirmation. Preservation of samples to investigate the possibility of GMD and full toxicological exami nation should be considered. The stomach is often distended, either because of attempted 'bag and mask' ventilation or microbial fermentat ion. The mesentery is inspected for tears and contusio ns (Fig. 8.9). Completeness of intestinal rotat ion is observed, along with the presence of volvulus, intussusception and herniae - all of wh ich are potential causes of intestinal obstruction, shock and sudden death - are sought.

Figure 8.9

Contusion in the mesentery close to the

duodenojejunal junction.

Dissection (infants and older children) I Organs should be removed in blocks and not piecemeal. In particular, the heart should remain attached to the lungs until completely dissected. Th e Rokitansky technique is suitab le but the following proced ure is easier: removal of (he intestines from the duodenojejunal fl ex ure to the rec tum (having checked the mesentery for contusions) (Fig. 8.9), then rem oval of the thoracic and upper abdominal viscera en bloc thus opening the inferior vena cava and abdominal aorta, followed by removal of genitourinary tract. When sexual assault is suspected, a cuff of perineal skin is removed in continuity with the lower genital tract and anus, usually including the coccyx, the pubic area and the med ial aspect of the thighs. Swabs for forensic exam ination should be taken before dissection is begun . Following removal of the viscera, the thoracic and abdominal cavities should be cleared of blood and fluid and their walls examined. The ribs should be carefully inspected for fractures. Rib fractures are often undisplaced in babies and in fants. Attention will be drawn to fresh frac tures by subperiosteal an d intramuscular haemorrhage. Older fracture sites will be supported by callus and are usu ally stable (Fig. 8. 10), although re-fracture can occur. Cal lus is particularly marked on the internal aspect of the rib and is readily palp able. Fractures at the posterior ends of ribs are easily missed and should be specifically sought, with the remova l of pali of the rib cage fo r radiographic and histological examin ation wh en there is suspicion of injury. Previous avulsion of the osteochondral junction of

155

the lower ribs (6-10) is common when there are fractures elsewhere and is seen as expansion of the internal aspect of the bone adj acent to the cartilage (see Fig. 8.20, p. 160). Stripping of the pleura to look for rib fractures in infants is not recommended. The stripping process results in tissue dam age, including any subperiosteal reaction and may render histological evaluation probl ematic. Th e upper airway is examined carefully and may be fixed before opening when trauma to the neck has occurred. Laryngeal fracture is unlikely but small haemor rhages may be present in the intrinsic lary ngeal muscles. FUliher microbiological samples can be taken from the lower trachea/main bronchi. A convenient meth od of opening the heart is shown in Figure 8.11. It is opened before separation from the lungs. Should a cardiomyo pathy be suspected, a horizontal slice through both ventricles, midway between base and apex, demonstrates it well (Fig. 8.12) without interfering with dissection; chamber connections and morphology, appea r ance of valves, septal defects and the origin and course of coronary arteries are examined. The appearance and thick ness of ve ntricular myoca rdium is noted. Any subendocar dial fibroelastic thickening or haemorrhage is noted. Heart and lungs are separated and weighed. Pulmonary arteries are examined for evidence of thromboembolus and hypeliension - both causes of sudden death in early life. The former is most likely to be found in the poorly mobile, postoperatively and follo wing the use of intravenous devices.

... ...

...

\ \ \ \ \

-

Figure 8.10 Thorax after evisceration; old posterior rib fractures with ca llus are readily visible.

\4 \ \. \ ...

\

"

\

...

...

...

"

"-,,- 2 " .... ....

\

...

\

...

\

\

\

... ...

\ \

.......

.........

...

...

...

"

Figure 8.11 Opening the heart, cutting lines are numbered sequentially (from Fetal and Neonatal Pathology, 4th edn, 2007, p. 39, figure 2.20, with kind permission of Springer Science and Business Media).

1 56 I


Figure 8.12 Transverse slice through the ventricular myocardium half way between base and apex. There is marked left ventricular hypertrophy in this ll-month-old infant with hypertrophic cardiomyopathy.

Subpleural petechiae are a common post-mortem finding in infants. Larger, blotchy or confluent haemorrhage is less common and may indicate an asphyxial episode (see Chapter 11, p. 218). Lung scarring may be present in babies who were born preterm and who have received intensive care. The stomach is opened and its contents noted. A sample may be retained for toxicological examination. Foreign material, such as paper or non-food items, should evoke a high suspicion of non-natural death. The nature of food residues should be related to the description of ante mortem events. The amount of food in the stomach is a most unreliable guide to length of survival after the last meal. One should remember that gastric aspiration may have been carried out in the accident and emergency department. When both stomach and intestines are found to be empty, careful note of the history and nutritional state is required. Microbiological samples from the intes tine are mandatory in these circumstances and detailed questioning of carers may be appropriate. Haemorrhagic infarction of the intestines, myocardium and sometimes brain is commonly seen in infants who have been subjected to intensive care procedures for periods of > 12 hours prior to death. Care should be taken not to over interpret these changes (see Chapter 11, p. 215). Pulmonary haemorrhage is common after attempted resuscitation involving ventilation but siderophages, seen on microscopic examination, require at least 2 days to develop.44

EXAMINATION OF THE BRAIN, SPINAL CORD AND EYE Before the cranial cavity is opened, the scalp and calvarium are examined for evidence of injury; if injuries are found then these are recorded as described previously. In the

Figure 8.13 Cranium opened by the modified Beneke technique. Bone flaps are reflected following incision of suture lines. There is a brown membrane attached to the parietal dura, due to organization of a subdural haemorrhage that occurred several weeks before death. newborn and in early infancy, the calvarium is opened using the modified Beneke technique. 45 It allows visualiza tion of bridging veins before the bony flaps are completely reflected and of ' membranous' adhesions that may be pre sent between dural and arachnoid membranes during organ ization of old subdural haematoma (Fig. 8.13). Any tearing of bridging areas is recorded and a search made for a related focal subarachnoid haemorrhage (Fig. 8.14) and thrombosis of torn veins (Fig. 8.15). The presence of extradural and subdural haematoma is noted. The former are unusual in early life because of the firm adherence of the dural membranes to the inner table of the calvarium, particularly along the suture lines, a phe nomenon that may introduce difficulty in removal of the calvarium following a circumferential saw-cut. The infant brain swells rapidly following hypoxia or trauma, largely obliterating the subdural space so that sub dural haemorrhage may be reduced to a confluent film over the convexities, running in the falcine fissure and with small collections in the cranial fossae. Any abnormality of the convexities is recorded, the brain is removed, weighed and fixed in 10 per cent buffered formalin before examination. It is not advisable to attempt photography of the brain prior to fixation, other than pic tures taken before removal of the brain from the skull base. The infant brain is particularly soft following oedema and

Examination of the brain, spina l cord and eye

I

157

Figure 8.16 Fresh infant brain with flattening and posterior separation of the hemispheres. There is stretching and tearing of the corpus callosum.

Figure 8.14 Superior convexity surface; focal subarachnoid haemorrhage may indicate the site of torn bridging veins.

Figure 8.17 Slice of the cerebral hemispheres after fixation; death followed a motor vehicle collision. There is haemorrhage in the right putamen/internal capsule and focal haemorrhages in the corpus callosum.

Fi gure 8.15 Surface of the brain after fixation from a baby with oJbdural haematoma and haemorrhage. Thrombosis of a torn ridging vein is present. . :"Poxic insult. Artefactual tearing of vulnerable structures, ch as the corpus callosum, can result from manipulation of the unsupported brai n (Fig. 8.16). When the brain is very - ft, weighing in the fresh state can be omitted. Following the removaJ of the brain, standard samples for rristological examination are obtained from the parietal dura w d the dural folds. Any dura with attached clot, organizing ~em brane or brown staining should be removed, additionally, - r histological examination. Hardman 46 describes the histo .ogical appearances of subdural haematoma with approximate _uration prior to death (Table 8.4, p. 153).

In babies, infants and young children, the spinal cord is most conveniently removed from the front. An intervertebral disc is incised in the lower lumbar region and the proximate vertebral body grasped and elevated; the pedicles can then be divided with bone forceps on either side up to the upper cer vical region. The cord is examined through its intact dural covering and any extraduraJ haemorrhage is noted. The nerve roots are incised on either side as far laterally as possible to preserve dorsal root ganglia and the cord is removed after incising the dura at Cllevel. The cord is fixed flat for optimal examination. This is easily achieved by carefully laying it on a strip of card and permitting adherence for 2 or 3 minutes before immersion in fixative. Examination of the fixed brain and cord (preferably by a neuropathologist) is carried out systematically. The brain is photographed prior to slicing and any abnormalities identified subsequently are also photographed (Fig. 8.17). Samples for microscopy should follow appropriate fetal and infant blocking schedule (Fig. 8.18). additionally, sam ples of any abnormalities are obtained.

158 I


Rand L frontal parasagittal

Rand L parietal parasagittal Rand L parietal convexity Rand L basal ganglia at level of mamillary bodies

affords a view of the total orbital contents so that any extraglobal lesion can be sampled. 47 It is important that vitreous sampling is omitted when detailed examination is considered appropriate. The eyes are fixed separately in labelled containers. Exam ination of the fixed eye is described by Lee.48 Photographs of any external lesions should be made together with a photo graphic record of the interior after opening before sampling for microscopy. Processing of the eye requires care to min imize artefactual distortion. Perls' Prussian blue reaction (PBR)-stained sections are mandatory when assault is likely and immunohistochemical examination against beta amyloid precursor protein of the optic nerve is more effective than haematoxylin and eosin staining for the demonstration of axonal swelling when optic nerve trauma is suspected. 49 In some of these cases, referral of the whole eye for specialist examination may be the safest option.

Rand L thalamus Rand L hippocampus at level of lateral geniculate body

Rand L occipital

Midbrain Pons Medulla Rand L cerebellar hemispheres, inCluding dentate nucleus vermis

Figure 8.18

EXAMINATION OF THE NEWLY BORN Detailed techniques of necropsy examination appropriate for the fetus and neonate are described by Wiggleswolth 50 and Keeling.4 5 The following observations are relevant to the examination of the newly born for medicolegal purposes. This may be required because the body was concealed, abandoned , born in the absence of appropri ately qualified attendants or was unexpectedly still born. Other situations when a medicolegal examination is required are when attending clinicians cannot complete a death certificate or if there are complaints by parents or others and following maternal trauma or death (see Chap ter 10). Important considerations during the examination of perinatal deaths are those of live birth and separate exis tence. These are discussed in Chapter 10, pp. 187-192.

Diagram for sampling of the infant brain for

histological examination. Any lesions are sampled in addition

Radiography

(from Fetal and Neonatal Pathology, 4th edn, 2007, p. 43, figure 2.24, with kind permission of Springer Science and Business Media, courtesy of Professor JE Bell, Edinburgh).

The spinal dura is incised anteriorly and posteriorly, and the cord surfaces photographed. The presence of blood or clot is noted. The cord is sectioned transversely from the upper cervi cal region. This can be done while it remains attached to the dura. Any lesions within the cord are photographed. Sam ples for microscopic examination are taken at identified levels, and the cord and dura are preserved in continuity so that other identifiable blocks can be obtained if required. The eye can be removed from the front (anterior approach) following incision of the conjunctival reflections and division of the intrinsic ocular muscles in turn. The eye is prolapsed and the optic nerve divided. In the young, it is easier to approach the eye from the floor of the anterior cranial fossa (posterior approach), which is thin. This

A single whole-body radiograph is not sufficient in susp i cious fetal or neonatal deaths; imaging should follow the procedures outlined on p. 147 earlier in this chapter. As well as providing a record of any fractures, radiographs in the perinatal period provide useful information about ges tation (and, therefore, viability) ;51. 52 they also provide good proof of skeletal malformations, which can contribute to a syndrome diagnosis. A radiograph may demonstrate gas in the stomach and intestines in live birth.

External Findings Weights and measurements mLlst be carefully recorded. A careful external examination is most important. Any changes of maceration are carefully recorded as they provide useful information about the fetal death to delivery interval. Serial maceration changes are tabulated (Table 8.5);

Examination of the newly born I Table 8.5

External changes of maceration by death to delivery

interval (after ref. BB)

Observed feature

No maceration No discolouration of cord insertion Desquamation ?! 1cm Cord discolouration, brown/red Desquamation face/back/abdomen Desquamation ?! 5 per cent of body surface Desquamation in two or more zones' Skin brown/tan in colour Moderate/severe desquamation Mummification (dehydration :t fetal compression)

Death to delivery interval

< 6 hours < 6 hours ?! 6hours ?! 6 hours ?! 12 hours ?! 18 hours ?! 18 hours ?! 24 hours ?! 24 hours ?! 2 weeks

'Sody zones: scalp, face, neck, chest, abdomen. back. arms, hand, leg, foot,

scrotum.

Ch anges of maceration are accelerated by fetal hydrops and retarded in

the presence of fetal growth restriction.

early changes of maceration are ill ustrated in Figs 10.4- 10.6 p. 184. The presence of excessive meconium staining indicates hypoxic fetal stress in the mature baby. If there is much meconium, blood or vernix caseosa on the skin it is advisable to remove it after initial photography so that the skin can be examined in more detail. Cutaneous pallor may be evident following significant fetomaterna l haemorrhage. 53 The presence and nature of any cutaneous injury is recorded and photographed. It is not unusual to find cutaneous petechial haemorrhages over the presenting part in fresh still birth, particularly when there is placental abruption. They are commonly found over the face, head and neck and, occasionally, on the chest wall in a mature fetus when vertex presentation is usual. They are often particularly prominent following placental abruption (see Fig. 10.10, p. 188) and should not be interpreted as evi dence of stra ngu lation or deliberate airways obstruction without corroborative evidence. Cutaneous petechiae, and sometimes more extensive bru ising, are seen on the legs following breech delivery or the arm if one has prolapsed through a partly dilated celvix. These findings are more usual in the premature fetus, for which breech presentation is more common. 54 At 32 weeks' gestation approximately 16 per cent of babies present by the breech, compared with around 5 per cent at term. The presence and nature of any dysmOlvhic features are noted. These may contlibute to a syndrome diagnosis, directly related to death. The presence oftvvo or more dysmorphic fea tures is an indication for chromosome examination. The umbilical cord and its insertion are examined and any discolouration or dehiscence is noted. The free end of the cord may indicate the method of division. Differences in appearance of the cord ends are described 55 - traction,

159

picking apart, and cutting with scissors or bl un t/sharp knives - and assessment is aided by dissecting microscopic examination. It may correspond with the free end of the cord attached to a placenta discovered elsewhere. The pres ence or absence of a clip or tie is noted and described.

Examination of The Scalp and Cranium EXTERNAL

Examination of the head and cranial contents is undertaken systematically. The head circumference should be approxi mately equal to the crown-rump length in the second half of pregnancy. A larger measurement raises the possibility of hydrocephaly, whereas a smaller one may result from crania l distortion or, in its absence, chronic in trauterine brain pathol ogy. An increase in the occipitomenta l diameter (see Fig. 10.9, p. 188) is a useful observation. Some moulding of the cranium is nOlmal but excessive moulding of the cranium is an indica tion of long labour. In vertex presentation there is often an area of localized oedema, usually with marked congestion and sometimes with frank haemorrhage, over the presenting part. INTERNAL

The scalp is incised from behind the ear over the posterior fontanelle to the opposite ear and reflected forwards and backwards, sufficiently far to completely expose the bones of the cranial vau lt. The presence of haemorrhage within the scalp is noted and a check is made for any corres ponding external injury. Marked congestion of the scalp is a very frequent finding in antepartum still births after vertex presentation. It should not be confused with tra uma. Histological examination shows no vital reaction. The con tour of the occipital bone is examined. Occipital osteodias tasis , in which the inferior pali of the OCCipital bone is displaced inwards resulting in damage to the brain or venous sinuses, may occur after breech delivery or, occa siona lly, following forceps delivery;56 it is eas il y missed if the sca lp is not ful ly reflected posteriorly. The posterior neck muscles are conven iently ex amined at this point and any contusion is photographed and sam pled for histological examination. The atlanto-occipital membrane sho uld then be incised under direct vision. Gentle pressure on the cranium wiiJ result in a flow of CSF, which is likely to be heavily blood stained when there is selious intracranial injury. The fontanelles and suture lines are obselved. Congestion or haemon'hage is sometimes seen at the margins of sku ll bones and probably indicates the stress of forcible displacement.

Cranial Cavity The cranial cavity is opened using the modifi ed Beneke technique (Fig. 8.19), which allows examination of the

160 I


Figure 8.20 Birth injury. Tear at the junction of the falx and tentorium follo wing instrumental delivery, displayed by removal of the cerebral hemisphere on the affected side.

Figure 8.19 Neonatal cranium opened using the Beneke technique; there is confluent subarachnoid haemorrhage, of hypoxic origin, over the right parietal region; this is not accompanied by significant subdural bleeding. superior surface of the brain while preserving the falx and tentorium for subsequent examination. Extradural haemorrhage is uncommon amongst peri-natal deaths because of strong adherence of the dural membrane to skull bones. Localized, non-space-occupying haemorrhage can accompany skull fracture. The presence and position of haemorrhage in the subdural and subarachnoid space is noted. The form er is the result of trauma; the latter may be traumatic when observed in the vicinity of torn bridging veins or when, as a result of hypoxia, the presence of multi ple petechial haemorrhages is likely, although confluent sub arachnoid haemorrhage of hypoxic oligin is recognized in the perinatal period, often over the temporal poles. Observation of the cortical gyral pattern provides useful information about fetal maturity. The gestation-related appearance is remarkably constant and is illustrated by Dorovini-Zis and Dolman 57 and Feess-Higgins and Lar roche 58 (see ref. 45). The falx and tentorium should be examined with care. This is best done by tipping the head forward then gently eleva ti ng each occipital pole in turn so that the posterior part of the falx and the tentorium can be viewed. The usual site of significant injury is from the free edge of the tentorium running into straight sinus (Fig. 8.20). Sheari ng tears in the free edge of the tentorium , not involving venous sinuses, are an indication of rapid moulding of the head and are not infrequent following spontaneous delivery, particularly in still birth. They do not, in themselves, contribute to death. Tears in the falx are less usual and it is imp ortant to be aware that lacunae, smooth-edged holes, can occur naturally within the falx during development.

In view of the incompleteness of myelination of the fetal brain, fixation of the whole brain before examination is essential otherwise important information may be lost.

Spinal Cord When intrapartum death occurs following in stru mental delivery and no intracranial patho logy is app arent, the cer vica l spinal cord should be removed within its bony cover ing using Yates' method. 59

Body Cavities Examination of thorax and abdomen follows a method appropriate to this age group.45.50 Petechial haemorrhages are numerous in the thoracic viscera follo wing acute hypoxic stress, and may be particularly prominent around the ductus arteriosus. They are particularly promin ent and numerous after placental abruption. Potentially fatal congenital anom alies seen in externally normal infants are desCIibed in Chapter 10, p. 193 . In the macrosomic fetus (>4000g) it is important to look for evidence of birth injury.

Placenta EvelY effort should be made to examine the placenta. It may contribute important information to case evalu atio n in most circumstances when there is a potential legal interest in a perinatal death .6o Examination of the placenta is detailed by Wigglesworth 5o and Keeling 45 . Cord length, weight and measurements should be recorded as they contribute to the overall assessment of the case. Gestation-related placenta weights for twins and singletons are given by Pinar et al 61 and cord lengths by Naeye 62 (see Appendix BJ. Histological examination of the placenta may contribute to the assess ment of the death to delivelY interval in stillbirth. 63 Help with interpretation of placental abnormality can be found in Benirshke et al,64 Fox and Sebire 65 and Khong 66 .

Examination of the newly born

I

161

.-\ltshuler67 and Macpherson 68 discuss the relevance and limitations of placental data and pathological abnormalities in relation to alleged obstetric malpractice.

Recognized Birth Injuries Birth injury is more common fo llowing instrumental, and sometimes operative, delivery. However, there are occasional case reports of birth inju ries following spontaneous delivery. Birth injuries are considered in more detail by Wig glesworth 69 and Keeling.70 After delivery in hospital it is important to look for signs of birth trauma such as a chinon following Ventouse delivery, bruising and abrasions in the shape of a forceps bl ade, and perhaps a linear skin incision following Cae sarean section. Scalp injury is a recognized complication of vacuum extraction. 7] Bruising of the legs is common fol lowing breech delivery, especially in preterms. In term breech delivery, it is important to look for predisposing fac tors, such as neuromuscular pathology or renal abnormal ity (because of oligohydramnios), which might be the underlying cause of death. Subaponeurotic (subgaleal) haemorrhage is an infre quent but serious complication of forceps or Ventouse delivery, or a combination of both methods (Fig. 8.21). 72 A large volume of blood can be lost into the su baponeu rotic space. Robinson and Rossiter 7J calculated blood losses exceeding 100 mL using a formula based on cranial diam eter and scalp thickness. Subperiosteal haemorrhage, particularly over the par ietal bones, is common (Fig. 8.22) and of little consequence. It may be found in live borns following spontaneous, easy vaginal delivery with vertex presentation, as well as fol lowin g instrum ental delivery. The amount of bleeding is limited by periosteal attachment at the margins of the bone and by the limited distensibility of the membrane. Although it may be found following difficult delivery, with other pericranial lesions, as an isolated finding, it makes little contribution to the overall assessment of the case. Subdural74 and cerebral haemorrhage7 5 and very occa sionally, extradural haemorrhage 76 or posterior fossa haem orrhage 77 can complicate vacuum extraction as well as forceps delivery. Subdural haemorrhage is almost always due to trauma. When present over the cerebral convexities it is the result of tearing of bridging veins; trauma here includes excessive moulding of the skull from obstructed labour or rapid moulding of the cranium in precipitate deliv ery. Minor, focal subdural haemorrhage is not uncommon following normal vaginal delivery.78 Evidence of these minor haemorrhages in the form of focal brown staining of the dura is not unusual in sudden infant death . Any sugges tion that major subdural haematoma is th e result of unas sisted delivery should be addressed very critically.79 Tears of the dural folds that extend into cerebral sinuses are rare in non-instrum ental delivery but cause catastrophic fatal haemorrhage. Subdural haemorrhage solely at the base of

Figure 8 .21 Birth injury. Subgaleal haemorrhage, massive blood loss into soft tissues. Instrumental delivery.

Figure 8 .22 Birth injury. Subperiosteal haemorrhage following spontaneous delivery; blood loss is trivial. the brain is unlikely to be traumatic and a local cause should be carefully sought. Fra ctures of the skull vault should be sought with care; th ey are not always apparent on radiographs. A single fracture in the parietal bone from the sagittal suture line running down towa rds the ear is seen occasionally follow ing forceps delivery or vacuum extraction. An undisplaced Iinear fracture is not of great significance in respect of cause of death, although it is an indication of difficult delivery. Of more significance is an accompanying sub aponeurotic or intracranial haemorrhage, or cerebral hypoxic injury. Clavicular fracture is the commonest birth injury. There is usually a history of difficulty in delivering the shoulders in a large baby. Bruisin g of the neck muscles (Fig. 8.23) and fracture of the humerus can occur in similar circumstances. It is essential to correlate any injuries found with events in labour. Babies in the extended breech position may suffer fracture of a femur (or occasionally both) when the legs are brought down. Rib fractures are exceedingly rare birth injuries. Careful attention should be given to delivery events, birth weight and events in the neonatal period

162 I

Post-mortem examination in babies and children Table 8.6

Samples for histological examination in perinatal and infant forensic deaths20,45

Figure 8.23 Birth injury. Bruising of anterior neck mu sc les. Instrumental delivery. befo re accepting birth injury as a cause for rib fract ures in an infant. Rib fractures are discussed further in Chapter 11. The commonest visceral injury is to the liver, when rup ture of a subcaps ular haematoma can result in catastrophic haemo rrhage. The baby is usually mac rosomic. A simil ar injulY is seen in preterm infants, particularly following breech delivelY, as the liver is poorly protected by the rib cage at this time. Splenic rupture is a rare birth injury.

HISTOLOGICAL SAMPLES Thorough sampling for histological examination is an essential part of perinatal, infant an d childhood post mortem examination. In ea rly life, much diagnostic infor mation is derived from microscopi c examination when macroscopi c ap pearan ces may be normal, non-specific or not understood by the inexperienced. Sampling should fol Iow a standard protocol (Table 8.6). It is the in vestigation most likely to make a positive contribution in SUDl. 2o Norma l his to logical appearances of organs in the infant period are illustrated in Valdes-Dapena et al. 40 In addition to convent ional sectio ns of fo rmalin-fixed para ffin-emb edded samples, it is important to reserve sm all fresh samples of heart, liver, kidney and adrenal gland for frozen sections in order to look for lipid infiltration ; when small in amount, lipid infiltration is probably st ress-related, but massive lipid infiltration is su ggestive of genetic meta bolic disease (see Chapters 11 and 12). These sa mples can be kept frozen, perhaps wit h a sample of spleen, for molecular studies should the need arise. If inhalation is suspected, a froze n sample of lung for lipid staining is also useful. In SUDI, it is advisable to examine lung sections stained fo r iron (PBR) to assess the possibility of previous pulmonalY haemorrhage. It may be useful in other circum sta nces, Wh en death occurs suddenly in the neonata l period, staining for reticulin is very usefu l in the evalu-ation of microscopic lung anatomy: it permits exclusion of congenital alveolar dysplasia and better assessment of the appropriateness of

la rynx Trachea Lung - five lobes, PBR reaction on all Heart - right and left free ventri cu lar wall, interventricular septum Kidney - two Liver - right and left lobes Small and large intestine Pituitary Thyroid Pan crea s Adrenal - two Gonad Diaphragm Costochondra l junction Any macroscopic lesions Dural fold Dura - parietal In SUOI (including sudden neonatal death)

Frozen section for oil red 0 staining from: He art Liver Ki dney Adrenal ~L u ng

In perinatal death

Pla centa X 2 Umbilica l cord Extra placental membranes lung maturity. An elastic stain, (Elastic van Gieson is my preferred technique) allows assessment of postnatal adaptation of pulmon ary vasculature, ventilation-induced damage and other residua of neonata l intensive care. Exa mination of the ca rdiac conduction system is desir ab le following instantaneo us death or observed rapid col lapse that is unexplained after conventional investigation. It should be considered when sudd en death follows cardiac surgelY and when a second sudden death occurs within the family. In these circumstances the heart should be retained complete with this in mind. Conventional sampling is desc ribed and illustrated by Davies et al. BO Michaud et alBI and Ashworth B2 describe a simplified method for analysis of the conduction system. It is imp ortant no t to over interpret minor differences in microanatomy, either in distributio n of conduction tis sue B3 or of the process of so -called 'resorptive degeneration' of the atrioventricular nodal tissue and the His bundl e. 83 ,84 The so-call ed marke rs of SIDS, pulmonary haemosiderin and the significance of minor degrees of infla mmation in SUD! are discussed in Chapter 11, pp, 209-212, 215-2 16 an d p. 210, respectively.

Exchange of information and multidisciplinary review I

Figure 8.24 Posterior end of rib trimmed for histological examination after fi xa tion and decalcification. A fracture with callus is present.

163

Figure 8.25 Whole section of the anterior end of a lower rib. There is expansion of the interna l aspect of the rib and irregularity of the osteochondral junction as a result of prior trauma.

Demonstration of Bony Injury Histological exa mination of bones following radiographic :dentification of fracture or unidentified localized abnor mality is essential. The bone(s) in question can be excised completely or a segment excised with a clear margin on all aspects of the area to be investigated. It is useful to re-X-ray the excised bone, either before or after fixation. These films are useful when sampling for microscopy. Sampling should be done following decalcifi cation, otherwise further damage to the bone is likely and histological assessment rendered more difficult. Blocks for microscopic examination are taken at right angles to the fracture line (Fig. 8.24) or along the long axis of the lesion (Fig. 13.25). Blocks should include cortical bone, periosteum and adjacent soft tissues. Histological examinatio n of frac ture contributes to assess ment of timing of injury, particu larly those that have occurred within 1 week of death, when radiological abnormality is minimal. The significance of fractures in perinatal and infant deaths are discussed further in Chapter 3 (pp. 51-581, Chapter 10 (p. J92) and Chapter 11 (p. 218).

RETENTION OF ORGANS In the course of the medicolegal post-mortem examination in babies and children, careful thought should be given to the need to retain organs. Many coroners and procurators fiscal are unwilling to sanction organ retention, particu larly the brain. It is importa nt that pathologists ensure that legal personnel are appropriately informed of the benefits of so doing in any particular case. It is difficult, and in some cases impossible, to examine the brain of a still born or young infant in the fresh state. The information obtained from an appropriately thorough examin ation of

the central nervous system is of utmost importan ce, in the context of both assessing injury when inflicted injury is suspected and in respect of cause of death in SUDI and pelinatal deaths. Local expelience of the contribution of formal neuropathological examination in deaths investi gated by a procurator fiscal is greater than that cited by the CESDI SUDI studies. 8s Brief (overnight) fixation of other organs, particul arly the heart, makes sampling for microscopic examination easie r and more accurate. In cases of inflicted injury, organs may require fixation so that they are in an appropriate condition for examina tion by another pathologist. In these cases, if there is doubt concerning the identity of lesions then the organs or tissues should be retained.

EXCHANGE OF INFORMATION AND MULTIDISCIPLINARY REVIEW In complex cases, it is important that there is regular exchange of information between all the professionals involved so that appropriate interpretation of findings ensues. Th e pathologist should ensure that the results of any ancillary investigations are available and that conclusions are based on the appropriate interpretation of all findings. Multidisciplinary reviews are conducted on all sudden and unexpected death in a number of areas within the UK, con vened either through hospital paediatric units, community paediatricians or via child protection agencies. Following the publication of an intercollegiate report, such reviews are likely to become standard practice throughout the UK. 86 The empha sis of such reviews is likely to vary depending on the lead agency and the composition of the review gro ups. Although these activities are time-consuming, they are productive both

164 I


in respect of child protection a nd in our understanding of causes and contributing factors in sum, putting in place app ropriate support for famili es and in the appropriate plan ning of selvices for chiJdren.o 1

21

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Byard RW, Krous HF. Petechial hemorrhages and unexpec ted in fant death. Legal Med (Tokyo) 1999; 1:193-7. Krous HF, Nad eau JM, Byard RW, Blackbourn e BD . Oronasal blood in sud den infant death. Am ] Fore nsic Med Path ol 200 1; 23 :346-51. Mayes C, Macleod C. When 'N AJ' means not act ually injured. BM] 1998; 318:1127 - 8. McCann J, Reay D, Siebert J et al. Postmortem perianal findings in children. Am] Foren sic Nled Patho/2006; 17:289-98. Valdes-D ape na M, McFeel ey PA, Damus KH et al. Histopa thology Atlas fo r the Sudden Infant Dea th Syndrome: Fi ndings derived from the Natio l1 al/llstitute of Child Health and Hum an Develop ment Cooperati1!e Epidemiological Study of Sudden Infant Death Syndrome (SIDS) Risk Factors. Washington : Armed Forces Institute of Pathology, 1993. Kro us H. The interna tional sta ndardize d autopsy protocol for sudden unexpected infant death. In Rognum TO (ed.) Sudden Infant Death Syndrome. New Trends in the Nineties. Os lo: Sca ndin avian Uni ve rsity Press, 1995, pp. 81-95.

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Perinatoi2002; 19:401-4. 77 Perri n RG, Rutka JT Drake JM et al. Ma nagement and outcomes of posterior fo ssa subdural hematomas in neonates . Neu rosu rgery 1997; 40:1190-9; discussion 1199- 2000. 78 Whitby EH, Griffiths PO, Rutter S et al. Frequency and na tural histo ry of subdural haemorrhages in ba bi es a nd relation to obstetric factors . Lancet 2004; 363 :846-51. 79 Salman M, Crouch man M. What ca n caus e subdura l haemorrhage in a term neo nate? Paediatr Today 1997 ; 5:42-5. 80 Davies MJ , Pomerance A, Lamb D. Tec hniques in exa mination and a natom y of the heart. In Dav ies MJ , Pomerance A (eds) The Path ology of the Hea rt. Oxford: Blackwell Sc ientific Pu blica tions, 1975, pp. 26-31. 81 Michaud K, Romain N, Taroni F et al. Evaluation ofa simplified method of th e conduction system a nalysis in 100 forensi c cases . Forensic Sci Int 2002; 130:13-24. 8 2 Ashworth MA. The cardiovascular system. In Keeling JW, Khong TY (eds) Fetal and Neonatal Path ology, 4th edn. London: Springer, 2007 , p. 613. 83 Ho SY, Anderson RH. Conduction tissue and SIDS. Am NY Acad Sci 1988; 533:176-90. 84 Ma tturri L, Otta viani G, Ramos SG, Rossi L. Sudden infant death syndrome (SID S): A study of cardiac conduction system . Cardiovasc Pat1lO1 2000; 9:137-45. 85 Keeling JW, McKenzie KJ, Ironside J et al. Does detailed neuropathological ex amina tion o f the fi xed brain in sudden, un expected dea th in infa ncy contribute to the evaluation of the death? J Pat/wi 2002 ; I 98(Suppl.) :2 4A.

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I

CHAPTER 9

I

PATHOLOGY OF NEUROLOGICAL ABNORMALITY IN EARLY LIFE Waney Squier

Introduction

166

cerebral palsy Timing of injuries by histology Acquired intra-uterine damage

Birth-related injury Stroke in the developing brain

Clinical manifestations of early brain damage:

167 167 169

INTRODUCTION

Examination of the nervous system forms a critical part of the autopsy exami nation of any infant who dies, whether suddenly and unexpectedly or following recognized illness. The cause of sudden infant death is not always proximate insult or disease; pre-existing diseases of, or damage to, the nervous system may cause sudden death. Babies with neuro logical disease, for example, are more pron e to aspiration of feeds and to epilepsy. Even quite extensive congenital brain damage acquired in utero or at the time of bilih may not present clinically until months or years later, while still hav ing the potential to cause sudden death . It may be that a 'secon d insult' is required, for example velY mild brain mal formation (microdysgenesis) is seen in patients with epilepsy but may not cause seizures until there is another insult such as trauma. Similarly, babies with metabolic or mitochondrial disease may become profoun dly unwell a nd die when chal lenged by a respiratory infect ion. In these babies careful exa mination of skeletal muscle with histochemistlY and review of pre-mortem biochemistry is necessary if an accu rate diagnosis is to be made. Chronic subdural haemorrhage may go quite unrecognized for weeks or months until dis covered by routine head circumference measurement or even by parental observation of increasing head size. The pathologist making an autopsy exa mination in sud den infant death is faced with an awesome task. Th ere will often be great pressure from those who have cared for the child in life to find a pa rticular cause of death . Opinions concerning the possibility of natura.1 or unnatural causes

Metabolic disorders Infections References

173 176 177 177 178

may be very strongly held. The findings in the brain are of paramount importance in such cases but may also be very subtle. If trauma is suspected the possible mechanisms must be fully considered and due attention paid to exami na tion of the stru ctures of the neck and spinal cord as well as the brain. Meticulous neuropathological examination can identify no t only the cause of neurological disease in childhood but, in the case of acquired damage, can also assist in evaluating when the damage has occurred. How ever, the effects of the terminal condition of the baby must be taken into consideration. Hypoxia and resuscitation, as well as a period of ven tilation , will lead to brain swelling and ge neral organ failure, disturbance of blood clotting, leaking from blood vessels and slowing or cessation of cel lular reactive processes, serious ly hampeling the ab ili ty to time the injUIY. Careful correlation with brain scans take n closer to the time of coll apse will assist in distinguishing primary injUly from these secondary changes. Neurological abnormalities may resu lt from genetic or meta bolic disease, diseases acquired in utero, during deliv ery, in the pelinatal period or in early life. Intra-uterine damage may not be symptomatic until weeks or months after birth, for example cerebral palsy is not usually definitively diagnosed until 5 years of age. Con versely, babi es damaged immediately before or during bilih tend to exhibit signs or symptoms such as floppiness, depression and asphyxia in the first days of life. Once the brain has been damaged there will be tissue loss followed by atrophy. Tissue regeneration and plasticity due to compensatory hyperplasia has been demonstrated in

Timing of injuries by histology

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the immature human brain.l Following even static and non-progressive insult, clinical signs may evolve due to atrophy of associated and connected brain areas.

fragments of cerebellum in the su barachnoid space at mul tiple levels of the spinal cord. Histologically, oedema is better seen in densely packed white matter tracts than in grey matter.

CLINICAL MANIFESTATIONS OF EARLY BRAIN DAMAGE: CEREBRAL PALSY

Cell Death

Cerebral palsy remains the mo st common form of chronic motor disability in children (1-2 cases per 1000 live births). The full effects of early damage may not be apparent until several years of age. Signs include abnormal control of movement or posture, cognitive impairment, seizu res and blindness. Sudden death may be due to seizures or swallow ing disorders and aspiration. Timin g the damage is crucial not only to the under standing the possible aetiology, but also it will be critical in any potential litigation. The cause of cerebral palsy remains unknown in the majority of cases. In term babies the most impoltant causes are stroke (17 per cent), maternal infection (12 per cent), mul tiple pregnancy (10 per cent) and birth asphyxia (6 per cent). Birth injury, genetic and metabolic diseases, fetal infections and toxins account for a small percentage of cases. 2

TIMING OF INJURIES BY HISTOLOGY Histological timing cannot be regarded as precise and must always be interpreted in the light of all the other aspects of the case, partiCUlarly the clinical history. Much of the data below has been previously presented with source refer ences.] The earliest reactions in the infan t brain are oedema, neuronal death and cellular reactive changes (Table 9.1). Timings must be interpreted with caution, palticularly if the baby was venti lated prior to death. During ventilation the brain may become very swollen and the blood supply compromised (respirator brain). In these circumstances the reactive processes may be slowed or otherwise modified. The dura retains a better blood sup ply via the emissary veins of the skul.! bones and in the case of subdural haemorrhage dural histology may prove to be a better indicator of timing.

Cerebral Oedema Brain swelling may begin within minutes of injUlY, reach in g a maximum after 1 week. The speed of swelling is sub ject to huge individual variation. It causes narrowing of the sulci and compression of the ventricles. On slicing the brain, the cortical ribbon may appear prominent, with soft ening and grey discolouration of the underlying white matter. Flattening of the gyri is uncommon as the unfused infant skull can accommodate considerable brain swelling without compression. However, it is not uncommon to find cerebellar tonsillar herniation and necrosis with displaced

Th e two best-described patterns of cell death are necrosis and apoptosis (Fig. 9.1). Necrotic neurones develop intense cytoplasmic eosino philia, the nuclear membrane lyses and the chromatin dis perses into a fine web. Cytoplasmic eosinophili a alone may be a reversible or artefactual change, often seen in surgical material. Nucleolysis is part of the irreversible process. These changes take less than 12 hours, in the adu lt brain they are thought to take 5-6 hours to develop but timing in the infant brain has not been accurately documented. Apoptotic cells undergo pyknosis, when the nucleus becomes shrunken, rounded and intensely basophilic. Later the nucleus forms multiple rounded densely staining masses (kalyorrhexis). Apoptotic cells are readily phagocytosed and cause no inflammatory response. This process probably takes 12 hours to complete but, again, accurate fig ures are not available for the infant. Apoptosis is a more frequent in the immature brain than in the adult brain.

Macrophage Response During the first 24 hours after hypoxic-ischaemic injury (HIl) , microglial cells (the intrinsic phagocyte population of

Table 9.1

Early responses to injury within the brain

Cerebral oedema Cell death Necrosis Apoptosis Macrophages Microgl ia Phagocytosis Gliosis Capillary reaction End othelial swelling Capillary proliferation Haemosiderin Mineralization Axonal damage" Beta amyloid precursor protein expression Silver staining bulbs Haematoxyli n and eosin staining bulbs "Timing from ad ult tissue studies.

