Copyright holder: Tyndale University, 3377 Bayview Ave., Toronto, Ontario, Canada M2M 3S4 Att.: Library Director, J. William Horsey Library Copyright: This Work has been made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws of Canada without the written authority from the copyright owner. Copyright license: Attribution-NonCommercial-NoDerivatives 4.0 International License Citation: Percy, Maire, Ivan Brown and Wai Lun Alan Fung. “Factors Causing or Contributing to Intellectual and Developmental Disabilities,” In A Comprehensive Guide to Intellectual and Developmental Disabilities, edited by Michael L. Wehmeyer, Ivan Brown, Maire Percy, Karrie A. Shogren and W.L. Alan Fung, Pages 175-194. 2nd ed. Baltimore, MD: Brookes Publishing Co., 2017. ***** Begin Content ****** TYNDALE UNIVERSITY 3377 Bayview Avenue Toronto, ON M2M 3S4 TEL: 416.226.6620 www.tyndale.ca Note: This Work has been made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws of Canada without the written authority from the copyright owner. Percy, Maire, Ivan Brown and Wai Lun Alan Fung. “Factors Causing or Contributing to Intellectual and Developmental Disabilities,” In A Comprehensive Guide to Intellectual and Developmental Disabilities, edited by Michael L. Wehmeyer, Ivan Brown, Maire Percy, Karrie A. Shogren and W.L. Alan Fung, Pages 175-194. 2nd ed. Baltimore, MD: Brookes Publishing Co., 2017. [ Citation Page ] A Comprehensive Guide to Intellectual and Developmental Disabilities Second Edition edited by Michael L. Wehmeyer, Ph.D. University of Kansas Ivan Brown, Ph.D. Brock University Maire Percy, Ph.D. University of Toronto Surrey Place Centre Karrie A. Shogren, Ph.D. University of Kansas and Wai Lun Alan Fung, M.D., Sc.D. University of Toronto • P A U L • H • BROOKES PUBLISHING CO ® Baltimore • London • Sydney [ Title Page ] • P A U L • H • BROOKES PUBLISHING CO ® Paul H. Brookes Publishing Co. Post Office Box 10624 Baltimore, Maryland 21285-0624 USA www.brookespublishing.com Copyright © 2017 by Paul H. Brookes Publishing Co., Inc. All rights reserved. Previous edition copyright © 2007. “Paul H. Brookes Publishing Co.” is a registered trademark of Paul H. Brookes Publishing Co., Inc. Typeset by Progressive Publishing Services, Emigsville, Pennsylvania. Manufactured in the United States of America by Sheridan Books, Inc., Chelsea, Michigan. Cover image ©istockphoto/mymrin. Chapter 1 definition reprinted from International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)-2015-WHO Version, Mental Retardation (F70-F79), Copyright (2015). Chapter 3 definition from the American Association on Intellectual and Developmental Disabilities (AAIDD). (2013). Definition of intellectual disability. Retrieved from http://aaidd.org/intellectual-disability/definition, p.1; reprinted by permis- sion. Chapter 47 excerpt from Bradley, E., Sinclair, L., & Greenbaum, R. (2012). Trauma and adolescents with intellectual disabilities: interprofessional clinical and service perspectives. Journal of Child & Adolescent Trauma, 5(1) (33-46), reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com. The publisher and the authors have made every effort to ensure that all of the information and instruction given in this book are accurate and safe, but they cannot accept liability for any resulting injury, damage, or loss to either person or property, whether direct or consequential and however it occurs. Medical advice should only be provided under the direction of a qualified health care professional. Most of the vignettes presented in this book are composite accounts that do not represent the lives or experiences of specific individuals, and no implications should be inferred. In a few cases, actual people’s stories have been used with permission. Library of Congress Cataloging-in-Publication Data The Library of Congress has cataloged the print edition as follows: Names: Wehmeyer, Michael L., editor. Title: A comprehensive guide to intellectual and developmental disabilities / edited by Michael L. Wehmeyer, Ph.D., University of Kansas, Ivan Brown, Ph.D., Brock University, Maire Percy, Ph.D., University of Toronto, Surrey Place