V O LU M E
T H I RT Y
S I X
INTERNATIONAL REVIEW OF
RESEARCH IN MENTAL RETARDATION
Board of Associate Editors
PHILIP DAVIDSON University of Rochester School of Medicine and Dentistry
ELISABETH DYKENS Vanderbilt University
MICHAEL GURALNICK University of Washington
RICHARD HASTINGS University of Wales, Bangor
LINDA HICKSON Columbia University
CONNIE KASARI University of California, Los Angeles
WILLIAM McILVANE E. K. Shriver Center
GLYNIS MURPHY University of Kent
TED NETTELBECK Adelaide University
MARSHA M. SELTZER University of Wisconsin-Madison
JAN WALLANDER Sociometrics Corporation
V O LU M E
T H I RT Y
S I X
INTERNATIONAL REVIEW OF
RESEARCH IN MENTAL RETARDATION Edited by
LARAINE MASTERS GLIDDEN Department of Psychology St. Mary’s College of Maryland St. Mary’s City, Maryland
AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier
Academic Press is an imprint of Elsevier 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 84 Theobald’s Road, London WC1X 8RR, UK Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands First edition 2008 Copyright ß 2008, Elsevier Inc. All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email:
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CONTENTS
Contributors Preface
ix xi
1. Newborn Screening for Intellectual Disability: Past, Present, and Future
1
Don Bailey 1. Introduction 2. Evolving Guidelines and Practices for Newborn Screening 3. Current Issues in Newborn Screening 4. The Nature of the Condition 5. Test Characteristics 6. Benefits From Screening 7. Summary and Future Directions References
2. Responsive Parenting: Closing the Learning Gap for Children with Early Developmental Problems
2 4 8 8 13 15 19 22
27
Susan H. Landry, Heather B. Taylor, Cathy Guttentag, and Karen E. Smith 1. 2. 3. 4. 5. 6.
Introduction School-Age Developmental Characteristics Shared Challenges for Effective Learning What is Responsive Parenting? What Supports Responsive Parenting? Evidence for the Specialized Support of Responsive Parenting for Core Deficits 7. Evidence from Longitudinal Studies for Closing the Learning Gap for At-risk Children 8. Evidence from Experimental Findings for Closing the Learning Gap 9. Summary and Conclusions, Implications and Future Directions References
28 30 31 36 38 39 44 45 50 54
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Contents
3. Trisomy 21: Causes and Consequences
61
Jeannie Visootsak and Stephanie L. Sherman 1. Introduction 2. Major Cause of DS: Meiotic Nondisjunction in Oocytes 3. Prevalence and Survival of Individuals with DS Throughout the Life Span 4. Etiology of DS-Associated Medical Disorders 5. Neurodevelopmental Outcomes of Comorbid Medical Conditions in DS 6. Psychiatric and Neurobehavioral Issues in DS 7. Summary References
4. Alzheimer’s Disease in Adults with Down Syndrome
61 64 72 77 82 87 89 90
103
Warren B. Zigman, Darlynne A. Devenny, Sharon J. Krinsky-McHale, Edmund C. Jenkins, Tiina K. Urv, Jerzy Wegiel, Nicole Schupf, and Wayne Silverman 1. Introduction 2. Down Syndrome/Alzheimer’s Disease Research Program References
104 108 135
5. Foolish Action in Adults with Intellectual Disabilities: The Forgotten Problem of Risk-Unawareness
147
Stephen Greenspan 1. Introduction 2. A Four-Factor Model of Foolish Action 3. Varieties of Foolish Acts Committed By Different Populations 4. Brain Damage and Foolish Action: FASD as an Exemplar 5. Research and Policy Implications 6. Conclusion References
6. Animal Models of Self-Injurious Behavior: Induction, Prevention, and Recovery
148 152 162 176 182 188 189
195
Stephen R. Schroeder, Pippa S. Loupe, and Richard E. Tessel 1. Introduction 2. Animal Models of Induction of SIB 3. Animal Models of Prevention of SIB 4. Animal Models of Recovery from SIB 5. Overall Summary and Future Directions References
196 199 209 210 220 224
Contents
7. Theoretical and Methodological Issues in Sibling Research
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J. Carolyn Graff, Susan Neely-Barnes, and Heather Smith 1. Introduction 2. Themes in Sibling Research 3. Theoretical Approach 4. Research Method 5. Frontiers and Directions for Sibling Research 6. Conclusion References
8. Understanding Individual Differences in Adaptation in Parents of Children with Intellectual Disabilities: A Risk and Resilience Perspective
234 235 240 245 265 269 271
281