Minutes to 1 week 5-12 hours 500/0)

Microscopic

Thickened laryngeal basement membrane Pulmonary congestion and oedema Mild inflammation of the upper respiratory tract Focal fibrinoid necrosis of the voca l folds Persistent haemopoiesis in the liver

Figure 11 .7 Herpes type 1 infection . The mother had oral herpes at delivery. The infant displayed non-specific symptoms followed by sudd en deterioration at 2 weeks of age. Slice of liver shows multiple cream, necrotic foci with a hyperaemic border.

SUDDEN DEATH IN NEONATES

Sudden death in the neonatal period (birth to 28 days of age) is less common than SUDI but is usually explained (Table 11.3). It is particularly important that the full range of inves tigations is completed. Although structural cardiac disorders can be easily demonstrated and there is usually some, albeit rarely specifIc, naked-eye abnormality in cardiomyop athy, the other common causes of sudden neonatal death may show little macroscopic abnormality. Group B streptococcal infection, both septicaemia and meningitis, is an important cause of death in this age gro up. Acute viral infections are important too. Herpesvirus infection has characteristic gross (Fig. 11.7) and microscop ic fIndings even when it has eluded pre-mortem diagnosis. Echoviral infection , particularly serotype 11, results in rapidly progressive and often fa tal ill ness. Pathological changes are less specifIc, but haemorrhagic necrosis of liver and adrenals is a common finding. 156 ,1 57 The infection is more likely to be fatal when acquired from the mother. 158 Other virus serotypes are sometimes involved. Fatal group B Coxsackievirus infection is also usually acquired from the mother. 159 Because the effects of perinatal hypoxia may be appreci ated only at microsco pic level, it is important that a formal neuropathological examin ation is made of the fixed brain.

Failure to do this will result in loss of important info rmation, particularly in respect of timing of ins ult (and may protect, rather than condemn , your obstetric colleagues). Although the majority of in fants with ~ -oxi dation defects will present during late infancy, a few will be ac utely, and perhaps cata strophically, symptomatic in the neonatal period. 16o,161 It is important that a fatty liver is not written off as due to peri mortem hypoxic change. As in later infa ncy, infection may be a predisposing factor - we have encountered such a death complicating sta phylococcal in fection. It is important to consider the possibility of GMDs if only to ensure that appropriate sa mpl es are reserved. 148

Which Post-mortem Findings are Compatible With the Conclusion of SIDS? MACROSCOPIC

Although a conclusion of SlDS is reached after excluding explained causes of SUDl, nevertheless there are some fIndings which, although not universally present nor spe cifIc, might almost be considered reassuring (Table 11.4). Several stud ies have identified an increase in dysmorphic features or minor malformations in SlDS.162-164 Although many SlDS babies appear well nourished at death, poor weight ga in has been identifIed in unexplained infant deaths. 165 A fall in centiles from birth weight to death weight might thus be anticipated, although differences between pre and post-mortem weights should be cautiously interp reted. However, a weight less than the 10th centile at death, particularly if accompanied by signs of dehydration or of

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Sudden unexpected death in infancy

Figure 11.8 Sudden infant death; large numbers of petechial haemorrhages are present in a normal-sized thymus, while the lungs are bulky and overlie the heart.

suboptimal care, for example extensive napkin delmatitis, demands careful consideration of the overall care of the infant. Frothy secretions may commonly be visible at the nares. They are pale in colour but may be blood tinged. Fixed dependent lividity over the face and front of the trunk indicates death in the prone position, but if the body is moved sholily after death then this very useful pOinter may disappear. The appearance of the thymus deserves paliicular atten tion. It is usually of normal size, previously often con sidered large. Reduction in thymic weight correlates with stress, often in the form of infection and indicates that the infant had been unwell for more than 24 hours.166 The cer vical extensions are usually pale in comparison with the thoracic part, which appears relatively congested. Thymic petechiae, particularly when found in large num bers in the thoracic portion (Fig. 11.8), are one of the most consistent findings in SIDS. They are often most numerous on the posterior aspect. Beckwith 167 found them in more than 80 per cent of his cases and considered them the result of respiratOlY obstruction with negative intrathoracic pressure. They were present in large numbers in 49 per cent of SIDS in another study, with a further 28 per cent having a few petechiae. IG8 In SIDS, petechial haemorrhages are frequently promi nent along the course of coronary arteries, seen in 48 per cent by Kleeman et al 1995. 168 Petechiae may be present subpleurally. They are typically small and multiple. They

were present in 61 per cent of Kleeman's SIDS cases. Isaksen and Helweg-Larsen 169 found subpleural pulmonary petechiae more frequently in infants in whom resuscitation had been attempted. In SIDS, when the baby has not been subjected to attempts to resuscitate with oxygen, the lungs are typically fully expanded and fill the chest. They do not collapse on slicing. SUDI is more common among pre-term babies and those who have been admitted to special care baby units. Evidence of residual bronchopulmonalY dysplasia in the form of scar ring or fissUling of the lung is not unusual. These cases have related pulmonalY histological abnormalities. 170 It could be argued that these deaths are, in fact, explained by circula tory decompensation triggered by minor infection. Frequently a small amount of straw-coloured fluid is seen within the pericardial sac. There is usually fluid blood within the heart; it is the result of post-mortem fibrinolysis said to be associated with the suddenness of the death. The foramen ovale is often valvular. The significance of an atrial septal defect has been debated, although Dancea et al ll3 record two cases with signs of right heart overload among their sudden cardiac deaths. Cervical and thoracic lymphadenopathy are unusual findings in SIDS, but mesenteric lymph nodes are frequently enlarged, ref1ecting the level of environmental antigenic stimulation in this age group. Peyers' patches are often prominent and may be hyperaemic. The stomach is often distended, particularly when resus citation has been attempted. Milk curd in the stomach is a common finding and does not necessarily mean that death occurred shortly after feeding. However, an empty stomach may indicate survival for some time after the last feed, but vomiting and gastric emptying during resuscita tion must be ruled out. l7l When the small intestine is also empty, the possibility of gastrointestinal infection and sub optimal care should be considered. Any gastric contents should be retained for analysis. The urinary bladder is frequently empty in SIDS.172 It is such a frequent finding in unexplained deaths that the presence of a full bladder raises my expectation of signifi cant pathology.

HISTOLOGICAL

Thorough histological evaluation is important in SUD!. It was the investigation most likely to yield significant infor mation in a UK multicentre study.4 Pul monary oedema and congestion are frequent findings in SIDS. Minor focal alveolar haemorrhage may accompany the oedema. This is the origin of the frothy fluid seen at the nares. There is often an increase in rOLlnd cell infiltration of alveolar walls. Peribronchial lymphoid aggregates are often present, but these are seen in most cases of infant death and are a marker of prior respiratory infection. 17) The significance of minor inf1ammation is a recurrent problem in SUDI. 32 Focal acute inflammation is frequently

~

Pathological findings in SUDI I

found (60 per cent of cases) in both the upper and lower respiratory tract in SIDS. The former is not likely to be a primary cause of death J74 unless it results in major narrow ing of the airway. The latter provokes the question 'How much pathology is required to equate with a cause of death?'. This is a difficult question and one that has been sidestepped on occasion. 16 Consolidation throughout sec tions from more than two lung lobes is a yardstick I have used. Gregersen et al 175 consider the extent of pulmonary disease a critical factor in deciding whether or not death is explained. Culture of a single bacterial pathogen from the organ in question and blood cultures is likely to influence interpretation of histological findings. Localized inflammation might acquire significance because of its localization, for example in the cardiac con duction system or brainstem. 32 These authors are uncertain of the significance of focal inflammation in both the meninges and myocardium, although an earlier publication appears to accept that significant myocarditis may be focal. 140 Basement membrane thickening in the vocal cord was a frequent finding in SIDS in one study.176 However, in a larger study Krous et al J77 found no difference in laryngeal basement membrane thickening between SIDS cases and a control group. More serious damage in the form of fibri noid necrosis of the vocal fold is seen in some SIDS babies. 17s In the kidney, glomerulosclerosis may be a striking finding. It is not significant and is seen frequently in explained death in this age group. J79 Persistence of haemopoiesis in the liver, which normally disappears soon after birth, is seen in many SIDS cases and has been promoted as evidence of repeated or chronic hypoxia. ISO, lSI Cytomegalovirus (CIvrv) inclusions have been recorded in SIDS babies for many years. Their incidence in salivary gland or mucous glands in the upper respiratory tract is no more frequent in SIDS than in explained SUDI. IS2 However, their association with microglial nodules in the brain stem has provoked the suggestion that, in this circumstance, the effect of crvrv infection is likely to be significant. ls3 Evidence of minor old periventricular leucomalacia is sometimes seen in SIDS babies (Fig. 11.9), present in one fifth of cases in a Canadian study.184 This is perhaps not surprising given the association with SIDS of low birth weight, pre-term delivery and neonatal morbidity. A more frequent finding is disruption of the ependymal lining of the lateral ventricles, which, when recent, results in atten uation of the columnar epithelial lining and, when longer standing, results in ependymal rosettes and attendant glio sis. Brainstem gliosis is a relatively common finding. ISS, 186 A variety of abnormalities of brainstem serotonergic sys tems have been described in SIDS following detailed mor phometric and immunohistochemical studies, including hypoplasia of the arcuate nucleus and subtle gliosis of sev eral brainstem nuclei. These are reviewed by Kinney and Filiano ls7 and Kinney.18s

211

Figure 11.9 SUDI, frozen section of liver. Microvesicular fat is present in zone 1; this amount of lipid is a frequent finding in unexplained infant deaths. Oil Red O.

Figure 11,10 Reperfusion injury in an infant who was on life support for hours after collapse at home. There is a small, old calcified lesion in the periventricular white matter on the right indicative of a pre- or perinatal ischaemic lesion.

A number of changes found at a histological level in SIDS have come to be regarded as markers of 'stress', i.e. non system-specific markers of illness. These changes are seen in many SIDS deaths, in th e thymus, liver, adrenals and the osteochondral interface (most conveniently accessed at the anterior ends of the ribs). A starry-sky appearance in the thymus, perhaps accom panied by minor cortical lymphocyte depletion, is compatible with a SIDS designation, but major cortical lymphocyte depletion or reversal of cellularity betvveen cortex and medulla indicates a longer (and probably more severe) episode of stress, 166 Minor lipid accumulation in the liver (Fig. 11.10) is a marker of minor stress. It is microvesicular and usually more

212 I


marked around central veins. Should fatty change be exten sive, the possibility of an inherited metabolic di sease as an explanation for death should be pursued. When there is pan lobular fatty change, particularly when macrovesicular steatosis is also seen (see Fig. 12.21 , p. 247), then the possibil ity of a GMD is high. Concomitant steatosis should be sought in the myocardium and proximal renal tubules and specific investigations for GMDs carried out. It is important to appre ciate the importance of severity when assessing fatty change. r cannot be the only pathologist to have conducted an inves tigation into the death of a second infant from the same fam ily who has been told by the pathologist who investigated the earlier one that he had noted gross hepatic steatosis but thoug ht that a fatty liver was a common finding in SIDS. Lipid depletion of the adrenal cOliex is another non specific marker of stress. 189 It is perhaps worth remembeling that lipid accu mulation in the adrenal cortex is, in fetal life, a marker of chronic anaemia, probably mediated via hypoxia. 190 Loss of regular transition at the osteochondral junction is a fre quent finding in SIDS, but more serious disruption is a marker of chronic growth disturbance. 191

Changes Induced by Attempted Resuscitation Minor excoriation around the mouth and on the tongue and pharynx may occasionally be seen. Resuscitation makes the interpretation of recent bruising aro und the nose, mouth a nd lower jawline problematic. Kaplan and Fossum 192 relate minor injuries in th is a rea to specific resuscitation manoeuvres. Gastric dil atation due to assisted ventilation is a common finding when resuscitation has been attempted. Ventilation with oxygen, which is subsequently resorbed, can result in pulmonary coJi apse even when carried out for a brief period. It is important to be aware of this phenom enon as it obliterates a typ ica l SIDS findin g, one w hich offers potential distinction between SIDS and hypox ia . Prolonged (greater than 12 hours) ventilation, usually instituted when cardiac electrical activity is elicited during resuscitation in hospita l, can produce a number of changes, particularly reperfusion injury. The general level of tissue preservation is very poor, unlike the usual situ ation in infant deaths, when histological examination is usually worthw hile. Not surprisingly, the brain is swollen and extremely soft. Reperfusion cerebral haemorrhagic infarc tion (Fig. 11.9) ca n occur in this situation. It is impOltant not to interpret this as an indicat ion of cerebral hypoxia occurring prior to the term ina l event. Similar changes may be present in the cardiac intraventricular septum (Fig. 1l.11). Pulmonary alveo lar and interstitial haemorrhage is also common. Focal haemorrhagic infarction may be seen throughout the intestine but may be confined to caecum and colon. Unlike necrotizing enterocolitis (NEC), seen particularly in the pre-term infant, all of the lesions are of similar age and have a diffuse margi n. They are often circumferential and

Figure 11.11 Horizonta l slice through the interve ntricul ar septum of an infant; there is extensive haemorrhagic infarction caused by ventilation for about 12 hours post collapse.

not preferentially along the antimese nteric border, as is often seen in the early lesions of NEe. Cardiopulmonary resuscitation (CPR) is an infrequent cause of rib fractures in infants because their ribs are very pliable. Only 1 infant out of 2 11 who unde rwe nt resuscita tion aro und the time of deat h susta ined rib fractures in a North American study.1 9J Bilateral fractures at the sterno chondral junction were found. We have seen similar but unilateral fractures in a single infant - an explained natu ral death following CPR (Fi g. 11.12) - and undisplaced lat eral rib fractures in a further case (Fig. 11.13). Feldman a nd Brewer 194 and Spevak et al 195 found no rib fractures in infants w ho had undergone CPR in their cases. Contrary to popular belief, professionals are more likely to cause injury during resuscitation than are amateurs, irrespective of physical mass or the use of in appropriate resuscitation techniques. On those infrequent occasions when resuscita tion does resul t in rib fractures, bleeding is min imal. Vis ceral injuries are similarly uncommon resuscitation injuries. 193 ,1 96 Focal disrupti o n of cortical bone of the anterio r tib ia during attempted intraosseous transfusion can produce a confusing radiological ap pearan ce and give rise to co ncern about the possibility of fracture.

Pathological Findings which Raise Concern About the Possibility of Non-Accidental Injury (NAI) (Table 11.5) EXTERNAL FINDINGS Petechial haemorrhages in the face or neck are unusual findin gs in SIDS and in healthy babies. In the latter gro up, most occurred below the nipple line. Only 2.5 per cent had

Pathological findings in SUDI I

213

Figure 11.12 (a) A rib cage with recent fractures at the anterior ends of three adjacent ribs; there is little associated haemorrhage. (b) Radiograph of affected ribs. The fractures are accompanied by irregularity of outline at their anterior ends. (c) Internal aspect of the ribs. Fractures are visible close to the osteochondral junction. (d) Histological examination reveals a fracture with haemorrhage but no reactive changes. Sudden collapse, attempted resuscitation, anomalous pulmonary venous drainage found at necropsy.

petechiae in the head and neck, and only 2.6 per cent had three or more petechiae in total. 197 Their presence raises the possibility of deliberate asphyxia (Fig. 11.14). When pre sent over the face, neck and upper chest, petechiae are sug gestive of chest compression.lg8-200 The infant should be carefully examined, searching for bruising around the face and circumoral pallor, tears at the frenulum (recent or healed) and abrasions or bruises on the inside of the mouth and lips corresponding to teeth. Collins 98 found little

evidence of contusions, petechiae or intraoral trauma in overlaying and considered that their presence should incline towards inflicted injurY. Conjunctival petechiae should be very carefully sought. Kleeman et al 168 found small numbers of conjunctival petechiae in 2.4 per cent of their SIDS cases. This has not been confirmed by others. Larger numbers of petechiae were seen in 21.9 per cent of babies dying as a result of trauma, including in five out of six babies dying from

214 I


Figure 11.14 Petechial haemorrhages on the neck and front of chest are not a usual finding in unexplained SUDI. Post-mortem rib fractures mid shaft in adjacent ribs. There is only very minor subperiosteal haemorrhage at the fracture lines. Figure 11.13

Table 11.5

Pathological findings causing concern in SUDI

Petechial haemorrhages face/neck Pallor around nose/mouth Torn frenulum Bru ises - even one is serious Heavily blood-stained secretions mouth/nose Blood in pharynx (seen by a doctor) Rib fractures - recent or old Any other injury Blotchy haemorrhages on lung Alveolar haemorrhage> 10% alveoli Siderophages in lung

strangulation. A combination of conjunctival petechiae and acute pulmonary emphysema was found in all of seven babies with asphyxia or strangulation, but not in cases of SIDS, other natural deaths or severe head injury in a study by Betz et al. 201 They considered the combination of two findings useful in distinguishing asphyxial death from SIDS. Development of petechial haemorrhages requires a com bination of hypoxic damage to small blood vessels, a func tioning circulation and an increase in venous pressure, not necessarily in that order. 202 It is unlikely, then, that resus citation will produce petechiae unless circulation and

blood pressure have been successfully restored during the process. 203 Blood or heavily blood-stained fluid issuing from mouth or nose or visualized in the pharynx is also a cause for concern. Nasal haemorrhage was reported in 15 per cent of SIDS cases in a study by Becroft et al,61 based on information extracted from a structured questionnaire. Babies with nasal haemorrhage shared epidemiological characteristics with babies who had pulmonary haemor rhage but not with intrathoracic petechiae. It was found (29 per cent) in babies subjected to imposed airways obstruc tion but not following explained ALTE.55 In a study of 58059 infants under 2 years of age referred to the accident and emergency department from a children's hospital 204 only 16 cases were found, clearly a rare event. Eight of these infants had visible trauma, four had thrombocytope nia and tYro cases were associated with ALTE; retrospective review drew concerns about child protection issues in 44 per cent of cases. Oronasal haemorrhage should be distin guished from the blood-tinged frothy fluid at the nares commonly seen in SIDS. When present, bloody secretions raise the possibility of asphyxia. Krous et al 205 suggest an origin from oronasal mucous membranes. Cutaneous bruises should always cause concern in SUDI. Even a single bruise in a non-mobile infant demands a clear explanation. Such 'minor' injuries must always be taken seriously. 171 Older infants who have some degree of mobility may exhibit an occasional bruise. It is important with any infant injury to consider carefully both the physical abilities of the individual and the explanation proffered by carers.

Pathological findings

Accidental bruises are usually over bony prominences. 206 Bruises of different ages are most concerning.

FRACTURES Fractures are not an expected finding in SIDS and must be clearly explained. Fractures with callus always predate ter minal events, probably by a minimum of 2 weeks, and are incompatible with the use of SIDS on the death certificate. Rib fractures are sometimes seen in extremely pre-term babies. They are accompanied by severe growth distur bance at the osteochondral junction (rickets). In most units, they are encountered less frequently than 20 years ago. 207,2oa However, rickets was described more recently among 39 per cent of very low birth weight babies in one unit, with fractures, most commonly of ribs, occurring in one-quarter of those affected.209 Fractures are unlikely to occur after the baby is weI] enough to leave hospital. Should birth injury be offered as an explanation for a frac ture, the age of the infant and details of mode of delivery are important factors. It is worth remembering that the most common birth-related fracture is clavicular, and a history of difficul ty in delivery of the shoulders should be anticipated. Femoral fractures (usually mid-shaft, sometimes bilat eral) can complicate difficult breech delivery but do not occur during vertex presentation. The most common skull fracture is parietal and linear and runs from the mid-part of sagittal margin of the parietal bone down towards the ear and usually follows instrumental delivery. Rib fractures are exceedingly rare birth injuries and sug gestion of this mode of causation should be viewed most circumspectly. Only nine cases have been reported world wide. Taken together, a pattern emerges of high birth weight, shoulder dystocia, delayed second stage of labour, instru mental delivery and symptoms in the first day or two of life. Symptoms include crepitus of the chest wall, tachypnoea and grunting respiration. That the fractures were unilateral is a useful distinguishing point.210-213

VISCERAL PATHOLOGY Injuries and foreign bodies in the mouth, pharynx or stom ach, particularly in premobile infants, should arouse suspi cion of NAI. 10 Intrathoracic petechiae are seen less frequently in traumatic deaths 168 and among bed-shaling infants 10) than in SIDS cases in all of the three expected sites. In contrast, small numbers of larger haemorrhagic subpleural haemor rhages are seen in some asphyxial deaths. When the asphyx ial insult is very acute, for example a foreign body in the larynx, very few petechiae may be present as death by parasympathetic stimulation may have preceded the onset of mechanical asphyxia. In rabbits, pleural petechiae were read ily produced by three episodes of sublethal airways occlusion but not by a single apnoeic episode.2J3

In

SUDI I

215

Pulmonary congestion and oedema, although seen in histological sections, is not a prominent naked-eye finding in SIDS.

PULMONARY HAEMORRHAGE/SIDEROPHAGES Histological findings causing concern in SUD! are largely confined to the lungs. The abnormalities that have proved most contentious are the presence of widespread alveolar haemorrhage and the presence of haemosiderin within the lung (Fig. 11.15).214 Minor (focal) pulmonary haemorrhage is common in the lungs of deceased infants and may be exacerbated by a long post-mortem interval. 215 Coffin et al 216 found that babies with pulmonary haemorrhage had a high frequency of obstetric and neonatal problems; there was a significant association with hyaline membrane dis ease and haemorrhage elsewhere. There are numerous causes of alveolar haemorrhage in neonates, including hypoxic stress, sepsis and haemostatic problems,216-218 not all of which are easily excluded by necropsy. In older infants, sepsis, heart failure (often sec ondary to CHD) and chronic pulmonary infection, as well as idiopathic pulmonary haemosiderosis (IPH), can give rise to haemorrhage. It is more prominent in babies who have been resuscitated. 2i s Yukawa et al 2J9 looked at the presence and extent of intra-alveolar haemorrhage in a consecutive series of SUD! investigated by a forensic pathology department. They concluded that alveolar haemorrhage involving more than five per cent of alveolar area in histological sections was probably a marker of airways obstruction. It was present in 73 per cent of babies thought to have been subjected to involuntary overlaying (accidental asphyxia) and in 45 per cent of cases in which there were suspicions of deliberate airways obstruction. Every consideration must be given to possible natural causes of pulmonary haemorrhage before asclibing the find ings to imposed airways obstruction. Concerns expressed about the more general application ofYukawa et al's219 find ings are the paucity of typical SIDS cases studied and no sig nificant difference between number of allegedly asphyxiated babies and SIDS cases having greater than five per cent haemorrhage.214 The finding that intra-alveolar haemor rhage was most common in those babies in whom over-laying was a possible factor in their death invokes the possibility that repeated non-fatal hypoxia played an important role in the haemorrhage, drawing a parallel with the development of petechial haemorrhages. The role of chest compression is unclear. 21 9 This group of babies was younger than the rest,214 a factor associated with more frequent, but scanty, pul monary siderophages in another study.220 As an isolated finding, intra-alveolar haemorrhage is not a clear marker for incontrovertible imposed upper airways obstruction but should initiate a critical review of the whole case. 214 Stewart and Fawcett,221 in an uncontrolled study, found pulmonary interstitial haemosiderin in one-half of 24

216 I


Figure 11.15 (a) Siderophages are present within the alveoli. (b) Low-power photomicrograph showing the extent of siderophage formation follo wi ng alveolar haemorrage.

consecutive SlDS deaths. Babies with siderophages were usually younger than those without. The autho rs postulated that haemosiderin might be a marker for 'near miss' events (ALTEs). Byard et al222 found more pulmona ry interstitial

haemosiderin in SID S infants with prior ALTEs (33.3 per cent) than in non-traumatized control infants (five per cent). Haemosiderin was found in 18 per cent of SIDS infants without ALTEs, a statistical ly non-significant difference. The authors concluded it was an unreliable marker of a pre vious ALTE. Becroft et al223 consider pulmona ry interstitia l haemosiderin a consequence of normal labour. Becroft and Lockett 224 found large numbers of intra alveolar siderophages in babi es whose deaths were caused by airways obstruction. They proposed that their presence should give rise to suspicion of imposed airways obstruction and that the lungs of all SUD I victims should be stained for iron. Pulmonary siderophages have been demonstrated in repeated airways obstruction. 225 Dorandeu et a1 226 found pul monary siderophages in 11 of 15 infants with non-accidental injury; all had intracrania l haemorrhage and 12 had other injuries as well. Alveolar siderophages are infrequent in SIDS cases. 21B,220.227-229 Krous et al230 found wide variati on in the number of intra-alveolar siderophages in a large group of unexplained infant deaths and were not able to distin guish such infants from babies dying from suffocation. Pulmonary siderophages have been described in leukaem ia.217 They have also been found post-operatively, in serio us sepsis and followin g ventilation, situations which might have caused hypoxic pulmonary damage. 2IB They have been see n in infants from homes with preceding water damage in substandard housing in Cleveland, Ohio,231 sug gesting a role for air-borne contaminants as pulmonary irritants. IPH has been found to occur in infants as well as in older children 232 and appears always to be symptomatic. It has been suggested that IPH can present as SUDI,233 but it is not clea r how confidently imposed airways obstruction was excluded in either study. Haemoglobin breaks down quickly in extravasa ted red cells, which are quickly pha gocytosed. Finely dispersed haemosiderin can be found after 24- 36 hours. Haemosiderin is ab undant at 5 days, and phagocytosed erythrocytes are recognizable. 234 Red cells have disappeared after abo ut 7 days. Inform ation about the persistence of siderophages from the lung is scanty. They are rapidly cleared from large airways (within 2 weeks) and from more peripheral parts of the airway within 4 weeks 235 in infants. Esterley and Oppen heimer 236 found that siderophages had disappeared from the alveoli after massive perinatal pulmonary haemorrhage within 2 weeks. It is reasonable to suppose that, whilst most alveolar siderophages are removed from the lung via the air ways, some macrophages will migrate to septal and pleural connective tissue and might remain there for several weeks after the initiating haemorrhage. ASPIRATION OF FOREIGN MATERIAL It seems likely that many babies respond to an asphyxial

insult by vomiting. Evid ence of major aspiration is a cause for concern. It shou ld be distinguished from the localized

Pathological findings in

SUDI I

21 7

Figure 11.17 Lipid-containing macrophages are present in alveoli at the periphery of a lung lobule.

Figure 11.16 Massive inhalati on in a baby found to have a diffuse neuronal migration disorder. There is brown discoloration of the lungs because of acid lysis of red blood cells.

and usually peripheral foreign body-type granulomata, which are the result of repeated, minor aspiration, often seen in young babies with oesophageal or lary ngea l prob lems. It is most unusual in the absence of a predisposing problem. This may be gastroenteritis, pyloric stenosis, diverse causes of intestinal obstruction, cerebra l palsy or other neurological problem. In a recently investigated case. brown discoloration in lung fissures (Fig. 11.16) due to acid lysis, extensive lipid in airways and terminal air spaces within the lung (Fig. 11.17) and a diffuse neuronal migra tion disorder were observed. The only evidence of cerebral abnormality at necropsy was localized polymicrogyria at one occipital pole.

HEPATIC SIDEROPHAGES

Dorandeu et al 226 found increased haemosiderin in the liver, predominantly in periportal Kupffer cells, in abused infants compa red with control infants who were victims of SIDS or accidental or explained death. They asc ribed this to a chronic increase in red cell breakdown . Increased iron in the liver is not unusual in infants with infection (usually within hepatocytes) and those with inherited erythrocyte a b no rmali ties. 237

Findings of Questionable Significance EXTERNAL

Cutaneous changes are sometimes overinterpreted in infant deaths. Dribbling can result in erythema and abrasions around the mouth or on the upp er chest and, when it leads to excoriation, might be interpreted as an injury. Sometimes excoriation takes place after death when the infant's cheek is bathed in acidic fluid from regurgitated gastric contents; a linear margin points to the artefact. Healing napkin dermatitis (nappy rash) can be pigmented and give rise to suspicion of bruising. A Mongolian blue spot, seen normally, but not always, in infants with pig mented skin, can simulate bruising; its localization around the natal cleft shou ld suggest the true nature of the lesion (see Fig. 8.7, p. 152). Vascular malformations can sometimes mimic injuries. If doubt persists after careful scrutiny, the diagnosis can be resolved by histological examination. Anal dilatation is common post mortem and should not, as an isolated finding, promote suspicion of abuse. McCann et al 238 have made a careful study of the post-mortem appearance of the anus in infants and children. They counsel against overinterpretation of an exposed pectinate line as tears or fissures. They stress the importance of tears and peri anal bruising to a conclusion that sodomy has been commit ted; swabs for DNA studies should be taken nonetheless. INTERNAL

The presence of gastric contents in the oesophagus, phar ynx, mouth and nose is a common necropsy finding in the

218 I


, ', •

I'

~,, _.

.

.

'_

-I

.. .. - .

t

Figure 11.19 Histological examination of an area of brown staining of the dura. Abundant iron is demonstrated by Perls' Prussian blue reaction. Iron persists in the dura for many months.

Figure 11.18 Infant aged 4 months. There is brown staining of the dura of tentorium and posterior falx owing to organization of focal subdural haemorrhage sustained at birth.

infant period. Sphincters relax after death, and moving the baby in the course of the removal to the mortuary will read ily disperse stomach con tents into the pharynx and beyond. When resuscitation is attempted, the presence of milk curd in the pharynx is frequently recorded. Attempted resuscita t ion will disperse this further, and milk curd in the upper airways and focally in large intrapulmonalY bronchi should not be interpreted as being a result of inhalation unless it is massive 31 (Fig. 11.16) and there is histological evidence of reaction in the form of extensive (frequently haemorrhagic) oedema and inflammatory cells within the lungs. Signifi cant gastric aspiration in infants will usually be accompan ied by evidence of a predisposing problem. Healing birth injury may give rise to suspicion of NAl. The most commonly encountered injUly is minor subdural haemorrhage, whose appeara nce should be commensurate with the age of the infant, i.e. it wi ll be red-brown and rec ognizable as a haemato ma, prob ab ly 1-2 mm thick, for 2, possibly up to 4, weeks post partum. Case et al23 9 estimate that these small haemorrhages occur in 20-30 per cent of asymptomatic neonates. Later th a n that, brown staining of the dura is apparent (Fig. 11.18). This may persist for sev eral months. Histological examination of the dura will reveal abundant coarsely granular haemosiderin on the surface and within the membrane itself (Fig. ) ).19).

An organizing cephalhaematoma is usually apparent as an irregu lar elevation on the parietal bone, and it may be bilateral. Most cephalhaematoma ta occur during uncom plicated vaginal delivery. A history of a difficult birth is unusual. Cephalhaematomata may be noticed only once bone is laid do wn beneath the elevated periosteum. Its appearance should correlate with post-natal age. Evidence of this new bone formation may persist for many years. The most common fracture susta ined as a birth injury is a mid-shaft fracture of the clavicle. There may be a history of shoulder dystocia, but most will not have this history. A lump over the clavicle may have been noted by the mother or health professionals prior to death. The radiographic an d histological appearance should be compatible with post natal age. Other long-bone fractures are rare birth injuries and occur in well-recognized circumstances. IS3

MICROSCOPIC Basement membrane thickening in the larynx is an incon sequential finding (see p. 211) . Explosive desquamation of bronchial and bronchoalveolar epithelium has been interpreted as evidence of pulmonary infection 240 but is a post-mortem artefact and may be found even when refriger ation of the body has been prompt. Peribronchial lymphoid aggregates are a normal finding in infants. Pancreatic isl ets often appear prominent in SlDS. They are usually sited towards the centre of the lobule and become more generally dispersed with subsequent acinar develop ment. This should not be interpreted as islet hyperplasia. Examination of the pancreas from an expl ained infant death is a useful compalison.

DEATH CERTIFICATION As SIDS is a conclusion reached by exclusion of recognized causes of death and its definition requires that a thorough post-mortem be performed, it is not appropriate to use the term on a dea th certificate unless certification is delayed until investigations are completed. This period is likely to

References I

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Fitzpatrick D. Inborn erro rs of metabolism in the newbo rn: clinical presentation and investigation. ] R Coli PhYSicians Erlillb 2006; 36: 147-51. 149 Emery JL, Variend S, Howat AJ, Vawter GF. Investigation of inborn errors of metabolism in unexpected infant deat h. Lancet 1988; 2:29-3J. 150 Lundemose JB, Kolvraa S, Gregersen N et al. Fatty acid oxidation disorders as primary cause of sudden and unexpected death in infa nts and yo ung children: an investigation performed on cultured fibrobla s ts from 79 children who died aged between 0- 4 years. ] Clin Patl7ol:

Mol Patho11997; 50:212-17. 151 Boles RG, Buck EA, Blitzer MG et aJ. Retrospective biochemical sc reening of fatty ac id oxid ation disord ers in post-mortem livers of 418 cases of sudden death in the first yea r of life.] Pediatr 1998 ; 132:924-3 3. 152 James CL, Keeling JW, Smith JW, Byard RW Total anomalous pulmonary venous drainage associated with fat a l outcome in infancy a nd early ch ildhood - an autopsy study of 52 cases. Pediatr Parhol 1994; 14:6 65 -78. 153 Keeling JW. The perinatal ne cropsy. In Keeling JW, Khong TY (eds) Fetal and Neonatal Pathology, 4th edn. London: Springer-Verlag, 2007, pp. 20-5 3. 154 Byard RW Idiopathic arterial ca lcitlcation and unexpected infant death. Ped Pathol Lab Med 1996 ; 16:985-94. 155 Champ C, Byard RW Pulmonary thromboembolism and unexpected death in infancy. ] Paedialr Child Health 1994 ; 30:5 50-1. 156 Berry PJ , Nagington J. Fata l infec tion w ith echovirus II. Arch Dis Child 1982; 57 :22 - 9. 157 Modlin JF. Perinatal echovirus infection: insights from a litera ture review of 6 1 cases of serious infection and 16 ou tbreaks in nurseries. Re/J Infect Dis 1986; 8:918-26. 158 Wang J, Atchison RW, Walpusk J, Jaffe R. Echovirus hepatic failure in infancy: report of four cases with speculation on the pathogenesis. Pediatr Devel Patl101 2001; 4:4 54 -60. 159 Kaplan MH, Klein SW, McPh ee J, Harp er RG. Group B coxsackievirus infections in infants you nger than three months of age: a serious childhood illness. Rev II/fect Dis 1983; 5:1019-32. 160 Wilcken B, Carpenter KH, Hammond J. Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child 1993; 69:292-4. 161 Kirk JM , La ing lA, Smith N, Uttley WS. Neonatal presentation of med ium-chain acyl-CoA dehydrogenase deficiency in two families.] Inheri t N/etab Dis 1996; 19:370-1. 162 Vawter GF, Koza kewi ch HPW Aspects of morph o logic va riation among SJDS-v ictims. In Tild o n JT, Roeder LM , Steinschneider A (eds) Sudden Infant Death Syndrome. New York: Acad em ic Press, J 983, pp . 133-44. 163 Molz G, Hal1mann H. Dysmorphism, dysplasia, and anomaly in sudden infant death. N Engl ] /vIed 1984; 311 :259. 164 Molz G, Brodzinowski A, Bar W, Vonlanthen B. Morphologic variations in 180 cases of sudden infant death a nd 180 controls. Am] Forensic Med Patho11992; 13: 186-90. 165 Blair PA, Nadin P, Cole TJ et al. Wei ght gain and sudd en infant death syndrome: cha nges in we ig ht z sco res may identify infants at increased risk. Arch Dis Child 2000; 82:462-9. J 66 va n Baarlen J , Schuurman H-J, Huber J. Acute thymus involution in infancy and childhood: a reliable marker for duration of illness. Hum Pathol 1988; 19: 1155-60.

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167 Beckwith JB. Intrathoracic petechial haemorrhages: a clue to the mechanism of death in sudden infant death syndrome? Ann Am Acad Sci 1988; 553:37-47. 168 Kleeman W J, Wiechern V, Schuck M, Trager HD. Intrathoracic and subconjunctival petechiae in sudden infant death syndrome (SIDS). Forensic Sci Int 1995; 72:49-54. 169 lsakasen CV, Helweg-Larsen K. The impact of attempted resuscitation in SIDS: post-mortem findings. In Rognum TO (ed.) Sudden Infant Death Syndrome. Oslo: Scandinavian Unive rsity Press, 1995, pp. 70-80. 170 Werthammer J , Brown ER, Neff RK, Taeusch HW Jr. Sudden infant death syndrome in infants with bronchopulmonary dys plasia. Pediatrics 1982 ; 69:301-3. 171 Berry PJ. Pathological findin gs in SIDS. J Ciin Path 01 1992 ; 45(Suppl.): 11-16. 172 Valdes-Dapena M. The pathologist and the s udde n infant death syndrome. Am J Pathol 1982; 106: 118-3 1. 173 Emery JL. Dinsdale F. Increased incid ence of Jy mphoreticular aggregates in lungs of children found une xpectedl y dead. Arch Dis Child 1974 ; 49:107-11. 174 Krous HF, Nadeau JM, Silva PO, Blackbourne BD. A comparison of respiratolY symptoms and inflammation in sudden infant death syndrome and in acc idental or infli cted infant death. Am J Forensic Med Pathol 2003; 24: 1-8. 175 Gregersen M, Rajs J, Laursen H et al. Pathologic cri teria for the Nordic study of SIDS. In Rognum TO (ed.) Sudden Infant Death Syndrome. Oslo: Scandinavian University Press, 1995, pp. 50-8. 176 Shatz A, Hiss J, Arensburg B. Basement-membrane thickening of the vocal cords in sudden infant death syndrome. Laryngoscope 1991; )01 :484-6. 177 Krous FH. Hauck FR, Herman SM et al. Laryngeal basement membrane thickening is not a reliable post-mortem marker for SIDS. Results from the Chicago Infant Monality study.

Am J Forensic Med Patho11999; 20:221-7. 178 179

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Adelson L, Kinney ER. Sudden and unexpected death in infancy and childhood. Pediatrics 1956; 17:663. Valctes-Dapena M, Hoffman HJ , Froelich C, Requeira O. Glomerulosclerosis in the sudden infant death syndrom e. Pediatr Pathol 1990; 10:273-9. Naeye RL. Hypoxemia and the sudden infant death syndrome. Science 1974; 186:837-8. Gilbert-Barness EF, Kenison K, Giulian G, Chandra S. ExtramedullalY hematopoiesis in the liver in sudden infant death syndrome. Arch Pathol Lab Med 1991; 115:226-9. Smith NM, Telfer SM, Byard Rw. A compa rison of the in cidence of cytomegalovirus inclusion bodies in submand ibul ar and tracheobronchial g lands in SIDS and non-SID S autopsies. Pediatr PnthoI1992; 12:185-90. Variend S. Infant morta lity, microglial nodules and parotid CMY-type inclu sio ns. Ea,.ly Hum Deuel 1990; 21 :31- 40 . Takashima S, Armstrong 0 , Becker LE, Huber J. Cerebral white maner lesions in sudde n infant death syndrome. Pediatrics 1978; 62: 155-9. Takas hima S, Armstrong 0 , Becker L, Bryan C. Cerebral hypo perfusion in the sudde n infa nt death syndrome? Brainstem gliosis and vasc ulature. Ann Neuro l 1978; 4: 257-62. Kinney H, Burger P, Harrell F, Hudso n RP. 'Reactive gliosis' in the medulla oblongata of v ictims of the Sudden Infant Deat h Syndrome. Pediatrics 1983; 72: 181-7. Kinn ey HC, Filiano JJ. Brain research in SlDS. [n Byard RW, KrOllS HF (eds) Suddell Infant D~ath Syndrome. Pmblems, Progress and Possibilities. London: Arnold, 2001, pp. 118- 37. Kinney He. Abnormalities of the brainstem serotonergic system in the sudde n infant death syndrome: a review. Pediatr Deuel Pathol 2005; 8:507-24.