Centre, Toronto, Karrie A. Shogren, Ph.D., University of Kansas, and Wai Lun Alan Fung, M.D., Sc.D., University of Toronto. Description: Second edition. | Baltimore: Paul H. Brookes Publishing, Co., [2017] | Includes bibliographical references and index. Identifiers: LCCN 2016028967 (print) | LCCN 2016035428 (ebook) | ISBN 9781598576023 (hardcover) | ISBN 9781598579062 (pdf) | ISBN 9781598575644 (epub) Subjects: LCSH: Developmentally disabled. | People with mental disabilities. | Developmental disabilities. | Mental retardation. | Developmentally disabled—Services for. | People with mental disabilities—Services for. Classification: LCC HV1570 .C66 2017 (print) | LCC HV1570 (ebook) | DDC 362.1968—dc23 LC record available at https://lccn.loc.gov/2016028967 British Library Cataloguing in Publication data are available from the British Library. 2021 2020 2019 2018 2017 10 9 8 7 6 5 4 3 2 1 [ Title Page Verso ] Contents About the Editors .... vii Contributors .... x Introduction .... xviii Acknowledgments .... xx I Intellectual and Developmental Disabilities in Today’s Context 1 What Is Meant by the Terms Intellectual Disability and Developmental Disabilities? Ivan Brown, Michael L. Wehmeyer, and Karrie A. Shogren .... 3 2 Historical Overview of Intellectual and Developmental Disabilities Ivan Brown, John P. Radford, and Michael L. Wehmeyer .... 19 3 Changing Perspectives on Intellectual and Developmental Disabilities Michael Bach .... 35 4 Trends and Issues in Intellectual and Developmental Disabilities Trevor R. Parmenter and James R. Thompson .... 47 5 International Human Rights and Intellectual Disability Paula Campos Pinto, Marcia H. Rioux, and Bengt Lindqvist .... 63 6 Advocacy and Legal Considerations to Ensure Civil Rights Peter Blanck, Tina Campanella, and Jonathan G. Martinis .... 79 7 Self-Advocacy Karrie A. Shogren .... 89 8 Making Services More Effective Through Research and Evaluation: An Introductory Guide Barry J. Isaacs .... 99 II Human Development 9 Introduction to Early Development: A Multidisciplinary Perspective Maire Percy and Chet D. Johnson .... 113 10 Introduction to Genetics, Genomics, Epigenetics, and Intellectual and Developmental Disabilities Maire Percy, Sheldon Z. Lewkis, Miles D. Thompson, Ivan Brown, Deborah Barbouth, and F. Daniel Armstrong .... 127 11 Introduction to the Nervous Systems William MacKay and Maire Percy .... 149 12 Brain Plasticity Jan Scholz and Jason P. Lerch .... 165 III Etiology and Conditions 13 Factors Causing or Contributing to Intellectual and Developmental Disabilities Maire Percy, Ivan Brown, and Wai Lun Alan Fung .... 175 [ Page ] iii [ Page ] iv 14 Down Syndrome Anna J. Esbensen and William E. MacLean, Jr. .... 195 15 Fragile X Syndrome Cynthia J. Forster-Gibson and Jeanette Jeltje Anne Holden .... 209 16 Autism Spectrum Disorder Adrienne Perry, Julie Koudys, Glen Dunlap, and Anne Black .... 219 17 22q11.2 Deletion Syndrome Nancy J. Butcher, Erik Boot, Joanne C.Y. Loo, Donna McDonald-McGinn, Anne S. Bassett, and Wai Lun Alan Fung .... 231 18 Fetal Alcohol Spectrum Disorder, Part I: Diagnosis, Neurobehavioral Functions, and Interventions in Children Catherine McClain, E. Louise Kodituwakku, and Piyadasa W. Kodituwakku .... 243 19 Fetal Alcohol Spectrum Disorder, Part II: Challenges in Adulthood Valerie K. Temple, Leeping Tao, and Trudy Clifford .... 257 20 Cerebral Palsy Darcy Fehlings and Carolyn Hunt .... 263 21 Other Syndromes and Conditions Associated with Intellectual and Developmental Disabilities Maire Percy, Miles D. Thompson, Ivan Brown, Wai Lun Alan Fung, and Others .... 273 22 Epilepsy W. McIntyre Burnham .... 313 23 Introduction to Behavior and Mental Health Maire Percy, Wai Lun Alan Fung, Ivan Brown, and Angela Hassiotis .... 323 IV Support and Intervention 24 An Introduction to Assessment, Diagnosis, Interventions, and Services Ivan Brown and Maire Percy .... 343 25 Introduction to Intellectual and Developmental Disability Service Systems and Service Approaches Ivan Brown, Diane Galambos, Denise Poston Stahl, and Ann P. Turnbull .... 357 26 The Roles, Skills, and Competencies of Direct Support Professionals Amy S. Hewitt and Matthew Bogenschutz .... 