Malin B. Olsson 1. Introduction 2. Risk and Protective Factors in the Field of Families with a Child with ID 3. Risk Factors 4. Protective Factors 5. Outcomes 6. Discussion 7. Conclusion References
9. ‘‘What do you Think if . . .’’: Using Vignettes to Study Attitudes Toward Adult Sibling Caregiving and Competence of Parents of Children with Disabilities
282 285 287 293 301 303 307 307
317
Brian M. Jobe and Laraine M. Glidden 1. Introduction 2. Topic 1: Young Adults’ Levels of Caregiving for Hypothetical Siblings 3. Topic 2: Stereotypic Views of Parental Competence and Family Expansion 4. Summary and General Discussion References Index Contents of Previous Volumes
318 320 326 331 337 343 351
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CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
Don Bailey (1) RTI International, Research Triangle Park, North Carolina 27709-2194 Darlynne A. Devenny (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Laraine M. Glidden (317) Center on Health and Education, Georgetown University, and Department of Psychology, St. Mary’s College of Maryland J. Carolyn Graff (233) University of Memphis, College of Nursing, Boiling Center for Developmental Disabilities, Memphis, Tennessee 38105 Stephen Greenspan (147) University of Colorado Health Sciences Center, Colorado 80045; Email: stephen.
[email protected] Cathy Guttentag (27) University of Texas Health Science Center, Houston, Texas 77030 Edmund C. Jenkins (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Brian M. Jobe (317) University of Maryland, Baltimore, Maryland 21228; Email:
[email protected] Sharon J. Krinsky-McHale (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Susan H. Landry (27) The University of Texas Health Science Center, Houston, Texas 77030 Pippa S. Loupe (195) Bureau of Child Research, University of Kansas, Dole Human Development Center, Lawrence, Kansas 66045-7555 Susan Neely-Barnes (233) University of Tennessee, College of Social Work, Memphis, Tennessee 38103 ix
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Contributors
Malin B. Olsson (281) Department of Psychology, Go¨teborg University, Go¨teborg, Sweden Stephen R. Schroeder (195) Bureau of Child Research, University of Kansas, Dole Human Development Center, Lawrence, Kansas 66045-7555 Nicole Schupf (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Stephanie L. Sherman (61) Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30033 Wayne Silverman (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Heather Smith (233) University of North Carolina, North Carolina 27599 Karen E. Smith (27) University of Texas Medical Branch at Galveston, Houston, Texas 77030 Heather B. Taylor (27) University of Texas Health Science Center, Houston, Texas 77030 Richard E. Tessel (195) Bureau of Child Research, University of Kansas, Dole Human Development Center, Lawrence, Kansas 66045-7555 Tiina K. Urv (103) Mental Retardation & Developmental Disabilities Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 Jeannie Visootsak (61) Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30033 Jerzy Wegiel (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 Warren B. Zigman (103) New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314
PREFACE
As you have come to expect in eclectic volumes of the International Review of Research in Mental Retardation, the range of focus in Volume 36 is broad. The empirical work described includes animal models and research as well as investigations with human participants. The core domains intersect with medical decision-making, intervention approaches, social psychology, and family issues. Two chapters focus on Trisomy 21/Down syndrome, although from quite different perspectives, and important theoretical issues are addressed in a number of chapters with intent sometimes to address the entire field of intellectual disabilities and other times a selected portion of it. As usual, both as editor and as reader, I owe a great deal to the individuals who provided expert review for these highly diverse original manuscripts. Collectively, they were able to span the breadth of the field of intellectual disability from its basic biological underpinnings to its applications for ameliorating learning problems. Three of these reviewers were members of the Board of Associate Editors