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189 Perez-Platz U, Saeger W, Dhom G, Bajanowski T. The pathology of the adrena l glands in sudden infant death syndrome (SJDS). Inr J Legal Med 1994; 106:244-8. 190 Becker AE, Becker MJ. Fat distribution in the adrenal cortex as an indication of the mode of intra-uterine death. Human Pathol 1976; 7 :495-504. 191 Sinclair-Smith C, Dinsdale F, Emery J. Evidence of duration and type of illness in children found unexpectedly dead. Arch Dis Child 1976; 51 :424-9. 192 Kaplan JA, Fossum RM. Patterns of facial resuscitation injury in infan cy. Am J Foremic Med Pathol 1994; 15:187-91. 193 Bu s h CM, Jon es JS, Co hle SO, Johnson H. Pediatric injuries from ca rdiopulmonary resuscitation . Anll Emerg Med 1996; 28:40-4. 194 Feldman KW, Breweer OK. Child abuse, cardiopulmonary resuscitation, and rib fractures. Pedia trics 1984 ; 73:339-42. 195 Spevak MR, Kleinman PK, Belanger PL et al. Ca rdiopulm o nary resuscitation and rib fractures in infants: a post-mortem radiologic-pathologic study. JAMA 1994; 272:617-18. 196 Price EA , Rush LR, Perper JA, Bell MD. Cardiopulmonary resuscitat ion- related injuries and homicidal blunt abdominal trauma in children. Am J Forensic Med Patho12000; 21 :307- 10. 197 Dow nes AJ, Crossland OS, Mellon AF. Preva lence and distribution of petechiae in well babies. Arch Dis Child 2002; 86:291-2. 198 Perrot U. Masque ecchymotique. Specific or nonspecific indicator for abuse. Am J Forensic Med Patlrol 1989; 10:95-7. 199 Byard RW, Krous HF. Petechial hemorrhages and unexpected infant death. Leg Med (Tokyo) 1999; 1 :193-7. 200 Oehmichen M, Gerling I, Meiilner e. Petechiae of the baby's skin as differentiation symptom of infanticide versus SIDS. J Forensic Sci 2000; 45:602-7. 201 Betz P, Hausmann R, Eisenmenger W. A contribution to a possible differentiation between SIDS and asphyxiation. Forensic Sci Jnt 1998; 91:147-52. 202 Rao V J, Wetli CY. The forensic significance of conjunctival petechiae. Am J Forensic Med Pathol 1988; 9:32-4. 203 Hood I, Ryan D, Spitz WU. Resuscitation and petechiae.

Am J Forensic Med Patho11988; 9:35-7. 204 McIntosh N, Mok JYQ, Margerison A. Epid emio logy of oronasal hemorrhage in the first two years of life: implications for child protection. Pediatrics 2007; 120: 1074-8. 205 Krous HF, Nadeau JM, Byard RW, Blackbolll"ne BD. Oronasal blood in Sudden Infant Death. Am J Forensic Med Parhol 2001 ; 23:346-51. 206 Sugar NF, Taylor JA, Feldman KW, Puget Sound Pediatric Research Network. Bruises in infants and toddlers. Those who don't cruise rarely bruise. Arch Pediatr Adolesc Med 1999; 153 :399-403. 207 Amir J, Katz K, Grunebaum M et al. Fractures in premature infants. J Pediatr Orthop 1998 ; 8:41-4. 208 Koo WW, Sherman R, Succop Pet al. Fracture and rickets in very lo w birth weight infants: co nservative management and outcome. J Pediatr Orthop 1989 ; 9:326-30. 209 Dabezies EJ , Warren PD. Fractures in very low birth weig ht infants w ith rickets. Ciin Orthop Relat Res 1997; 335:233-9. 210 Barry PW, Hocking MD. Infant rib fracture - birth trauma or non-a ccidental injury? Arch Dis Child 1993; 68:250. 211 Bullock B, Schu bert CJ, Brophy PO et al. Cause and clinical characteristics of rib fractures in infants. Pediatrics 2000; 105:e48.

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212 Durani Y, Depiero AD, Rib fractu re and birth trau ma, Ann Emerg Med 2006; 47 :2 10,2 15, 213 Campbell CJ, Read DJ(, Lung petechiae - their pathophysiology and diagnostic sig nificance in co t death, Aust Physiol Pharmacol Soc 197 8; 9 : 143, 214 Berry PJ, Intra-al veo lar haemorrh age in sudd e n infant death syndrome: a cause for concern? ) Ciin Pa thol 1999; 52 :553-4, 215 Hanzlick R, Pu lmon ary hemorrhage in deceased infants: ba selin e d ata for fu rther study of infant mo rtali ty, Am) Forensic Med Path 01 2001 ; 22: 188-92, 216 Coffin CM , Schechtman K, Col e FS, Dehner LP, Neonata l and in fantil e pulmo na ry hemorrhage: an autopsy study with clinica l co rrelation , Pediatr Pathol 1993 ; 13:583-9, 21 7 Golde DW, Drew Wl, KJei n HZ et a l. Occult pu lmona ry haemorrh age in leukae mia, BM) 1975; 2: J 66 -8, 218 Keeling JW, Maxwell RS, Busuttil A. Haem osideri n in infant lun gs, ) Pa thol 1998 ; 184:29A, 219 YlIkawa N, Carter N,RlItty G, Green MA. Intra-alveo lar haemorrh age in sudden infant death syndrom e : a cau se fo r concern?) Ciin Pathol 1999 ; 52:581-7, 220 Berry PJ, Lee J, Alveolar s id erop hages a nd the sudd en infant death synd rome,) Pathol 1998 ; 184:27A. 22 1 Stewart S, Fawcett J. Interstitia l haemosid erin in the lungs of sudden infan t death sy ndrome: a histol ogica l hallmark of 'near-m iss' episodes? ) Patlwl 1985 ; 145 :53 -8, 222 Byard RW, Stewart WA, Tel fer S, Beal SM, Assessment of pulmon ary and int ra thymic hemosiderin deposition in sudd en infant death sy ndrom e, Ped iatr Pathol Lab Med 1997 ; 17:275- 82. 223 Becroft DMO, Thompso n JMD, Mi tchell EA. Pulmonary interstiti a l haemosiderin in in fa ncy: a common con seq uence of normal labour. Pedia tr DelJel PatllOl 2005; 8 :448- 52, 224 Becroft DM, Lockett BK, Intra-a lveo lar pulmona ry sid erophages in sudden infant death: a marker for previous impose d suffocation, Pathology 1997; 29 :60-3, 225 Milroy CM. Munchausen syndro me by proxy and in tra al veolar haemosid erin. Int) Legal Med 1999; 1112 : 309-12. 226 Dorandeu A, Peri e G, Jouan H et al. Histolog ical demonstration of haemosiderin deposits in lungs and liver from victims of chronic physica l child ab use. Int) Legal Med 1999; 11 2:280-6 , 227 Fagan DG, Ha emosiderin in pulmonary macrophages from SUD , SIDS and deaths in an fVTVA.) Patho11997; 182:49A.

228 Han zli ck R, Del aney K. Pulm onary haem os iderin in dece ased infants: baselin e data for furth e r study of infant mortality. Am) Forensic lVled Pat/wi 2000; 21:319-22, 229 Schlu ckebier DA. Coo l CD, Henry TE et al. Pulmon ary sid erop hages and unexpected infant death , Am) Forens ic Med Pat/wi 2002; 23:360-3. 230 Krous HF, Wixom C, Chadwick AE et aL Pulmona ry intra alveo lar siderophages in SIDS and suffocation: a San Diego SID S/SU DC project report, Pediatr Deliel Pathol200G; 9:103-J4. 231 Monta na E, Etzel RA, Allan T et aL En vironmenta l risk factors associ ated with pe diatric idiop athic pulmon ary hemorrhage and hemosid eros is in a Cleveland community. Pediatrics 1997 ; 99:3 1-8, 232 Pappas fVlD , Sa rn a ik AP, Meert KL et aL Idiopathic pulmonary hemorrhage in infa ncy. Clinical features and management with high frequency venti lation, Chest 1996; 110 :553 -5. 233 Cutz E, Perrin DG, Vujani c GM, Ackerly C. Idiopathic pulmonary haemos iderosis (IPH) presenting as sudd en unex pected de ath SUD in infancy (Ab stract), Anales Espanoles de Pediatria 1999; 92(Suppl.):52, 234 Mu ir R, Niven J SF. The loca l form ation of bl ood pigments,

) Pa rhol Bacteriol1935; 41:183-97. 235 Sherman JM , Winnie G, Thomassen MJ et al. Time course of hemos iderin production a nd clearance by huma n pulmonary macrophages, Chest 1984 ; 86:409- 1I. 236 Este rley JR, Oppe nheimer EH. Massive pulmonary haemorrhage in the newbo rn, Pathol og ic considerat ions. ) Pediatr 1966 ; 69:3-11. 237 Rushton DI. Liver and gallbl adder. In Kee lin g.JW (ed.) Fetal And Neona tal Pathology, 3 rd edn, Lond on: Springer-Verlag, 2001, pp, 409-39, 238 McCann J , Reay 0 , Siebert J et al. Postmortem perian al findings in children, Am ) Foren sic lVled Path ol 1996; 17:289-98 , 239 Case ME, Graham MA, Handy TC et al. The National Association of Medical Examiners Ad Hoc Committee on Shaken Baby Synd rome, Position paper on fatal abusive head injuries in infan ts and young children, Am ) Foren sic

Med Path o12001; 22:112-22, 240 Bodian M, Hes lop B, Sudde n infan t death syndrome , 1n Siim J-C (ed,) Proceedings of the Eighth 11Iternational Co ngress of Paediatrics, Basel, 1956. Copenhagen: Williams 8: Wilkins, 1960, p. 91.

I

CHAPTER 12

I

SUDDEN NATURAL DEATH IN INFANTS AND CHILDREN Dick Variend

Introduction Cardiovascular causes of sudden death X-linked hypohidrotic (anhidrotic) ectodermal dysplasia Intracranial haemorrhage, neoplasms and malformations Gastrointestinal causes Fatal anaphylaxis Sickle cell disease Haemorrhage as a cause of sudden death Respiratory causes of sudden death Epilepsy and sudden death

225 226 235 236 239 239 240 240 240 242

INTRODUCTION

Sudden death refers to the instantaneous death of an appar ently healthy person, but in practice the definition is extended to include all deaths within 24 hours from the onset of symptoms. The period between the onset of symptoms and the time of death is called the 'terminal event'. The term 'sud den' generally describes the rapidity of the death and the term 'unexpected' describes the surprising nature of the death . There is a wide range in the degree to which death may be expected. Some conditions, most notably cardiovascular in origin, are more prone to cause sudden death, and preced ing knowledge of t heir existence tends to redu ce the level of surprise. By their nature, sudden deaths tend to occur at home, in the ambulance or soon after arrival at hospital. As might be expected, sudden deaths have enormous impact on the family, the community and medical attendants. They are relatively uncommon occurrences but, when they occur, tend to foster suspicion and, in the United Kingdom, are genera lly dealt with by the coroner or procurator fiscal. Many causes of sudden death are age related. Explained sudden deaths in the first year of life are more likely to be due to an infection or congenital abnormality (e.g. congenital

Deaths from acute asthma Diabetes mellitus Genetic metabolic disorders Other bacterial infections Deaths related to obstetric events and premature birth Miscellaneous causes of sudden natural death Sudden unexplained death in older children Sudden natural death in the early neonatal period Sudden death associated with 'intermediate' pathology References

243 243 244 247 248 248 249 249 249 250

heart disease), whereas deaths associated with asthma , epilepsy and diabetes mellitus are more likely to affect the ado lescent years. The terminal event may be non-existent, non-specific or insignificant. Some patients (or their carers) may not fully perceive the severity of the symptoms that precede death, and this may delay summoning medical assistance. A lack of self-perception has particular relevance in conditions such as asthma and hypoglycaemia. Symptoms may be modified by medic atio n. Th e underlying disease mayor may not be symp tom atic. vVhen symptoms are present the terminal event can be variable in duration, depending on the under lying disease. Those dyi ng fro m hypertrophic cardiomyopa thy or congenital aortic stenosis can be expected to have a short terminal event. It might be argued that distinction should be made between sudden death in apparently healthy subjects and in those with recognized preceding illness (e.g. achondroplasia, cardiovascular disease). It is debatable, however, whether the latte r group should be included in the definition of sudden death. The inability of the very young to adequately communi cate symptoms may partly account for their increased vul nerability to sudden death. The discrepancy sometimes

226 I

Sudden natural death in infants and ch ildren

encountered between the account given and the gravity of the post-mortem findings may be explained by failure of the patient (or attend ant) to fully appreciate the seriousness of symptoms . Sudden death is often accompanied by emotional turmoil in the fam ily, and this may affect fam ily members' ability to give a clear account of events leading to death. Relevant information may come to light only after the autopsy has been completed. On the other hand, family members (or med ical attendants) may accurately perceive symptoms but misinterpret their significance. Fo r instance, the parents of a young child may mistake melaena for diar rhoea and not feel the need to ask for urgent medical advice. Severe haemorrhage may thus go unnoticed. A history of chronic disease (e.g. diabetes mellitus, aller gic asthma and epilepsy), w hile clearly very useful, does not always clarify the mechanism of sudden death. The cause of death in such a n individual as determined at post-mortem may be entirely unrelated to the clinically diag nosed entity. Sudden death is well known to be associated with certain syndromic entities (e.g. achondroplasia, La rsen 's syndrome), and knowledge of the relevant pathop hysiology may point the pathologist to the system affected. Deaths occurring during exercise are more likely to be associated with the cardiovascular system and , in such cases, a positive family history or evidence of preceding cardiac dys rhythmia may be helpful. The cause of sudden death at the time of autopsy may be obvious to the naked eye or on microscopic analysis; those without discernible findings require further diligent search or special investigations. After available investigation has been exhausted, those without morphological substrate are suitably referred to as 'physiolo gical deaths' which theo ret ically may cover causes such as cardi ac arrhythmia, con vulsion, laly ngeal spasm or unstable respiratory control. They cover a wide age spa n and may affect the velY yo un g or o ld er child. Medical intervention frequen tly prolongs life following a sudden loss of consciousness or cardiovascular collapse, with death following a period of intensive care. The circu latory collapse and the medical intervention that foUow often produce changes at post-mortem that are likely to mask the picture produced by the initial event. Separation of such ischaemic or reperfusion injuries from changes directly caused by the initial event is important in deter mining the underly ing cause. The results of biochemica l and enzymological studies may be difficult to interpret in such 'lingering' deaths. These cases are generally in cl uded in the definition of sudden death. The distinction between explained or unexplained sudden death often depends on the thoroughness of the autopsy investigation, the experience of the pathologist and avail ab ility of laboratory resources. When facilities are ava il ab le for t he investigation of genetic metabolic disease, the num ber of explained sudden deaths is more likely to increase. In some cases the relevance and significance of certain lesions found at autopsy may be difficult to determine. Pathologists

may, for instance, vary in their interpretation of the severity and/or exten t of certain diseases (e.g. pneumonia or hydro cephalus) and this may have a sig nificant bearing in dete r mining the cause the death in any particular individual. Such t1ndings, on the other hand, may be regarded as coin cidental. Death ma y also be accelerated when infection affects a pa tient with congenital or acqu ired immune deficiency or when the disease is caused by a part icularly vilUlent infec t ive agent.

CARDIOVASCULAR CAUSES OF SUDDEN DEATH Sudden cardiac death in children is far less frequent than in the adult population, and condi t ions that predispose to such deaths in the young are quite different from those preva lent in later years. The preva lence of cardiovascular disease as a cause of sudden death is difficult to determine because of variation in definition of sudde n death and inconsistency in the examination of the conduction system of the heart. In the series of Lambert et al,] the following heart con ditions accounted for 52 per cent of the cases of sudd en death: congenital aortic ste nosis, Eisenmenger's syndrome, cya notic congenital heart disease with pulmonary stenosis and hy pel1rophic obstructive ca rdiomyo pathy. Arrhythmia, hypo xia and coronary insufficiency are recog nized modes of sudden card iac death but, in a substantial proporti o n of the cases, the mechanism is ill-defined. I

Cardiac Malformation Unrecog nized congenital ca rdiac malformation is an impor tant cause of morta li ty in the first year of life. 2 Of 185 cases of infant death from congenital heart disease investigated, 70 per cent had previously diagnosed heart disease; in the remaining 30 per cent, the heart disease was unsuspected or unconfirmed. Of those with unsuspected heart disease about one-half had other severe abnormalities, mainly related to trisomy 13, 18 and 21. Two babies with severe aortic steno sis (both aged 2 months) and interlUption of the aortic arch (aged 6 days) died sud den ly at home. The authors speculated that 200 babi es died each yea r in the UK from unsuspected congenital heart disease. Of these, one-half of the heart defects were unassociated with other malformations. After infancy, death from congenital heart disease is more likely to be due to abnormalities of the coronary arteries, post-operative congenital heart disease, aortic valve stenosis, conduction system abno rmalities and dissection of the aorta complicating Marfan's syndrome, aortic isthmic coarctation or isolated bicuspid aortic valve. 3 The mechanisms of death in this group include co ronary thromboemboli c phenomena,4 fatal cardiac alThyth mias and severe pulmonary vascular dis ease.] Post-operative congenital heart disease is an imp0l1ant cause of cardiac dysrhythmia leading to sudden death;5 the

Cardiovascular causes of sudden death I

defects mostly affected are tetralogy of Fallot, tra nsposition of the great arteries and double-outle t right ventricle. An older age at the time of operation appears to be a significant risk factor for sudden death. Of 20 patients reported by Steinberger et al 6 who died suddenly at the age of less than 12 months, 13 (65 per cent) had a cardiac abnormality, 10 of which were anomalies of the coronary aliery and, of these, 5 were initially consid ered to be sudden infant death syndrome. Congenital aortic stenosis is a rare but well-recognized cause of sudden death,l and preceding symptoms such as syncope, fatigue, shortness of breath a nd dyspnoea on exertion are often present. Dea ths tend to predominate in the second decade of life and are often precipitated by exertional exercise. B Intimal tears and aortic dissection leading to intraperi cardi al rupture and cardiac tamponade is a recognized com plicat ion of undiagnosed aortic coarctation.] Patients with Eisenmenger's syndrome (pulmonary obstructive vascular disease secondary to communication between the systemic and pulmonary circulations) have a moderately high risk of sudden death, with many of the deaths occurring in the sec ond decade. I A ventricular septal defect is a common cardiac anomaly, and the releva nce of its discovery at autopsy in the sudden death of an infant or young child is often difficult to assess. 9.10 Marked cardiac hypertrophy, pleural and intraperi toneal effusions , pulmonary oedema and 'heart failure' cells in the lungs are features of decompensation and implicate the septal defe ct in the cause of death. 9 A multinational study of 186 cases attributed sudden death to ventricular septal defect in two cases (one per cent), suggesting its rarity as a cause. I A ventricular septal defect may also form the basis of Eisenmenger's syndrome, resulting in sudden death much later in childhood or in the second decade of life. I Williams' syndrome is a malformation complex charac terized by typical facies, mental retardation, mild growth deficiency and cardiovascular disease. Patients are at increased risk of sudden death from cardiac deformities that comprise supravalvar aorti c stenosis, bilateral outflow tract obstruction and coronary al1elY stenosis . Myocardial ischaemia, with or without cardiac arrhythmia, from coro nary aliery stenosis is the most likely mechanism of death, II but severe bilateral outflow obstruction may also cause sudden de ath . Abnormal elastin is thought to be responsible for the cardiovascular disease, and the condi tion is linked to the elastin gene on chromosome seven. ll

227

deaths occur in winter months.17 Of 207 cases of sudden death among individuals aged between 1 and 21 years, Neuspiel and Kuller 20 found myocarditiS to be the predomi nant cause of cardiac death. Human myocarditis has been associated with a number of viruses, most commonly of the coxsa ckie group.21 Presenting symptoms are related to the age of the patient, and older subjects may complain of chest pain, but symptoms are more often non-specific, especially in infants.22 Myocarditis may also present with cardiac failure. Pathological findin gs include cardiac dilatation, mottling of the myocard ium and variable opacification of the endo cardium. There is usu ally a diffuse interstitial mononuclear inflammatory infiltrate with a predominance of lymphocytes on microscopic examination (Fig. 12.1).12,16 Interstitial oedema and scattered foci of necrotic muscle fibres are usu ally present. Both ve ntricles and atria may be involved. Viral inclusions are usually absent. The lesion may be foc al or dif fuse and may show a predilection for the endocardium or subepicardial region. Specialized areas such as the conduc tion system may be involved. A subepicardial distribution is often ass ociated with pericarditis. The heart weight is often mildly to moderately increased, suggesting a latent phase of myocarditis despite a short clinical history. 12 However, when involvement is confined to areas such as the conduction sys tem , the heart weight may be normal. 19

Myocarditis Myocarditis is an important cause of mortality in infants l2 and older children,J3-15 and sudden death is a well-recognized presentation. 16,17 This may be related to ventricular asystole, ventricular fibrillation or conduction defects. IB ,19 Infants are more commonly affected than older children, and more of the

Figure 12.1

Microscopic view of the myocardium from a

7-year-old girl who collapsed at home and died soon after arrival in hospital. Extensive mononuclear cellular infiltrat ion of the myocardium is seen.

228 I

Sudden natural death in infants and children

The heart may be specifically affected ('isolated' myocarditis) or cardiac involvement may be part of a gen eralized involvement ('incidental' myocarditis). 12, 17 A prob lem often faced by the pathologist, and for which there is no easy answer, is how many foci of inflammatory cells in the myocardium are sufficient to cause death. 16 Noren et al 17 demonstrated the presence of viral myocarditis as a coincidental finding in two children who suffered violent deaths. This calls for caution in attributing death to viral myocarditis in children who die unexpectedly. It is important to save samples of heart muscle in aJl cases of sudden death for virological investigatio n. Diagnostic methods advocated for clinical investigation are also appli cable at autopsy. These include serology for specific viral antibody, viral culture using tissue or fluid and morphologi cal determination of the vil1Js in infected cells; the last may be au gmented by specific probes for viral antigens or nucleic acid sequences using in situ techniques for probe visualiza tion. 22 Molecular techniques such as polymerase chain reac tion (PCR) have proved valuable in identifying viral genome in formalin-fixed paraffin-embedded tissue.2J - 25 Contraction band necrosis in 'neuro genic cardiomyopa thy' and catecholamine-induced cardiomyopathy may cause minor inflammatory changes that should not be interpreted as myocarditis. 26 ,27 Myocarditis can also occur with any bac terial infection (meningococcus, diphtheria, Staphylococcus aureus, pneumococcus, gonococcus and Haemophilus injlurnzae).28 With the notable exception of diphtheria, car diac involvement in these cases is likely to be incidental. In acute rheumatic fever, pancarditis occurs in 50-75 per cent of children and acute rheumatic carditis may present as sudden death.29 Sudden death in a 6-year-old girl with acute rheu matic carditis complicating by thromboembolic occlu sion of the left anterior descending coronary artery has been described. 4 Acute myocard itis has also been reported in patients with dermatomyositis 30 and Kawasaki's disease.31

Over 50 per cent of cases are inherited as an autosomal dominant trait (familial hypertrophic cardiomyop athy).33,35 The disease may commence in infancy, and death has been recorded in infants as young as 1 year of age. 3 Studies in affected families, however, do not show Signifi cant num bers of infant deaths.32 Genes on five loci on separate chro mosomes are now known to be responsible for the familial disease.32 Of the three genes that have been identified, the best characterized so far is the one that encodes for ~ heavy chain myosin, which is found in abou t 50 per cent of affected families. At least 30 different point mutations are kno wn for this gene. Characteristic of this condition is an increase in ventricu lar muscle mass, with histology marked by myocyte disarray (disorganization), broad and misshap en individual myocytes and circular alignment of myocytes around central foci of connective ti ssue 32 (Fig. 12,2). Interstitial and replacement myocardial fibrosis and acute or subacute myocardial necro sis may be present. 3 The histological changes are maximal in areas of macroscopically thickened wall. The exact mechanism of sudden death in this condition is still unclear, but theories include inappropriate circulatory reflexes leading to haemodynamic collapse,36 arrhythmia an d conduction abnormalities. 37 Cases with the histological char acteristics of HCM may occur in the absence of hypertro phy,16,36 Consequently, extensive histological examination

Cardiomyopathy HYPE RTRO PHIC CARDIOMYOPATHY AND VARIA NTS, Hypertrophic cardiomyopathy (HCM) is a primary myocar dial disease of unknown cause characterized by a hypertro phied, non-dilated left ventricle in the absence of another cardiac or systemic disease,3 2 Symmetrical and asymmetrical forms exist. It is essentially a disease of young subjects, who are often asymptomatic. Clinical findings are ventricular hypertrophy, predominantly involving the ventricular sep tum, with dynamic obstl1Jction to left ventricular outflow, Because of variable phenotypic expression, the incidence of the condition is difficult to assess,33 It is the most common cause of sudden exertional death in yo un g persons, and males are more often affected than females. A combination of young age, a family his tory of sudden death owing to HCM and unsustained ventricu lar tachycardia identifies a subset that is esp ecially prone to sudden dea th. 34

Figure 12.2

Microscopic view of the myocardium showing

myofibre disarray and misshapen myofibres in an 8-year-old girl who died of hypertrophic cardiomyopathy.


may be required in cases of sudden death to confinn or exclude the di agnosis. A spectrum of disorders is responsible for other cases of HCM that are increasingly attributed to metabolic, genetic and molecular disease (e.g. fatty acid oxidation defects, mitochondrial disease, glycogen storage disease types 2 and 3, Gaucher's disease, GM 1 and GM2 ga ngliosidosis, sialidosis and mannosidosis). Cardiomyopathy occurs in about 25 per cent of patients with Noonan's syndrome J5 and the myocardium in affected patients is histologically indistin guishable from familial HCM.J8 Other associations include Friedreich's ataxia, Turner's syndrome and some disord ers of neural crest tissue. 16 Catecholamine-induced cardiomyop a thy has been reported in patients with phaeochromocytoma. Neonatal cardiomyopathy may follow poorly controlled maternal diabetes. J9 Affected infants are usu ally macrosomic reflecting the growth hormone effect of insulin. An underly ing anatomica l malformation of the heart must be excluded. Ventricular hypertrophy may persist for up to 2 years when such patients are followed by echocardiography.J2 Some vacuolar and hydropic changes of the myocardium are seen microscopically, but the myocardial fibre disarray and inflammatory infiltration that characterize classic HCM do not occur. Cardiac dilatation, which is also sometimes seen, may be secondary to hypo glycaemia and acidosis?9 Sudden death can occur from severe left ventricular hypertrop hy from any cause.J2

229

of the endocardium is seen macroscopically. Twelve cases (seven per cent) of endocardial fibroelastosi s were included in the 186 cases of sudden cardiac death in children sur veyed by Lambert et al. 1 Secondary endocardial fibroelasto sis may be superimposed on cardiac malformation or myocardial disease, and sudden death may be related to the underlying disease. 4J

ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA (RIGHT VENTRICULAR CARD IOMYOPATHY) Arrthythmogenic right ventricular dysplasia (ARVD) or car diomyopathy is a diso rd er of heart muscle 44 ,45 of unknown prevalence. 46 ,47 The disease is often familial (about 30 per cent of cases) with an autosomal dominant inheritance 46 and appears to be related to abnormal developmen t of the myocardium. 47 A gene for ARVD has been mapped to chro mosome 3p23. 48 Sudden death or a rrhythmia of ri ght ven tricular origin is the usua l mode of presentation. Symptoms ra rely appear before 20 years of age and death often occurs during exertion. 44 ,45 The rate of sudden death is about one per cent of cases per year. 47 The usual macroscopic appearance at autopsy is marked dilatation of the right ventricle with replacement of its free waJl by adipose tissue;49 microscopy confinns the presence of adipose tissue or fibrofatty tissue (Fig. 12.3). Inflammatory

DI LATED CARDIOMYOPATHY Dilated cardiomyopathy, an uncommon disorder in child ren, is characterized clinically by biventricular dilatation and reduced myocardial contractility.4o It acco unts for a dispro portionate number of deaths in paediatric practice, and the condition has been associated with sudden death,5,41 altho ugh the causative mechanism is poorly understood. Macroscopic pathological features are an increased left ventricular mass and decreased left ventricular wall thick ness.J2 Myocyte hypertrophy, myocyte myofibrillaJY loss, interstitial fibrosis a nd increased numbers of interstitial lym phocytes co nstitute the histological picture. Interstitial fibrosis, myocyte hypertrophy and absence of myocyte damage per mits the condition to be distinguished from acute myocarditis. As in hypertrophic cardiomyop athy investigation should be directed at an underlyin g cause,40 but in the majority of children dilated cardiomyopathy is idiopathic. A favoured view is that some cases are a sequel to viral myocarditis. 16,22,42

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ENDOCARDIAL FIBROELASTOSIS Endocardial fibroelastosis is customarily divided into pri mary and secondary types. 29 Most infants with the primary form of the disease die in the first year of li fe and sudden infant death is a common presentation. The affected ventri cle may be constricted or dilated and fibro elas tic thickening

Figure 12.3

The fre e wall of the right ventricular myocard ium is

extensively replaced by adipose tissue consistent with a diagnosis of arrhythm ogenic right ventricular dysplasia.

230 I

Sudden natural death in infants and chi ldren

cells are seen in about 25 per cent of cases, raising the possi bility of an infectious or a genetical ly determined immune process in some of the cases. Heart weight is normal or only moderately increased.45 Similar histological features are rarely seen to involve the left ventricle.47 As some degree of adipose tissue is often seen in the free wall of normal right ventricle, the amount of adipose tissue required for the diag nosis of ARVD is sometimes unclear. 49 ,50 ARVD and Uhl 's anoma ly are now considered to be two distinct morphological entities. 49 Uhl 's anomaly refers to absence of the right ventricu lar parietal myocardium, the endocardium and epicardium being directly apposed; the condition usually presents in neonates and infants with congestive cardiac failure . HISTIOCYTOID CARDIOMYOPATHY

Histiocytoid card iomyopathy (or oncocytic cardiomyopa thy), is a rare condition beset with a multitude of syn onyms, The entity is sometimes regarded as a tumour of the myocardium (see below), 51 Females less than 24 months of age are chiefly affected. 52 The clinical presentation is vari ab le, with congestive cardiac failure, arrhythmias or sud den death all being encountered. In a large revlew,52 68 per cent of the patients were reported to experience cardiac arrhythm ia before their death, Sudden death occurred in 22 per cent of the cases. The aetiology is unknown, but the characteristic myocardia l changes may represent the final common path way of a number of different aetiologies,53 Familial occur rence has been reported S3 At auto psy the heart is hypertrophied with left ventric ular prominence. The myocardium is pale and may show tan -yellow nodules. The endocardium may be thickened. Light microscopy shows groups of large polygonal cells with foamy to granular cytoplasm scattered within the myocardium (see Fig, 11.2, p. 206) . Their distribution may be diffuse, focal or multifo cal. Any part of the heart can be involved and the conduc tion system may be affected predominantly.54 Ultrastnrctura ll y, the swollen cells contain numerous enlarged mitoc hondria and myofibrils and occasional lipid vacuoles that are displaced towards the cell periphery. Sma ll dense bodies may be found within the mitochondria. Accompanying cardiac malformation has been described, and the patient reported by Koponen and Siegel (1996)54 had Peter's anomaly and congenital glaucoma. A defect in complex III of the respiratory chain has been demonstrated in one case, 52 However, the condition differs from mito- .. chondrial cardiomyopathy in several respects: • In mitochondrial cardiomyopathy, all myocytes are affected; whereas in histiocytoid cardiomyopathy, involvement is focal. • In mitochondrial cardiomyopathy, the mitochondria are consistently abnormal in shape. In histiocytoid cardiomyopathy, they are stnrctura lly normal or abnormal but are numerically increased. 52

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Figure 12.4 Different abnorma l ang les of origin of the coronary artery wh ich may be associated with sudden death. (al. normal ang le; (b), angle of origin less than 30°; (c), coronary artery is invested in the aortic adventitia as it departs at an acute angle.

Anomalous Coronary Arteries Sudden death associated with anomalous coronary arteries covers a wide age range (neonates, infants, children and young adu lts). Death is commonly associated with exertion and the anomaly is an important cause of sudden death among athletes. 41 Sudden infant death syndrome may be mimicked in the very young,55.56 indicating that death is not always related to exercise. In one autopsy series the inci dence of anomalous coronalY arteries as a cause of sudden infant death was estimated to be 0.4 per cent. 56 One patient reported by these authors had coexisting vascular abnorma l ities. A wide range of anomalies were described: 3,6,41.57,58 (I) an ectopic origin from the wrong coronary sinus, eccentric origin from the correct sinus or a high aortic origin; (2) ostial stenosis, i.e. an internal diameter that is smaller than the artery 1-2 mm from the aorta (this includes a slit-like ostium); (3) an abnomral angle of origin (Fig. 12.4), i.e. the ang le between the aortic lumen and coronary ostial lumen (normally 90 degrees) is between 30 and 45 degrees (proba bly abnormal) or less than 30 degrees (definitely abnormal); or (4) an ostial 'flap' or 'ridge' - a type of ostial stenosis usu ally associated with an acute angle of aortic origi n or origin from the wrong aortic sinus. These various lesions may occur alone or in combina tion, as exemp lifi ed in a 12-year-old child who died sud denly and was shown to have several different anomalies of the left coronary artely. These included a high aortic ori gin, an aortic intramural segment ('intussusception'), inter positio n between the pulmonary artery and ao rta, as well as an intramural course. 58 Lesser degrees of complexity are also descri bed. 55,57 An ectopic origin (anomalous origin from the wrong aortic sinus) is the most common pattern, and origin of the left coronary artery from the right coronary sinus is more


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common than origin of the right coronary artery from the left coronary sin us. 59 The following, singly or in combina tion, may contribute to ischaemia of the myocardium: a stenosed ostium or one with an acute angle of take-off; a course interposed between the pulmonary and aortic trunk (Fig. 12.5); and investment of the coronary artery in the aortic adventitia as it departs at an acute angle. An origin of one coronary artery from the other close to its com mencement is also reported. 56 Coronary arteries arising from the wrong coronary sinus causes sudden death from ventricular fibrillation owing to poor perfusion of the mus cle mass. Over two-thirds of patients do not have a history of syncope or chest pain ; a history of palpitations may, however, be apparent in old er subjects. Because of the sma ll size of vessels and difficulty with dissection in sma ll babies, the anomal ies are easily over looked, especially when the coronary ostia are normally located. Infants do not usually show myocardial ischaemia on microscopic examination. 56 By contrast, foci of myocar dial necrosis, fibrosis or contraction bands are often found in the ventricular myocardium of older individuals. 3.5.41 . Other anoma lies of the coronary arteries associated with sudden death include aplasia/hypop lasia, aneurysm and fis tula. The significance of intramyocardial tunnelling (intra mural coronary artery) as a cause of sudden death is controversial. 5o Some consider an intramyocardial mid segment of the left anterior descending artelY as a normal variant,6l while others view as significant a deep and long intramyocardial course.57 The latter authors recorded an

231

intramyocardial course from 10 to 25 mm and a depth from 4 to 8 mm in cases of sudden death. While these deaths were mainly of older individuals, one was a 14-year-old boy. Origin of the left coronary artery from the pulmonary trunk (Bland-White-Garland syndrome) is a rare malforma tion. The relative low pressure of the pulmonary artery is inadequate for perfusing the left ventricular myocardium and most affected subjects die in infancy from cardiac failure. 29

Kawasaki's Disease This is a systemic febrile vasculitis with multisystem involvement, whose cause is unknown. Children under the age of 5 years are predominantly affected. 3l Eighty per cent of patients are diagnosed before the age of 5 years. 52 The condition is reported world-wide and, in developed coun tries, males are affected more often than females. It is the most common cause of acqu ired heart disease in children. 53 Kawasaki's disease and infantile polyarteritis nodosum are now considered to be the same entity. An infective aetiol ogy is suggested by the observed clustering of cases. The incidence in Blitain is estimated to be 3.4 per 100000 chi ld ren aged less than 5 years.63 The case fatality in Britai n in 1990 was 3.7 per cent. Six deaths were reported in Britain in 1990; in only one case was the diagnosis made in life. Clinical features are the presence of fever for about 5 days, lymphadenopathy, characteristic changes in the peripheries (erythema of the palms and soles, desquamation of the fin gers and toes and pelipheral non-pitting oedema), bilateral conjunctivitis, buccal inflammation (injected pharynx, dry cracked lips, strawberry tongue, mouth ulcers) and a poly morphous exanthem. 64 Hydrops of the gall-bladder is increasingly recognized. Three-quarters of affected patients show a transient rise in the serum concentration of IgE. 62 Sudden clinical onset is usual. There are four major stages in the development of the disease: 10 • an 'acute febri le' stage which lasts 1-11 days; • a 'subacute' stage which lasts 11 to 21 days and is associated with thrombocytosis; • a 'convalescent' stage from 21 to 60 days; and • a 'healed ' stage. Vasculitis is often widespread but the coronary arteries are always affected 52 (see Fig. ILl, p. 206). The heart is the most severely affected organ, and coronary arteritis with aneurysmaJ formation occurs in 20-30 per cent of cases. 53 Aneurysms more commonly affect the left coronary artery. The prognosis for resolution is favourable unless the aneurysms are 'giant', as these are more often associated with myocardial infarction. 3! Recurrences may occur,65 and coronary aneLllysms/dilata tion and giant aneurysms are more common in this subset. Other organs often affected are the kidneys, spleen, testis, pancreas, adrenal glands and liver. There is correlation between the severity of the autopsy findings and the duration of the illness. Most deaths occur in

232 I


the subacute and heali n g stages. Sudden unexpected death may occur many years later, following recanalization of thrombosed coronary arteries,lo and sudden death has been reported in a fit athlete during exercise with evidence of pre ceding Kawasaki disease. JI Overlapping features, including the clinical demonstra tion of coronary aneurysms, have been reported bet"feen group A streptococcal infection and Kawasaki's disease. 66

Abnormalities of Cardiac Conduction While myocardial disease, such as hypertrophic cardio myopathy, myocarditis, histiocytoid cardiomyopathy and tumours, may cause sudden death consequent upon involvement of the conduction pathway, abnormalities of the cond uction tract may coexist with certain types of con genital cardiac malformations or the conduction tissue may be damaged during their operative repair. 29 Fibromuscular hyperplasia of the sinoatrial nodal an d atriovent ricul a r nodal arte ri es may cause paediatric sudden death from car diac arrhythmia. 67 On the other hand, fatal arrhythmias may result from intrinsic defects of the conduction tissue that are not obvi ous to the naked eye. 30 .6B For precise diagnostic categoriza tion, such cases require formal examination involving extensive serial sectioning. In practice, this is time-consuming and associated with such a low positive yield that it does not gene rally form part of the routine examinatio n of the heart in cases of sudden death. Conduction defects may thus be easily overlooked and many such deaths are simply referred to as showing no structural cardiac disease. 41 The long QT syndrome (LQTS) is significantly associated with ventricular fibrillation and the risk of sudden death. The condition can be inherited as an autosomal dominant disorder (Romano-Ward syndrome),69 with ab norm ali ties at six different loci identified.1° A recessively inherited syndrome w ith deafness is also recognized .7o Vigorous physical exertion often precedes vent ricula r fibrillation. In these cases there is no discernible abno rmality on histolog ica l examination of the conduction pathway. IS Risk factors for sudd en death in such indi vidua ls include a history of syncope, congenital deafness and a fami ly history of sud den cardiac deathS Preceding symptoms th at suggest a conduction defect include syncope and dizziness. A preceding abnormal elec trocardiogram (ECG) recordin g or a family history of con duction defect is valuable in these cases, and likely to ex plain an arrhythmic cardiac arrest. In their absence, the significance of any histological cha nges of the conduction tract is merely speCUlative. Opportunity for clinical diagno sis in these cases is precluded by the intervention of sudden death of the patient. Accessory pathways of th e conduction system may cause re-excitation and re-entry lea ding to fatal arrhyth mias. The Wolff-Parkinson-White pre-excitation syndrome

may occur in isolation or be associated with other abnor malities, for example Epstein 's anomaly, rhabdomyoma of the heart. These abnormal pathways produce early stimula tion of the ventricle and are associated with a variety of electrocardiographic patterns. Many patients remain asymp tomatic however, but sudden death in this group is well recognized. Heart block may be congenital or result from acquired causes. Marked degrees of atrioventricular (AV) block may produce Stokes-Adams attacks and are rarely caused by endodermal heterotopia of the AV node (mesothelioma of the AV node). Some congenital abnormalities of the conduction system (e.g. simple absence of the short segment of the right bundle branch or the penetrating portion of the main bundle of His) are stable and do not seem to progress. IS Babies born to mothers with systemic lupus erythemato sus are at considerable risk of congenital AV block but the prognosis is rem arkab ly good in such cases, and those affected may not develop syncopal attacks until much later in life. Death among infan ts with preceding congenital heart block or those w h o die in association with maternal connective tissue disease should be tested for anti-La (SS-B), anti-Ro (SS-A) and even anti - UIRNP antibodies. 29 Heart block has been described w ith Kearns-Sayre syndrome, Kartagener's syndrome and certain X-linked myopathies. 10

Occlusive Disease of the Coronary Arteries Infantile arterial calcification is a rare disease mainly affect ing infants,71 with reports of siblings affected. Low levels of plasma cell membrane glycoprotein-l nucleoside triphos phate pyrophosphohydrolase have been demonstrated in an affected infant. 72 The same group subsequently demon strated mutations in the EN??] gene 7J Alieries throughout the body are involved, with the exception of the brain and spinal cord. Of the 62 cases reviewed by Moran (1975),71 10 presented as sudden death, preceded by respiratory distress in 5. The age of death ranged from 2 days to 28 months, with 85 per cent of affected infants dying within 6 months. Clinical diagnosis is possible with rad iological study. The ECG changes, when available, are mostly compatible with myocardial ischaemia. Cardiac enlargement is common and the myocardium is often infarcted. Intra-uterine ultrasono graphic diagnosis has been made in familial cases. 74 Microscopically, there are calc ific deposits with fragmen tation of the internal elastic membrane of arteries along wit h variable degrees of fibrointimal proliferation and luminal narrowing. 71 ·75 An inflammatolY reaction is typically absent. An alieriopathy with features similar to those found in idio pathic infantile arterial calcification has been reported in children with acquired immun e deficiency syndrome (AlDS);76 one of the cases described by these authors showed myocardial infarction associated with thrombus formation in a coronary aneurysm.