373 27 Responding to Cultural and Linguistic Differences Among People with Intellectual Disability Tawara D. Goode, Wendy Alegra Jones, and Joan Christopher .... 389 28 Behavioral Intervention Rosemary A. Condillac and Daniel Baker .... 401 29 Challenging Families, Challenging Service Systems: A Positive Intervention Model J. Dale Munro .... 413 30 Psychopharmacology in Intellectual and Developmental Disabilities Jessica A. Hellings and Kenneth Boss .... 425 [ Page ] v 31 Speech, Language, and Communication Assessments and Interventions Nancy Brady and Laura Hahn .... 447 32 Augmentative and Alternative Communication Cathy Binger and Jennifer Kent-Walsh .... 461 V Intellectual and Developmental Disabilities Through the Life Span 33 The First 1,000 Days of Fetal and Infant Development Maire Percy, Karolina Machalek, Ivan Brown, Paula E. Pasquali, and Wai Lun Alan Fung .... 475 34 Early Intervention for Young Children Elaine B. Frankel, Kathryn Underwood, and Peggy Goldstein .... 495 35 Maltreatment of Children with Developmental Disabilities Ann Fudge Schormans and Dick Sobsey .... 509 36 Education for Students with Intellectual and Developmental Disabilities Michael L. Wehmeyer, Karrie A. Shogren, and Ivan Brown .... 527 37 The Transition from School to Adult Life Ivan Brown, Michael L. Wehmeyer, Kristine Weist Webb, and Janice Seabrooks-Blackmore .... 541 38 Work and Employment for People with Intellectual and Developmental Disabilities Richard G. Luecking and Amy Dwyre D'Agati .... 557 39 Lifestyles of Adults with Intellectual and Developmental Disabilities Pat Rogan .... 569 40 Providing Support that Enhances a Family's Quality of Life Heather M. Aldersey, Ann P. Turnbull, and Patricia Minnes .... 583 41 Sexuality and People Who Have Intellectual and Developmental Disabilities: From Myth to Emerging Practices Dorothy Griffiths, Stephanie Ioannou, and Jordan Hoath .... 597 42 Parenting by People with Intellectual Disability Marjorie Aunos, Maurice Feldman, Ella Callow, Traci LaLiberte, and Elizabeth Lightfoot .... 609 43 Gender Issues in Developmental Disabilities Kruti Acharya, Abigail Schindler, and Tamar Heller .... 631 44 Aging Philip McCallion, Nancy Jokinen, and Matthew P. Janicki .... 639 VI Health 45 Ethics of Decision Making and Consent in People with Intellectual and Developmental Disabilities John Heng and William F. Sullivan .... 655 46 Physical Health Tom Cheetham and Shirley McMillan .... 665 47 People with Intellectual and Developmental Disabilities and Mental Health Needs Jane Summers, Robert Fletcher, and Elspeth Bradley .... 679 [ Page ] vi 48 Nutritional Considerations for Children with Intellectual and Developmental Disabilities Diana R. Mager .... 695 49 Alzheimer's Disease and Dementia: Implications for People with Down Syndrome and Other Intellectual or Developmental Disabilities Vee P. Prasher, Matthew P. Janicki, Emoke Jozsvai, Joseph M. Berg, John S. Lovering, Ambreen Rashid, Wai Lun Alan Fung, and Maire Percy .... 709 VII The Future 50 Future Trends and Advances in Intellectual and Developmental Disabilities Michael L. Wehmeyer and Karrie A. Shogren .... 737 Index .... 745 [ Page 174 ] 13 Factors Causing or Contributing to Intellectual and Developmental Disabilities Maire Percy, Ivan Brown, and Wai Lun Alan Fung WHAT YOU WILL LEARN • Importance of education about factors that cause or contribute to intellectual and developmental disabilities (i.e., risk factors) • Overview of causal or contributing factors • Biomedical, social, behavioral, and educational risk factors • Prevention of intellectual and developmental disabilities • Comorbid sensory impairments and mental health disorders • Future directions in the field The purpose of this chapter is to draw awareness to different factors that can cause or contribute to intellectual and/or developmental disabilities. There are several reasons why this chapter is important. First, obtaining an explanation for why a person has been diagnosed with intellectual disability as early as possible (i.e., an early diagnosis) provides relief to families and others who care