and I am especially grateful to Mike Guralnick, Richard Hastings, and Linda Hickson for their continuing support in multiple ways, as well as to Elisabeth Dykens who coauthored a chapter in this volume. Listed in alphabetical order, the following additional reviewers provided timely and constructive comments: Rhonda Black, Monica Cuskelly, Bob Edgerton, Charlotte Hobbs, Rodney Howell, Jim Leffert, Mark Lewis, Gael Orsmond, Sonja Rasmussen, Curt Sandman, Davida Sears, Travis Thompson, Steve Warren, and Michael Watson. The first two chapters focus early in the lifespan. In Chapter 1, Don Bailey gives us a peek into the future as he anticipates the brave new world of newborn screening for intellectual disability. He cautions us that economic and cultural factors cannot be divorced from medical decisionmaking and that challenges lay ahead regardless of the course that is charted. Susan H. Landry, Heather Taylor, Cathy Guttentag, and Karen E. Smith address a different set of challenges in Chapter 2 on responsive parenting. They review the importance of the parental role in early development of children with spina bifida, Down syndrome, and very low birthweight. Their longitudinal research with children from this last group provides
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convincing evidence that risk can be ameliorated with effective environmental manipulations such as contingent responsiveness and rich verbal input. Jeannie Visootsak and Stephanie L. Sherman also focus on Trisomy 21 leading to Down syndrome. Their emphasis is on the causes of meiotic nondisjunction in oocytes, the most frequently occurring etiology of Trisomy 21, as well as how associated defects affect neurodevelopmental outcomes. Their emphasis is on children, but they do briefly address symptoms of dementia arising later in the lifespan, an excellent segue into Chapter 4 on Alzheimer’s disease in adults with Down syndrome by a research team that has been studying this condition for many years. Warren B. Zigman and his seven coauthors document that despite the elevated risk for Alzheimer’s disease faced by adults with Down syndrome, substantial variability in outcomes is part of the profile, and is interesting and important both for science and human services. Stephen Greenspan takes us on quite a different journey in Chapter 5 in which he develops and explains a new (but rooted in historical writings) theory of the core deficit in mental retardation/intellectual disability. Even the title—Foolish Action in Adults with Intellectual Disabilities: The Forgotten Problem of Risk-Unawareness—in intriguing, and its promise of provoking an examination of the meaning of mental retardation is fulfilled by the end of the chapter. You may not agree with everything that Steve Greenspan has written here, but you will, nonetheless, be glad that he has written it. In Chapter 6, Stephen R. Schroeder, Pippa S. Loupe, and Richard E. Tessel (deceased) review five decades of research on animal models of selfinjurious behavior (SIB), concluding that four models have been especially productive in inducing it. Some readers will be especially interested in the authors’ own 10-year program of research involving research for training from recovery from SIB, as it has important implications for treatment. In the next three chapters, the focus is on family. J. Carolyn Graff and her coauthors, Susan Neely-Barnes and Heather Smith (Chapter 7) and Malin Broberg Olsson (Chapter 8), review extensive research databases with an aim to understanding the themes and issues that have dominated their field. Siblings are in the forefront in Chapter 7, whereas parents are the primary interest in Chapter 8. Nonetheless, some of the core constructs, such as adaptation, risk, and resilience, and the factors that influence them are themes in both the chapters. My coauthored chapter with Brian M. Jobe is squarely in the tradition of the experimental psychology of intellectual disability. In taking this approach, we tackle two different domains of family—sibling caregiving and judged parent competence. We propose and (I hope) persuade that the use of vignettes to study the attitudes of people about disability issues has value both for the data it contributes to the field and also the didactic and training opportunities it affords.