233

Table 12.1 Causes of coronary artery dysplasia in infants and children Fibrous muscular dysplasia Idiopathic arterial calcification Chronic arsenic poisoning Congenital rubella Tuberous sclerosis Neurofibromatosis Acquired immunodeficiency syndrome Homocystinuria Down's syndrome Menkes'syndrome

Fibromuscular dysplasia is a segmental, non-atheros clerotic vascular disease of unknown aetiology mainly causing renal vascul ar disease, but other arteries may be involved. Young adults are usually affected and its occur rence is rare in infancy a nd childhood. Myocardial infarc tion due to fibromuscul ar dysplasia affecting the coronalY artery has been reported as a cause of sudden death in infants and children.77,78 Myocardial infarction with cardiomega ly has been reported in children with chronic arsenic exposure from drinking water. 79 This occurred as part of a ge neralized arterial disease of irregu lar distribution and progressive course, but apparently sparing the arteri es of the lung and brain. Microscopically, there was intimal fibroblastic thick ening of the media of small-sized arteries. The endothe lium, internal elastic lining, media and adve ntitia were uninvolved. Widespread vascular dysplasia in a child with tuberous sclerosis leading to variable luminal nan-ow ing of the coro nary, superior mesenteric, renal and common iliac arteries has been reported;80 these a uthors described a 9-month-old infant who developed an aOliic aneurysm. Fatal haemor rhage followed dehiscence of the aortic graft. Occlusive artelial disease has also been reported in patents with homocysteinuri a,8 J and followin g congenital rubell a syndrome, S2 neurofibromatosis 1,83 Menkes' syn drome 84 and, rarely, Down's syndrome. 85 A list of conditions that may cause abnorm alities of the corona ry arte ries is presented in Table 12.1. Corrado et al 57 referred to the sudden death of a 14 year-old g irl whose coronary ostia were nan-owed by Ta kayasu arteritis.

Tumours of Cardiac Muscle ------Primary cardiac tumours are uncommon but are associated with potentially lethal conditions producing conductive and haemodynamic abnormaliti es that often result in sud den death.

Figure 12.6 The cut surface of the heart sho ws multiple tumours of the myocardium alternating with areas of congestio n from an infa nt who died from cardiac rhabdomyomas.

ENDODERMAL HETEROTO PIA OF THE ATRIOVENTRICULAR NOD E Previously referred to as mesothelioma of the AV node, the lesions are frequently associated with heart block and sud den death. Gross examination of the heart may show a small raised nodule immediately above the septal leaflet of the tri cuspid valve, just antelior to the coronary sinus in the right atrium. Microscopically, the lesion comprises multiple cysts, gland-like structures or nests of epithelioid cells within a fibrous stroma. 86 The tumours may be missed if sections of the AV node are not exa mined in cases of sudden death. These lesions have now been convincingly shown to be due to endodermal inclusions. Associated cardiovascular malfor mation may be present. 87 The entity is sometimes refen-ed to as the 'smallest tumour causing sudden death'. RHAB DOMYOMA Rhabdomyoma is the most common tumour of the cardiac muscle. In 30 per cent of cases, death occurs at birth or in the neonatal period and one-third of cases are associated with tuberous sclerosis.s7 The tumours may be isolated or multi ple (Fig. 12.6), but diffuse infiltrative patterns have been

234 I


Figure 12.8 The left ventricular myocardium from an 8-month old boy shows a large well-circumscribed tumour with a solid trabeculated cut surface typical of cardiac fibroma.

Figure 12.7 The microscopy of cardiac rhabdomyoma shows 'spider' cel ls chara cte ri zed by ce lls with clear to vacuolated cytoplasm wi th myofibrillar strands extendi ng between nuclear and cytop lasmic membrane and a central or eccentric nucleus. described. The cause of death is outflow tract obstmction or cardiac arrhythmia. Microscopically, large cells with clear cytoplasm and small nuclei (so-called 'sp ider cells') consti tute the microscopic picture (Fi g. 12.7). Most cases of sudden death due to the tumour are sporadic. B6

FIBROMA The seco nd most common cardiac tumo ur, fibroma of the heal1, also ca uses death secondary to outflow tract obstruction or arrhythmia. A well -circumscribed grey-white mass betvveen 3 and 10 cm in diameter is_ the usual gross appearance (Fig. 12.8), cysts may occur. The tumour is most often located in the interventricular septum. Microscopy shows fibroblast-like cells in a colla genous matrix, reminis cent of fibrom atoses of the soft tissues (Fig. 12.9).B6,87 The tumour may occur as a component of Gorlin's syndrome.

MYXOMA Myxomas are rare in infants and children. s7 Most occur as sporadic lesions, arise withi n the left atrium and may reach up to 10 cm in diameter. Su dden death is related to dis turbed cardi ac haemodynamics or systemic emb olization of tumour fragments. Myxomas rarely involve the right side of the heart, where they are capable of causing massive pulmonary embo lism. Bs

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OTHER CARDIAC TUMOURS Cardiac haeman gioma is a rare cause of sudden death in child re n. A previously asympto matic 13 -year-old girl who was found unresponsive in bed was reported by Krous et a\. B9 Autopsy showed haemangiomatous invo lvement of

X-linked hypohidrotic (anhidrotic) ectodermal dysplasia I

the ventricular conduction system. Death was thought most likely to have been arrhythmic in origin. Swalwe11 90 repolted a benign teratoma of the interven tricular septum causing sudden death in 2.5-year-old girl who had no preceding medical problems. Krous et al 51 analysed 68 cases of tumour-associated sud den deaths in children from the literature. Of those involving the heart, there were 23 cases of oncocytic cardiomyopathy (histiocytoid cardiomyopathy), 12 cases of cardiac fibroma, seven cases of rhabdomyoma, three cases of myxoma and one case each of neuroma, teratoma and mesothelioma. In one case of oncocytic cardiomyopathy, one case of cardiac fibroma and the case of neuroma the lesion was considered incidental and unrelated to the cause of death.

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il Pulmonary thromboembolism is an unusual cause of sudden death in children. Predisposing factors include recent sur gery, congenital heart disease, indwelling venous catheters, sepsis, arteriovenous malformation and occult malignancy.91 Of 17 500 autopsies reviewed by these authors, eight cases (0.05 per cent) showed pulmonary thromboembolism; their ages ranged from 1 month to 13 years. The source of the embolus may not always be demonstrated at autopsy. Unexpected death from massive pulmonary embolism was reported in three infants.92 The underlying conditions were necrotizing enterocolitis , a ventriculoatrial shunt for hydrocephalus and idiopathic arterial calcification. Birth control medication may predispose to pulmonary embolism in teenagers. 59 Sudden death from thromboembolism of the left anterior descending coronary artery complicating acute rheumatic heart disease in a 6-year-old girl and complete atrioventricular canal defect in an 18-year-old girl with Down's syndrome were reported by Stahl et al 4 Thrombosis and pulmonary embolism is a recognized complication of homocysteinuria (cystathionine B synthase deficiency).81 Any blood vessel can be affected, even the intracranial dural sinuses. Microscopically, the arterial lesion comprises marked fibrous intimal thickening, split ting and fraying of the muscle fibres , in the media with increased interstitial collagen. The internal elastic lamina may also be affected. Lipid deposition is not a feature. Potential causes of sudden death in this condition include pulmonary embolism, myocardial infarction and cere brovascular accident.

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90 per cent of the mortality is related to cardiovascular com plications that include mitral valvular regurgitation or aortic dilatation, dissection and nIptlire. Aortic dissection with nIpture and haemorrhage into the pericardial cavity causing cardiac tamponade is a common mode of death.3.4 1,93 An intimal tear is usually located in the ascending aorta and histological examination of the aortic wall shows cys tic medial necrosis, characterized by fragmentation of the elastomuscular media and accumulation of basophilic material. Spontaneous dissection of the coronary a11ery rarely causes sudden death, 57 but this is not confined to cases of Marfan's syndrome. Cystic medial necrosis may occur with aortic coarctation (Fig. 12.10) and in patients with an isolated bicuspid a011ic valve in the absence of Marfan's syndrome. 3 Patients with Ehler-Danlos type IV syndrome are also at increased risk of vascular nIpture. 8

Marfan's Syndrome

X-LINKED HYPOHIDROTIC (ANHIDROTIC) ECTODERMAL DYSPLASIA

Patients with Marfan's syndrome display a characteristic habitus: tall stature, arachnodactyly, bilateral ectopia lentis, high arch palate, dolichostenomelia and striae distensae. Linkage analysis has shown that the fibrillin gene on chro mosome 15 is associated with Marfan's syndrome. 8 Up to

The condition is characterized by an absence or diminution of eccrine sweat glands, eczematoid rash, thin sparse hair, oligodontia and peg-shaped teeth. The incidence is estimated to be in 1 per 100000 live births.94 The condition carries a sub stantial mortality and morbidity, and death occurs in about

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Figure 12.11 Mid-sagittal view of brain from a 12-month-old girl with achondropl asi a. There is marked forebrain hydrocephalus and necrosis of the upper cervical cord due to a small foramen magnum.

30 per cent of cases. 95 There is an increased risk of chest infec tion and atopic disease. Because of the deficient number of eccrine sweat glands, patients are unable to perspire and con sequently develop fatal heat intolerance 94 Mucus production is also deficient in the respiratory and gastrointestinal tracts. An inexplicable improvement in the patient's general condi tion occurs with increasing age.

Achondroplasia Achondropl as ia is the most common type of osteochon drodysplasia; it is inherited as an autosomal dominant tra it. Recent studies suggest that sleep apnoea is common among affected individuals,96 involving both obstructive and cen tral mechanisms. Compressive myelopathy and dysfunction at the cervicomedullary junction is caused by a small fora men magnum, and sudden infant and childhood deaths have been reported. 97 Macroscopic or microsco pic necrosis of the spinal tissue at the level of the foramen magnum may be seen (Fi g. 12.11).

Tuberous Sclerosis Complex Tuberous sclerosis is a dominantly inherited condition characterized by genetic heterogeneity. The birth incidence is about 1 in 6000. More than 70 per cent of cases will be new mutations. Early skin manifestations are hypomelanic macules and shagreen patch. Subungual fibromas and facial angiofibromas occur later. Cardi ac rhabdomyomas, giant-cell astrocytomas and renal disease are other patho logical lesions .93 The polycystic renal disease of tuberous sclerosis usually affects infants and young children, while the angiomyolipomas tend to occur at or after puberty. At least 80 per cent of children presenting with cardiac rhab domyomas will have tuberous sclerosis. 93 The incidence of

tumours in patients with tuberous sclerosis approaches 50 per cent,99 but their size and number tend to regress with age. The majority of individuals presenting in childhood h ave epileptic seizures. 98 The preCise mechanism of death is not always clear. Sud den un expected death in infancy has been reported to occur either from cardiac arrhythmia or blood flow obstruction secondary to rhabdomyoma. Patients with tuberous sclerosis may develop Wolff-Parkinson-White syndrome, which may initiate fatal cardiac arrtbythmia and is probably related to the presence of the cardiac tumour. 100 Rarely, a renal angiomyolipoma ruptures with life threatening retroperitoneal haemorrhage. 98 Aortic aneurysm secondary to vascular dysplasia in a child w ith tuberous sclerosis has been reported. so

INTRACRANIAL HAEMORRHAGE, NEOPLASMS AND MALFORMATIOI\IS Sudden unexpected death m ay result fro m intracranial haemorrhage secondary to a generalized bleeding disor der lOI or the haemorrhage may be related to intracranial pathology (Fig. 12. 12). Contrasting with subdural or extradural haemorrhage, sudden unexpected death follow ing parenchymal haemorrhage is more likely to be associ ated with natural disease . Arteriovascular malformations (Fig. 12.13) and aneurysms a re important sources of cata strophic bleeding. 2o ,JOI Intra-crani al a neurysms are found with uncorrected aortic coarctation, familial multiorgan cystic disease or autosomal dominant polycystic kidney disease (ADPKD). While fatal subarachnoid haemorrhage in ADPKD usually presents in adulthood,I02 infants and children are rarely affected. A family history is extremely helpful in making a diagnosis. The cerebral anelllysm may be masked or destroyed by the haemorrhage and, consequently, may be difficult to find at post-mortem examination. Intracranial aneurysms in childhood have been reported to occur as a complication of renal hypertension . 103 The intracranial pathology mayo r may not be clinically apparent prior to sudden death.l04 These authors reported 10 deaths from intracrania l haemorrhage, secondary to tumours (four cases) , berry a neurysm (one case) and vascu lar malformations (five cases); the presence of four vascu lar malformations was assumed at autopsy as their positive identification was difficult owing to the marked tissue destruction. Such haemorrhages may be due to micro angiomas. lOl An additional cause of intracranial bleed in older female patients is eclampsia. Four cases of intracerebral haemorrhage reported by Liv ingston and Brown 101 compbcated a pre-existent coagulopa thy. In two cases this was thrombocytopenia (associated with aplastic anaemia and acute lymphoblastic leukaemia) ; one child had haemophilia and one case was thought to be a late manifestation of haemorrhagic disease of the newborn. Minor trauma was a factor in the case of the haemophilia.

Intracranial haemorrhage, neoplasms and malformations

I

2 37

J8,... Figure 12.12 Cut surface of the cerebellum shows haemorrhage into a tumour which wa s subsequently demonstrated to be low grade astrocytoma. The patient was a 4-year-old girl who had apparently been in good health and had died suddenly.

o

Figure 12.13 Microscopic view of an arteriove nous malformation which caused catastrophic intracerebral haemorrhage in a lO-year old girl. There is vascular prominence with irregular thickening of some of the vessels. Elastic van Gei son stain (EVG). The clinical course of idiopathic thrombocytopenic purpura is rarely complicated by intracranial haemorrhage. The inci dence is estimated to be 1 in 1000 patients. lOS Sudden death from undiagnosed primary intracranial tumours per se rarely occurs. Abu al Ragheb et al (1986)106 found seven cases of sudden death secondary to intracranial

Figure 12.14 The tip of the intraventricular part of a ventriculoperitoneal shunt that had become ensnared in choroid plexus. causing obstruction to cerebrospina l fluid egress in a young child with shunt- treated hydrocephalus. neoplasm in 1055 autopsies. including one in a 6-year-olcl and one in an 18-year-old. Preceding symptoms mayor may not be present and, when present, relate mainly to increased intracranial pressure. epilepsy, focal neurological deficit or psychiauic manifestation. l07 Loss of consciousness may pre cede sudden death. Sudden mass effect, haemorrhage into or adjacent to a tumour l04 obstructive hydrocephalus lO8. 109 and epiIepsyilo are some of the mechanisms responsible for death. An unusual case of spontaneous sub a rachnoid haemor rhage in a 5-month-old girl who died suddenly was reported by Byard et al; III collagen analysis showed virtual absence of type III collagen, diagnostic of type IV Ehlers-Danlos syndrome. The Dandy-Walker malformat ion is a well-recognized but a rare cause of sudden death .112 Autopsy examination may provide the first indication of the presence of the mal formation. The mechanism of death is unclear, but brain stem ischaemia from local pressure abnormalities in the unshunted posterior fossa may be responsible. Sudden death occasionally occurs in children with a colloid cyst of the third ventricle. I08 Owing to its critical location in the anterior part of the third ventricle, the lesion may obstruct cerebrospinal fluid drainage and lead to acute hydrocephalus. Histologically, these are unilocular cysts conta ining eosinophilic debris and lined by cuboidal/columnar epithelium, which may be ciliated. Hydrocephalus may be congenital with and without spina bifida. Acquired hydrocephalus may follow or accompany intraventricular haemorrhage, meningitis or neoplasms. Patients may present with respiratory arrest. 113 Focal and generalized convulsions are common with shunted hydrocephalus and may result in status epilepti 114 Factors precipitating convulsions include infection CUS. and shunt-related complications (Fig. 12.14).

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Encephalitis and Leucodystrophies Sudden deaths in infancy and childhood are rarely ascribed to encephalitis. The clinical course of herpetic encephalitis in chiJdren or young adults may be rampant, and in the neo natal period severe general ized disease caused by herpes simplex virus infection can also be rapidly fatal. Cerebral involvement as part of a severe disseminated infection in the neonate may a lso occur with coxsackievirus infection, a nd there is predilectio n for involvement of the brainstem and spinal cord. liS Sudden death at home in two siblings associ ated with an encephalitic process has been reported by Howat et al. I1 6 An aetiological agent was not discovered. Shields et a l l1 7 reported sudden death in two female patients secondary to the autosomal recessive form of adrenoleucodystrophy and to Alexander's disease.

Adrenal Hypoplasia/Insufficiency Adrenal hypoplasia in infancy may be secondary to brain malformation or occur in isolation. liS Weakness, weight loss, hyperpigmentation , hypotension, gastrointestinal symptoms and vitiligo are the main symptoms of chronic adrenocortical insufficiency. 119 By contrast, the symptoms and signs of acute adrenal failure are non-specific and are those found in any serious illness. Adrenocortical insuffi ciency presenting later in chi ldhood is more likely to be of autoimmune origin (Addison 's disease) .11 9.120 Favara et al 121 reported severa l deaths in infants, with an age range from a few hours to 24 months, with undiagnosed adrenal hypoplasia without central nervous system malfor mation. There was a strong male predominance. Sudden death was recorded in four of the infants. The morphology of the adrenal glands was variable and all were normally shaped but miniature in size. In a ll cases the combined adre nal weight was less than 2 g. One patient died during induc tio n of anaesthesia. Two infants were born small-for-dates. Pregnancy-induced maternal hypertension was present in just over 50 per cent of mothers whose infants had con genital adrenal hypoplasia. 122 The condition was unsus pected in life, and unexpected clinjca l deterioration occurred in three cases. An 'adrenal crisis' tends to occur in patients with previ ously diagnosed adrenocortical insufficiency and in whom, during intercurrent infection, corticosteroid replacement therapy is not increased. However, Molander lJ referred to a sudden death during exertion from adrenal insufficiency in a previously asymptomatic 19-year-old male. Fibrosis and calcification of the adrenal glands were found at autopsy. Al Sabri et al 120 reported the sudden death of a 12-year-old gi rl with autoimmune Addison's disease. Biochemical abnormalities included hyponatraemia, hyperkalaemia, hypercalcaemia , haemoconcentration, hypoglycaemia and metabolic acidosis. Autopsy revealed depletion and atro phy of the adrenal cortex.

Haemorrhagic Shock Encephalopathy Syndrome Haemorrhagic shock encepha lopathy syndrome is a rare and devastating disorder, with a sudden-onset symptom com plex, usually in previously healthy infants and chil dren. 123 ,124 Symptoms include fever, shock, haemorrhage, diarrhoea and encephalopathy (coma, seizures). Laboratory investigation during hospitalization shows progressive dete rioration of renal function, falling haemoglobin and platelet counts, evidence of disseminated intravascular coagulation, hyper-natraemia, hypoglycaemia, metabolic acidosis, raised serum transaminases and hyperammonaemia. 123 ,124 At autopsy the brain shows oedema, softening and infarc tion.1 24 Hepatic steatosis, hepatic necrosis and small intes t ina l vi llous blunting are other common findings, as are bleeding from the nasotracheal tube and intravenous access sites. Microbiological cultures and toxicological screening are uniformly negative. The aetiology is unknown and the differ ential diagnosis includes heat stroke due to overwrapping, toxic shock syndrome, septic shock, haemolytic uraemic syn drome, Reye's syndrome, metabolic disorders, viral haemor rhagic fevers and poisoning. 124 The age disttibution of the condition is between ) 7 days and) 5 years. The modal age is 3 months, with more than 80 per cent of the patients presenting before 1 year of age. 12S Boys are more commonly affected than girls. There may be a family history of a neurologica l disorder or unexpected death in infancy. The prodromal illness varies from a few hours to several days. Of 33 patients with follow-up information, 22 died, and many of the survivors were neurologically dam aged.125 In my practice the incidence of this condition has declined considerably over the past several years.

Reye's Syndrome This is a rare and serious disorder chiefly affecting chi ldren, characterized by a non-inflammatOlY encephalopathy with hepatic dysfunction in which the diagnosis is made on com bined clinical, biochemical and histological parameters. The internationally accepted case definition is age under 16 years; unexplained non-inflammatory encephalopathy with one or more of t he following: serum hepatic transaminases raised more than three times the upper limit of normal, plasma ammonia level raised to more than three times the upper limit of normal and characteristic fatty infiltration of the liver. 126 In Britain, the epidemiology ofReye's syndrome differs from that in the USA in so far as the mean age is 14 months compared with) 1 years, and there is no clear asso ciation with influenza. 127 The onset of the illness is marked clinically by profuse effortless vomiting, progressing to extreme lethargy and coma. A coagu lopathy and hypog lycaemia are common. Jaundice is rare. Poor outcome is associated with early onset of seizures, profound hypo glycaemia and coma.

Fatal anaphylaxis I

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At autopsy the brain is oedematous and the liver appears pale due to panlobular fa tty change . These light microscopic findings, however, lack specificity and may be seen in many other conditions. '28 Electron microsco py is widely recommended to confirm the di agnos is, I29 and swo llen and pleomorphic liver cell mitochondria are the ultrastructural hallmarks. 126 The decline in the number of cases of classic Reye's syn drome has been partially attributed to warnings against aspirin exposure durin g viral prodromes in children under 12 years of age and the increased diagnostic awareness of genetic metabolic diseases that mimic the syndrome. ' 27 ,130 Consequently, Reye's syndrome has become an entity comprising a number of 'Reye-like' inherited metabolic disorders,I3 1 includin g p-oxid ation defects, organic acid disorders and urea cycle defec ts. '30 ,'J2 Classical Reye's syn drome has thus become a diagnos is of exclusion, l26 Medium-chain acyl CoA dehydrogenase deficiency is the most common metabolic disorder masquerading as Reye's syndrome. Previous unexplained sibling deaths or similar illness, a previous history of ge netic metabolic disease or unexplained illnesses (e.g. hypoglycaemia, fits) should prompt appropriate investigation. Haemorrhagic shock and encephalopathy syndrome and mitochondrial disease should also be considered in the differential diagnosis,

GASTROINTESTINAL CAUSES Delayed presentation of congenital diaphragmatic hernia has been reported as a cau se of sudden death in two male infants and a 2-year-old girl. 133 The mechanisms of death were mediastinal compression and cardiorespiratory col lapse. One of the infants died in his sleep and was thought to have succumbed from sudden infant death syndrome. The small size of the diaphragmatic defect in these cases probably contributed to th e delayed onset of problems. Small bowel incarceration and infarction as a result of mesodi vertic ular band are reported to have caused sudden dea th in i nfan ts aged 30 and 31 months. lJ4 We have previously encountered a 3-year-old girl whose sudden death was caused by to rs ion of the intestin e in the absence of malrotation (Fig, 12.15).

FATAL ANAPHYLAXIS Acute ana phylaxis is an immediate type IgE antibody mediated hypersensitivity reaction. The clinical spectrum includes hypo tensio n, bronchospasm, angio-oedema and laryngop haryngeal oedem a. IJ5 ,l36 The full-blown clinica l picture may be preceded in some patients by less fulminant symptoms such as itching of the skin, flushin g, generalized warm th or evidence of smooth muscl e contraction, l37 Fatal or near-fatal ana phylactic reactions occur in children and ado lescents,l38 and even infants may be

Figure 12.15 Extensive haemorrhagic infarction of the small bowel secondary to volvulus which caused the sudden collapse and death of a 3-year-old girl.

affected. IJ5 The subjects are often highly atopic, with asthma , allergic rhinitis and atopic dermatitis. Apart from various foods, recognized allergens include drugs, pollens and venom from stinging insects. IJ7 " 39 The offending allergen can be identified in most instances, but occasionally is not found. Mast cell tryptase measurement has been recommended as a useful test for anaphylaxis and has served as a diagnos tic marker at autopsy.lJ5 "'Vbilst tryptase remains stable in samples up to 4 days at room temperature, freezing of sam ples at - 20°C is recommended if the assay cannot be carried out immediately. J40 Elevated levels are not absolutely spe cific for anaphylaxis and may be found in post-mortem serum in other conditions such as sudden infant death syn drome and trauma. 140 Total serum IgE and allergen-specific IgE antib odies may also be usefully measured. l4l The period between onset of ac ute anaphylaxis and death varies considerably, but without medica l interven tion most patients expire within a few hours. 137 An allergic reaction may be conSiderably enhanced in patients receiving p-blockers. l42 Patients with cow's milk protein intolera nce who are challenged with milk following a period of cow's milk protein avoidance are es pecially at risk of developing acute anaphylaxis, Autopsy findings in ac ute anaphylactic deaths are non specific, for example pulmonary congestion and oedema with variable intra-alveolar haemorrhage, Changes may

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be enhanced by efforts at resuscitation . 1J7 Other findings include increased tracheobronchi al secretions, laryngeal oedema and pulmonary emphysema. An autopsy diagnosis of acute anaphylaxis cannot be made on morphological grounds alone and appropriate clinical information is esse ntial. IJ6 In cases of fatal reaction to insect stings, the site of the sting may be found.

SICKLE CELL DISEASE Sickle cell disease is more common in the black population and the clinical course is generally more severe in homozy gous than in heterozygo us individuals. Most deaths occur in patients with haemoglobin SS, but young subjects with haemoglobin SC are also at risk.143 Polymerization of deoxygenated sickle haemoglobin produces sickling of red blood cells leading to veno-occlusive crises. Predisposing factors include dehydratio n, fever, acidosis and hypox aem ia. Sudden death in infants and older children has been repolted . 144 Generalized convulsions are also recognized. Sudden death in infants with a sickle cell trait may be asso ciated with anaesthesia. Infarction of the small bones of the hands and feet, sickle cell dactylitis, aplastic and haemolytic clises and splenic sequestration are recognized complications. Splenic sequestratio n crisis, the most severe complication, causes death from circulatory collapse due to marked pooling of blood within the spleen. Th is is particularly common in infants under 2 years of age. 144 Acute infection is a com mon precipitating factor. At autopsy the organs are pale except for the spleen, which is enlarged and engorged. Sickled cells in capillaries may be visualized at microscopy, but sickling as such does not necessarily imply that it has occurred ante-mortem. 144 Purulent meningitis, cerebral infarction, cardiomegaly, splenic infarction and bone mar row hyperplasia are other auto psy findings. In the USA the peak incidence of death was found to be between one and three years and the major precipitating event was infection. 145 The causative agent most commonly isolated was Streptococcus pneumoniae. Pneumococcal septi caemia in childhood is observed less frequently because of the widespread use of immunization and antibiotics. 143 The major cause of death in the second decade is a cerebrovascu lar accident. Other causes of death include acute chest syn drome secondary to pUlmonary vasc ular occlusive disease,J46 a condition that tends to affect older subjects and may lead to chronic lung disease and pulmonary hypertension.

HAEMORRHAGE AS A CAUSE OF SUDDEN DEATH Haemorrhage produces death through mass effect and dis tOltion of vital structures (intracra niai), asphyxia (lung) or exsanguination (gastrointestinal or intraperitoneal).

Sources of intracranial ha emorrhage have been dis cussed earlier. One study l5 found 13 out of 169 sudden deaths to be primarily due to haemorrhage; these were mainly intra cra nial haemorrhage and usually secondary to an arteriovenous malformation. One death followed rup ture of a tubal pregnancy. The aetiology of pulmonary haemorrhage has been out lined by Cutz l47 and, broadly, may be separated into pri mary idiopathic pulmonary haemosiderosis and second ary pulmonary ha emorrhage. The latter includes immunolog i cal causes and vascular, infectious and bleeding disorders. Idiopathic pulmon ary haemosiderosis has been recognized as a cause of sudden death.lo Gastrointestinal sources of haemorrhage include oesophageal varices, peptic ulceration and vascular malformations.

RESPIRATORY CAUSES OF SUDDEN DEATH Abnormalities of the Trachea Tracheomalacia may be congenital or acquired. The con genital type is exceedingly rare,148 and cases have been reported in association with Larsen's syndrome, pulmonary vascu lar sling, bronchopulmonary dysplasia and tracheo oesophageal atresia. Tracheal collapse with life-threatening airflow obstruction is a recognized complication following repair of tracheo-oesophageal fistula. 149

Acute Epiglottitis Acute ep iglottitis, an acute life-threatenin g condition, is one of the most serious manifestations of infection with Haemophilus injluenzae type b. The clinical diagnostic cri teria are a red swollen epiglottis (Fig. 12.16), inspiratory stridor or difficulties with swallowing and pyrexia. 150 Chil dren are most commonly affected, but the case fatality is lo w in all age groupS.1 50, 151 Trollfors et ali SO reported six childhood deaths in their series of 485 children. Four died at home or were dead on arrival in hospital. The other two arrived in hospital deeply comatosed, With current immu ni zation schedules, the incidence of acute epiglottis in the Western world may be expected to decrease sharp ly.

Retropharyngeal Abscess Retrophary ngeal abscess is most commonly reported in children less than J years of age. Clinical features include fever, neck swelling, stridor and pharyngeal swelling. In one series about half of the patients were less t han 12 months old, one-third were less than J months of age and three patients presented in the neonatal period. Preceding upper respiratory infection was present in 45 per cent of

Respiratory causes of sudden death I

Figure 12.16 Marked reddening and swelling of the epiglottis in a child whose death was due to acute epiglottitis. patients. 152 Clinical diagnosis can be difficult in infants and young children as the onset of infection may be insid ious with few signs and symptoms. 153 The condition causes acute upper airways obstruction . Stridor is unlikely in children over J years of age. Two . 152 Inone 0 f deaths were reported among t he J 1 patients. these (a J-month-old baby) the diagnosis was made at autopsy. Another mechanism of death in patients with retropharyngeal abscess is rupture of the abscess. leading to pneumonia and haemorrhage. A useful diagnostic method in life and at autopsy is a lateral radiograph of the neck to demonstrate the increased depth of the retropharyngeal space. Other important radio logical features are a visible fluid level in the abscess cav ity or gas in soft tissues. The bacteriology of retropharyngeal abscess has been weLl documented and includes mixed aerobic and anaero bic infections;153.154 others l52 have reported a mixture of Gram-negative bacilli and anaerob es, although Staphylo coccus aureus was the most common single organism iso lated. Three children had pure isolates of Klebsiella.

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Figure 12.17 A large amount of acute inflammatory exudate and necrotic slough are seen in the lumen of the trachea from a child who died from bacterial tracheitis.

cases. Parainfluenza virus (I, 2 and J) is the most common preceding viral pathogen. 155 Clinical presentation is characterized by fever, barking cough, hoarsness, shortness of breath, cyanosis, stridor and respiratory distress. 156The epiglottis is noted to be normal but the trachea contains copious purulent secretions (Fig. 12.17). Complications included pneumonia, septic shock, adult-type . . 156 respiratory distress syndrome and tOXIC shock syndrome. Rarely a pseudomembrane extends to involve the whole tra , cheobronchial tree, and the oesophagus an d stomac I1. 157 . II y at ns . k . 158 Children with Down's syndrome are especla In a review of 110 patients,155 the mean age was 54 months, the majority being less than J years of age. Males were more often affected than females . More than 80 per cent of patients required endotracheal intubation and res piratory support. Cardiopulmonary arrest occurred in IJ pat ients, four of whom died. Corynebacterium diphtheriae rarely causes tracheitis in the absence of marked supraglottic involvement.

Bacterial Tracheitis

Acute Bronchiolitis

Bacterial infection of the trachea is usually superimposed on preceding viral infection. Staphylococcus aureus and Haemophilus influenzae are responsible for the majority of

Bronchiolitis is an infection of the lower respiratory tract caused by one of a number of different viruses. It is prima rilya clinical diagnosis 159 and the clinical picture is typified

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and become progressively narrowed and obstructed by sub mucosal oedema and mucus plugs. Air trapping and lobular collapse ensue. 160 The presence of RSV can be determined by viral culture or commercially available methods such as enzyme-linked immunosorbent assay (ELISA), immunofluorescent anti body and enzyme immunoassay tests. The immunofluores cent technique is more sensitive and specific than viral cuI ture. 159

Pulmonary Veno-Occlusive Disease This is a rare and usually fatal condition. 165 The aetiology is unknown. The clinical picture is inconsistent, but patients usually present with progressive or exertional dys pneoa. Sudden infant death has been reported. 166 Histolog ically, the pulmonary veins show total or partial occlusion by intimal fibrosis with or without recanalization. Fresh thrombi may be superimposed. The veins are not uniformly involved and some may be normal. 165 Secondary changes may be observed in pulmonary arteries.

Pulmonary Arterial Hypertension Figure 12.18

Microscopic view showing intraluminal inflammatory

exudate and peribronchiolar inflammation in an infant who died from acute bronchiolitis due to respiratory syncytial virus infection.

by acute wheezing following an upper respiratory illness. Hyperinflation is the most frequently observed radiological abnormality. Respiratory syncytial virus (RSV) is by far the most com monly isolated pathogen. Less common agents include parainfluenza viruses types I and 3, adenovirus, rhinovirus, and Mycoplasma pneumoniae. RSV is a major cause of the disease in infants, whereas the other agents tend to affect older children. '59 The mortality from RSV bronchiolitis in infants who are otherwise healthy is less than one per cent. 160 Some infants are at greater risk of severe or fatal RSV infection, and these include premature infants l61 and those with congenital heart disease, 162 bronchopulmonary dysplasia, 160.1 63 immune defi ciencyl 64 and pulmonary hypertension. 160 Life-threatening complications of RSV bronchiolitis include supraventricular tachycardia and pneumothorax. 159 RSV replicates in epithelial cells. 159 Epithelial necrosis with cilial destruction is the earliest microscopic change and, subsequently, an inflammatory infiltrate composed of lymphocytes, plasma cells and macrophages invades the peribronchial spaces (Fig. 12.18). Airway swelling, slough ing of necrotic debris, loss of cilia and increased mucus pro duction predispose to luminal obstruction. Bronchioles with a diameter ranging from 300/.Lm to 7 5 ~.m are affected, 160

Severe primary or secondary pUlmonary vascular obstruc tive disease is an important cause of sudden death. I ,59 Eisenmenger's pathophysiology is secondary to a large underlying shunt, usually a ventricular septal defect, reversed patent ductus, atrioventricular canal or secundum type atrial septal defect. The age at death spans the first decade of life, but sudden death resulting from Eisen menger's syndrome tends to occur in older children and adolescents. A large number of primary pulmonary dis orders may also lead to pulmonary arterial hypertension .29

EPILEPSY AND SUDDEN DEATH A shorter lifespan among epileptics compared with the gen eral population is well recognized. 167,1 68 Status epilepticus, which is a life-threatening condition, is reported to occur in some 16-24 per cent of children with epilepsy. 169 The risk of death in status epilepticus is directly related to the speed with which the seizure is controlled. 17o Sudden unexpected deaths in epilepsy, in the absence of continuous fitting, take longer to recognize. 170 Such deaths are referred to as sudden unexpected death due to epilepsy (SUDEP) and may be related to the underlying disorder or to the effect of earlier seizures. The majority of these deaths are unwitnessed, 171 and victims are often found in bed. 20,1 67,170 Most deaths are seizure related and no gross or microscopic pathology at autopsy are appar ent, pulmonary oedema and organ congestion usually being the only findings. The underlying pathophysiology of these

Diabetes mellitus I

deaths is uncertain, but proposed mechanisms involve auto nomically related cardiac arrthymias l67 and ictal apnoea .J72 Poor seizure control and poor compliance with an tiepileptic therapy do not ap pear to be significant factors in SUDEP. 173 A toxico logy screen should fonn pa rt of the au topsy proto col and the heart should be examined in detai l. A serum dmg level lower tha n the therapeutic ran ge do es not necessari ly imply fa ilure of compliance, and sh ould not be in terpre ted by the pathol ogist as a factor in the cause of death. 174 Moreover, the relevance of post-mortem blood lev els of anticonvulsants many hours after death is unclear, as so me degrade more rapidly than others.1 6S The possib ility of adverse cardiovascular effects of carbamazipine in SUDEP in children cannot be ignored. 175 When evidence su ggestive of a seizu re is found, for example a bitten tongue, limb injuries or an empty bladder, this sh ould be record ed. However, should this evidence be absent, a seizure canno t be excluded. It is recommended that when children are fou n d wi th thei r head immersed in water, de ath should be recorded as ep ilepsy- rel ated death, rather than SUDEP. Card iac arrhythmias rarely give ris e to 'epilepsy',1 76. 177 and death in such cases may be erron eously attributed . A prolonged QT interval may be responsible and au topsy examination is unlikely to r eveal any abnorm ali ty.