for the child. Second, an early diagnosis facilitates access to sup- ports and services earlier than in the absence of a diagnosis; in some cases, these may prevent actual or further impairment from developing. Third, an early diagnosis may help to prevent recurrences of certain types of intellectual and developmental disabilities within an affected individual’s family. Fourth, hav- ing information about the causes of intellectual and developmental disabilities helps administrators and policy makers allocate funding for supports and services, because these often are geared to specific types of disabilities. Finally, before an explanation is sought for what may have caused intellectual or developmental impairments, professionals and fam- ilies should consider any negative consequences that might arise from a child becoming “labeled.” Some- times, complex ethical, legal, and social issues can arise that might interfere with obtaining medical or life insurance or with employment, or labels might upset family members. Should such concerns arise, it is important that appropriate guidelines, laws, poli- cies, or strategies be developed and implemented to guard against them (Percy, 2007; Percy & Brown, 2011). OVERVIEW Using criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edi- tion, Text Revision (DSM-IV-TR), intellectual disability has been estimated to affect approximately 2%-3% of the general population worldwide, the prevalence being lower in developed than developing countries (American Psychiatric Association [APA], 2000). On the basis of DSM-5 criteria, the prevalence is approximately 1% (APA, 2013). However, in a study of 1997-2008 data representative of U.S. households, as many as 1 in 6 children in the United States is affected by some type of developmental disorder, [ Page ] 175 [ Page ] 176 including attention-deficit/hyperactivity disor- der (ADHD), intellectual disability, cerebral palsy, autism spectrum disorder (ASD), seizures, stuttering or stammering, moderate to profound hearing loss, blindness, learning disorders, and/or other develop- mental delays (Boyle et al., 2011). Most cases of intel- lectual disability are mild, with less than 0.5% being severe (Rauch et al., 2012). Intellectual disability is sometimes classified as syndromic (in which intellectual impairments asso- ciated with other medical and behavioral signs and symptoms are present) and nonsyndromic (in which intellectual impairments appear without other med- ical and behavioral signs and symptoms). Syndromic intellectual impairments account for 30%-50% of cases (Kaufman, Ayub, & Vincent, 2010; Rauch et al., 2012; Srour & Shevell, 2014.) Many different factors that cause or contribute to intellectual and developmental disabilities have been identified. One quarter to one half of intellec- tual or developmental disability diagnoses are asso- ciated with genetic factors (Srour & Shevell, 2014). Although some publications report that the cause of intellectual disability is unknown in up to half of cases, a population study in a middle-income coun- try identified causal factors in approximately 90% of a birth cohort (Karam et al., 2015). Studies of children indicate that 1.5 times as many males are affected with intellectual disability as females, but the male- to-female proportion decreases with increasing severity of intellectual impairment (McLaren & Bryson, 1987). In autism spectrum disorder (ASD), the most widely reported male-to-female ratio is 4-5:1 (Lai, Lombardo, Auyeung, Chakrabarti, & Baron-Cohen, 2015). The American Association on Intellectual and Developmental Disabilities (AAIDD) focuses on four different types of factors that cause or con- tribute to intellectual disability (biomedical, social, behavioral, and educational) and on the timing of exposure to these factors (prenatal, perinatal, and postnatal) (AAIDD, 2010). Biomedical factors include genetic disorders and various factors adversely affecting health. Social factors include adverse fam- ily social interactions, lack of access to health care, and parental neglect. Behavioral factors include any behavior that adversely affects