Preface
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Finally, writing this preface is a bittersweet task for me. This volume is the penultimate one for my editorship, and the last one that is eclectic and singly edited. After Volume 37, which I will coedit with Marsha Seltzer with Families as its theme, the Series Editorship will be assumed by Bob Hodapp of Vanderbilt University. Indeed, as I write this preface, Bob is developing Volume 38. Please contact him for information about the Series as it moves forward. He has some exciting plans and I am grateful to have him as my successor. To all the readers, regular or occasional, I thank you for your interest and urge you to continue your loyalty to the International Review of Research in Mental Retardation. LARAINE MASTERS GLIDDEN
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C H A P T E R
O N E
Newborn Screening for Intellectual Disability: Past, Present, and Future Don Bailey* Contents 2 4 8 8 13 15 19 21 22
1. Introduction 2. Evolving Guidelines and Practices for Newborn Screening 3. Current Issues in Newborn Screening 4. The Nature of the Condition 5. Test Characteristics 6. Benefits From Screening 7. Summary and Future Directions Acknowledgments References
Abstract Newborn screening began in the 1960s with a condition causing severe intellectual disability, phenylketonuria, a disease that could be remediated through a dietary change that prevented intellectual disability. Since then newborn screening has become a significant public health initiative offered in every birthing hospital in the United States, sometimes for more than 50 conditions. The landscape of newborn screening is changing rapidly, however, as a result of new gene discoveries, technological developments, advocacy efforts, and private market forces. Soon it will be possible to screen for many conditions causing intellectual disability, but for which there will be no immediate medical treatment, evoking issues related to the ethics of disclosing genetic information about ‘‘untreatable conditions’’ and the support systems that would be necessary to help families and children cope with this information. Fundamental questions have been asked about the likelihood of various costs and benefits of early identification, prompting a whole new set of demands for data on the efficacy of earlier psychosocial interventions and the timing of treatments. This
* RTI International, Research Triangle Park, North Carolina 27709–2194
International Review of Research in Mental Retardation, Volume 36 ISSN 0074-7750, DOI: 10.1016/S0074-7750(08)00001-3
#
2008 Elsevier Inc. All rights reserved.
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chapter reviews the history and current status of newborn screening for intellectual disability, envisions a likely future of possible genetic disclosure, and identifies research questions that will need to be answered to help inform public policy.
1. Introduction The history of newborn screening is well-known and has been described extensively in a number of publications (e.g., American Academy of Pediatrics Newborn Screening Task Force, 2000). Of special relevance to the International Review of Research in Mental Retardation is that the disease that prompted the development of newborn screening was phenylketonuria, a well-known cause of intellectual disability. Individuals with untreated PKU typically have moderate to severe intellectual disability. A dietary change can almost completely prevent intellectual disability from occurring, but to be effective, the altered diet must begin shortly after birth, since damage caused by untreated PKU is difficult to reverse. Unlike Down syndrome, the phenotype for PKU is not obvious at birth through symptoms or physical features, and can only reliably be detected for purposes of prevention through a diagnostic test. Robert Guthrie’s work in developing a technique using blood spots to cheaply and easily detect PKU made newborn screening for this condition technically possible, and subsequent research showed dramatic differences in IQ scores of individuals treated following early identification (e.g., Berry, O’Grady, Perlmutter, & Bofinger, 1979; Koch & de la Cruz, 1999). These powerful data set the stage for advocacy efforts that led to newborn screening for PKU. However, it took nearly a decade for screening to be established in every state, as the United States had not established a public health infrastructure for newborn screening, policies had not been set establishing criteria for selecting conditions to be screened, and concerns were expressed about both the specificity of the treatment and uncertainties about whether every identified child actually needed treatment (Watson, 2006). In the ensuing years, newborn screening has grown into a mature public health program in the United States and continues to expand. But this expansion has been variable across states due to variations in such factors as laboratory capabilities, financial resources, governmental leadership, and advocacy efforts. Until recently most states in the United States screened for fewer than 10 conditions. Intense lobbying by various advocacy groups, advances in screening technology, and a recent task force report issued under the auspice of the American College of Medical Genetics (Watson, Mann, Lloyd-Puryear, Rinaldo, & Howell, 2006) have led to a significant expansion of the number of conditions screened just in the last
Newborn Screening for Intellectual Disability