DEATHS FROM ACUTE ASTHMA Asthma is a common disease and, des pite advances in tbe treatment, there is still a hig b ra te of mortality and morbid ity amon g children. Deaths from as th ma are usually as a result of prolonged attacks tha t fail to respond to conve n tional measures, status asthmaticus. Sudden unexp ected death is a lso recognized but occurs less freq uen tly.17B Zach an d Karner l79 reported sudd en deaths in two gi rls, one aged 14 years and one aged 9 years, receiving anti asthmatic medication. In both cases the gi rls ' condition was regarded as moderately severe and well stab ilized. These deaths might be explained by inappropriate percep tion of the severity of the attack by the p atie nt. Of 30 childhood asthma-related deaths reviewed by Car swell,l so the mean age at death was 8.5 years; 19 died at home or in transit to hospital and 11 died in hospita l. One child died within one hour of the sta rt of the attack; three died less than 12 hours after the start and seven died after more than 12 hours. Deaths occurred mainly at night or in th e evening. Only 12 patients in this stud y we re known to be receiving prophylaxis. Unexpected death in asthma patients is especia ll y pro nounced in adolescent an d preadol escent years, and may be related to treatment non-use/abuse, which is ren owned to occur at this age. lSI The increased frequ en cy of deaths from asthma at night or in the early morning has been lin ked to diurnal va ria tion in airflow limitation. ls2 Risk factors for sudden death include the occurrence of previous

243

life- threatenin g asthmatic episodes, hospital admissions for as thm a in the year preceding death, poor access to medical ca re, inadequate medica l ma nagement a nd psy chological and psychosocial problems. IS} Previous stero id treatment, by suppressing the ad ren a l axis, m ay lead to adren al insufficiency and a pred isposition to unexp ected de ath. Recognized mechanisms of death are severe asphyxia du e to airflow restriction IS4 or cardiac arrhythmia from myocardial irri ta bility secondalY to excessive use of ,B2 an tag onists. Hypokalaemia, which may be partly expl ained by ~ 2 antagonists, can cause cardia c a rrhythmia or gene r ali zed muscle weakness, co ntributing to sudden dea th. 135 Life-threa tenin g eve nts are includ ed among the adverse effects of aminophylline. IS) The hi gh mortali ty from asthma in t he 1960s was attrib uted to the excessive use of press urized beta ago nist aerosols, the so-called 'aeroso l hy pothesis'. ls6 Whilst the debate concerning the role of th ese aerosols con tinues, it is difficult to discount fa ilure to promptly and adequatel y treat the asthmatic attack in su ch cases. It has been ques ti oned whether lun g fun ction in such cases is ever normal shortly befor e the fatal attack JB2 Apart from abrupt airway narrowing and medication related deaths, an imp ort ant factor may be u nsuspected pulmonary pathology. lSI Among 13 unexpected asthma deaths in subjects aged between 9 and 19 years, Kravis and Kolski lSI id entified a cause in five cases: pneumothoraces, histiocytic bronchopneumonia, iso lati on of Kl ebsiella pneumoniae, eosinophilic pn eumonia and foc al bronchio litis obliterans. Macroscopic fi n din gs in acute deaths from asthma are bulky, hyperinflated lungs, surgical emph ysema and, rarely, pneumothorax. Microsco py shows intraluminal bronchial and brochiol a r mucinous plu gs, epithelial basement mem brane th ickening, peribronchial smooth muscle hypertro phy, mucus gland hyperpl as ia a nd submucosal cellular infiltration, often with large numbers of eosinophils. 17s Asthmatics are also at increased risk of developing severe or fa tal anap hyl ax is,14 1.142 and this possibility sh ould be considered in the event of sudden death in a patient who suffers from asthma. Thi s is especially relevan t as acu te ana phyla xis may present cl inically as respiratory distress. Mea surement of the semm tryptase level may assist in making the distinction.

DIABETES MELLITUS Despi te modern treatment, in sulin-depe ndent diabetes mel litus (IDDM) in childhood still carries Significant morta l ity.IB7·IBB Most deaths are attributable to metabolic complications, and those related to diabetic ke toa cidosis a re most common, foll owed by hypog lycaemia. IB9 Sudden unexpected death is reported in cases of di abeti c keto ac i dosis,190 and the a dol escent age group is mostly affec ted .

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Cerebral oedema is an important comp li cation in such cases and carries a poor prognosis. 191 After death , the blood glu cose is raised and the urine contains ketones, but ketones may be absent in the aketotic form of diabetic coma. Post-mortem determination of blood glucose is unreli able. 190 The presence of glucose in the urine may also be misleading as glucose may have been administered intra venously. The site of blood sampling at autopsy has an important influence on the blood glucose level. 192 Thus, samples taken from the right side of the heart often show sp uriously high gl ucose levels as a result of glycogenolysis , espec ially if death is accompanied by an 'alarm' reaction or cardiac massage is performed . Sampling from the periph eral vein, by contrast, often shows a glucose level that is spuriously low due to continuing glycolysis after death. Glucose in the vitreous can be more usefully meas ured, 190.192 but the level decreases rapidly after death. So lon g as the sample has been taken peri mortem into a fluo ride tube, this w ill reflect blood glucose level s at that time and a normal glucose level should exclude hypoglycaemia providing, of course, that the patient has not received glu cose infusion prior to admission. 193 High levels of vitreous or peripheral venous glucose probably do indicate uncontrolled diabetes, especially if concentrations of ketone bodies in the blood or urine are also raised. Measurement of glycated haemoglobin has been suggested as a more reliable indicator. 194 Absence of insulin in ante-mortem blood carries more weight than in a post-mortem sample; by contrast, raised insulin values in post-mortem blood are useful in excluding diabetic ketoac idosis. 190 Histology of the pancreas may provide useful informa tion providing the post-mortem interval is short and a utolysis is minimal. 195 Changes include acinar atrophy, reduction in the number and size of Langerhans islets, insulitis, distortion of islet architecture and histochemical demonstration of a reduced number of insulin-producing B cells. 195 Glycogen may be increased in the renal tubular epithelium (Armani-Epstein nephropathy), but this is not a constant feature. Othe r histo log ical findings are microvesic ular fatty change of the liver and vacuolization of hepatic nuclei; these are, however, non-specific and may be found in other conditions. The 'dead in bed syndrome' constitutes a puzzling group among patients with IDDM. The subjects are without clini cal evidence of late complications. They are usually on insulin and there is often a history of one or more noctur nal hypoglycaemic attacks in the previo us 6 months. 196 They are generally observed to be in good health on the preceding day and are found undisturbed in bed the fol lowing morning. 196 ,197 Children and young adults account for some six per cent of all such deaths under the age of 40 years. The most likely cause is thou ght to be hypogly caemia with associated events such as ca rdi ac a rrhyth mia 198 or respiratory depression. 196 Hypoglycaemia is difficult to confirm and, as the post-mortem often does not

reveal a cause, the diagnosis is usually inferred from t he clinical history.

GENETIC IVIETABOLIC DISORDERS Factors that should prompt consideration of genetiC meta bolic disease in cases of sudden death are parental consan guinity, maternal HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, previo us Reye-like ill ness or infant deaths in the family (from known genetic metabolic disease or unex plained), a previous acute life threatening even t (near-miss cot death), fasting or recur rent hypo g lycae mia, neonatal hypotonia, dysmorphism, en la rgement of the live r and/or spleen. A pale (fatty) liver or hepatic fibrosis, cardiomegaly and severe brain oedema are important markers of metabolic disease at autopsy. The possible metabolic causes of sudden death in the paediatric group are wide-ranging. 199

Mitochondrial Abnormalities These comprise defects of fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS). A Reye-like illness or sudden death is exceptionally reported in association with defects of OXPHOS. In defects of OXPHOS abnormalities are likely to involve a single organ or several systems simulta neously. A diagrammatic scheme of intramitrochondrial ~ -oxidation of fatty acids an d its interrelationship with the respiratory chain complex is shown in Fig. 12.19. 200

FAm ACID OXIDATI ON DEFECTS Enzymes that have been associated with sudden death are shown in Table 12.2. All of these inborn errors are inherited as an autosomal recessive trait. Very long-chain acyl coen zyme A dehydroge nase (VLCAD) deficiency usually presents in early infancy with hypoglycaemia, recurrent vomiting, liver dysfunction, cardiomegaly and a tendency to cardiac arrest.200.201 Presentation as sudden infant death is well rec ognized.202.203 Compared with the other defects, VLCAD is more likely to be associated with cardiomegaly, although sudden death and severe illness in the neonatal period have been reported. 204 Only a few patients with short-chain acyl CoA (SCAD) deficiency are recorded, 202 and its association with sudden death is unclear. 203 Primary carnitine defici ency and carnitine palmitoyl transferase type II (CPT II) deficiency often present with cardiomyopathy, whereas carnitine palmitoyltransferase type I (CPT I) deficiency usually presents with a Reye-like illness, but occasionally cardiac arrhythmia occurs in the neonatal period. 205 Fat oxidation is impaired as the trans fer of long-chain fatty acids across the mitochondrial membrane is dependent on carnitine transporter and carni tine palmitoyltransferase. 202

Genetic metabolic disorders I

245

Long-chain fatty acid

1

Ligase

acyl-CoA

1

Carnitine palmitavl transferases I and /I Carnitine aeVI-earnitine translaease

SCAD, MCAD vLCAD

Enavl-CoA hvdratase -I :lJ

3-hydroxyacyl-CoA : NAD+

~

"

C Z

g 3-Hvdroxvaevl-CoA dehvdrogenose

NADH+H + 1

o z

,:t> m Z

N

-

other 10%

24 hours, or died

without waking Andersson et al 2003 40

W Swede n

All ages,

All grades or fatal

Peak incidence

All ages:

Morta lity for seve re

and

lO-year

TBI, ide ntified from

0- 9 years

Fal l at same level

TBI ha s redu ced from

retrospecti ve

age band s

AEtE discharge register

0-9 years 35%

310/0, fall from height

40% in early 1980s

and death registers

10-19 years 20%

27%, MVC 160/0, hi t

to - 10% in 1999

ICD 9 cod es 850-854

Overall, 2.50/0

by object 15

328 I

8 9

to

11

12

13

14 15

16 17 18 19 20

21

22

23

Heat-induced injury or death

Istre GR, McCoy MA, Osborn L et al. Deaths and injuri es from hou se fires. N Engl } Nled 2001; 344: 1911-16. McLoughlin E, Marchione M, Han ger L et al. Smoke detecto r legislation: its effects on owner-occupier homes. Am } Publ Health 1985; 75:858-62. Ahrens M. US Experience with Smoke Alarms and Other Fire Alanns. Atlanta, GA: Quincy [MA) National fire Protection Associatio n, 2004. Mill er R, Reisinger K, Blatter M, Wu cher F. Pediatric co unselling and subseq uent use of smoke desecraters. Ani J Publ Health 1982; 72 :392-3. Carlson A, Uden G, Karlsson ED. Burns injuries in sma ll children, a population-based study ill Sweden . } Clin Nursing 2006; 15:129-34. Anderson RA, Watso n AA, Harland WA. fire deaths in the Glasgow a rea: general cons iderat ions and patho logy. Med Sci Law 1981; 21: 175-83. Napier DH. Haza rdou s materials and· the gases they produce. Med Sci Law 1977; 17 :83-90. Kojima T, Nishiyama Y, Yashiki M, Une I. Post mortem formation of carbon monoxide. Forensic Sci Int 198 2; 19: 243-4. Anderson RA, Ha rl a nd WA. Fire deat hs in the Glasgow area: the role of hydrogen cyanide. Med Sci Law 1982 ; 22:35 -40. Hettiaratchy S, Dz iew ulski P. ABC of burns: pathophysiology a nd types of burns. BM} 200 4; 828:1427 -9. Knight B. Burns and sca lds. In Kn ight B [ed.) Forensic Pathology, 2nd ed n. London: Arno ld, 1996, pp. 305- J 7. Weaver AlVI, Himel MHM, Edli ch RF. Immersion scald burns: strate gies for preventio n. J Emerg lVled 1993; 11 :39 7-402. Erdmann T, Felman K, Rivara F et a!. Tap water burn prevention: the effect of legi slati on. Pediatrics 1991: 88:572-7 . Sm ith GA , Knapp Jf, Barnett TM, Shield s BJ. The rockets· red glare, the bomb s bursting in the air : fireworks- related injuries to children. Pediatrics 1996; 98: 1-9. D'Regenio P, Cafaro L, Santon3sras i F, Taggi F et al. Capodanno Senza Danno: the e ffects of an intervention program o n fireworks injuri es in Nap les. Am J Pub' Healtlr 1996; 86:84-6. Walker AR. Emergency department management of house fire burns and carbon monoxid e pOiso ning in chi ldren. Cur Opin Pediatr 1996; 8:239 -42.

24 Wo lf SE, Rose JK, Desai MH et a!. Mortality determinants in massive pediatric burns. An analysis of 103 chil.dren with ;'80% TBSA burns [;'700/0 full thickness). Ann Surg 1997; 225: 554-65, discussion 565-9. 25 Ayoub C, Pfeifer D. Burns as a manifestation of ch ild abuse and neglec t. Alii J Dis Child 1979; 133:910- 14. 26 Sto ne NH , Rinldop L, Humphrey CR et a1. Chi ld abuse by burnin g. Surg Clin North Am 1970; 50:141 9- 24. 27 Showers J, Ga rrison KM. Bu rn abuse; a four -yea r study. J Traumn 1988; 28: 1581 - 3. 28 Hight DW. Bakalar HR , Lloyd J. Inflicted burns in children: recognition and treatment. JAMA 1979; 242:517 - 20. 29 Keen JH, Lend rum J, Wolman B. Inflicted burns and scalds in children. BM} 1975; 4:268-9. 30 Hobbs CJ. When are bum s not accid enta l? Arch Dis Child 1986; 61:357-61. 31 Lenoski IF, Hunter KA. Speciflc patte rn s of inflicted burns injuri es . J Trauma 1977 ; 17:842. 32 Canady JW, Thomps on SA, Bardach J. Oral commissure burns in chi ldren. Plost Recon struct Surg 1996; 9 7:738-44, discu ss ion 745, 74 6-55. 33 Luce E. Electrical burns. Clin Plast Surg 2000; 27:133 - 43. 34 Andronicus M, Oates RK, Peat J et a1. No n-accid enta l burns in children. Bums 1998; 24:552 - 8. 35 Benger JR, McCab e SE. Burns and scalds in pre-school children atte ndin g accident and emergency: accid ent or abuse? Emerg Med J 200 1; 18:172-4. 36 Ga rcia CT, Smit h GA, Cohen DM, Ferna ndez K. Electrica l injuri es in a pediatric emergency depa ltment. A nn Emug IVIed 1995; 26:604-8. 37 Nguyen BH, Mac Kay M, Bailey B, Klassen TP. Epidem iology of electrical- and lightning-related deaths and injuri es amo ng Canad ian ch ildren and you th. Injurv Pre" 2004; 10:122 - 4. 38 Jain S, Bandi V. Electrica l a nd li g htning injuri es. Crit Care Clin 1999; 15:319 - 31. 39 Lee RC. Injury by electrical forces: pathophysiology, manifestations, and thera py. CUlT ?robl Slirg 1997 ; 34:677-764. 40 Rai J, Jeschke MG, Barro w RE , Herndon DN. Electrica l injuries: a 30-year review. J Trauma 1999 ; 46:933 - 6. 41 Bailey B, Gaudreau! t p, Thivierge RL, Turgeon JP. Cardiac mon itoring of children with hou seho ld electrical injuries. Ann Emerg Med 1995; 25:612-17.

I

CHAPTER 16

I

ASPHYXIAL DEATHS IN CHILDREN Anthony Busuttil

Abuse of inhalants (solvent abuse)

Overlaying and wedging

329 330 330 330 330 331 331

Strangulation

331

References

Petechiae Scene of death Traumatic asphyxia in children Entrapment asphyxia Foreign body inhalation Plastic bag asphyxia

The term 'asphyxia' comes from the Greek sphygmos (meaning absence of a pulse) and is applied to pathological unnatural states in which the body is deprived of oxygen while there is a concomitant excess of carbon dioxide, i.e. a hypoxaemia (hypoxia) and hypercarbia (hypercapnoea) together. This may result in loss of consciousness with the coma thus produced leading to death. Children die from mechanical asphyxia in many situations and exhibit simi lar pathological changes that one would expect in an adult dying in a similar situation. In the international classification of diseases, accidents caused by asphyxia are classified under E91O-E913: • E910 = Accidental drowning and submersion. • E911 = Inhalation and ingestion of food causing obstruction of respiratory tract or suffocation. • E912 = Inhalation and ingestion of other object causing obstruction of respiratory tract or suffocation. • E913 = Accidental mechanical suffocation.

PETECHIAE This pathological feature has long been recognized in the forensic context. As a finding of medicolegal import, petechiae were first described by Ambrose Tardieu in 1855. 1 It was, at one stage (and perhaps by many still is),

Hanging by a ligature Drowning and near drowning Imposed airways obstruction Reverse suspension Chemical asphyxia Prevention

332 332 332 333 333 333 333 334

considered to be pathognomonic and an almost sine qua non of asphyxia. These are haemorrhages arsing from tiny blood vessels, probably mostly venules (capillary haemorrhages may be too small to be visible naked eye being 1-2 mm lesions or smaller), which rupture when the pressure within them is increased and the endothelial lining is distended beyond its innate elasticity. Contribution by hypoxaemia is likely in that the vessel wall is also affected by a decrease in oxygen tension, becoming leaky and pennitting the extravasation of red blood cells. These lesions tend to occur at sites where the connective suppot1ing tissue is loose, provided that the pres sure is locally raised in the specific area. 2 Thus an applica tion of a sphygmomanometer cuff at a level sufficient to occlude, selectively, the venous supply for a period will result in petechiae formation distal to the edge of the cuff. Another cause of petechial haemorrhages is a blood clotting problem. A low platelet count from any cause, for example idiopathic thrombocytopenic purpura, aplastic anaemia, or leukaemia, may produce petechiae. Excessive capillary fragility such as Henoch-Schonlein purpura may have a similar effect (see Chapter 4). Petechiae may also be found when there is toxic damage to the endothelium, particularly in association with dissemi nated intravascular coagulopathy, as in coliform and meningococcal septicaemia. In septicaemia, petechiae tend to

330 I

Asphyxial deaths in children

be widespread. They are also found in situations when microembolic phenomena occur, such as fat and air embolism, amniotic fluid embolism and sub-acute bacterial endocarditis. In asphyx ia, these haemorrhages tend to be dis tributed externally above the level of the obstruction and not below the level, and are thus commonly found: on the palpe bral and bulbar conj unctivae ; on the face - mainly around the eyes; behind the ears (pinnae); and on the mucosal sur faces of the lips and nose. In children it is not uncommon to find these haemolThages in a single site only and not neces sarily the eye. 3,4 They may be present over the face a nd ante rior chest wall in still births and in early neonatal deaths of babies who die as a result of acute hypoxic/ischaemic insult, particularly retroplacental haemorrhage (see Fig. 10.10). They also occur naturally in normal children, albeit in sma ll numbers. In a total of 116 children under the age of 1 yea r, who were fully examined in child surveillance clin ics in Newcastle-upon-Tyne, Downes et al fo und that 27.6 per cent of children had one or more petechi ae, 8.6 per cent two or more, and 2.6 per cent had more than two. s Petechiae can also occur if the child has been experienc ing pronounced and recurrent Valsalva manoeuvres, as with coughing (for example pertussis infection , bronchioli tis, vomiting [gastroenteritis], crying, straining, temper tantrums). This may also explain why petechiae may be discovered after active cardiopulmonary resuscitation. 6 They a lso occur interna ll y with any form of hypoxaemia as the final common pathway for death. They are character istic of the sudden infant death syndrome, in which they are found on the thymus, the epicardium and the pleurae. 7 - 9

environmental catastrophes such as earthquakes and gas explosions, will show features above the level of obstruc tion associated with t his condition. Another accidental asphyxial cause of death in yo ung children is being run over at low speed by reversing cars, not infrequently driven by one of the other members of their own family and sometimes in their own driveway. The child's short stature precludes their visibility to the driver with a consequent accidental knocking over of the child who, having a low centre of gravity, will tend to fall below the ve hicle rather than being lifted up and over the car. Many children surv ive this type of insult, provided that the duration of appl ication of the compressive force is not prolonged, the velocity of imp act is low and the weight of the object trapping them is not considerable. 13 - IS Very often they present with features of cerebral anoxia and convulsions. They frequently have visceral injuries and extensive soft tissue crushing injury. Drag marks in the shape of directional scuff abrasions are often found on the body, indicating the direction in which the vehicle has moved over the child's body. Many of these children are yo unger than J years and boys predominate. This matter is a serious public health issue. In Aus tralia, 16 this type of accident acco unts for 8 per ce nt of pae diatric pedestrian fatalities, in New Zealand 10.7 per cent and in the USA 20 per cent. 17 ,18 Ultrasonic transceivers located on the rear bumpers have been introduced as prox imity warning devices.

SCENE OF DEATH

The inquisitive nature of children during play actIVIties may result in their entrapment in objects and spaces from which they are not able to extricate themselves and thus they die as a consequence. Discarded chest freezers, fridges, old safes, large tnmks and suitcases adopted by children as play areas.can cause such problems. Entrapment in the luggage compaliments of cars (car trunks, boots) may have a similar effect. In the latter, there may also be the added effect of heat if the vehicle has been parked in a particularly hot day at sites where the sun is shin ing directly on to it; heat stroke (hypertherm ia) may develop in such cases in addition to asphyxial changes. Such deaths can occur if the outside temperature exceeds 29.5"C. Cars parked in direct sunlight can reach interna l temperatures of 55°C to 78°C when the outside temperature is 27 -38°C. The less well ventilated the space in which the child is trapped, the more likely is it that excessive internal temperatures are reached . This temperature rise occurs within about 15 min utes of co nsta nt exposure to tllis temperature. 19,20

As with aU other deaths it is essential that the death scene is thorou gh ly examined 10 in all cases when asphyxia appears to have been the mode of death. In this respect, if the baby has already been moved it maybe usefu l to seek a reconstruction of the in cident of w here exactly the dead child was found, by using dolls that can be manipulated by the carers in line with their recollection of events. I! These interactions with the family may be very emotionally fraught and have to be carried out with great sensitivity by police officers or others who have been specia lly trained . 12

TRAUMATIC ASPHYXIA IN CHILDREN In this situation the thoracic cavity is transfixed and no respiratolY movements are thus possible. There are classic signs of congestio n above the obstruction, central cyanosis and petechial haem orrha ge formation also above the obstructio n, usually ending at about the level of the clavi cles. Children who are trapped under masonry and other items, for example in explosions, in the course of crowd stampedes, in the course of warfare and as a result of other

ENTRAPMENT ASPHYXIA

FOREIGN BODY INHALATION An aspirated foreign object, which is splid or semisolid, can lodge in the lalynx, trachea or main bronchi of a child. If the

Strangulation I

object is large enough to occlude the airway completely, it will lead to immediate asphyxia by preventing any gaseous exchange in the lungs and death results within minutes. Pas sage of the object beyond the calina may still be quite dan gerous and can cause serious breathing problems; it may also result in death from bronchospasm in those who are susceptible. Common objects include seeds, nuts, bone frag ments, nails and screws, small toys and pins. 2J.22 As the angles of bifurcation of the main stem bronchi are acute, for the first 15 years of life foreign bodies may find their way into either side of the lower airways.23 Once aspi rated, objects may subsequently change position or migrate distally, particularly after spontaneous or external attempts at removal of the object, after thumping on the back of the patient or attempting to make him or her cough or retch. This may cause delayed obstruction. Inhaled vegetable mate rial may swell over subsequent hours or days, and cough, stridor, wheeziness, breathlessness and cyanosis may ensue. Other objects, such as peanuts and other organic foreign bodies, may, in addition, excite an acute inflammatory response with tissue swelling, which makes the level of asphyxia gradually worse; children aged 1-3 years are more at risk and death results at a rate of 0.7 per 100000 per annum in the USA. This is due to the tendency of young children to put everyth ing into their mouths and the way in which they chew food. Because their molars are unerupted they tend to use their incisors; objects a nd fragments of food are then propelled posteriorly, thus exciting a reflex reaction and a tendency to inhalation. 24 ,25

PLASTIC BAG ASPHYXIA In the later 1950s, polythene bags started to be used for packaging and as supermarket carrier bags. It was soon reported that children had died directly as a consequence of these plastic bags being placed over the head, although not necessarily secured around their neck. 26 In most countries, it is now obligatory by law that all polythene bags used for wrapping have holes intrinsically cut into them close to the base to allow air to enter if they are slipped over the head; however, this legislation does not cover such household items such as rubbish bin bags, carrier bags etc., and the role of child carers cannot be overestimated with respect to the prevention of these deaths. The imm ediate cause of death in these deaths was at one time thought to be due to a decreasing oxygen concentra tion within the bag and rebreathing of carbon dioxide, with consequent narcosis and loss of consciousness. Physical obstruction of the nose and mouth may also have aided and abetted this mode of death. In addition, it was pro posed that the bag becam e electrostatically charged and adhered to the face, aided by condensation of water vapour from the expired air. However, as there is a dearth of typi cal asphyxial features and the persons concerned looked pale and placid, it was postulated that other phenomena

331

were at play. Knight 27 suggested an overstimulation of the sympathetic nervous system (resulting in arrhythmias, par ticularly ventricular fibrillation) caused death. In some of these cases in older children, a gas or a vapour, for example solvent vapour, may have been intro duced into the polythene bag and this may also have influ enced directly the mode of death.

OVERLAYING AND WEDGING Overlaying is the accidental death of a child by smothering resulting from a larger individual sleeping on top of the baby in the course of deep sleep or sleep induced by extraneous intoxication . This has been a well documented condition since biblical times 28 and tended to be much commoner in Victorian times 29 when parents in a state of inebriation may have taken to bed a large number of their children. 3o This hazard is greatest in infants below the age of 5 months but can occur in children of up to 2 years of age. 3J ,32 The rolling over by the adult to co me to lie on top of the child exerts pressure on the child 's face against bedding, the mattress or into the body of the sleeping adult or a co-sleeping older child. Owing to the pressure being exerted on the child's chest, he or she is unable to cry out and attract attention. Some of these babies show no pertinent clinical signs, often not even petechiae. 33 Some babies show the presence of contusions and abrasions, as well as an unusual distribution of the lividity demonstrati ng the points of compression. Indeed, it is stated that if a child who appears to have died of overlaying shows other exter nal blunt force injuries, it is likely that the child has been the subject of non-accidental injury.34,35 In wedging, the child may be wedged by the bed's co-occupants against a wall, between the mattress and the wall, the bed frame or an adjacent piece of bedroom furniture, the cot sides, railing in the cot sides, the head- or footboard of the bed, other co-sleepers including other children etc., with similar consequences. 36,37 Another hazard has been associ ated with co-sleeping on waterbeds. Kirchne.-J7 identified 515 such deaths in children below the age of 2 years during a 7 year period. These included 121 deaths due to overlaying by a parent, sibling or by other adult - with 77 per cent of the deaths involving children younger than 3 months; 394 deaths due to wedging in beds - 296 on regular ad ult beds, 79 on adult waterbeds - with onJy two involving previous alcohol or drug abuse, 10 on adult day beds, nine in adult-sized beds fitted with bed rails. 38 The larger the number of persons occu pying the beds and the higher the weight of the occupants, the greater is the risk involved. Unsafe sleeping environments for babies are further discussed in Chapter 11.

STRANGULATION Non-intentional, accidental self-sJrangulation of young children with loose wires, cords and other potential ligatures

332 I


found commonly around the house and often in close proximity to their beds are well documented. 39 - 4 ! Entangle ment in such cords was responsible for 14.3 per cent of Amer ican childhood deaths. Other causes were plastic bags, bedding (non-plastic), cords of blinds or curtains, cords by which dummy teats (pacifiers) were attached to them and other types of cord. 32 An intravenous tubing set was also reported as hav ing caused such a fatality in a I-month-old boy and a near fatality in an 8.S-month-old boy,42 and the wiring of an apnoea monitor, which was non-fatal, in another baby.43

HANGING BY A LIGATURE Deaths by hanging in children below the age of 14 years are uncommon. Much of the published literature relates to individual case reports, with no epidemiological studies being undertaken. 44 - 46 Cases usually occur against a back ground of unhappiness or frank depression. A history of poor achievement at school, parental and peer bullying and similar adverse effects come to light after death when a psychological review is carried out. There may have been previous attempts at self-harm. Autoerotic unintentional deaths from suspension have been reported in children aged 9 years and above. 47 - 49

the low oxygen tension causing endothelial cellular dam age and hyperpermeabili ty with leakage of body fluids into the extracellular space. 51 Hyponatraemia may also develop if large quantities of fresh water are swallowed or if the syndrome of inappropriate antidiuretic hormone secretion occurs. Inhalation of 13 mL/kg of fluid can result in signifi cantly impaired gas exchange. Fresh water, being hypo tonic, damages type 2 pneumocytes and causes a disruption of alveolar surfactant. Sea water draws fluid from the blood into the alveoli and thus dilutes surfactant, resulting in lower residual pulmonary functional capacity and pulmonary oedema, with development of an acute res piratory distress syndrome. There may also be plugging of small airways by debris, which increases airway resistance. Release of inflammatory chemical mediators from the lungs leads to local vasocon striction. Biochemical changes may lead to cardiac dys rhythmia or asystole due to hypoxaemia. There may also be metabolic acidosis and acute pulmonary coextension. In the USA, for each death from drowning (about 1500 children per annum) an additional four hospital admissions per drowning death occur after submersion incidents. 52 ,53 Drowning and near drowning are further discussed in Chapter 18.

DROWNING AND NEAR DROWNING IMPOSED AIRWAYS OBSTRUCTION Drowning is defined as death from asphyxia within 24 hours of submersion in water. Near-drowning refers to sur vival for 24 hours after a submersion episode. Drowning by definition is fatal but near drowning may also be fatal. 50 Drowning in children is often classified according to the temperature of the water into which immersion has taken place: warm-water drowning at temperatures greater than or equal to 20°C, cold-water drowning in temperatures less than 20°C, and very cold-water drowning when the tem perature is less than or equal to 5°C. When a person is submerged in water and attempts to breathe, he or she may inhale or aspirate water into his or her airways, and laryngospasm may develop, thus leading to deceased oxygenation, hypoxaemia and brain death. Vomiting may occur at this time and gastric contents may also be aspirated into the airvvays, further complicating matters. About 10 per cent of persons who drown do not inhale water or gastric contents. In near drowning the cardinal features are those of hypoxaemia of the internal organs. This may affect the brain, but also and perhaps more importantly in the sur vival situation, the lungs. Most individuals will aspirate less than 4 mL/kg of body weight; 11 mL/kg body weight is required for the aspirated fluids to alter the blood volume and about twice this level is needed to alter electrolyte levels in the blood. Thus fresh water has earlier effect than salt water. In most patients who survive, hypovolaemia is a frequent finding owing to

One form of child abuse that has been shown to occur under the age of I year is for the parent, usually the mother or another carer, to obstruct the mouth with a soft object such as a pillow, clothing or by pressure against her breast or in some other way. The child does not seem to struggle too much or too ovelily and develops hypoxia and cyanosis; he or she may also demonstrate convulsions due to cerebral hypoxia and, eventually, a respiratOlY and cardiac arrest. This may occur when a mother with psychosocial problems is attempting to attract attention to herself, formerly referred to as Munchausen's syndrome by proxy. Coveli video surveillance has been used to document such abuse, with a strong debate as whether this is ethical and legal. 54 Whether the end (namely convincing the Crim inal Court of the abuse by the compelling evidence of a video) justifies the means is dubious in the mind of many of the professionals involved in such cases. This form of surveillance was first used in 1983 55 and since then several reports of it have appeared. 56 - 62 The method used is to have the child attached to a multifunction polygraph (recording respiratory raster, ECG, EEG, pulse rate, blood pressure) in a cubicle, thereby ensuring that the infant cannot be moved away from the area of surveillance and thus having physiological criteria that can be compared and timed with images recorded on camera. These children present with an aClJte life-threatening event, 'breath holding attacks' or recurrent convulsions.

--

--

---

-----------------------------------

----

Prevention I

It may be extremely difficult to differentiate between a nat ural phenomenon and abuse phenomenon.63 It can be extremely difficult to find any signs of the external airways obstruction, although a very careful search for bruising on the face, on the inside of the lips and cheeks should be made; in the mucosa l sites bruising may be accomp anied by minor abrasions. Internally, the presence of haemosiderin in the lungs, within both alveo lar cells and in the interalveolar septa, is of great significance. In the acute phase there will have been haemorrhage within alveoli and this may give rise to frothy frank ly blood-stained fluid emerging from the nose and mouth.

ABUSE OF INHALANTS (SOLVENT ABUSE) Inhalants, usually hydrocarbons, are breathable chemical vapours that produce mind-alteri ng effects similar to the effect of alcohol consumption or the use of controlled dnlgs. They are an ingredient in many househoJd products, such as agents used in cleaning, decorating, painting (turpentine, white spirit), sta ins, vamishes, g lu es, air fresheners, hair con ditioners, dry cleaning agents, shoe polish, colour markers, na il polish removers, spot removers and degreasers and deodorants, as well as in fuels such as petrol (gasoline), butane and lighter fuel. Anaesthetic agents, such as ether, chloroform, halothane and nitrous oxide, may be used in a similar manner. The so lvents are taken in to the body by: squirting directly into the mouth from cans and canisters, inha ling from bags or an aerosol can, sn iffin g directly from the lid of the container, breathing in directly (huffing) or after application of the substance in a rag or handkerchi ef. Plas tic bags containing the vapour may be placed directl y into the mouth. There are about 1400 compounds that can act in this manner, including nitlites, alcohols and halo genated compounds, in addition to hydrocarbons. Death may occur in a variety of ways: • direct acute toxicity of the brain, leading to respiratory a nd cardiac arrest; • cardiac arrhythmias brought on by the substance inhal ed, followed by cardiac arrest; this may be brought about by sudden SPUltS of muscular activity and release of a bolus of catecholamines, as if the subject while under the influence is chased and made to run away; • suffocation by the item being used to present the vapo ur to the mouth, for example plastic bag or balloon; • vomiting w hile unconscio us from the effects of the inhalants; • suffi xa tion by displaci ng air from the lungs with an irrespirable vapour; • acute parasympathetic stimulation with inhibition if me substances cause irritation and/or cooling of the upper gullet or n asophary nx;

333

• accidents while und er the influence of these substa nces, due to loss of judgement and impairment of other cognitive functions; • burns produced by inadvertent ignition of the inflammable accelerant used; • long-term toxic effects of the solvent on the marrow, liver, kidneys and brain; • chronic respiratory problems due to chronic bronchitis and recurrent inhal ation al or chemical pneumonitis. Note that in some older children, these substances may be used as sexual aid in the course of autoerotic activities. In cases when such abuse is suspected, there may be lit tle to find at autopsy. There may be a rash around the mouth and blisters where the substance had been app lied and produced a solvent degreasing effect on th e skin. The so lve nt may still be appreciable through its smell at autopsy. One lung should be retai ned in a nylon fibre bag to allow 'a ir' to be sampled from it directly from its airways for gas chromatography assay. The blood , the liver and the kidneys can also be assayed toxicologically. Histology may confirm chronic changes in the internal organs particularly the lungs. No petechial haemorrhages are found either internally or externa lly, except in the few instances of suffocation.

REVERSE SUSPENSION This is perhaps a rarity, which may occur in children dur ing play activity when death results from exhaustion of breathing du e to splinting of the diaphragm 64 ,65 by the upwards displacement of abdominal contents. Death occurs slowly from ex haustion of respiratory effort.

CHEMICAL ASPHYXIA This term is applied to situations when irrespirable gases find their way into the child's environment. For example, carbon monoxide in fires and from exhaust fumes (in closed garages) and from charcoal fires (barbecues) in an enclosed space, chlorine escaping from swimming pools, hydrogen sulphide and methane from refuse tips, old mines and slurry pits are among the gases that can cause death after inha latio n. These events usu ally involve older, active children and, more frequently, boys, in common with many environm ental mishaps.

PREVENTION As incidents involving asphyxia are common, public health offiCials, community doctors, midwives and health visitors have been involved in several programmes aimed at alerting parents to the dangers of asp hyxia. 66 In severely

334 I


disab.led children accidental asphyxial deaths are more common. 57 In the neonate and in young children below the age of 12 months sleeping practices also have to be care fully scrutinized to enquire that they are not potentially dan gerous to the child. 6B - 72 Co-sleeping in particular should be viewed with some discretion, particularly if the parents indulge in smoking and drinking of alcohol. 73 75

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2 3 4 5

6 7

8 9

10 II

12

13 14 15 16 17

18

19 20 21 22 23

Tardieu A. Etude medico -lega le sur les sev ices et ma uva is tra itmen ts exe rces sur des enfants. Ann Hyg Publ tvled Legale 1860; 13 :36 1-98. Luke JL. Conjunctival petechiae. IV Eng/} iVIed 1971 ; 28 4:1101. Rao VJ , Wetli CW The foren sic sig nifica nce of co njun ctiva l petechiae. Am } Forensic ivfed Pathol 1986; 9:32 4. Jaffe FA. Petechial haemorrha ges. Am } Forensic iVIed Patl10l 1994 ; 15:203 -7. Dow nes AJ, Crossland OS , Mell o n AF. Preva lence and distribution of petechiae in well babies. Arch Dis Child 2002; 86:291-2. Hood I, Ryan 0 , Spitz WU. Resuscitation and petec hiae. Am } Forensic iVIed Pat/101 1988; 9:35-7. Beckwith JB. Intrathoracic petechial hemorrhages; a clue to the mechanism of death in SlOS. Ann N Y Acad Sci 1988; 533:37-47. Krous HF, Jordan J. A necro psy study of distribution of petechiae in non-SlOS. Arch Pathol Lab Med 1984; 108:75- 6. Kleeman WJ, Wiechern V, Schuck M, Troger HD . Intrathoracic and subconjunctival petec hi ae in SlOS . Forel1sic Sci lilt 1995; 72:49-52. Bass M, Kravath RE, Gla ss L. Death-scene inves ti ga ti on in sudden infant death. N Engl} Nled 1986; 315 : JOO-5. Iyasu I, Hanzlich R, Rowl ey 0, Willin ger M. Proceedings of 'Workshop on Guid elin es for Scene Investigat ion of SlO S'. } Forensic Sci 1994; 39 :11 26 - 36. CDC. Guid elines for dea th scene investigation of sudde n, unexplained infant deaths: recommenda ti ons of th e interagency pane l on SlOS. MMWR 1996; 45:RR-IO. Haller JA, Donahoo JS. Traumatic asphyxia in ch ildren: pathophysiology and management.} Trauma 1971; 11 :453-7. Campb ell-Hewson G, Egleston CV, Cope AR. Traumatic asphyxia in children. Accidel1t El11 erg iVIed 1997; 14(1):47-9. Sarihan H, Abes M, Akyazici R et a!. Traumatic asphyx ia in children. Cardiovasc Surg 199 7; 38:93 -5. Holland AJA, Liang RWY, Sing h SJ et al. Driveway motor ve hi cle injuri es in children. iVI}A 2000; 173: 192 - 5. Brison RJ, Wicklund K, Mueller BA. Fata l pedestrian injuries to yo un g children: a differe nt patte rn of injury. Am } Public Health 1988; 78 :79 3- 5. Roberts I, Norto n R, J ackson R. Driveway-related c hild pedestrian injuries; a case control study. Pediatrics 1995; 95:405-8. Sumra ll RE, Petty CS, Holman W. Temperature in closed auto mob iles in hot weather. Forensic Sci Gazette 1976; 7:7-8. Surpure J. Heat-rela ted illness a nd the a uto mob il e. Ann Em erg iVIed 1982; It :263-5. McGuirt WF, Ho lmes HD, Feehs R et a l. Tracheo-bron c hial fo reign bodies. Lm)'ngoscope 1988; 98:615- 18. Weiisberg D, Sc hwartz I. Foreign bodies in the tracheo bronchial tree. Chest 190 7 ; 1: 730 - 3. Cleveland RH. Symmetry of bronchia l angles in chi ldren. Radiology 1979; 11 3:89 - 93.