functioning, such as maternal alcohol or substance abuse. Educational factors include lack of accessibility to educational experiences that support adaptive skills, such as family support and/or special education, especially early in life. Sometimes the term environmental is used to denote health-related, social, behavioral, and educational factors. Prenatal means occurring before birth; perinatal relates to the period shortly before and after birth (traditionally, from the 20th week of gestation to the 28th day of newborn life). Postnatal means after birth (traditionally, the first 6 weeks after birth). Nongenetic factors are some- times referred to as environmental factors. Factors involved in intellectual and develop- mental disabilities are often referred to as risk fac- tors. Many forms of intellectual and developmental impairment are thought to result from more than one factor (McLaren & Bryson, 1987). Risk factors can be causal or contributing. The term causal implies that the factor (or factors acting in combination) actually causes the intellectual impairment or devel- opmental delay (i.e., that the probability of causing the intellectual impairment or developmental delay is 100% or close to this). Contributing implies that the factor(s) in question is/are not sufficient on its/their own to cause the intellectual impairment or devel- opmental delay. Conversely, some factors can help to prevent intellectual impairment or developmen- tal delay or reduce its severity. The study of factors involved in intellectual and developmental disabili- ties is complex and challenging. For example, having an extra chromosome 21 is known to cause Down syndrome, and Down syndrome is associated with intellectual disability. However, the degree of intel- lectual disability in people with Down syndrome is highly variable, and the nature of this variability is not yet understood. This may involve multiple bio- medical and/or psychosocial factors. Susser (2002) noted that ideas of what are causal factors in human disease have “changed over the years as societies, understanding of disease, and technical resources have changed." Furthermore, this field of study con- tinues to evolve (Xiang et al., 2015). An introduction to risk factors for intellectual and developmental disabilities should include a brief review of genetics, the “nature versus nur- ture" debate, the subspecialty of genetics called epigenetics, and brain plasticity. A Brief Review of Genetics Every cell in the human body contains 46 chromo- somes: 23 from the mother and 23 from the father. Chromosomes are structures in the nucleus of the cells made up of tightly coiled strands of DNA. [ Page ] 177 Along these strands are sections referred to as genes. Genes contain information that both enables the body to grow and work and determines how the body grows and works. Genes are passed from parents to children. Twenty-two of the 23 chro- mosome pairs are called autosomes; these are not involved in sex determination. The chromosomes that determine sex (the sex chromosomes) are the X in females and the Y in males. Females have two X chromosomes; males have one X and one Y. DNA is also present in mitochondria, the energy-producing organelles of cells. Mitochondrial DNA is inherited from the mother. When the first cell is formed from the mother and father, mitochondria from the father are destroyed. In this first cell, very occasionally a chromosome (or more) is structurally not normal, or there can be too many or too few of them, or they can be changed in very minor ways. Sometimes genetic abnormalities are inherited from one parent or from both parents, but sometimes they are not and occur de novo (i.e., spontaneously; Nussbaum, McInnes, & Willard, 2015). Inheritance of a genetic disorder can be dominant (a mutation in just one of two copies of a gene is sufficient to cause a problem) or recessive (mutations are needed in both copies of a gene to have an effect). There is no controversy that eye and hair color are specified by variants of specific genes encoded in each human cell. A Brief Review of Nature versus Nurture The nature theory