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few years. Most states now screen for more than 40 conditions, and this number is likely to continue to increase over the next few years. Internationally, newborn screening programs vary widely by region. Most countries screen for many fewer conditions than does the United States (Bodamer, Hoffman, & Lindner, 2007; Borrajo, 2007; Padilla & Therrell, 2007; Saadallah & Rashed, 2007; Therrell & Adams, 2007). Cross-country differences are accounted for by a wide range of variables, including limited financial resources, differences in the incidence rate of selected conditions across countries, variable advocacy initiatives, and differences in cultural perspectives and values (Pollit, 2007). In some regions, there are countries that have no newborn screening program at all, or if they do, it focuses on only a few conditions and is not universal. For many developing countries, newborn screening may pale in comparison to much larger risk factors (e.g., stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anemia) that must be addressed to reduce adverse outcomes and avoid the loss of developmental potential in millions of young children worldwide (Engle et al., 2007; Walker et al., 2007). A recent commentary stated ‘‘Few things we do in preventive medicine have been as remarkably successful as has newborn screening’’ (Howell, 2006a, p. 229). Despite this glowing assessment, however, the continued expansion of newborn screening is a topic of much current debate. Historically this debate has pitted ‘‘advocates’’ (often parents of affected children whose condition could have been prevented or lessened had newborn screening been available) against a more conservative public health system that insists on strong evidence for proven benefit (reduced morbidity and mortality) in a cost-effective fashion. However, rapid advances in technology will likely lead to testing platforms in the next 5–10 years in which literally hundreds of conditions or gene variants could be screened cheaply and simultaneously, making the cost of adding a new condition irrelevant from a laboratory perspective. This likely scenario has led to renewed and intensified discussions about problematic ethical, legal, and social issues surrounding the disclosure of complex genetic information at birth (Bailey, Armstrong, Kemper, Skinner, & Warren, 2008; Botkin et al., 2006), and expanding conceptions of what constitutes ‘‘benefit’’ when determining whether to screen for a particular condition (Bailey, Skinner, & Warren, 2005; Bailey, Beskow, Davis, & Skinner, 2006; Grosse, Boyle, Kenneson, Khoury, & Wilfond, 2006). A 2004 review revealed 282 molecularly identified genes related to intellectual disability (Inlow & Restifo, 2004). More have subsequently been discovered, and the authors estimate that hundreds more mental retardation genes remain to be identified. Obviously, only a few of these conditions are currently included in newborn screening. As gene discovery and technological innovation proceed at a rapid pace, how do genetic conditions causing intellectual and developmental disabilities fit into
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newborn screening, both now and in the future? To answer this question, we begin by reviewing the evolving criteria for newborn screening over the past 50 years. Issues evoked in a possible ‘‘second-generation’’ of newborn screening are described and an aggressive research agenda is proposed to assure that expanded screening maximizes benefit and minimizes harm.
2. Evolving Guidelines and Practices for Newborn Screening Since the possibility of widespread genetic testing through programs such as newborn screening was first realized, several major organizations have formed committees and issued reports to guide decision-making about newborn screening. These include the World Health Organization, often referred to as the seminal work on this topic led by Wilson and Junger (1968), the National Academy of Sciences (Committee for the Study of Inborn Errors of Metabolism, 1975), the Institute of Medicine (Andrews, Fullarton, Holtzman, & Motulsky, 1994), the American Society of Human Genetics and the American College of Medical Genetics (ASHG/ACMG, 1995), the National Institutes of Health in partnership with the Department of Energy (Holtzman & Watson, 1997), and the American Academy of Pediatrics Newborn Screening Task Force (AAP, 2000). For the most part, these reports have been remarkably consistent in their recommendations. Newborn screening should be conducted for conditions that meet four core standards: (1) The condition must be a significant public health problem, one that has serious consequences for the infant’s physical health, development, or life itself, and occurs frequently enough in the population to warrant universal screening. (2) A screening test must be available that is economical, acceptable to parents, rapid, and very accurate, with virtually no false negatives (missing no children who actually have the condition) and only a small number of false positives (unnecessarily incurring the expense of follow-up testing and heightening anxiety for parents). (3) There must be a demonstrable benefit to the infant, almost always defined as a medical treatment or nutritional intervention that reduces morbidity and mortality associated with the condition. (4) A comprehensive system of services must be in place so that primary care providers and families get screening information in a timely fashion, families receive adequate information and support, and appropriate treatments and follow-up services are available. Despite these standards, however, states vary widely in the conditions actually screened, for several reasons. From the beginning, newborn screening was determined to be a state, not federal, responsibility. Each state operates an independent newborn screening program through its