24 Byard RW. Mec han isms of death in in fa nts a nd young children fol.l.o wing fore ign body ingestion. } Forensic Sci 1996; 41 :438-41. 25 Baharloo F, Veyckemans F, Fra nci s C et al. Tracheo-bronchial fore ign bodies: presentation a nd management in children and adults. Chest 1999; 115 : 1357 - 62. 26 Plast ic bags (Ed itoria l). BM} 1959; 1 :1463-4. 27 Knight B, Sa ukko P. Forensic Pathology, 3rd edn. Oxford: Oxford University Press, 2003 . 28 The Bible, 1 J<jngs Ch . 3 v.19. 29 Templeman C. 258 cases of suffocation of children. Edin Med } 1891; 38:22- 6. 30 Nakam ura S, Wind M, Dane ll o MA. Review of hazards associated w ith chi ldren placed in adult beds. Arch Pediatr Adolesc iVIed 1998; 1 53: 10 19- 23. 3 I Drago DA, Dannenberg Ai. Infant mechan ical suffocation dea th s in the United States 1980-1997. Pediatrics 1999; 15 3: 103 -59. 32 O'Hara M, Harruff R, Smialek J , Fow ler D. Sleep location and infa nt s uffocat io n : how good is the evidence? Pediatrics 2000; 10 :9 15-20. 33 Moore L, Byard RW Path o log ical fInd ings in hang ing and wedgin g deaths in infants and yo un g children. Am } Foren sic

ivIed Pa tl101 199 3; 14 :296- 302. 34 35 36

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Collins K. Death by overlaying and wedg ing: a 15-yea r retrospective study. Am} Foren sic iVIed Patho1200 1; 15 : 155-9. Mitchell E, Kraus HF, Byard RW Pathol ogica l findin gs in ove rl aying.} Clin Forensic iVIed 2002; 9:133 - 5. Byard RW, Beal S, Bourne AJ. Potentially dangerous sleep ing environment and accidental asphyxia in infancy and ea rly ch ildhood. Arch Dis Child 1994; 71 :497-500. Kirchner JT. Deaths associated with small children sleeping in adult beds. Am Acad Fam Phy 2000; March I , www.aaf.org/afp. Nakamura S, Wind M, Danello NA. The pediatric forum: should infants sleep with their parents 7 Arch Pediatr Adolesc ivIed 2000; 154:1171-3. Nixon JW, Kemp AM, Levene S, Sibert JR. Suffocation, choking and strangulation in children in Eng land and Wales; epidemiology and prevention. Arch Dis Child 1995; 72:6 - 10. Rauchschwalbe R, Mann NC. Pediatric wind ow cord strangulations in the United States, 1981-95. }AMA 1997; 72: 1696-8. Sabo RA, Hanigan We, Flessner K et a!. Strangulation injuri es in children.} Trauma 1996; 40:68-72. Garros D, J<jng WJ, Brady-Flyer Bet a!. Strangulation with intravenous tubing; a previously und ec id ed adverse even t in children. Pediatrics 2003; III :732-4. Emery JL, Taylor EM, Carp ente r RG, Wa ite AJ. Apno ea monitors and accidental strangulation. BM} 1992; 304 :11 7. Petruk J, Shiels E, Cummings GE, Francescutti LH, Fatal asphyxiations in ch ildren involving drawstrings in cloth in g. Can Med Assoc} 1996 ; 155: 1417- 19. Bya rd RW, Ma rcopo ul os D et al. Early adolescent suicide; a co mparati ve study. } Clin Forensic Med 2000; 7:6-9. Wyatt J, Wyatt PW, Sq uires T, Busuttil A. Hang ing deaths in children . Am } Foren sic Med Pathol 1998 ; 19 :3 43-6. Feldm a n KW, Simms RJ. Stra ng ulatio n in children: epidemiology a nd clinica l co urse. Pediatrics 1980; 65: 1079-85. Cooke CT, Cadden GA, Hilton JMN. Hanging dea ths in children. Am } Forensic Med Pathol 1989; 10:98- 104. Uva JL. Autoero ti c asphyxiation in the United States. } Foren sic Sci 1995 ; 40:574 - 8 1. Bya rd RW, Lipset J. Drowni ng deaths in tod d lers and pre ambulatory children in South Austra lia. Am} Forensic iVIed Path ol 1999; 20:328-3 2.

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51 Nodlkel JH. Drow ning. N Engl ] Med 1993; 328:253-6. 52 American Academy of Pediatrics Committee on Injury and

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Poison Prevention. Drowning in infants, children and adolescents. Pediatrics 1993; 92 :292-4. Wintemu te GJ. Childhood drowning and near drowning in the United States. Am ] Dis Child 1990; 144:663-9. Byard RH. Covert video surveillance in Munchhausen syndrom e by proxy - ethical comprom ise or esse ntial technique? Med ] Aust 1994; 160 :352-6. Rosen CL. Frost JD, Glaze DG et al. Ch ild abuse and recurrent infant apnea.] Pediatr 1986 ; 109 : 1065- 7. Southall DP, Stebbens VA, Rees SV. Apnoe ic episodes induced by smothering. Two cases identified by covert video surveillance. EM] 1987; 294:1637-41. Samuels MP, McLaughlin W, Jacobson RR. Fo urteen cases of imposed airway obstruction. Arch Dis Child 1992;

67:162-79. 58 Byard RW, Burnell RH. Covel1 video surveillance in

Munchausen syndrome by proxy: ethics compromise or essential technique? Med ] Austr 1994; 160 :352- 4. 59 So uthall DP, Plunkett MCB , Banks MW et al. Covert video recordings of life-threatening child abuse: lessons for child protection. Ped iatrics 1997; 100:73 5-60. 60 Foreman OM, Farsides C. Ethic al use of covert videoing techniques in detecting Muncilausen synd rome by proxy. BM] 1993 ; 307:611-13. 61 Thomas T. Covert video surveill anc e. New Law] 1994; 62

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14: 141-4. 66 Towner E, Errington G. The Epidemiology oj Choking in

Childhood and [l17pli catiollsjo r PrelJentiol1. A report prepared for the Department of Health in London, 2002. 67 Ama nuel B, Byard RW. Accidental asphyxia in severely disabled children. ] Paediatr Child Health 2000 ; 36:66- 8. 61l Beal SM, Byard RW. SIDS in South Australia 1968-97. Part 3: Is bed sharing safer in infants? ] Paediatr Child Health 2000 ; 36:552-4. 69 Byard RW, Beal SM. 'V'-shaped pillows and un safe infant sleeping.] Paed ia rr Child Health 1997; 33:171 - 3. 70 Byard RW, Bourne AJ, Beal SM. Mesh side cots: yet another

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335

potentially dangerous infant sleeping environment. Forensic Sci [l1t 1996 ; 83: 105- 9. Moore L, Bourne AJ, Beal S et at. Unexpected infant death in association with suspended rocking cradles. ] Forensic Med Patho11995; 16 : 177-80. Byard RW, Beal SM. Simpson A et al. Accidental infa nt deaths and stroller prams. Med] At/st 1996; 165:140-1. Byard RW. Is co-sleeping in infancy a desi rab le or dangerous practice? ] Paediatr Child Health 1994; 30: 198 - 9. Byard RW. ls breast feeding in bed always a safe practice? ] Paediatr Child Health 1998; 38:498-9. Scragg R, Mitchel l EA, Taylor A et al. Bed sharing, smok ing and alcohol in the SIDS. BM] 1993; 307: 1312-18.

I

CHAPTER 17

I

ACCIDENTAL INJURIES IN CHILDREN

Anthony Busuttil

Overview of paediatric trauma Bicycle helmets Falls Playground injuries Sports injuries on snow and ice Riding injuries

336 338 339 340 340 341

OVERVIEW OF PAEDIATRIC TRAUMA

Tra uma of children has always been a major public health concern in that a significa nt degree of disability, loss of schoo ling and mortality arise as a consequence. Three major sUlveys that looked at these aspects are: (1) the Canadian Hospital Injury Reporting and Prevention Pro gram (CHIRPp),l based on 16 out of the 750 hospitals in Canada; (2) the Australian National Injury Surveillance and Prevention Program;2 and (3) the programme commis sioned by UNICEF Innocenti Research Centre of Florence) (Table 17.1). The annual hospital health-care spend in the USA accrues to abo ut £5.1 million 4 for injuries incurred by children. In 1971, deaths from injuries in countries that belong to the Organisation for Economic Co-operation and Development (OECD) in the 1- to 14-year age group accounted for about 25 per cent of mortality in chi ldh ood (Table 17.2) . In the 1990s, more than one in three deaths in this age group were the result of injury. This has not changed in any appreciable manner since then. In such assessments of paediatric trauma, recorded sur veys vary in the cut-off point in relation to the ages con sidered. It is often the case in many of the published series that persons up to 18 years of age are considered. This may skew the figures, given the increased activity of adoles cents over the age of 14, a nd the high incidence of injury after the age of 12 years. It is unlikely that children under

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Agricultural injuries Prevention Older children and substance abuse Accidental poisoning Hypersensitivity References

341 341 341 342 342 342

the age of 2 years are involved in many serious accidents, an d any injury below the age of 1 year is sufficiently uncommon that it should always be treated with a mod icum of suspicion .5 A careful match should be attempted in all instances between the findings on medical examination/ investigation and the narrative given by the carers to doc tors as to how the accident occurred. Furthermo re, the for mat and data conventions followed by different countries vary,6 as does the accuracy of data coding.7 In general terms, boys are injured abo ut twice as often as girls,S except in household injuties when girls tend to pre dominate. The difference between sexes increases after infancy and continues through a ll age groups into adoles cence. 9 The largest gro up of injured chi ldren is between the ages of 5 and 9 years, followed by children aged 1-4 years and children aged 10-14 years. Infants under 1 year have the lowest rate. JO The vast majotity of injuries occurred between noon and midnight when children are most likely to be out of the structured schoo l environment. The two most common sites of injuries were the road and home. II Other places included recreation areas, public places, schools 12 - 14 and, less fre quently, farms and workpl aces. Children from deprived backgrounds are more prone to injury. This may be related to a lack of adequate supervision, increased risk-taking and a greater proportion of the ch ild's day spent on the street. 15-18

~

Overview of paediatric trauma I

Table 17.1

337

Mortality (deaths per 700000) from injury: ch ildren aged 7- 74 year53

UK Canada USA New Zealand Australia Mexico Denmark Spain Italy Czech Republi c Portugal Korea

All injuries

Transport

Fire and flames

Falls

Poisoning

Drowning

Firearms

Intentional

Others

6.06 9.68 14.06 13.67 9.53 19.75 8.10 8.12 6.14 11.95 17.76 25.57

2.91 4.33 5.76 6.93 3.37 6.05 3.99 4.02 3.30 4.64 8.65 12.59

0.66 1.01 1.65 0.82 0.68 0.62 0.52 0.30 0.18 0.34 0.6 0.91

0.26 0.20 023 0.58 0.22 1.09 0.13 039 0.51 0.61 0.75 1.18

0.12 0.12 0.17 0.13 0.14 0.55 0.05 0.17 0.12 0.49 0.46 0. 75

0.39 1.26 1.74 1.87 1.97 3.30 1.07 1.12 0.46 2.23 1.34 5.14

0.0 1 0.12 0.4 0.14 0.04 0.35 0.07 0.05 0.03 0.03 0.06 0

0.80 1.45 2.74 1.74 0.85 2.90 0.94 0.33 0.50 1.61 4.23 1.08

0.91 1.19 1.37 1.46 1.26 4.89 1.33 1.74 1.04 2.0 l.67 3.92

From the WHO mortali ty database, with perm ission.

Table 17.2

Mortali ty fram injuries in Organisation for Economic Co-operation and Development (DECO) countries, by age and

gender 1991- 7995, per 700000 af the population

Age (years) 1-4

Boys Girls

21 14

5-9

16 7

10-14

16 7

From the WHO mortality database, with permission.

The use of the term 'accident' to describ e such traumatic episodes is often a misnomer, as few of th ese injuri es are actually due to unpredictable irremedi a bl e ev ents and situ ations; rather they are more often due to interaction with the environment in which children are living and playing, the products that they use and the level of supervisio n t hat they are allocated. Many of these injuries a re preventable and thus the main thrust of the investigation a nd ana lys is of figures from childhood injuries should be in attem pts at prevention. 19-21 There is no simple correlation between mOltality staris tics and non-fatal injury data. 22 FUithermore, the relarive population m ortali ty data are hig her in Eastern Europea n countries. 23 Why this should be so is difficult to determine but, at least in palt, it may be re lated to the different perception of the seriousness of injury a nd a populist fatalistic attitude; there may be a tendency to decry the seriousness of injury combined with Jess willingness to seek medical help for injury until it is too late.

Accident Proneness in Children Intrinsically the behaviour of children is based on curiosity and constant activity. Many paediatricians would class as

abno lmal an inactive, sedentary young child . This combina tion of childhood inquisitiveness, mobility and activity te nds to be impulsive and experimental. This is superimposed on a n obvious backdrop of inex perience and a n inherent imma turi ty of social and intellectual skills to cope wit h adverse situat ions as and w hen they present th emselves. By their very nature, children take risks and are sensation seeking. All of th is compounds their proneness to injury.24 Falls are therefore inevitable. The graspi ng and pulling of objects towards the infant may result in objects being pulled on to the child, and to scalds and burns.25 As the child's territory expands and manual dexterity and p hysical strength improve, play activity becomes more adventuro us and the opportunities for injuries increase. As organized sporting activities are taken up these further raise th e prob ability of injury, be this in organized and team sporting activity - participation in team sports such as rugby, soccer and hockey - or, more simply, in such recreational activiti es as kicking a ball, riding a bicycle or using a sWing. 26 The more v igoro us the sport (e.g. karate, judo, Tae Kwon Do, boxing and skateboarding) the more likely is the occurrence of inju ryY The role of carers in ens uring that the children do not take excessive risks, and indeed to be t here to rescue them from the hazardous situ at ions in w hi ch they find them selves, is essential. When the carers are employed in this capacity by nurseries and schools, there is an ex pectation of a duty of care. Sometimes - indeed , increasingly fre quently - this is called to account in a cou rt of law when this duty is perceived to have been breached. 28 Participa tion in sport also carries with it the possibility and, per haps, in more viol ent sporting activity, a probability, of almost inevitable injury. This willing, wholehearted partic ipation by the child with the sanction of his pa rents, often expressed legally in th e max im volenti non fit iniuria ('to one who is willing, no ha rm is done'), m ay decrease the culpa bility and answerability of the carer when things go wrong

338 I


but it also bears the expectation and responsibility from them that all that can be done to supervise children's activ ities - to decrease the risk, to provide protective clotting and equipment - has been fulfilled in full exercise of their duty of care. 29

Causes and Mechanisms of Injuries Falls are the leading cause of injuries. Among young chil dren these are often from fu rniture, such as cllanging tables, sofas and couches, cribs, beds or fallin g down stairs, pal1ic ularly in walkers,JO during momentary periods of inattention by their carers or because of the activity of older siblings. As toddlers begin to explore, the oppOl1Unity for falls from heights increases; this includes recorded falls down stairs. Less common are falls from balconies, porches or out of windows;Jl these inciden ts are more frequent in warmer climates when children have more open access . Nearly 20 per cent of the children adm itted after falls have fallen 2.5 metres (8 feet) - the height of one storey or more. The next major mechanism of injury is motor vehicle crashes with children as occupa nts. Most crashes involve collisi ons with other vehicles. Only one-quarter of those chil dren injured have been using some kind of protective restraints, such as child safety seats or safety belts. Many unrestrained children were hurled aro und inside the car dur ing a collision or thrown out of the car through windows or doors. Breast-feeding in the car or holding a child in one's lap is dangerous as the child will be unprotected during a crash. Many other children are injured fatally when they walk, cycle or play on the roadway and are struck by motor veh i cles.J2 Thousands of children are killed annua lly on the roads but most of the deaths are incurred when the child is on foot. There is correlation between the number of child hood fatalit ies on the roads and the size of the popUlation of a country : the bigger the child population and the lower the socioecon omic status, the higher is the likelihood that unsu pelvised children are on the road and thus find their ways into the path of moving traffic. This may also be the reason for the disproportionately higher incidence among children of certain ethnic groups.JJ Many of the deaths occur in the urban location at speeds of less than 30 miles per hour and usually within a Sh0l1 distance away from their homes. Most of these deaths occur in the holiday periods and a t other times during the parts of the day w hen the children are not actually at school. Thus more injuries occur in the summer months. The institution of school crossing patrols manned by retired individual s and the training of children in road safety has produced major dividends in terms of reducing co llision-related injuries and deaths amo ng chil dren; the aims have been to teach children to be vigilant and to improve their skills in quickly integrating and assessing movement, relative velocity, distance and depth in relation to moving motor vehicles, along with the inter pretation of road signs. 34 The setting aside of exclusive

cycle tracks in urban areas has also assisted in the decrease of such incidents. J5 ,36 Children are most frequently hit while walking along the side of the street, during play in the street or while darting into or crossing the street. Children are occasionally hit by motor vehicles while bicycling, but they may also be injured when fallin g off their bicycles after hitting objects such as trees, kerbs or walls. Few of those children admitted to trauma units after bicycling-related injuries, were wearing helmets. 37 Other motor vehicle-related injuries involve motorcycles, all-terrain vehicles and recreational vehicles. Children with hearing impairment from any cause, including chronic ot itis media a nd 'glue ear', are more prone to accidents as they may not be aware of vehicles in their vicinity.

Consequences Many injuries occur while a child is engaged in some kind of activity such as nll1ning, playing, climbing or bicycling. Even when the child is in a more station ary position, such as rid ing in a car, the child is part of an activity involving motion and speed. The combined effects of motion, speed and impact can injure many regions of a child's body. Two or more body regions were affected in about one-half of the children. Chil dren typically had multiple injUlies that resulted in several diagnoses: head inj ury is the most frequent diagnosis among children recorded, followe d by fractures to the bones of extremities and torso. The third most frequen t diagnosis is open wounds, mostly lacerations. The severity of injuries is directly linked to how the chi l dren were injured. Children who are injured in motor vehi cle crashes and as pedestrians are more likely to have four or more functional limitations. The force and speed of col lisi ons are factors determining the severity of injuries. Chil dren injured by falls are less seri ously injured and have fewer functional limitations.

BICYCLE HELMETS Experienced, careful bicycle riders crash every 4500 miles on the average. Head injury causes 75 per cent of our 800 plus an nual deaths from bicycle crashes. Medical research shows that a bicycle helmet can prevent 85 per cent of cyclists' head injuries. 38.39 A helmet reduces the peak energy of a sharp impact. This requires a layer of stiff foam to cushion the blow when crushed. Most bicycle helmets do this with the use of expanded polystyrene (EPS), the white picnic cooler fo am. Once crushed, EPS does not recover. Another foam, expanded polypropylene (EPP), does recover but is much less commonly utilized. A stronger EPS called GECET appeared in 1992 and is widely used now and another synthetic foam, expanded polyurethane (EPU), is used in Taiwan as it has a

Falls I

unifonn cell structure and crushes without rebound; it is heavier and requires a manufacturing process that is not environmentally friendly. The spongy foam placed on the inside a helmet is for comfort and fit, not for impact. The helmet must stay on your head even when the head is hit or bumps on to a hard unyielding surface, more than once in a moving traffic incident: usually there is a bump with a ca r first, and then with the road. It thus needs a strong strap and an equally strong fastener. The helm et should sit level on the head and cover as much as possible of its surface contour. Above all, with the strap fastened, one should not be able to get the helmet off your head by any combination of pulling or twisting. If it comes off or slips enough to leave large areas of the head unprotected, the straps must be readjusted otherwise a better-fitting hel met will be requ ired . The strap must feel comfortably snug when riding the cycle. Most helmets made of EPS foam ha ve a thin plastic outer s hell. The shell helps the helmet skid easily on rough pavement to avoid jerking of the neck during such an impact; it also holds the EPS together after the first impact. Some excellent helmets are made by moulding EPS in the shell rather than adding the shell later. Excessive vents in the helmet mean less actual area con tact with the head, which could concentrate force on one point. 'Aero' helmets are not noticeably faster and in a crash the 'tail' could snag or knock the helmet aside. Skinny straps are also less comfortable. Dark helmets are hard for motorists to see. Rigid visors can snag or shatter in a fall. Helmet standards do not address these problems a nd should be reconsidered. There can be little doubt that bicycle helmets have pre vent some of the more serious head injuries and undoubtedly they have saved the lives of young cyclists. 4o - 42 However, it has been observed that some children, particularly older children, need to be objectively convinced that helmet wear ing is indeed not just useful in preventing injUl)' and that the money spent on their purchase rather than other cycl in g clothes and accessories is money well spent. Above all cycle helmets had to be shown not to make their wearers less 'cool' and trendy but vice versa, and also that their use makes the wearers appear more professional. 43 A variety of strategies have been devised worldwide to encourage the purchase and wearing of cell helmets with varying success levels. 44- 47

FALLS All children trip and fall, indeed from the time that initially they stand up on their own two feet. Falls a re more com mon while the muscle tone is not fully developed but become more frequent once aga in when gait allows chil dren to explore farther and when their innate inquisitive ness takes them further afield. Contusions, haematomas, lacerations and abrasions tend to occur at the site of such fa ll s. OccaSionally, if more

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severe force is in volved or in falls from a height, fractured long bones a nd closed head injuries may occur 48 The incidence of injury depends to a major extent on the height from which the fall occurs and also on the terrain that the chi ld lands on - the harder and more compact the latter, the higher is the incidence and severity of injury.49 The height of climbing frames, swings, etc. is another factor involved in injury causation and the height of the fa ll is directly related to the severity of the injuries sus tained by children in playgrounds. Injuries are more likely to occur with equipment that is two 2 metres above the ground ,5o so that reducing the height of swings, monkey bars and other equipment improves safety. Reports of children falling out of windows are all too frequent in the summer. Height off the ground and landing surface are two critical factors in the injuries to children that result from falls. Height is directly related to the speed at wh ich a child falls and the force of impact upon landing. Falls are particularly common among children of p re school age who are developing their balance and learning to walk, climb and run ; however, their physical skill s develop sooner than their abilities to anticipate the conse quences and risks of their actions. Amongst falls from heights, about one-quarter of chil dren fell from w indows. Examples of other falls from heights include falls from roofs, out of trees, from ski lifts, off porches or balconies and down flights of stairs. Even escalator falls have been known to cause serious injuries. 51 The incidence of injuries among children h as a distinct seasonal pattern, with an increase in the warmer months of the year. This is even more so for falls from windows as they are more likely to be open in warmer weather. Tod dlers and pre-school children are particularly vulnerable as they lack the judgement needed for risk assessment an d safety precautions. Falls occurred in th e chi ld's hom e in 96 per cent of the cases. Falls from two- to three-storey win dows were most common (72 per cent), followed by fo ur to five storeys (18 per cent). Only 8 per cent of children admitted to trauma centres fell from firs t-sto rey windows; however, 3 per cent fell from six storeys or more. Head injuries, with or without dam age to other body regions, occur among 65 per cent of the children . A small child 's head is at special risk for injury from a fall because it is disproportionately large and heavy in relation to the rest of the child 's body. Height, rate of fall and the force of impact have combined effects that result in injuries to multiple body regions in about one-half of injured children. The greater the height of the fall, the higher the death rate. Among the children who fell from windows, six storeys or more, 8 per cent died. Among those who fell four to five storeys, 5 per cent died; among those who fell two to three storeys, 2 per cent died. Non e died who fell from one storey. Upon hospital discharge, 73 per cent of the children who fell from windows had no identified functional limitations. For the 21 per cent who had one to' t hree limitations, these were most commonly in bathing, dressing, walking and

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se lF-Feed ing. By contrast, the children with four or more functional limitations at discharge had more difficulties in cogn ition , behaviour speech, vision and hearing, reflecting the severity of head injuries in this group. Among t he chil dren who fell from six or more storeys, 42 per cent had one to three limitatio ns; 8 per cent had four or more limitations. More functional limitations were identified as the height of t he fall increase d; children who fell from four to five storeys had the largest proportion of functional limitations - four or more. Ho wever, because more children died who fell from fi ve storeys or more, there were fewer surv ivors in that group with four or more limitations. Almost one-half (47 per cent) of the falls occurred on playgro unds in recreational areas, one-quarter (25 per cent) occurred at home, and almost one-fifth (19 per cent) occurred on sc hool playgro unds. About 90 per cent of these injuries occurred in falls from playground eq uipment: sw ings, slides, climbers (monkey bars, jun gle gyms or other climbing apparatus) and trampolines. Children fell from dif ferent types of playground equipment depending where the equipment was located. At home, children most often fell from swings or trampolines, whereas at schoo l and in recre ation areas they most often fell from climbing equipment. Children of different ages fell from different types of playground equipment. The youngest children fell most often from slides, whereas older children fell most often from climbing equipment. Seven of the children died in the hospital: six from head injuries and one as a result of a severed sp in al cord. Three of these children fell from slides, two fe ll from sw in gs, o ne fell from monkey bars and one fell from a trampoli ne. Four of the children who died fell from playground equ ip men t at home; the other three fe ll fro m playground equ ip me n t in a recreational area .

PLAYGROUND INJURIES Playground s a re considered as oases from road traffic places w here children can safely enjoy themselves and indeed develop interpersonal, social and team skills. As childhood obesity is bandied around as being of epidem ic proportions, t he impo rtance of play activities cannot be overemphasized. Ho wever, playgrounds - whether at hom e, at schoo l or at rec reational areas - can also be dan gerous. To be safe, all public and private playgrounds must be well designed , we ll mai nta ined a nd used properly. Chil dren need good su pervision , and sho uld be taught how to play safely. Children enjoy experi men tatio n a nd explo ration and will incur risks, w hether calculated or hapha z ard, a nd thus although play areas have to be challenging and inn ovative to keep the ch ildren 's interest, there should also be a backdrop of safety built into playgrounds. Mod ern playgrounds wi ll often h ave eq uipment such as a seesaw, merry- go -round, swings, slide, climbing frame, walking bridge, jungle gym, c hin-up bars, sandbox, spring

rider, monkey bars, overhead ladder, trapeze/trapeze rings, pl ay houses and a maze. Th e scope of many of these items is to assist children to deve lop physical coordination, strength, and flexibility, as well as providing recreation and enjoyment. Common in modern playgrounds are 'play structures' that li nk many different pieces of eq uipment. A little more than one-half of the children injured are boys, with the largest percentage of injured children in the age bracket of between 5 and 9 years 0ld s2 Protective surfaces (suc h as rubber mats, wood mulch, bark or soft sand) of sufficient depth should be installed und er and aro und playground equipment; 53 there is no place for concrete, asphalted s u rface or sto ne slabs. 54 .55 This, togeth er with t he removal of monkey bars from parks, resu lts in a significant reduction of inju ry rate. 56 Equipment must be insta lled properly, with sufficient space a round it. Pl aygro und eq uipment needs to be inspected periodically for structural defects, peeling paint or splinterin g wood a nd these should be repa ired. Protective surfaces under playground equipment should also be inspected periodically, as surfaces such as wood chips or sand lose their protective quality if they get compacted by regul ar usage or are worn awayS7

SPORTS INJURIES ON SNOW AND ICE Areas with cold te mpera tures, snow and ice can make ideal conditions for recreation, but sports on snow and ice create specia l ha za rds for children. Over one-half of the children with t his type of injury are injured while sledging; the next largest groups have injuries caused by skiing, snowboard ing or playing hockey - fewest children were injured while ice-skating. Falling or hitting objects such as trees, rocks or fro ze n ground injured most children. Head injury was the most frequent diagnosis. One out of four children had broken or fract ured bones or had multiple injuries or required sur gery. The average length of hospital stay was 6 days. More than 14 days were spent in the hospital by on ly 10 pe r cent of the children . The combination of speed with a fall or coUision on ice and snow increases the risk of serious injuries . Over one half of the children had head inj uries and few, if any, of these children had been wearing helmets. Data from a study of sk i rental fac iliti es in 1999 looking at 353 rental shops in five European countries (France, Austria, Germany, Sw itzerl and and Ita ly) had shown that 71 per cent failed to meet the sta ndard and abo ut 13 per cent just about reached an acceptable level. In tota l, 70 per cent of rental facilities still set the bindings incorrectly 66 per cent of bindings in children were found to have been set dangerously hi gh. 58 - 60 At the biannual [SSS sy mposium held in Japan in 200 5, injury statistics presented from Scotland, Fra nce and Iran show a rate'expressed as injuries per 1000 part icip ant days of 1-2 per 1000 fo r alpine skiing

Older children and substance abuse I

and 3-4 per 1000 for snowboarding and ski-boarding. More common injuries are knee injuries in alpine skiers, wrist injuries in snowboarders and lower leg injuries in ski-boarders. Children as a group are twice as likely to be injured as adults, especially if using rental gear and on their first day of skiing as were those who had received less than five formal lessons and those skiing with friends. Children were shown to be more frequently injured on lift systems and as a result of bindings failing to release. In relation to the use of protective equipment by skiers the debate about helmet use continues. In Norway, the rates of use amongst those injured were 31 per cent (alpine ski), 26 per cent (snow board) 26 per cent (telemark ski) and 28 per cent (ski-board). In Sweden, where about 58 per cent of all people on the slopes now wear a helmet, a 28 per cent rela tive increase in the risk of a head injury was observed in non-helmet wearers. The main protective effect of headgear is against more minor injmies such as abrasions and bruises. The helmets in use at present simply cannot do much in high-speed impact accidents. Wrist guards were devised to reduce the incidence of wrist fractures amongst snowboard ers but there are currently no international standards for them, so it is velY difficult for a boarder to decide which to use and which is the best buy. Release bindings had led to a reduction in the number of lower leg fractures and may reduce the number of knee injuries that were still occurring. International standards have still to be agreed for them.

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forbidding children below the age of 13 years to drive a tractor on private ground. Children are also prevented by law from riding as passengers on farming machinery. This applies not only tractors, but also to harvesters and trailers. Quad bikes are quite popular on farms and are often an irresistible attraction to children; crashes with these have resu Ited in injury and deaths.

PREVENTION A major public health issue 71 is the effective prevention of injuries and fatalities from injuries in children and, in most countries, there is a constant active monitoring of the incidence of serious injury and fatalities resulting from accidents; any patterns that emerge from such studies are addressed and this occasionally involves new Jegisla tion. 55 ,55.72 Preventative measures that are adopted are reg ularly audited in terms of their effectiveness and fine tuned as required.73 The availability of guidelines and legal sanction have enabled the commencement of, and the frequent successful completion of, litigation procedures in the civil and, more rarely, the chimerical courts, in addition to public inquests and fatal accident inquiries.

OLDER CHILDREN AND SUBSTANCE ABUSE RIDING INJURIES Each year children are injured and some die as a result of incidents while riding a horse. An adult horse can weigh over 500 kg, gallops at speeds up to 65 km per hour and kicks with the force of 1.8 times its weight. About 65-75 per cent 51 - 54 of children admitted after riding accidents have been riding the horse, with most injuries occurring to the head and in the limbs. Many of the fatalities and injuries can be avoided or have a reduction their severity through a combination of better adult supervision and the use of appropriate protective helmets. 55 .55

AGRICULTURAL INJURIES Children in farming communities often assist their families during peak harvest times and indeed may seek employ ment as fruit and vegetable pickers during vacation peri ods. In the course of holidays on farms, children may also find themselves in trouble with farming equipment. This problem is well recognized in Britain as it is in Australia 57 and in the USA;68 between 1979 and 1988, 167 children died in farming accidents in Britain and about 300 children die annually in the USA.69 Tractor-related injuries are the most common in Britain,l° even although there is legislation in existence

In the older age groups, alcohol use, solvent misuse 74 and drugs may creep into the picture; in addition young adoles cents may carry weapons as part of gang culture or for alleged personal protection from bullying and other preda tory behaviour. 75 In other countries firearms may be used in much the same way and because of easy access to them, injuries and deaths often result from them. More than one person per week dies from volatile sol vent abuse (VSA). The average home has 30 kitchen and bathroom products that can be abused, including: butane gas cigarette lighter refills, liquefied domestic gas, solvent based adhesives, deodorant aerosols, pain relief sprays, aerosol air fresheners, hairspray, other aerosols, correction fl uids, petrol, certain paints, paint thinners and removers, clry cleaning agents, petrol lighter fuel, nail varnish and varnish remover, some shoe and metal polish, and plaster remover. In 2001, VSA was responsible for seven times the number of fatalities than those related to ecstasy (3,4 meth ylenedioxymethamphetamine [MDMA]). The 2003 annual report from the European Union's drug agency warned that VSA is an often overlooked problem, with a big impact on public health of young people; the use of solvents and inhalants is the next common substance misuse after cannabis and alcohol in 15- to 16-year-olds. One in seven 15- and 16-year-olds in the UK sniffs solvents to get high. More than one person dies every week in the UK from the effects of solvent abuse - between 70 and 100 each year.

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The dru gs charity SOLVE IT says so lven t abuse kills 60-75 youn g people each year. One- thi rd of young people that die from VSA are first-time so lvent abusers; in 1997 in 37 per cent of deaths there was no prior known history of abuse. Most deaths from VSA occurred in the 14-18 age ran ge . Solvent abusers can be male or female, al thou gh there are higher numbers of solvent-related de aths in boys, probab ly due to differences in sniffing behaviour. Sniffing so lvents may cause intox ication similar to the effects of alcoho l,76 so a so lvent sniffer may become drow sy, confu sed, an d aggressive, may take more risks than they would when sober, a nd so on. Accidents, there fore, are quite comm on and so metimes fatal. 77 Over one half of the deaths that have been linked to solvent sniffing appear to resu lt from the direct toxic effects of t he chemi cals that w ere sniffed , but other de aths result from acci dents, choking on vomit or suffocati on. Deat hs are often sudden, and often a mechanism of death invo lv ing cardiac arrest app ears to be the cause . Gas fuels continue to be associated with the majori ty of deaths, accountin g for about two-thirds of VSA deaths. Sniffing the butan e gas in li ghters causes a cardiac arrhythmia. 7s .79 Possession or abuse of a vo latile substance is not a c riminal act in itself, although shopkeepers can be fi ned under the Intoxicating Substa nces (Supply) Act 1985 if they knowingly sell to an abuser who is und er 18 year old. The investigations of such deaths require carefu l sampling; to enabl e later sampling of the air wi thi n the low er airways, it is essential to retain a lun g, with its main bronchus tied up securel y.8o.sl

ACCIDENTAL POISONING The innate inquisitiven ess of children and th eir tendency to sample and taste wha t th ey encoun ter in t heir immediate environm ent may result in accidental poisoning by: con sumption of mushrooms, benies, fruits and vegetation grow ing wild, which are intrinsically poiso no us; and the sampling of liquids held in bottles, including alcoholic bev erages, or other containers of liquids found in the house or in ga rages and outho uses. They are attrac ted by the colour, odour and labels of bottles and contain ers. Poisons range from med icines (such as a nalgesics, contraceptive pills, iron tab lets, vitamins an d antidepressants) to com mon fluids or items foun d in the ho use (cleaning fluids, a lco hol, cigarettes, c ray ons and button batteries) to dangerous garden plants (fox glove and lab urnum seeds). Samplin g by children of medication not intended fo r th em is a recurring prob lem, particularly if the tablets and capsules in questions are coloured a nd resem ble sweets. Poiso ning is the fourth most co mmon ca use of accidental deaths in children. Children under 5 years of age, as well as ado lescents, are pro ne to poisoning but accidental ingestions are most com mon in ch ildren under 5 years old . Abo ut 90 per cent of a ll poisonings occur at ho me, the most common sites being the ki tche n and the bathroom . Unintentional pOisonings

occur most frequ ently whe n routines are disrup ted, for exa mpl e moving and vacations. Chi ld safety caps have help ed decrease the number of p oisonings but they are not 100 per cent effective and should not give a fals e sense of security.82,83 It goes without sayin g that a ll potential poi sons should be prop erly lab ell ed, stored out of reach of children and locked away. In a household where drugs are misused it is po ss ible for a child , even a tod dler, to gain access to liquids, su ch as methadone, and co ntrolled substances of abuse, such as heroin or cocain e powder, which they inges t with the con sequence of serious harm as a direct effect of such inges tion. Passive smoking of cannabis fr om parents smoking close to the child in enclosed restricted environm ents has been known to result in inhal at ion of enough smoke to result in intoxication of the child .

HYPERSENSITIVITY Allergies with the potential for a fatal hypersensitivi ty respo nse have become more freq uent over the years S4 - at least in the public perception. According to the Natio nal Institute of Allergy, food allergy occurs in 6-8 per cent of children und er the age of 4 years, as well as 4 per cent of adults. About 30000 episodes of anaphylaxis and 100-200 deaths per year occur in the USA. At present, the only ways to manage food allergies are to avoid the food s that cause reactions and to treat the sympto ms caused by allergic reac tions. About 20 per cent of th e population worldwide can be considered to have som e form of atopy; this is more common in infants and children und er the age of 3 yea rs. B5 ,S6 Nut allergy is parti cularly important;S7 the inadvertent consump tio n of nuts by children who happen to be sensitive to them may cause deaths unless immediate action is taken. In the UK, 5 out of the 20 fatal a naphylactic re actions reco rded each year are due to food .s8 In addition to peanuts, the foll owi ng fo ods can result in life-threaten ing reac tions on re-exposure: tree nuts, seafood, seeds and cows' milk. 89 - 93 A number of these children always cany with th em an emergen cy pack that contains t he equipment required for an adrenalin injec tion, along with instructions as to how it shou ld be used if they were to develop an acute hypersensitivity respo nse;94 these are carried to school or other extra-domestic sites. 95 Children with bronchial asthma and wh o are kn ow n to respo nd adv ersely to external allergens, su ch as cats, may also develop potentially life-t hreateni ng episodes if exposed acutely to t he antigen .

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to increase c hil dren's helmet use. Am} Publ Healt/r 1993; 83:667-74. MacKay M. P layground injuries. Injury Prev 2003; 9: 194 -6. Cha lm ers DJ , Ma rshall SW, Lan g ley JD et al. Heig ht a nd surfacing as risk factors for injury in fa ll s from playground equipment: a case co ntrol study. InjU/)' Prev 1996; 2:98 -1 04. Laforest S, Robaitaille, Lesage D et al. Surfa ce charac teristi cs, equipment height, and the occurrence and severity of playground injuries. Injury Preli 2001; 7:35-40. Platt SL, Fine JS, Foltin GL. Escalator-related injuries in children. Pediatrics 19 97: 100 :E 2. Lilli s KA, Jaffe DM. Playgrou nd injuries in children. Pediatr Emerg Care 1997; 13: 149-53. Laforest S, Robita ill e Y, Dorval D et al. Severity of fall injuri es on sand or grass in playg rounds. } Epidemiol Community Health 2000; 54:475- 7. Ro sevea re CA, Brown JM, Barclay Mcintosh JM, Chalm ers DJ. An intervent ion to red uce playground equipment hazard s. injury Prev 1999; 5: 124-8 . Sosin D, Su rface-specific fall injury rates on Utah school playgrou nd s. Am} Publ Health 1993; 83:733-5. Mott A. Rolfe K, Ja mes R et al. Safety of su rfa ces and eq uipment for c hildre n in playgro und s. Lancet 199 7: 349 : 1874- 6. Sub ve rt JR, Mott A, Rolfe K et a l. Preventing inj uries in public playg round s t hro ug h partnership between health services a nd loca l a uth ority: co mmuni ty interwoven study. BM} 1999; 318:159 5-8. Mayr J , Russel 0, Sp itzer P et al. Playground accidents. Acta Paediatr 1995; 84:573-6. Macar1hur C, Hu X, Wesson DE, Parkin Pc. Risk factors for severe injuries associated with falls from playground equipment. Accident Anal Prev 2000; 32:377-8 2. Langran MA. Summa ry of the research presented at the 16th In ternationa l Sy mposium of the ISSS held in at Mount Arai, Japan, Ap ril 2005. www.ski-injury.com. Barone GW, Rodgers BM. Pediatrics equestrian injuri es : a 14-yea r rev iew.} Trauma 1989; 29:245-7. Bond GR, Christoph RA, Rodgers BM. Pedi atric eq uestrian injuri es; assessing the impact of helmet use. Pediatrics 1995; 95:487-9. Holland AJA, Roy V, Goh V et al. Horse-related injuries in chil dren. Med} Aust 2001; 1756 ;609-11. Ghosh A, Di Scala C, Drew C et al. Horse-rel ated injuries in pediatric patients.} Pediatr Surg 2000 ; 35: 1766 - 9 . Aronso n H, Tough Sc. Horse-rel ated fatalities in the p rovince of Alberta 1975-1 980. Am} ForC'l1sic fVlt:'d Pat/lOl 1993; 14:28-30. Ch itn av is JP, Gibbins CLMH, Hirigoyen M et al. Accidents with horses. What ha s cha nged in 20 yea rs? Inj!lI)' 1996; 27: 103 - 5. Byard RW, Gilbert J, Lipset J , James R. Farm - and tractor related fatalities in South Australia. } PC'diarr Child HC'olrh 1998; 32:139-41. Cogb ill TH, Busch HM, Stiers GR. Fa rm accidents in ch ildren. Pediatrics 1986; 76:562-6. Rivara FP. Fatal and non-fata l farm injuri es in the United States. Pediatrics 1985; 76:5 67 - 73. Cameron D, Bishop C, Sibert JR. Farm accidents in children. EM} 1992; 305:23-5. Millward LM , Morgan A, Kelly MP. NH S Hea lth Development Agency. Health Developm ent Agency. Prevention and Reduction of Accidental Injury in Children and Older People. Evidence briefing, June 2003. Grayling T, Hallam K, Graham D et al. Streets Ahead: SaJe and Liveab/{:, Streets Jor' Children. London: In stitute for Publi c Policy Research, 2002.

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73 Town er E, Dowswell T, Mackereth C, Jarvis S. What Works in Preventing Uninte ntional Injuri es in Chi ldren and Young Ado lescents 7 An Updated Systemat ic Review. London: Hea lth Develop ment Agency, 2001. 74 Sva nstro m L, Haglun d BJA. Evidence-based Safety Promotion and Injury Prevention - a n Introducti o n. Department of Publ ic Hea lth Sciences, Di vision of Soc ial Medici ne, Karolin ska lnsti tutet, Stockho lm , Sweden, 2000. 7 5 Ano nymous. Solvent abuse: Little progress a fter 20 years (Editori al). 8M} 1990: i:J00. 76 McKeganey N, Norrie J. Association between illegal drugs a nd weapon carry in g in young people in Scotland; schools' survey. EM} 2000: 320:982-4. 77 Joseph DE, Parke r S. inl7alants. Drugs oj Abuse. New York: United States Drug Enforcement Administration , 2005. 78 First Nations and Inuit Health Committee, Canadian Paediatric Soc iety (CPS). Inhalant abuse. Paediatr Child Hea lth 1998; 3:123- 6. 79 Shep herd RT. Mechanism of sudden death associated with volatile substance abuse. Hum Toxicol 1989; 8:28 7-91. 80 Anderson HR, MacNair RS , Ramsey JD. Deaths from abuse of substances : a national epidemiological study. EM} 19 85 ; 290:304-7. 81 www.tox la b.co. uk/vo la tile.htm and www.toxlab.co. uk/dasguide.htm. 82 S ibe rt JR , Clarke AJ, Mitc hell MP. Improvements in child res ista nt co ntai ne rs. A rch Dis Child 1985; 60:1155 - 7. 83 Rodge rs G. The sa fety effects of child-res istant pack aging fo r ora l prescripti on drugs : two decades of experie nce. }AMA 1986 ; 275: 166 1-5. 84 Isolauri E, Huurre A, Salminen S, Impivaa ra O. The all ergy epide mic ex tends beyond th e past fe w decades . Ciil1 Exp A llagy 2004; 34:1007-10. 85 Host A, Halken S. A prospective study of cow milk a llergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immun o log ical type of hypersensitivity reaction. Allagy 1990; 45 :5 87 - 96. 86 Sampson HA, Scanlon SM. Natural hi story of food hypersensitivity in children with atop ic dermatiti s. } Pediarr 1989; 115:23-7. 87 Bock SA, Atkins FM. The natural histolY of peanut alJergy. } Allng.l' Ciill illll11ullol 1989; 83:900-4. 88 Pumphrey RS. Lessons for management of anaphy laxis from a study of fata l rea ctions. Clin Exp AI/{:'rgy 2000; 8: 1144-5 0. 89 Pa llares D. Allergy to macadamia nut. A 1111 Allergy Asthma 1111111ullol 2000; 85:385-6. 90 YUll gin ge r .liN, Sweeney KG, Sturn er WQ e t a l. Fata l food induced a naphy laxis. }AMA 1988; 260: 1450-2. 9 1 Sa mpso n HA, Mend e lso n L, Rose n JP. Fatal a nd near-fatal anaphy lac tic reaction s to food in chil dren a nd ado lescents. N ElIgl} MC'd 1992; 32 7:330- 4. 92 Bock SA, Mun oz - Fu rl ong A, Sampson HA. Fata liti es due to anaphylactic react io ns to foods. J Allergy Clin Immunol 200 1 ; 1: 191-3. 93 Yunginger JW, Nelson DR , Squi llace DL et aJ. Laboratory investigation of deaths due to anaphylaxis. ) Forensic Sci 1991; 36:857-65. 94 Simons FE, Chan ES, Gu X, Simons KJ. Epinephrine for the out-of-ho sp ital (first aid] treatment of anaphylaxis in infants: is the ampOUl e, syringe, need le met hod practical? ) Allergy Clin Immunol 200 1 ; 108: 1040-4. 95 Simons FE, Gu X, Silv er NA, Simo ns KJ. EpiPen Jr versus EpiPen in young children weighing 15 to 30 kg at risk for anaphylaxis. ) Allergy Clin Immunol 2002; 109: 171-5.

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I

CHAPTER 18

I

DROWNING AND NEAR DROWNING John Pearn

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The pathophysiology of drowning

349

e causes of childhood drowning: a perspective

Forensic immersion syndromes

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346

References

351 359

troduction

TRODUCTION

J:o wning remains one of the most common causes of death early chil dhood . In developed and affluent countries, after ?: child has passed th e neonatal period, immersion incidents ~main one of the three principal causes of death.l,2 In many :----_

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Figure 21.4 A short tandem repeat (STR) profi le. An electrophoretogram show ing the deoxyribonucleic acid (DNA) profile of a sample analysed at nine STR loci (three on each horizontal row) and a sex-determining region, ame logenin (labelled AMEL on the second row), using the comm ercial Profiler Plus® kit (Applied Biosystems, Foster City, CAl. Each peak represents a different allele and the number in green below the peaks denotes the number of times the particular STR sequence is repeated. Where two peaks are seen at a particular STR locus, for example, 14 and 15 for D3S 1358 on chromosome 3, the individual has a diffe rent number of repeats on their homologous chromosome 3s; where a singl e peak is seen at a particular STR locus, for examp le, 13 for D8S1179 on chromosome 8, the individual has the same number of repeats on both copies of their homologous chromosome 8s. In this example a single peak representing the X chromosome is seen at the amelogenin locus, indicating that the sample was from a female. (Courtesy of Dr JR Gilder, Forensic Biomatics, Inc., Fai rborn, OH, USA.)

with the advent of lo w-copy-number (LeN) DNA analysis, it is possible to obtain a DNA profile from as little starting material as a single cell or the few epidermal cells left behind in a fingerprint, and trace quantities of DNA that may sub sequently be analysed may be deposited simply by touching articles or surfaces. 31-35 However, the evidential value should be treated cautiously and the serious technical and interpre tative issues relating to such evidence should be taken into account. Once a DNA sample has been extracted, it is amplified by a process called the polymerase chain reaction (peR) in order to generate a sufficient quantity of DNA for detec tion. 36)7 peR is a technique that revolutionized molecular biology w hen it was developed in the 1980s, and its intro duction enabled the shift from RFLP to STR profiling. It provides a simple and readily automated way to replicate specific preselected regions of the genome so that, from a small number of initial copies of the specific DNA sequence of interest, millions of copies of that sequence can be gen erated in a cyclical process. During each cycle of the reac tion, the number of copies of the targeted templ ate sequence of interest is doubled, resulting in an exponential in crease in the tota l amount obtained after multiple cycles. In the case of STR profiling, the target sequences within the genome are a selection of STRs distributed on different chromosomes of the genome. With the use of commercial kits, it is possible to amplify as many as 10 SIRs in a single reaction tube . These kits app ly a fluorescent label or tag to the different STRs to enable them to be detected and

differentiated from each other. The kits have been designed and validated for specific conditions and quantities of tem plate DNA, conditions not met by the aforementioned LeN analysis. In order to compensate for the trace levels of DNA that would not otherwise be detected, LeN analysis increases the number of rounds of peR amplification, but the cost is an increase in potential artefacts. Spurious alleles can be detected and genuine alleles may fail to show Up,34 casting severe doubts on the acceptability of the results as being of a sufficient evidential weight for a court of law. Amplification of selected STRs of the sample DNA results in a mixture of amplified STR fragments of different length that need to be separated and visualized. This is done by a process of gel electrophoresis or, more recently, capillary electrophoresis, which separates the labelled fragments on the basis of the electric charge and size of the fragments. 38 The fluorescent dye-l abelJed fragmen ts are passed through a reten tive material (either a polyacryla mide gel or viscous polymer), wh ich retards their migration through the material under the action of a potential difference. Shorter fragments pass through the material more quickly and are detected by a laser detector and registered as a peak on the electrophore togram before the longer fragments. In this way profiles from different samples can be generated and compared. In addition to the SIR loci that are analysed, a gene on the sex chromosomes called amelogenin is also typed in order to identify the sex of the source of the sample. Although much of the X an d Y chromosomes differ from each other and are non-homologous, there are some stretches of the chromosomes

-

Forensic DNA analysis I

that show homology, and the amelogenin gene is one of these. There is a difference in size between the X amelogenin gene and the Y amelogenin gene, which can be differentiated on the basis of the size of the PCR products when the amelo genin gene is amplified in the same way as the SIR loci described above. When only a single peak corresponding to the X version of the gene is detected, the sample is taken to be from a female; when two peaks corresponding to the X and the Y copies of the gene are detected the sample can be considered to be from a male. Considering any locus that is typed, we cannot be absolutely confident in our interpretation in every case. Genetics is no exception to the rule that biological systems have their anomalies, and there are times when a sample shows only an X amelogenin signal when the true source is in fact male. As for all the STR loci, it is possible for DNA to be present at too Iowa concentration or to be too badly degraded to be detected, or for the reaction to fail; thus, a negative result does not necessarily mean there is no sam ple present. Potentially more interesting and problematic, in terms of forensic investigations, are cases in which a mutation may exist in an individual, resulting in anomalous results. For example, the Y amelogenin gene has been found to be deleted in a number of individuals, including specific Indian populations ; conventional sex typing would suggest that these males were female, with considerable consequences for forensic casework. J9 - 42 Such events are not restricted to the amelogenin locus; mutations giving rise to anomalous results can occur at any locus.

INTERPRETATION

If two samples analysed by STR profiling give the same result at all the loci examined, the samples are said to 'match' (Fig. 21.5). A match tells us that the two samples could have originated from the same source but is not defin itive in identifying the source of the sample. Who knows if one continued to compare additional regions of the genome whether a difference between the 'matched' samples might in fact be identified? One could tell this for certain only by sequencing the entire genome of the two samples, which is an unrealistic expectation given current technology. So it is important to remember that failure to show a difference should not be regarded as confirmation of identity - it is all down to statistical probability, which will be discussed later. On the other hand, if two samples do not match, i.e. they do not share the same combination of repeat numbers ,at every STR analysed, they would be deemed to have come from different individuals because there has been a failure to illustrate identity. Alternatively, the result may be incon clusive. This may be because the DNA is of poor quality or present in too Iowa quantity to produce sufficient data, or the data that are produced may be ambiguous or one may be unable to interpret the results, for example, in the case of mixed samples.

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III Figure 21.5 Comparison of short tandem repeat (STR) profiles at three STR loci (D3S 1358, vWA and FGA) from different sources. The profiles of samples ta ken from four suspects were compared with that of a blood stain found at a crime scene. The comparison shows that only suspect 3 'matches' the blood sample at these loci, i.e. shares every allele at each locus in common. The rema ining suspects would be excluded as a source of the blood stain. (Courtesy of Dr JR Gilder, Forensic Biomatics, Inc., Fairborn, OH, USA.)

It is worth noting that, in an analysis of DNA by STR pro filing, scientists are not able to tell if the sequence of As, Cs, Gs and Ts of two matched samples identified as having the same-sized SIR PCR product and concluded to share a par ticular number of repeats at the SIR locus is actually the same over the whole of the SIR region. What is being looked at are differences in lengths of sections of the genome rather than the actual sequence across the entire length. It is possi ble for two amplified STR products to show the same length. indicative of being the same, while actually differing in sequence when they are examined in greater detail. The investigative value of a match is typically presented in terms of the 'random match probability' (RMP). which expresses the likelihood that the match occurs by chance in the population. The RMP is the result of a calculation using statistics derived from population studies and assumptions that originate from the study of population genetics, in

402 I

Forensic DNA profiling

particular the Hardy-Weinberg equil ibrium. 43 ,44 Analysis has shown that in a stable, randomly mating popul ation, devoid of selective pressures that would alter the frequency at which existing alleles are found in the population , it is possible to predict the frequency of the possible genotypic combinations of these alleles in the population. 45 ,4G Using statistics, one can get an idea of the likelihood th at the given profile would arise by chance in the population from which the frequency estimates of the different a lle les have been derived and, hence, the weight of the evidence. One should not lose sight of the fact that the data derived from the population databases are based on predictions established from relatively small samples of individuals in the popUlation; the results genera ted are based on probabilities. The RMP is calculated by mult iplying together each of the predicted fr equen cies of occurrence of the profiled genotype for the STRs that have been typed in the sample using t he product rule to determine the probability that the given genotype would occur by chanceY The product rule can be used because each STR typed is situated on a differ ent chromoso me and, as describ ed at the start of this chap ter, c hromosomes segregate to the ga metes randomly and are inherited independently of each other. Th e number of STR loci analysed depends on whichjuris diction one is in and, thus, the pow er of discrimin ation ofthe resultant RMP. In the UK, 10 STR loci are routinely exam ined at present, whereas in the USA 13 loci are looked at, the latter number providing a greater power of discrimination. Despite the fact that such analyses are typically prese nted in terms of extremely sma ll RMP chance matches, in the order of one in a billion in the UK COUlts 48 and smaller in the USA, it is of note that Jeffreys has argued that we should be analysing as many as 16 STR loci to increase the power of discrimination in light of the increasing number of individ uals entered on the national DNA databases aga inst which the crime scene profiles are compared. 49 This is because the greater the number of profil es on the DNA databases with which unknown samples are compared, in order to identify a match, and thus a source of the sample, the greater t he probabi lity of a chance match. One only needs to look aro und at differe nt ethnic and racial populati ons to see that interpopulat ion genetic dif fere nces exist. As such, it is important to generate popul a tion databases for different race groups because certain alleles will be found to ex ist at a higher frequency in some populations than in others, for exa mple, the frequ ency of the nine-repea t allele at the D1 3S317 STR lo cus is 4.5 times higher in the US Hispanic popul ation than in the US African-American popul ation (Hisp anic frequen cy = 0.15357; African-American = 0.0 32955) (data taken fro m Butler2B ) . If one were to calculate the RMP for a sample based on data from a popul ation other th an the true source of that sampl e, one may end up with an RMP that misrep rese nts the true likelihood of a match. Whether the differ e nces would be statistically significant w he n dealing w ith

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RMPs of the order of one in billions or less is debata ble, but for a calculation based on an incomplete profile in which not all the STR loci tested have generated a result, thus resulting in hig her probabilities fo r the RMPs being calcu lated, discrepancies may be more significant. The issue is ge nerally addressed by calcul ating an RMP based on the population da tabase that generates the most co nservative results, i.e. those most favourable to the defence in cases in which a suspect's DNA is found to match a DNA sample fro m a crime scene. Further issues regarding population structure may be take n in to account when deriving the predicted genotype fr equencies for population databases when one is dealing with populations with a hig h level of inbreed ing. It will be apparent that the closer the relationship of two indiv idu als, the more DNA they will have in commo n and, thus, the more likely it is for individuals from inb red populations to share a particular STR allele than would be the case for two non-related individuals in a randomly ma tin g population , i.e. the conditions of random mating fo r Hardy-Weinb erg equilibrium are not satisfied. If a susp ect a nd the true per petrator of a crime are blood relatives then their genotype frequencies will not be independent and a correction fa ctor or para meter measuring the popul ation differentia tion/ substructure, denoted as or FsT , is required. 47 ,48.50,51 An alterna tive to the RMP for the presentation of DNA evi dence is likelihood ratios. A likelihood ratio expresses the ratio of two alternative probabilities of the same evidence under different hypotheses. In the context of DNA evidence, when a suspect's DNA profile matches a crime scen e sample profile, there are two possible hypotheses : either th e sus pect's profile matches because his biological sample was found a t the Clime scene or the sample came from some unrelated individual who has not been arrested and who happens to match the suspect by cha nce. The like lihood ratio is usually calculated by dividing the likelihood of the prosecu to r's hypoth esis (the first above hypothesis) by the likelihood of the defender'S hypothesis (the second above hypothesis).47, 5! In its Simplest form, the likelihood ratio is the inverse of the RMP. However, things become more com plicated when alternative scenarios for the evid ence that is seen are presented, or if the DNA sample is a mix ture from more th a n one contributor. To give a feel for the numbers, a likel ihood ratio of 1000 or greater provides velY strong sup port for the prosecution's hypothesis, a likelihood ratio of 100-1000 provides strong supp ort and a likelihood ratio of 10-100 provides moderate supportY

e

SAMPLE COLLECTION AND PROCESSING The ge nera l principles underly ing DNA evidence as applied to a crim inal case involving a child, e.g. the identification of a n unknown child's body or remains or other forensi c investigations, are no different from those of an adult con text. Typically, a DNA sample believed to be central to the

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DNA evidence/child sexual offence I

crime or investigation - be it a blood sample, a sample of saliva swabbed from a bite mark or, in the case of alleged child sexual abuse, semen extracted from underwear, bed clothing or an intimate sample - is analysed to produce an STR profile, which is used to link a suspect to a crime scene. The profile is compared with a reference profile taken from a suspect, identified on the basis of additional evidence in the case or, if no leads are originally present to identify a suspect, with profiles lodged on a national DNA database. A profile on its own is of no investigative value unless there is a profile with which to compare it. Samples on such DNA databases may be associated with a known and named indi vidual or they may be from anonymous samples collected from previous unsolved crime scenes, which enables sus pects to be matched with crime scene profiles or crime scenes to be associated via matches. The legislation governing the power to collect DNA sam ples and retain profiles on the databases varies from nation to nation. In the UK such powers are wide-ranging, and DNA can be collected from anyone suspected of a record able offence and profiles retained indefinitely, regardless of conviction or acquittal of the suspect (Police and Criminal Evidence Act 1984 [amended]), but in other jurisdictions the power of the criminal investigative authorities may be much less. From the point of identification of a crime scene or sub ject from which a sample for DNA analysis is collected to the point at which a profile is generated and interpreted, strict adherence to protocols, an unbroken chain of custody of the evidence and careful sample handling must be adhered to. 53-55 The risk of contamination of a sample and the need for correct handling to avoid it cannot be overemphasized; pro fessional bodies have described procedures and guidelines to help ensure quality control and quality assurance in these processes, for example, the Federal Bureau of Investigation (FBIl-appointed Technical Working Group on DNA Analysis Methods (TWGDAM), now known as the Scientific Working Group on DNA Analysis Methods (SWGDAM), and the DNA Advisory Board (DAB).53,55,57 A case may be lost if doubt can be cast on whether samples have been correctly handled risk of contamination, compromise of a sample or poor handling - the most noteworthy of which is the trial of O.J. Simpson, accused of the murder of Nicole Brown Simpson in 1994;30,58 false convictions may be secured as a result of bad practice. 59 DNA is ubiquitous: we are all continuously shedding DNA and leaving a trace of our movements in this way. In fact, we need not even have been at a location ourselves in order for our DNA to be found there. It may be deposited by secondary or tertiary transfer, being carried and subsequently deposited elsewhere by an animate or inanimate object. 5O - 55 Individuals who pass through a crime scene after the event could unwit tingly leave their DNA, implicating themselves in the process. Likewise, it is possible for DNA to be present at a scene prior to the event and collected when samples were taken,55 or,

403

depending on the nature of the sample, a perpetrator may be able to suggest a plausible reason for the presence or his or her DNA at a Clime scene, leading to termination of an inves tigation. 57 It is crucial, therefore, that there is evidence to link samples directly to the event; that all persons entering the crime scene and crime scene officers, scientists or other indi viduals collecting samples take precautionary steps to avoid contaminating evidential samples with their own DNA, be this from sneezing, coughing, shedding skin or the like on to the sample; that clean equipment and gloves are used when handling each sample; that protective clothing is worn to limit contamination from the sampler; and that the samples are securely sealed and appropriately transported and stored to prevent degradation of the sample. 53 During processing of the samples, it is imperative that case samples and reference samples are handled separately and that samples that have not been amplified by PCR are kept away from those that have been amplified. It takes only a minute amount of ampli fied contaminant DNA to swamp any DNA present in a case sample, resulting in only the contaminant amplified DNA being detected, at the expense of the genuine sample DNA, when the two are simultaneously subjected to PCR. Plas ticware and consumables used in the analytical steps are another potential source of contamination as they may be contaminated when they enter the laboratory,55,68 and the problems of contamination are particularly apparent when LCN analysis is conducted. 34 ,54,59 Forensic laboratories have sbict standard operating procedures to which they adhere, such as the DAB Quality Assurance Standards of recommen dations for forensic laboratories, in order to standardize and validate procedures. 70 Despite all these efforts, errors will arise, be they the result of human factors, the nature or quality of the sample or technical or biochemical artefacts, and this should not be overlooked. 71 - 73 There is debate as to whether the exceed ingly small RMP figures that are presented in court are unfairly prejudicial when they are not accompanied by esti mates of these errors, particularly when the RMPs presented are smaller than the probability of laboratory error. How ever, some argue that a meaningful statistic for an error in a particular case cannot be provided. 74

DNA EVIDENCE AND CHILD SEXUAL OFFENCE The major problem facing the forensic investigation in cases of alleged child sexual abuse, and which is not unique to DNA evidence per se, is that the majority of cases arise ret rospectively, which presents several difficulties in terms of gathering forensic evidence (see Chapter 1). A number of other issues that relate to DNA analysis in such cases are also of relevance to DNA evidence in a more general sense, for example mixed samples, DNA quantity considerations and Y chromosome STR typing; discussion and introduction of these in the context of sexual abuse investigation seems appropriate.

404 I


In the typical case of sexual abuse that comes to attention only months or years after the event, the opportunity to obtain DNA samples has passed by the time investigation begins. However, other indications, such as evidence of pregnancy or sexually transmitted infections, wh ich may be investigated using DNA techniques, can be highly probative should the opportunity for collection of immediate post coital samples not present itself. The occurrence of sexually transmitted infection in a child is unlikely in the event that sexual contact had not occurred, though vertical transmis sion is a possibility, and one also needs to be aware that con sensual sex with an infected partner may have taken place, rather than abuse. In one study, genital human papillo mavinls (HPV) infection, detected by the presence of HPV DNA from perineum and vaginal samples, was found in some of the sexually abused preadolescent girls examined but not in children in whom sexual abuse was excluded, the majority of the HPV DNA-positive cases being subclinical infections.75 It is noteworthy, however, that the incidence of sexually transmitted infections in victims of child abuse is low, a reflection of the generally low incidence of infection in perpetrators. In a recent study in Edinburgh, Scotland, sexually transmitted infection was seen in less than 10 per cent of referrals. 76 The appropJiateness of DNA testing for sexually trans mitted infectious agents using nucleic acid amplification test (NAATs)77 in suspected cases of child abuse has been ques tioned because of t he potential for false-positive results, with a possible consequence of false convictions. 78 .79 However, it is paramount that the well-being of the child is prioritized in any investigation and that the child's health is not compro mised at the expense of gathering forensic evidence. While NAATs may not be as specific as traditional culture tests, they show increased sensitivity. From a medical perspective, the downside of a false- positive result is limited to the cost and side-effects of superfluous antibio tic treatment com pared with the long-term potential serious health conse quences for the individual of untreated infection. 8o From a legal perspective, given that culture tests are sti ll the only test currently accepted by the UK courts 81 and some labora tories no longer conduct culture tests, having implemented NAATs alone,82 there are issues relating to obtaining suitable forensic evidence. The recommended approach is to take tvvo swabs so that a n initial NAAT-positive result can be con firmed by culture,81 though this involves additional distress and discomfort to the child. If pregnancy follows sexual abuse, it may be possible to gather evidence as to the likely father by way of DNA paternity testing of offspring or aborted fetal material ,83,84 a technique that is discussed later in this chapter. Although child sexual abuse includes a spectrum of activities from intercourse to physically less intrusive sexual ab use of a minor, whether samples taken for DNA analysis are informative depends on many factors. These include the nature of samples in relation to the offence; the time since t he offence; whether a male perpetrator ejaculated during

the abuse, was azoosperrnic, oligos permic or used barrier protection; and whether the victim subsequently washed, changed his or her clothes, ate, rinsed his or her mouth, uri nated or defecated, all of which can diminish the quality or quanti ty of detectable DNA, or even remove all traces of detectable DNA. In the event that a child does present in an acute case, conflicting opinions have been expressed about the value of ta king intimate fore nsic samples up to 72 hours after the event in prepuberta l victims 85 as recommended by the American Academy of Pediatrics. 86 It is important to weigh the distress and discomfort that may be inflicted on the victim against the likelihood of evidence being found. Christian et al 85 argue that, if one is seeking evidence of semen or sperm in a vaginal swab sample to provide objec tive evidence of sexual contact with a child who does not have a previous sexual histoty, data detived from adult cases is inappropriate to prepuberta l situations. While the litera ture reveals marked differences in survival time of sperm cells in different body orifices, the generally accepted maxi mum times for observin g sperm heads range from 24 hours in the mouth to 7 days in the vaginal cavity, and in the region of 2-3 days in the anus and rectum .87,88 This argu ment 55 may be va lid in the case of cytological observation of sperm cells or the detection of semen by, for example, acid phosphatase activity or the presence of phosphate-specific antigen (PSA), which have a shorter period of detection BG ,89 However, g iven the sensitiv ity of DNA analysis and its abil ity to detect trace material refractoty to other detection methods, particularly using LCN techniques,31-34 one should not discount the possibility of obtaining DNA evidence beyond the time periods suggested by Christian et al. 85 In one study, evidence of male DNA, detected by Y-STR ana lysis, was found in over 90 per cent of vaginal or ana l swabs taken from child sexual assault victims up to 72 hours after the incident,9o supporti ng the fll1dings of others that Y-STR DNA amplification can produce positive resu lts in swabs cytologically negative for spelm cells. Such negative results wo uld usu ally have led to tennination of biological investigation,91 illustrating the va lue of conducting the DNA analysis. The presence of Y-chromosome DNA in a high vaginal swab from a fe male would be interpreted as tanta mount to evidence of intercourse, and in the case of a minor, where consensual sex is not a defence aga inst statutoty rape, is highly probative evidence of abuse. There are practical considerations, in the case of a sma ll child, in ensuring that internal samples genuinely represent material exclusively of an internal nature. The anatomy of a young girl does not lend itself easi ly to collection of such samples, and care has to be taken to avoid contact with external regions of the child 's body. There may be perfectly acceptab le re asons for male DNA to be present on a child's body, particul arly if male relatives have frequent contact with a child, and sampling of t his material could lead to inappropriate conclusions being drawn, incrimin ating an innocent person. In this respect the use of the colposcope with the magnification and illumination that it affo rds has

-

.

Y chromosome STR typing I

assisted in the collection of non-contaminated intimate samples.

Y CHROMOSOME SHORT TANDEM REPEAT TYPING As mentioned above, if one can detect the presence of Y-chromosome DNA in a sample then, barring syndromes with abnormal chromosome complement or structure, one can conclude that male DNA is present. Such evidence is particularly useful in the case of all eged sexual abuse by a male against a female, although typing the Y chromosome of a sample has add itional valuable applications, including paternity testing and the identification of missing persons. If an internal vaginal sample is taken from a girl under the legal age for sexual intercourse and Y-chromosome DNA is detected, this is convincing evidence of abuse. In theory, one could test for male DNA using the amelo genin locus by conventional SIR typing, the X and Y amelo genin alleles being of different size. The problem with this approach is the frequently encountered imbalance in the rel ative quantity of any male DNA that would be present in sam ples routinely taken from the female victim in an alleged case of sexual abuse, i.e. vaginal, anal or oral swabs. Such samples typically comprise a vast excess of female DNA, usually from host epithelial or inflammatory cells, with only traces of male DNA, typically in the form of sperm cells, although epithelial and inflammatory cells may also be present, the last two being morphologicaJly indistinguishabl e from the female equivalents. Given the imbalance in the amount of male and female template DNA added to the PCR, there would be pref erential amplification of the female DNA to the extent that male DNA may go undetected. This is analogous to the situa tion described earlier of a DNA sample to be typed being con taminated with PCR-amplified DNA, due to poor laboratory practice, and swa mping the sma ll amount of DNA present in the sample, leading to preferential re-amplification and detec tion of the contaminant DNA. As ever, absence of detectable DNA is not evidence of absence. One way to get round this problem is to type a series of SIR loci which are specific to the Y chromosome (Y-SIR typing),92,93 so that female DNA is not amplified in parallel and a male-specific profile or Y-SIR haplotype results. There are hundreds of STRs distributed on the Y chromosome,94 and by typing a chosen set of these one can identify the par ticular Y haplotype of an individual male, i.e. the closely linked alleles of that individual at the chosen loci. One gets more information about the source of the samp le using Y-SIR profiling than if one was just to type the amelogenin locus to determine maleness because of the variation that exists in the Y chromosome between non-related males and between different ethnic, racial and geographic groups. However, the power of discrimination of Y-STR typing in no way approaches that of conventional autosomal STR typing. This is because the Y chromosome is passed from father to

405

son, essentially unchanged in sequence, so all male offspring through the generations descended from one particular male will share the same Y chromosome and, hence, the same Y-chromosome haplotype. Thus, given a Y-chromosome haplotype alone, it would not be possible to conclude that the man who was the origin of a DNA sample was its source, or whether it came from a blood relative such as his brother, son, father, grandfather, grandson, or uncle on his father's side of the family. A number of internet-accessible Y-SIR databases have been established,92 which vary in the number of SIR loci for which informatio n is avail ab le. For example, the frequ ently used and largest Y-SIR haplotype reference database (YHRD) was established in 2000 with the objectives of generating ' reliable Y-SIR haplotype frequen cy estimates for minimal and extended Y-STR haplotypes to be used in the quantitative assess ment of matches in forensi c and genealogical case work' and assessing the 'ma le population stratification among world-wide populations as far as reflected by Y-SIR haplotype frequency distributions'.95 The database can be searched for frequency data and geographical distribution data of a particular haplotype, both of which may aid in a forensic investigation ; however, the haplotypes entered cur rently vary in the number of SIR loci for which data are available. In 1997, a 'minimal haplotype' was recommended that typed seven 10ci 96 for which data are ava ilable for all entries on the YHRD SIR Database. Since then, European labo rato ries have moved towards typing nine loci , and SWGDAM recommends typing 11 loci. 97 Kits for these and additional loci are commercially ava ilable, and current prac tice is moving towards 17 loci being analysed routinely, further increasing the discriminatory power of the analysis. It is likely that the foc us in the future will move towards supplementing the information derived from Y-SIRs with single-base sequence variations, called single nucleotide polymorphisms (SNPs). Various ways are used to try to enri ch a fema le/male mixed sampl e for the male cell component in order to assist in the analysis and maximize the chance of getting an inter pretable Y-SIR haplotype data. For example, differential DNA extractio n techniques may be employed, which take advantage of the increased resistance of sperm cells to par ticular reagents routinely used to digest cells during the DNA extraction step of ana lysis. Epithelial or other non-sperm cells are initially lysed and separated from residual sperm ceJls, which can then be processed separately?O,98 Antibodies specific to sperm cell antigens coupled to magnetic beads 30 or laser microdissection (LM) techniques 30 ,99.lOo may be used to directly capture sperm cells and, more recently, fluores cence in situ hybridization in conjunction with LM has been developed as an effective way to isolate not only sperm cells, but also male epithelial and inflammatory cells. 101 , I02 The latter technique presents a solution to the problem of deposited semen samples that are devoid of sperm cells as a result of a medical conditions or vasectomy, and offers a way to include not only sperm cells, the subject of previous

406 I


analysis, but also additional male cells, which will boost the quantity of extractable male DNA in small samples. As with conventional STR typing, the result of Y-STR typing can lead to an individual being excluded as the source of a sample, if the two Y haplotypes do not match. The results may be inconclusive, for the same reasons as dis cussed previously, or they may lead to an individual being included as a possible source of the sample, when the sam ples show sufficient similarity that they could have origi nated from the same individual. In this case, in a court setting, the findings are typically presented as being unable to exclude the suspect (the individual found to match the haplotype) as the donor of the crime sample, but also unable to exclude all patrilineally related male relatives, as well as an unknown number of unrelated males, as potential donors.92 Courts often seek some kind of statistical meaning to this conservative statement. The RMP calculation described above is not appropriate because, unlike the auto somal STR loci that are typed for conventional STR profiling, which are located on separate chromosomes and, hence, inherited independently of each other, the Y-STR loci are inherited together as a group of linked loci on all but rare occasions. Instead, an indication of the probability of a coin cidental match may be evaluated using the counting method or a Bayesian-approach haplotype surveying method. 92 • lo] The counting method is the simpler and expresses the num ber of times the given haplotype is found in the database that has been searched and upper-bound confidence limits that can be placed on the haplotype's frequency. The signif icance of inferences made from these calculations is highly dependent on the size of the database used. The 20th release of the aforementioned YHRD STR Database included 46831 seven-loci 'minimal haplotypes'. Of these, 44974 were typed for the nine European recommended loci and 17935 for 11 SWGDAM recommended loci. 95 The US National Center for Forensic Science is currently in the process of creating a National US Y-STR Haplotype Reference Database, which will contain data on ll-loci haplotypes. The database is to be created by compiling and consolidating existing govern ment, commercial and academic Y-STR databases and will allow continuous updating of haplotypes entered on the database by retyping existing samples as new STR loci are introduced to create extended haplotypes.lOJ.l04 Making allowances for advancing technology and new typing tech niques in this way shows foresight, but raises some of the highly contentious issues that exist in relation to whether only profiles of samples or actual DNA samples of DNA database entries should be retained once an entry is lodged on a DNA database. In the context ofY-STR typing and forensic applications, interesting data are coming forth suggesting a way in which the common biological attribute of the Y chromosome shared by male relatives might be exploited in conjunction with another commonly shared feature of many male rela tives, namely their surname, in societies in which the custom is for the family name to pass through the male lineage. 105.106

Sharing a surname in such societies significantly elevates the probability of sharing a Y-chromosome haplotype, leading to the proposal that the establishment of a large surname-Y-chromosome haplotype database might be of intelligence value in a case devoid of other leads and when male DNA central to the case has been identified, for exam ple, in a rape case. By comparing the Y-chromosome haplo type of such a sample against the database, a potential surname of the source might be identified and lead to iden tification of a pool of potential suspects. Because many indi viduals share a Y-chromosome haplotype, existing databases do not attempt to attach identity to an entry. There are unde niably many barriers to the success of this proposed approach, including non-paternity events, surname chang ing, adoption, the existence of more than one founder of a particular surname, whether the theory holds true for com mon surnames and mutations. Civil liberty and privacy issues in establishing and using such a database need to be addressed. The method would not be able to conclusively exclude or include any individual as a perpetrator, and more research is required if the proposed approach is to become a realistic option, but it is interesting to be aware of new opportunities to exploit genetic information that may come to fruition.

MIXED SAMPLES Y chromosome-specific short tandem repeat typing is of value when more than one male perpetrator may have con tributed to a sample because it reduces the number of possi ble allelic combinations that one is trying to analyse and is useful in the event of a mixed male and female sample. Where more than one individual contributes to a sample. then multiple peaks representing multiple alleles may be seen on the electrophoretogram of a conventional STR analysis. If two individuals contribute to a sample then up to four different alleles could be detected at anyone locus if both individuals were heterozygous at the locus; in the case of three contributors there could be up to six different alle les. Such scenarios introduce additional practical and inter pretative problems over conventional sample analysis. 107 - 11l How does one know which of the possible allelic combina tions to attribute to the different contJibutors? One approach is to attempt to allocate alleles on the basis of the strength of the signal (peak height or peak area on the electrophore togram), working on the assumption that if one of the con tributors' DNA was in excess of the other at the start of the PCR, then the alleles initially present in greater quantity would produce larger peaks after amplification. This may not hold true in every instance, however, and in cases where near-equivalent quantities of DNA from more than one indi vidual are present, all signals detected being of similar inten sity, the approach will not be possible. If one considers the scenario of five or more peaks, things get even more compli cated in trying to detem1ine how many different individuals

406 I


analysis, but also additional male cells, which will boost the quantity of extractable male DNA in small samples. As with conventional STR typing, the result of Y-STR typing can lead to an individual being excluded as the source of a sample, if the two Y haplotypes do not match. The results may be inconclusive, for the same reasons as dis cussed previously, or they may lead to an individual being included as a possible source of the sample, when the sam ples show sufficient similarity that they could have origi nated from the same individual. In this case, in a court setting, the findings are typically presented as being unable to exclude the suspect (the individual found to match the haplotype) as the donor of the crime sample, but also unable to exclude all patrilineally related male relatives, as well as an unknown number of unrelated males, as potential donors. 92 Courts often seek some kind of statistical meaning to this conservative statement. The RlVIP calculation described above is not appropriate because, unlike the auto somal STR loci that are typed for conventional STR profiling, which are located on separate chromosomes and, hence, inherited independently of each other, the Y-STR loci are inherited together as a group of linked loci on all but rare occasions. Instead, an indication of the probability of a coin cidental match may be evaluated using the counting method or a Bayesian-approach haplotype surveying method. 92 , IOJ The counting method is the simpler and expresses the num ber of times the given haplotype is found in the database that has been searched and upper-bound confidence limits that can be placed on the haplotype's frequency. TI1e signif icance of inferences made from these calculations is highly dependent on the size of the database used. The 20th release of the aforementioned YHRD STR Database included 46831 seven-loci 'minimal haplotypes'. Of these, 44974 were typed for the nine European recommended loci and 17935 for 11 SWGDAM recommended loci. 9s The US National Center for Forensic Science is currently in the process of creating a National US Y-STR Haplotype Reference Database, which will contain data on ll-Ioci haplotypes. The database is to be created by compiling and consolidating existing govern ment, commercial and academic Y-STR databases and will allow continuous updating of haplotypes entered on the database by retyping existing samples as new STR loci are introduced to create extended haplotypes. 103 ,104 Making allowances for advancing technology and new typing tech niques in this way shows foresight, but raises some of the highly contentious issues that exist in relation to whether only profiles of samples or actual DNA samples of DNA database entries should be retained once an entry is lodged on a DNA database. In the context of Y-SIR typing and forensic applications, interesting data are coming forth suggesting a way in which the common biological attribute of the Y chromosome shared by male relatives might be exploited in conjunction with another commonly shared feature of many male rela tives, namely their surname, in societies in which the custom is for the family name to pass through the male lineage. lOS, 106

Sharing a surname in such societies significantly elevates the probability of sharing a Y-chromosome haplotype, leading to the proposal that the establishment of a large surname-Y-chromosome haplotype database might be of intelligence value in a case devoid of other leads and when male DNA central to the case has been identified, for exam ple, in a rape case. By comparing the Y-chromosome haplo type of such a sample against the database, a potential surname of the source might be identified and lead to iden tification of a pool of potential suspects. Because many indi viduals share a Y-chromosome haplotype, existing databases do not attempt to attach identity to an entry. There are unde niably many barriers to the success of this proposed approach, including non-paternity events, surname chang ing, adoption, the existence of more than one founder of a particular surname, whether the theory holds true for com mon surnames and mutations. Civil liberty and privacy issues in establishing and using such a database need to be addressed. The method would not be able to conclusively exclude or include any individual as a perpetrator, and more research is required if the proposed approach is to become a realistic option, but it is interesting to be aware of new opportunities to exploit genetic information that may come to fruition.