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department of health, often guided by an advisory committee. Decisions about which conditions to include are entirely the responsibility of states, and therefore much variability has been due to state-by-state variations in laboratory capacity, advocacy efforts, or professional initiatives. As new conditions were discovered, new treatments developed, and new technologies created, cross-state discrepancies became more obvious. To address this problem, in 2000, the March of Dimes launched a national campaign, mobilizing local chapters and volunteers to advocate that each U.S. state and territory screen all infants for a core set of 10 conditions: PKU, congenital hypothyroidism, congenital adrenal hyperplasia, biotinidase deficiency, maple syrup urine disease, galactosemia, homocystinuria, sickle cell disease, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, and hearing impairment (Howse, Weiss, & Green, 2006). This campaign was buttressed by a simultaneous call from the American Academy of Pediatrics Newborn Screening Task Force (2000) for a national agenda on state newborn screening programs and a subsequent report from the U.S. General Accounting Office (2003) highlighting cross-state discrepancies in screening and urging action to insure equity in access to comparable screening tests across the country. In 2003, the Health Resources and Services Administration in the U.S. Department of Health and Human Services established a Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children to advise the Secretary of Health regarding newborn screening policy and practice. But almost as soon as these efforts had begun, other forces began pushing for even greater expansion, a movement catalyzed by the introduction of tandem mass spectrometry (MS/MS) as the technology of choice for newborn screening (Materin & Rinaldo, 2003). MS/MS dramatically expanded the number of disorders that could rapidly be detected in a single blood spot, with great precision and cheaply. In fact, the cost of detecting one condition was essentially the same as detecting multiple conditions. As states began to acquire tandem mass equipment or have access to regional labs with MS/MS capacity, they quickly faced important decisions about how to report MS/MS results, as some detected conditions did not meet the traditional criteria for newborn screening (i.e., no treatment available). Since the equipment is expensive and not every state could afford it, for several years MS/MS actually increased cross-state discrepancies in the number of conditions screened. But it also provided advocacy groups further ammunition to push for standardized expanded screening across all states. Since the authority to determine screened conditions rests with states, federal agencies faced a fundamental dilemma: How to support expansion and standardization of screening in the absence of any mechanism for requiring it. To address this issue, the Maternal and Child Health Bureau of the Health Resources and Services Administration funded the American College of Medical Genetics to convene experts and reach consensus
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on: (1) an expanded set of standards for deciding which conditions should be included in newborn screening and (2) a uniform screening panel based on current best knowledge about a set of candidate conditions. A scoring system for evaluating conditions was developed, and nearly 300 experts and other stakeholders were invited to use the system to evaluate one or more of 78 potential conditions for screening, resulting in nearly 4,000 ratings (Watson et al., 2006). As a result of these efforts, the committee recommended that all states screen for a core panel of 29 conditions for which there is an accurate screening test and strong agreement on the overall benefits of screening. The committee also recommended 25 additional ‘‘secondary targets,’’ conditions for which there was less agreement about the desirability of screening (e.g., very rare conditions or those for which there is no current treatment), but which would necessarily be identified when using techniques such as MS/MS to identify the 29 core conditions. The scoring system developed by the expert group to evaluate conditions for newborn screening is displayed in Fig. 1.1. Fourteen categories are proposed with scoring criteria for each. Some items are given more weight than others, based on the committee’s evaluation of their relative importance. The maximum score a condition could be rated is 2,100 points. Interestingly, no disease or condition received a perfect score. The highest mean score was assigned to MCAD deficiency, with a score of 1,799. MCAD is an autosomal recessive disease that affects the body’s ability to metabolize fat. Undetected, MCAD can result in death (30–50% death rate) if a child goes for even a relatively short period of time without eating (over 10–12 h), as might occur when the child has some other illness. The main treatment is to avoid fasting and aggressively treat any illnesses. Other conditions receiving high scores include congenital hypothyroidism (loss of thyroid function that leads to intellectual impairment, treatable by thyroxine supplements; score of 1,718), PKU (1,663), biotinidase deficiency (a condition in which the body is unable to reuse or recycle the vitamin biotin, resulting in delays and physical impairments, treatable by a form of biotin that does not bind to protein or other molecules; score of 1,542), and sickle cell anemia (1,533). Neonatal hyperbilirubinemia also received a high score (1,584) but was not recommended for screening due to lack of a test. The scoring system, expert ratings, and full recommendations were published in a special supplement to Genetics in Medicine (Watson et al., 2006). In the remainder of this chapter, these components are collectively referred to as the ACMG report. The scoring system, which was developed by a subcommittee known as the Newborn Screening Conditions and Criteria Work Group, is referred to as the Newborn Screening Condition Evaluation Tool. The 29 conditions recommended for newborn screening are referred to as the Core Panel. The conditions recommended as ‘‘reportout’’ conditions (those that do not fully meet the standards for newborn
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CRITERIA
CATEGORIES
SCORE >1:5,000 >1:25,000
Incidence of condition
>1:50,000 >1:75,000