MIXED SAMPLES Y chromosome-specific short tandem repeat typing is of value when more than one male perpetrator may have con tributed to a sample because it reduces the number of possi ble allelic combinations that one is trying to analyse and is useful in the event of a mixed male and female sample. Where more than one individual contributes to a sample, then multiple peaks representing multiple alleles may be seen on the electrophoretogram of a conventional STR analysis. If two individuals contribute to a sample then up to four different alleles could be detected at anyone locus if both individuals were heterozygous at the locus; in the case of three contributors there could be up to six different alle les. Such scenarios introduce additional practical and inter pretative problems over conventional sample analysis.107-lll How does one know which of the possible allelic combina tions to attribute to the different contlibutors? One approach is to attempt to allocate alleles on the basis of the strength of the signal (peak height or peak area on the electrophore togram), working on the assumption that if one of the con tributors' DNA was in excess of the other at the start of the PCR, then the alleles initially present in greater quantity would produce larger peaks after amplification. This may not hold true in evelY instance, however, and in cases where near-equivalent quantities of DNA from more than one indi vidual are present, all signals detected being of similar inten sity, the approach will not be possible. If one considers the scenario of five or more peaks, things get even more compli cated in tlying to determine how many different individuals

--

Mitochondrial DNA I

might have contributed to the sample. There are numerous scenarios depending on whether the contributors are het erozygous for alleles or homozygous for alleles and whether individuals share alleles in common . Mixture analysis is complex and should not be considered definitive. loa Sophis ticated software is available to assist in the interpretation of these profiles,112 but one is justified in being wary of over reliance on algorithms, just as one is justified in being wary of human error and misinterpretation or evaluation of such complex scenarios.

ADDITIONAL SAMPLE PROBLEMS AND SOLUTIONS Clearly, there are many practical and technical hurdles to be overcome when analysing DNA in the case of alleged child sexual abuse. The problems of failing to obtain a sample of suitable quality or quantity will determine whether an interpretable profile or Y haplotype is obtained, be it mixed or otherwise. However, if one spreads the net wider and looks at the ge neric situation where the identity of the source of a DNA sample is being sought (this could be samples collected in connection with abuse, murder, kidnap, the identification of the remains of a body follow ing a natural or man-made disaster, or any other investiga tion one may wish to consider), then other pitfalls may hinder successful analysis, over and above the potential for contamination of DNA irrelevant to the case in hand,109 which has been touched on ea rlier (see p. 403). Amplification of a sample by PCR may be a complete or partial failure due to partial or complete degradation of the DNA or as a result of the presence of PCR inhibitors in the sample that have not been removed during extraction of the DNA. Degradation may be the result of enzymatic, chemical or environmental factors,30, 113 including warm humid con ditions, contamination with soil bacteria or gastric contents, or exposure to the air, fire or chemicals. Fai lure to amplify DNA may be caused by exposure to ultraviolet (UV) light or by a variety of contaminating substances depending on the sample, e.g. humic compounds in soil, haem in blood, poly saccharides and bile salts in faeces, melanin in hair or tiss ue, urea, certain lubricants used on proctoscopes or specula when collecting sampl es or by leather and textile dyes such as indigo, used to dye denim, to name a few. 30,I09,114 Clearly, not only the collection, handling and storage of the samples, but also the environment and treat ment experienced by the sampl e since its deposition have to , be considered. Deliberate attempts may be made by a perpetrator to eliminate incriminating evidence, for example, setting fire to remains, which can adversely affect DNA analysis. STR typing of cremated remains is considered unreliab le and by some to be unsuitable for forensic purposes,115 although others have been able to get successful STR profiling results even from badly charred remains. 116,11 7

407

MITOCHONDRIAL DNA

In some cases there may be no way around the problems of poor quality or quantity of a sample, but it is worth bearing in mind that an alternative to nuclear DNA as an investiga tive tool can be found in the form of mitochondrial DNA (mtDNA). STR and Y-chromosome typing use nuclear DNA as a template and length of SIRs as the basis of discrimina tion and source attribution of a biological sample. However, our cells also have a DNA component contained in their mitochondria, the organelles that are the site of energy pro duction in the celJ. 118 The mitochondrial genome is much smaller than the DNA content of the nuclei, being approxi mately 16.5 kilo bases compared with over 6.4 billion bases in the DNA of the 46 nuclear chromosomes. 119 However, although our cells contain only one nucleus, with one copy of each maternally and paternally inherited allele that are STR typed, there may be hundreds of mitochondria per cell, with each mitochondrion having an average of four or five copies of mtDNA. It has been estimated that on average there are 500 mtDNA molecules per cell, 120, 121 which is highly advantageous if one is faced with very sma ll biological sam ples with nuclear DNA at sub-SIR detection levels because the higher copy number of mtDNA per cell increases the likelihood of recovery of detectable DNA. Another advantage of mtDNA is its increased resistance to degradation, so that in samples in which nuclear DNA can no longer be analysed it may be possible to get genetic informa tion by analysing the residual mtDNA component. For exam ple, mtDNA from human skeletal remains from the Vietnam War which had been exposed to extreme environmental con clitions, including heat and humidity, for at least 17 years has been successfu lly extracted and analysed despite unsuccess ful attempts to type nuclear DNA.122 Mitochondrial DNA has also been sequenced from ancient remains including the Ice man, also known as Otzi, found in the Alps in 1991 , who lived more than 5000 years ago,i23 as well as from Nean derthal fossilsl 24 and from the mammoth. 125 It is worth bear ing in mind, however, that the environment experienced by these remains may have been conducive to survival of DNA, for example, the frozen state of the Iceman. Successful extraction of mtDNA, far less nuclear DNA, is in no way guaranteed, particularly when the sample has been subjected to adverse environmental conditions. While mtDNA may have its advantages, there are down sides too, the main one being the low power of discrimina tion. In a somewhat analogous way to inheritance of the Y chromosome, mtDNA has a characteristic inheritance pattern, being inherited only through the maternal line. It is only the mother of any offspring who passes on mtDNA to her sons and daughters. Mitochondrial DNA that is pres ent in the sperm cell does not enter or survive in the fertil ized egg. 121 There have been reports suggesting rare instances of paternally inhelited mtDNA, but others have questioned the authenticity of these findings as being truly paternally derived mtDNA sequences. 126 It is generally

408 I


accepted that, with the exception of mutation events, all siblings and maternal relatives have the same mtDNA, so it is not possible to identify the source of a particular mtDNA sample to the degree of specificity with which nuclear DNA may be attributed. For forensic purposes mtDNA is analysed by sequencing two specific sections of the mitochondrial genome that show the most interindividual variation, namely hypervariable regions I and II. The sequence results of an analysis are reported in terms of differences relative to a reference sequence l27 of the hypervariable regions. 121 When an unknown sample and a known sample are compared and they share the same sequence, it is not possible to exclude the known sample as being the source of the unknown sam ple, but, analogous to the case ofY-STR typing, nor can one exclude all individuals originating from the same maternal lineage. If more than two differences in nucleotide sequence are seen, the known sample is excluded as the source of the unknown sample. If there is one difference in the sequences, the result is said to be inconclusive to account for mutations that have been seen to occur from mother to child. 128 Mito chondrial DNA has a higher mutation rate than nuclear DNA, and tracking the conservation of a particular sequence through generations and the emergence of mutations has been a useful tool in genealogy studies, acting like a molec ular clock, and has provided support for the 'Out of Africa' hypothesis of human genesis from a woman who lived 200000 years ago. 129. 130 A consequence of mtDNA's susceptibility to mutation can give rise to a situation of heteroplasmy whereby an individ ual can possess mtDNA molecules with different sequences. As there are multiple mitochondlia and multiple mtDNA molecules, if a viable mutation alises in a subset of these molecules they may be passed on as the cells divide, giving rise to mixed populations of mtDNA molecules in an indi vidua1.121.131 Whether more than one mtDNA sequence is detected on sequencing a sample from an individual exhibit ing heteroplasmy will depend on the relative proportions of the different populations of mtDNA molecules in the sample analysed, which may vary from cell to cell and from tissue to tissue. Heteroplasmy appears to be a more common phe nomenon than previously thought 13l and the consequences for forensic analysis should be taken in to account when interpreting results. This appears to be particularly relevant in relation to hair samples, which are often found at crime scenes and used as evidence in a case. Because the root of the hair is needed for nuclear DNA analysis and is lacking in many hairs from crime scenes, mtDNA is more frequently performed and heteroplasmy has been found to be more common in hairs than in other tissues. 132 Probably the most famous example in which DNA evidence was found to exhibit heteroplasmy was in skeletal remains identified as Tsar Nicholas II from exhumed remains believed to belong to members of the Russian Royal family murdered at Ekaterin burg in 1918. The investigation concluded that both Tsar Nicholas II and his brother exhibited heteroplasmy.1 33,134

As for Y haplotypes, a statistical estimate of the signifi cance of a match is needed when mtDNA sequencing fails to exclude an individual as being the source of an unknown sample. The process is similar to the Y haplotype evidence, being a reflection of the frequency at which the given mtDNA sequence occurs in established mtDNA databases. 121

PATERNITY TESTING Inheritance of mtDNA and the Y chromosome provides a means of tracking blood relationship through the genera tions, but often one wishes to have a more definitive means of detelmining the biological parentage of a child. Proof of paternity or maternity may be needed to settle inheritance disputes, child maintenance responsibilities or immigration applications, not to mention the psychological and relation ship issues and problems that go along with doubts in trust and fidelity of relationships. The principles behind paternity testing may also be employed to assist in the identification of the remains of an unknown when no reference sample of the individual is available, if there is evidence to support parentage by individuals who can provide samples. DNA paternity testing uses STR typing and the princi ples behind the manner by which DNA is inherited from our parents. It will be appreciated that, because any indi vidual inherits half of his or her genetic material from each biological parent (one copy of each of the chromosome pairs), the presence of genetic material that is not consis tent with this mode of transmission, i.e. of SIR alleles not present in the alleged parents, is strong evidence that the alleged parents are not in fact the biological parents. In most cases, the biological mother is known and one is seeking to determine whether an alleged father could be the biological father, though it may be the father who is known and it is maternity that is being investigated. Alternatively, one may be faced with the more difficult situation that only a parent and alleged child are available for analysis 135 or it is necessary to determine, in the case that the mother is known, whether two children have the same or a different father. 136 In the first of these scenarios in which the mother is known, if one SIR types the mother, the alleged father and the child, and compares the mother's alleles with those of the child at each SIR locus, it may be possible to determine the allele that the father must have passed to the child, the 'obli gate allele'. For example, if the mother has alleles 15, 16 at a particular SIR locus and the child has alleles 13, 15 then the child must have inherited allele 15 from the mother and, hence, must have inherited allele 13 from the father. If the father has alleles 13, 14 then he could not be ruled out as the father on the basis of DNA evidence, but nor could any other man carrying allele 13 at this locus. If, on the other hand, the mother was 13 , 15 and the child was 13, 15, then it would not be possible to nalTOW the father'S contribution to a sin gle allele because the mother could have passed on either allele 13 or allele 15. A man with either a 13 or a 15 allele

Paternity testing I

could have been the father, i.e. there would be more possible men who cou ld have fathered the child. Obviously, one looks to more than a singl e STR locus when conducting this analy sis to determine if the alleged father has alleles consistent with fatherhood at each locus typed; the greater the number of loci examined, the greater the evidential weight. Tf a n alleged father cannot be excluded as the father, on the bas is of his genotype being inconsistent with those required to fi t the genealogy, then one needs to have a sta tistical measure of the weight of this evidence as indicative of paternity. This is most commonly presented in terms of the combined paternity index (CPl), though the probability of paternity, which is based on a Bayesian approach, is also w idely used. 121, IJ7 - 139 The paterni ty index is a likelihood ratio w here the proba bility of obtaining the observed genotype in the child at a particular locus, given that the alleged fa ther is t he biologi cal father, is di vided by the probability of obtaining the observed genotype, g iven that a random man is the father. Tn order to determine the probability of obtaining the observed genotype, given that a random man is the father, one uses the allele frequencies of the obligate allele from population databases of the race of the alleged father. Tn order to obtain the probability of obtaining the observed genotype, given that the alleged father is the biological father, one looks at his genotype. If he is homozygous for the obligate allele the probability would be 1 because there is no alternative allele that he could have passed on to a child; ifhe is heterozygous for the allele the probability would be 0.5, because there is an equal chance that he passed on either of his altern ative alleles. 121, IJ8 Having calculated the paternity index for each locus, a CPI is calculated by multiplying the paternity indexes for each locus analysed. A cpr of 100 is accepted to establish 99 per cent probability of paternity and a CPI of greater than 1000 indicates that the probability of paternity is greater than 99.9 per cent. A CPI of 100 is the genera lly accepted minimum standard for inclusion,140 although some laboratories use a hi ghe r cpr as their minimum.141 In the context of paediatric cases, paternity testing is not just applied to the situation where one wishes to iden tify the father of the subj ect of the case; t he subject may be the mother, for instance in the case of statutory rape. By DNA profiling feta l material from a borted pregnancies and from the child (mot her) one can determine the likelihood that a given suspect was t he father an d, hence, guil ty of statutory rape. 8J It is important to appreciate that no CUlTent DNA test is definitive and there a re a numbe r of issues relating to pater nity testing that need to be considered. As stated earlier, relatives share a highe r proportion of their genome than random men, so problems may arise if a relative of the real father, for example, father, brother or son, is being consid ered as the biological father. One study found that, in over 31 per cent of cases, an un cle could not be excluded as the father, with five cases showing no mismatches. These five cases would have resul ted in paternity by the uncle being

409

identified had he been the only putative father tested. 142 Other studies also highlight the problem of relatives being mistaken as a biological father; 14J a way to determine more definitively if a given allele is inherited from a given indi vidual would be of great value in preventing potentially mis taken conclusions. Determining the parental origin of alleles would also be of help in cases in which the mother is not available for test ing and DNA is availabl e only from the child and alleged father, in the case that t he mot her and child share the same heterozygous genotype and when multiple male relatives are suspected of incest. A novel test has been proposed that migh t be app licable to these cases. It would look at genomic imprinting that resul ts fro m epigenetic modifications, which change the chemical structure of the DNA without altering the underlying DNA sequence.144-146 Certain genes have been shown to exhibit this phenomenon, commonly by way of DNA methy lation, with the changes being parent specific. It is possible to detect these changes; thus, there may be a way of determining the parental origin of a particular allele. The approach has been proposed for forensic investigations and paternity testing, 147, 148 and it will be interesting to see if it becomes a routine part of forensic DNA analysis, add ing strength to support the RMP, where not only the same alle les are shown to match a suspect but a common geno mic imprinti ng pa ttern is observed. On a related vein, analys is of epigenetic differences has also been proposed as a potential way to differentiate between monozygotic tw ins. As dis cussed above, monozygotic twins inherit the same ge ne tic sequence, and it has been shown that they are epigenetically indistinguishable at birth and in the early years of life ; how ever, older twins exhibit detectable differences in epigenetic modifications of particular sequences t hat were acqu ired during life. This may be one way to differentiate between identical twins.149 While the increase in shared alleles between relatives may lead to problems in identifying the real father in a paternity case, it is worth mentioning that, because relat ives have more alleles in common, the effect of th is in incestu ous relationships gives rise to an increased level of homo zygosity in the offsprin g, which may be used as an ind icator of incest. 150 CPT or alternative statistics may be reported when an alleged man is not excl uded as the biological father. But on the basis of ge nea logy, how different do the alleles need to be from the alleles we would expect the father to have in order to lead to an exclusion? DNA paternity testing works on the same basis as blood group testing, proposed in the 19205, 151 and late r refined, as a means of investigating paterni ty disputes, but may add a greater degree of discrim ination. Rather than looking at the phenotypic effect, i.e. the observed effect of our genetic material, namely what blood group an individual is, 29 DNA typ ing looks at the genetic material itself, which provides more information. Despite frequently being overl ooked today, blood group testing was, and still is, an effective way of, relatively quickly and

410 I


cheaply, excluding an individual as being the source of a samp le or the biological father of a child. If the blood groups did not match a suspect when trying to identify the source of a sample, then a suspect could be excluded or, in the case of a paternity dispute, if the offspring's blood group was not consistent with the possible combinations that could have arisen from the mother and alleged father, then the individ ual in question is excluded . Despite this appa rentl y clear-cut log ic, things may not be quite as simple as far as DNA profiling is co ncerned, for reasons to be explained below, and, from histo rical cases, court decisions have not always followed the scientific theory and evidence for blood group testing. For instance, in the famou s paternity dispute in 1946 involving the actor and director Charlie Chaplin, the apparent clear impossibil ity of fatherhood, on the basis of blood group testing, was not viewed as bei ng conclusive, and Chaplain was ordered to pay child support to the child of Ms Joan Berry.152.153 In 1983, Shaw l52 stated 'Motherhood has always been a biological certainty; now fatherhood will be as well. We will have come one step closer to equality of sexes.' Little did he anticipate the consequences of errors that have been, and no doubt will continue to be, made in conducting in vitro fertili zation (NFl. A growing number of cases have come to light in which embryos have been transferred to the wrong . woman, so that she has been impl anted with another woma n's eggs; the wrong spelID has been used to inseminate eggs; or both errors have occurred. 154 ,155 It has been admit ted that these mix-ups are a regular occurrence in fertility clinics in the UK;156 similar cases have arisen in other coun tries. 157 ,150 Th e majority of cases t hat have come to light involve white parents having a black child, or vice versa. This is the most readily apparent way of detecting any mis takes. How many other cases go undetected is open to ques tion. Paternity testing is one way that ca n bring the errors to the fore . The ramifications of such events for the parties involved cannot be underestim ated, encompassing psycho logical trauma, legal parenthood and custody issues as well as compensation considerations. 155 ,158-1 60

Mutation and Anomalous Genotypes While the decision in the Charlie Chaplin paternity case has been cliticized, given what appeared to be an impossibility of blood group inheritance, using DNA analysis, failure to exclude an individual as a parent, even when alleles of the alleged father do not appear t o fit those expected, do es have scientific reasoning. The fact is that SIR loci, like any region of the genome, are susceptible to mutation. 161 In fact, these regions of the genome are particularly susceptible to muta tion and show a high rate of mutation during gamete forma tion, when the cells undergo meiosis, which can lead to allel ic change from one generation to the next. 162-165 This can result in an allele in the offspring being different from the parental allele from which it was derived, and without further testing

might lead to a conclusion of non-paternity being dra wn. 166- 169 Mutation rates vary across the SIR loci and some may be as high as 0.3 per cent of meiotic events. 165 Evidence of two mutations occuning between generations in several cases has led to a minimum of three independent allel ic inconsistencies being required for a putative father to be excluded as the biological father. 167 ,168 When there is doubt whether inconsistent alleles are due to mutatio n or a genuine excl usion of the alleged father, typing the Y chromo some SIRs of the child, if male, may provide further evidence to show a genuine exclusion or not, as the case may beY6,1 70 The mutations discussed above relate to ge rmline events, which are passed from parent to child and affect all the cells of the offspring, though somatic mutations may also arise in cells other than the parental gametes. If a mutation arises at an STR immediat ely post fertilization and that STR is subject to forensic ana lys is, then the resulting cells of the offspling will have a profile that differs from that expected on the basis of genetic inheritance. All the child 's cells will carry the mutated allele and not the parental one. This has consequences for pat ernity investigations. It is not just in paternity investigations that mutations can affect the outcome of t he investigation. Somatic cell mutations in SIRs can lead to anomalous profiles with more than two alleles being seen per locus 171, 172 and discrepan cies in results of comparison of profiles, even if the profiled sa mples originated fro m t he same individual. If a mutation a rises in a subset of cells that are profiled , and the mutated cells are at a level above the threshold of detection, a com parison between pro files of cells of a different tiss ue, or a sample of cells lacking a sufficient proporti on of mutated cells for detection, can lead to the possibility of a common source of the samples, and thus a match, being missed. This may be of relevance if, for example, blood cells sampled at a crime scene have a different profile from those of buccal cells taken as a reference sample from a suspect. Individuals who possess cells with different genotypes that have arisen from a single zygote by way of mutation are known as mosaics. 173, 174 An individual may also possess cells of differen t genotypes because of ch imerism resulting from natural anomalous events in which more t han one zygote fuses to create a single individual; 175-1 78 when cells derived from a different zygote are present in a single indi vidual (e.g. if dizygotic twi ns exchange blood across a pla centa l79 ,lool or as a result of medical intervention, be it bone marrow or organ donation.181-184 In the case of bone mar row transplantation, for example, it is possible for false identification to ar ise when the donor may, in fact, be the guilty party, but because the recipient harbours cells shown to match the donor's cells left at a crime scene the recipient may be falsely accused or convicted. 185 It will be apparent that chimerism and mosaicism can lead to inappropliate exclusion of the true source of a sample, when looking for a match, and to the exclusion of a biologi cal parent as being so if the possibility of the phenomenon is not taken into account during an investigation. 175 ,176, 186

Identification: body remains/missing persons I

The problem of the perception of the infallibility of DNA evi dence was highlighted in the media-grabbing case where a mother was accused of committing benefit fraud because it was alleged that the she could not have mothered the children in question and risked them being taken in to care. It was only after her third child's birth was witnessed, and DNA evidence also showed that baby appeared not have been her child, that it was discovered that she was a chimera. The cells giving rise to her offspring were of different genotype to those typed during the maternity investigation. 177

parent. The best it can do is provide evidence in terms of sta tistical probability and it is up to a jury or those concerned to determine if it fulfils their criteria of proof.

IDENTIFICATION OF BODY REMAINS AND MISSING PERSONS

The Use of Mitochondrial DNA and the Y Chromosome in Paternity Cases As mentioned above, the Y chromosome may be used to pro vide additional information in cases where there may be uncertainty over whether a mutation has arisen from father to child. There may be occasions when paternity is in dispute and samples of the putative parent are not available, which causes practical problems. Sometimes, material may have been taken for medical investigations and, if it has been stored, it may be accessed and used as a source of DNA.166 Obviously, this is not always possible, and one approach that might be adopted in the case of a male offspring is analysing the Y chromosome haplotype of male relatives of the puta tive father, given that the Y chromosome is passed from father to so n and, barring mutation, aU these family relatives would share a common Y chromosome. This was put in to practice in the attempt to address the long-standing histori cal controversy over allegations that the US President Thomas Jefferson fathered the sons of one of his slaves, Sally Hemmings. The first source that on e would look to in order to type a deceased's Y chromosome would be known male offspring of the alleged father, but Jefferson had no surviving sons. Instead data were gathered from male-line descendants of two sons of the president's paternal uncle, male-line descendants of the two men Jefferson was alleged to have fathered (Thomas Woodson and Eston Hemmings) and male line descendants of the sons of Jefferson's sister, also suspected of fathering one of Hemming's children. Analysis of the Y chromosome haplotypes excluded Jeffer son of fathering Thomas Woodson, but the younger son, Eston Hemmings, sha red the same Y chromosome haplotype as Jefferson 's relatives, providing support that he may have been Jefferson's illegitimate son. 187 However, the very fact that Jefferso n's male relatives had a common Y haplotype also means that any of Jefferson's male relatives alive and capable of fatherhood at the time co uld not be ruled out as the father and the president was only one of several candi dates, despite the incriminating publicity the results of th e study attracted. 188 The lack of conclusive evidence has meant the descendants of Jefferson's daughters have not accepted the relationsh ip,1 89 highlighting the fact that DNA evidence cannot conclusively identify an individual as being the source of a sample or an individual as being a biological

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The loss of a child is devastating for any parent, and one can not overemphasize the importance of closure for families in the event of such tragedies by way of positive identification that their child has actually died. If the remains of a deceased person can be identified, this can put an end to uncertainties or hopes that a child may have sUlvived and can enable return of the body or remains to the next of kin for appropri ate burial, events that may be of deep psychological and reli gious significance and comfort at a time of distress. DNA analysis is one way that can assist in the identifi cation of human remains, but the approach is not without problems. Not only does one have to address the state in which the remains are found , which is often far from ideal because of degradation or decomposition, but one needs to acquire a reference profile with which to compare that of the remains. There is also the issue that following some incidents, for example, explosions, body parts may be frag mented and widely dispersed, adding to the difficulty of reunify in g an identified whole body. If the remains show few signs of decomposition, it will generally be possible to obtain DNA from blood samples or internal soft tissue which has been largely unaffected. As the degree of decomposition increases, blood becomes less of an option and superficial soft tissue may exhibit signs of putre faction, in which case tissue or muscle deep er within the body and/or bone marrow may yield DNA suitable for STR profiling. When remains are at an advanced state of decom position, bone marrow may still be able to provide material for a DNA profile but, as decomposition progresses, the extraction process increasingly faces problems of cell debris, decomposition products and contaminants that can inhibit the PCR reaction, and thus need to be removed. If bone mar row does not yield a profile then hair may be STR typed, if the root rema ins, or mtDNA from the shaft may be sequenced. Alternatively, DNA could be extracted from skeletal struc tures, which is also the option when remains are fully skele tonized. The resistance of structures such as bone and teeth offers protection to DNA contai.ned in the bone matrix or tooth pulp; however, this, in turn, requires special proce dures to extract and purify it. The level of nuclear DNA that can yield an STR profile from these sources is low; sequenc ing the more resistant mtDNA may be the only option avail able. On rare occasions one may be faced with naturally mummified or desiccated remains, which present their own challenges, particularly if there is a degree of decomposition. Extracting DNA from soft tissue of such remains has given little, or marginal, and inconsistent success in STR profiling (Jason Eshl eman, personal communication; Carlos Morales,

412 I


personal communication), though extracting and typi ng DNA from bones and teeth of such remains does not appear to offer significant problems over other sources of bone and teeth (Tim Clayton, personal communication; Jason Eshle man, personal commu nication) . DNA has been extracted and sequenced from dried superfici al parts of Egyptian mummi fied remains, suggesti ng that it is possible to get genetic information from such material, but the DNA in this case was in a fra gmented state, making its suitability for STR analysis questionable. It was only one of many samples studied that indicated that recoverable DNA might be obtained. 190 It is possible tha t natural and artificial mummi fication may affect the success of extraction. Despite these issues and potential problems, DNA analy sis has been of Sign ificant value to investigating teams in major incidents or mass disasters over the years. Although techniques such as visual identifi cation, odontology, anthro pology, fingerprint analysis, radiology and facial reconstluc tio n can go a long way in helping to identify remains, they may not always be appropriate or possible. DNA analysis has succeeded in many investigatio ns, in conjunction with these tech niques, or in cases in which other techniques have been unsuccessful. For example, in 1998 a tragic fire in Manila resulted in the death of 23 children between the age of six months and eight years. The bodies were initially buried unidentified, but three mon ths later the burial site was exhumed in an attempt to identify the remains. 191 Exhumation recovered 22 bodies, and a combination of autosomal and Y chromo so me typin g was carried out on 21 of the bodies that had not been otherwise identified. The identification process was assisted because th e identity of the children present at the tragedy was known, though this may not always be the case in such investigations. It was also possible to deter mine the approx imate age range of the re mains, which was of further benefit. Ten of th e exhumed bodies were believed to be sibling pairs and 11 were unrel ated to each oth er. 191 Despite the bodies hav ing been burnt, buried an d exhumed, DNA analysis succeeded in matching 18 of the remains with a known ch ild. In two of the cases mothers were able to provide reference mate ria l in the form of stored umbilical tissue from their child, which had been kept in accordance with Philippine custom an d which provided a positive identification . 192 Iden tificatio ns of the other children, for whom ante mortem reference sa mples were not ava ilable, was achieved by patern ity-type ana lysis using autosomal STR profiling, as well as by comparison ofY haplotypes, by analysing DNA reference samples from 10 mothers, three fathers and a paternal grandfather of two children for whom a paternal sample was unava ilab le. Y haplotypes were valuable in iden tifying not only father/grandfather to son/grandson rela tionships but also those of sibling brothers. 191 In the Manila fire tragedy, the remains had been subject to extreme conditions so it was no t su rprising that a full profile was not obtained for evelY sample typed. Where

alleles cannot be identified at evelY 10CllS, th e evidential weight is lower but va luable information can still be obtained, as illustrated by this case. Having an ante-mortem reference sample of a mlss1l1g individual with which to compare DNA profiles of remains goes a long way to aiding the process of identification, and over the years such samp les have been taken from tooth brushes, hairbrushes, clothes, towels and leftover food with bite marks.30.193 It is important to realize, however, that sllch items are mobile and may have been used by someone other than the owner and, hence, might cany DNA of someone other than the individual in ques tion. Archived medica l samples are a very useful source to turn to for ref erence material if they are available. The paternity-type approach, using pedigree analys is to identify remains when reference material is ava ilable from the pa rents of a ch ild suspected to have di ed, is commonly used. Knowing each parent's alleles, one can predict the range of possible genotypes that their child could have and eliminate remai ns that do not cOITespond to these. If a match is identified, the li kel ihood that the remains are the biologi cal child of the couple rather than the child of an unrelated co uple can be determined statistically. Admittedly there can be a velY large number of possi ble combinations (for a 10 loclls profile this cou ld be as high as 1048576), but the approach has been used successfully in many mass disasters. For example, after the Waco, Texas, incident of 1993 - when the remains of 61 individua ls were recovered in varying states of preservation, some in a n advanced sta te of putre faction and others badly charred - 26 positive identifications were made in this way.194 It is also possible to gather suf ficient inform ation when a single paren t is available as a reference sample, 195 though the statistical weight of the evi dence will be less, and comparison with a sibling's genotype may also be helpful. In aeroplane traged ies, families are often present together on the same flight and the common ality of alleles across the generation can be used in identify ing family members. The 9/11 disaster of 2001, when 2792 people were killed in a terrorist attack on the World Trade Center, must surely have been one of the most challenging investigations, and those w ith the task of recoveling and identifying the remains faced lo gistical, technical, practical, scien tific and medical difficulties. Although direct matches with referen ce samples were used where possible to identify the remains, other DNA techniques, including the paternity approach, were also employed. 196 It will be appreciated that in paternity analysis there is always the chance of a coincidental match. A particular all ele at a locus is shared not only by a parent and child, but also by approximately 1 in 1000 random pairs of indi viduals, so an attempt was made to minimize the number of false-positive matches obtained during the identification process. 197 The number of false-positive results is related to the size of the reference list and the number of victims, and therefore is a major consideration in investigations such as

Identification of an unknown profile I

the 9111 tragedy, but it should also not be overl ooked in investigations invol ving smaller numbers of victims. As men tioned previ ous ly, the state of the remains can affect the amount of information that can be obta ined from STR analysis. Poor-qu ality DNA may not provide results for the alleles present at all loci typed, or it may resu lt in iden tifica tion of only a sin gle allele in a hete rozygous individual when there really should be two alleles; one always needs to be aware of the possibility of this so- ca lled allelic dropout. In many cases, the reason for poor SIR resu lts is that the STR fragment in the sa mple is no t intact along its whole length, as it should be. As DNA degrades it fragments into smaller pieces a nd breaks may occur within the SIR; thus, the true alleles are not detected. It may be possible to design PCRs for STR profiling that look at smaller sections of DNA, 198 and commercial kits adopting this approac h are no w available ; the sma ller t he targeted DNA being identified, the greater the chance it remains intact. Where there are deficiencies in SIR typing, mtDNA may be sequenced, as discussed ab ove, or the in format ion gathered from partial STR profiles may be sup plemented by, or rep laced, with SNP data. 199 SNPs are single base sequence variations between indiv iduals at a particular positio n in the gen ome. These sites are ab undant (estimated 10 million) throughout the genome, but because they are mostly biallelic they lack the polymorphic variation across the population that SIRs exhibit. 2oo However, if one geno types a DNA sample at many SNPs, one can approach the discriminatory power of SIR profiling. Estimates vary as to how many are needed, but it is likely that between 50 and 100 may be required,199 consistent with the 70 used in rela tion to the 9/11 investigation. 196

IDENTIFICATION OF THE 'ABANDONED BABY' OR FETAL MATERIAL AND AVENUES FOR IDENTIFYING THE SOURCE OF AN UNKNOWN PROFILE The approac hes described above, which are used to identify the remains of a ch ild , ha ve been geared towards identify ing a previously know n livi ng individual, either by directly matc hing a profil e with a reference sam ple from the indi v idual or through pedigree analys is. However, one may be faced with the scenario of an aba ndoned newborn or fetus requirin g investigation. In such a scenario t here will be an endeavour to iden tify the mother. Whethe r maternal DNA can be recovered from the scene to ass ist will depend on the post-partum circum stan ces and the conditi on in which the newborn is found. Ma ternal DNA has successfully been recovered and pro filed from placental material found abandoned with a wrapped dead newborn, as well as from blood found on the wrappin g material. Using the profile, it was possible to determine the mothe r of the baby in this case. 83 Obviously, this outcome requires that a reference sample is available fro m the mother fo r comparison. For exam ple, entries on a

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413

nationa l DNA database can be searc hed agai nst the profile in question or from a woman suspected of being the mo ther during the investigation. Placental material is an ideal source of maternal DNA in such circumstances, but it may not always be available. In another repolied case, a live newborn was fou nd abandoned in a box but no pl ace ntal materia l was found with the baby. It was, however, possible to obtain a profile of the mother by extracting maternal DNA from vernix caseosa on the ha ir and body of the newborn, which conta ined maternal blood. 83 One should be aware of the potential for such mate rial being relevant and useful in similar investigations. A more problematic scenario is the case of the abandoned baby fou nd long after deli vely. The rem ains may have decomposed, with the concomitant difficulties of obtaining DNA profiles discussed previ ously, or there may be circum stances in which the deceased has been concealed or the environment has been conduci ve to mummification. As men tioned earlier, DNA profiling of desicca ted material is prob lematic. [n the case of a mummified baby, there is the addition al issue that bone and teeth, a commonly used source of DNA in the case of remains, will be unavailable if the neonate's bone is cartilagi nous and teeth have not erup ted. Despite the difficulty in obtaining suitable genetic informa tion from desiccated tissue, profiles have been obtain ed from mummified tissue from babies, though in these cases there was no accompa nying decomposition of the bodies, which may have contri buted to the successful results. [f no maternal DNA is found with the fet al remains but a DNA profile of the baby can be obtained, genetic analysis resorts to the pedigree type of analysis: comparing the baby's profile with those of suspected parents in a paternity testing approach to look for consistent transmission of alleles. As stated above, the statistical weight of such an analysis is less than if information is available from at least one parent. 195 The problem is obtaining DNA from a suspected mother when there may be no lead to the parents. However, this is true of any investigation centring on DNA. An SIR profile alone provides no meaningful information other tha n the sex of the individual. What fo llows desc ribes possible means of identifying a candid ate so urce when there is no match with existing profiles on national DNA datab ases or with suspects in the case, these being the first two options to consider. Typ ing the less specifi c mtDNA or Y chromosome might be of assistance in spread ing the net wider: identifying a match might go so me way in identifying a possible pedigree that may lead to a parent, but this type of investigation may also lead to nothing. A similar technique, so-called 'familial searching', is also increasin gly being used. In this case, rather than searching existing databases for a profile that matches all alleles at all loci, a less stringen t search is employed, allow in g profiles with some allelic mismatches to come to light. The logic beh ind this approach is that such profiles might belong to relatives of the true source, who would be expected to share more all eles in common than a random individual,

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Foren sic DNA profiling

and it may be possible to home in on the true source of the sample through a family member. The techn ique has been used successfully20' but raises many ethical issues and remains highly controversiaI.202-204 As with many genetic based investigations, there is the potential to uncover other wise unknown non-blood relatio nshi ps in individuals believed to be true relatives, with ramifications for family relationships that shoul d not be considered lightly. A number of studies have pointed to the potential to obtain an indication about the physical charactelistics of a source of DNA in a forens ic investigation in which no matching reference sample is found, based on the fact that the physically recognizabl e characteristics of an individual are, at least in part, genetically determined.14.2os-207 Acquir ing information about the race of the source of the sample has also been proposed, based on inter-racial genetic differ ences. However, moving from looking at physically incon sequential as pects of our genetics in the form of rou tinely analysed STRs, currently believed to have no influence on our characteristics or health, to more personal and sensitive information is something that wiJi have social implications that need careful consideration, particularly when such information is unlikely to be conclusive and may be of no investigative va lue, given the com plex play of genetic and environmental facto rs t hat make us who we are.20B-2IQ In the specific case of the abandoned baby or fetus, one may come across rare cases in wh ich there are indications in the deceased of a genetically inherited condition, for exam ple the charactelistic features of Down's syndrome. 173 In such cases prenatal genetic testing of the fetus may have been carri ed out, and it may be possible to co mpare the pro file of the baby with stored clinical samples. A match wi th a clinical sample could lead to the parents through medical records. With increased use of electronic medical records, th is approach could become a more realistic prospect in the future. Admittedly these are tenuous possibilities, requiring significant investigative power and resources, and one has to accept that DNA evidence may not provide constructive evidence in an investigation. There may be times when an investigator wants to know the age of the source of a sample, for example if a newborn is illegally removed from hospital, or to determine if fet al blood is present in putative products of conception in crim inal abortion investigations. Physical chara cteristics can be of some help in some cases, but inte resting research has identified a method that can differentiate between blood fro m a newborn less than a day old , blood from an infant less than four months old and blood from infants over four months of age by assaying the expression levels of particular haemoglob in genes, which exhibit a highly age specific expression pattern .211 Implementation of this ap pro ach in forensic investigations may provide va luable inform ation for future investigations. Rath er than looking at the DNA itself, one is looki ng at the translated product of DNA, ribonucleic aci d (RNA), which acts as a intermedi ary in translating genes into an end product.

DNA DATABASES

In this chapter, mention has frequent ly been made of DNA databases. Currently, national DNA databases are the norm, com ing under national legislation and management, wi th the nations' authorities having varying powers to collect and analyse samples from individuals depending on the severity of the suspected crime. In the UK, authorities have the power to take and analyse a DNA sample from anyone suspected of having committed a recordable offence. These samples are entered on th e UK National DNA Database, the largest data base in the worl d, where they are cross-checked against exist ing entries on the database to look for a match. Profiles may be from individuals convicted of a crime, fro m previous arrestees or from samples taken from unsolved crime scenes; matches connecting crimes with named known individuals or linking crimes with other crimes can be made. Under English law samples taken from a suspect remain on the UK National DNA Database indefinitely, regardless of whethe r the suspect is co nvic ted, acquitted or never brought to trial. Authorities in other countries or states have lesser powers to take or retain samples, and there is significant valiation throughout the world. The question is whether full harmonization of laws and intercountry procedural standardization can ever be established. The Combined DNA Index System (CODIS) oper ates in the USA, and it enables laboratories to exchange and compare DNA profiles at a state and national level. The exis tence of an Interpol DNA database and DNA Gateway enables the sharing of data across nations, so there are moves towards global cooperation. One has to wait to see whether a truly international database is esta blished containing every one's profile with the a im of assisting in solving Clime at an internationa l level. This is something aspired to by some, but, unsurprisingly, a view not shared by many, who feel that such a move constitutes a serious violation of civil liberties. DNA has had a major impact on the field of forensic sci ence and investigations. Without DNA we would not be here as living beings; without DNA a nalysis, undeniably, many investigations would have gone unsolved, but we should be aware that the techniques have their limits. DNA provides only one piece of evidence in any case, and any resul t and statistical likelihood of a chance match needs to be cons id ered in the context of the case as a whole.

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