supports the idea that even more abstract traits such as intelligence, personality, aggression, and sexual orientation are encoded in a person's DNA. The nurture theory, on the other hand, proposes that behavioral aspects of humans originate only from the environmental factors of upbringing. There was considerable debate over sev- eral decades about whether nature or nurture pre- dominates in matters of child development. It is now generally agreed that both play important roles, that they interact in sometimes complex ways, and that the relative importance of nature or nurture varies considerably from one person to another. A Brief Review of Epigenetics Epigenetics is the study of changes in gene activity that are caused by things other than the makeup of the genes themselves. From conception to the end of life, genes are coded to function in specific ways that determine growth and changes over the lifespan, but genes are not always active. Through biochemical processes collectively known as genetic imprinting, genes can be turned “on" or “off"—something like a light switch-or they can be “dimmed"—something like a light-switch dimmer. One imprinting process involves the addition of methyl groups to particular cytosine residues in DNA, a process called methyla- tion. This is often a good thing. For example, dur- ing the early adolescent years, genetic imprinting permanently turns off certain growth genes so that the body stops growing taller; otherwise, a person would continue to grow taller and taller through- out life. A second example of imprinting involves silencing of many genes on one of the two X chromo- somes in females at an early stage in development. This is so that females have approximately the same number of active genes on their two X chromosomes as males do on their one X. An interesting aspect of epigenetic research that has emerged in recent years is showing that life's events, positive or nega- tive, can also influence genes being turned on or off. For example, prenatal exposure to alcohol has been found to result in unique DNA methylation changes in offspring, both in mice and humans (Laufer et al., 2015). Thus, although understanding of epigenetics is in its infancy, epigenetic research is helping to resolve the nature versus nurture debate. Environ- mental factors and experiences can indeed shape who people are and have profound consequences about how they live (Percy & Brown, 2011). A Brief Review of Brain Plasticity The term brain plasticity (or neuroplasticity) refers to changes in neural connections that occur in the brain when people learn new things or memorize new information (see Chapter 12). Using the brain in new and different ways causes it to create new “path- ways" that did not previously exist. These changes can occur throughout life, which makes clear the importance of mental exercise at all life stages. Stud- ies point to the involvement of epigenetic processes in these brain changes. For example, whereas DNA methylation (addition of methyl groups to DNA) is necessary to inhibit genes involved in memory sup- pression, DNA demethylation (removal of methyl groups from DNA) is important in activating genes whose expression is positively correlated with mem- ory formation (Miller & Sweatt, 2007). The next four main sections highlight different risk factors that cause or contribute to intellectual [ Page ] 178 and developmental disabilities. The first three main sections deal with factors that are biomedical in nature, and the fourth deals with social, behavioral and educational risk factors. BIOMEDICAL RISK FACTORS FOR INTELLECTUAL AND DEVELOPMENTAL DISABILITIES: INTRODUCTION This risk factors introductory section explains why the developing fetus is particularly susceptible to damage by certain risk factors and provides an over- view of biomedical risk factors. Fetal Vulnerability The developing fetus is particularly susceptible to damage at certain developmental stages (Table 13.1). Substances and agents that induce the production of physical deformities in the fetus, including the central nervous system, are called teratogens. See also Chapter 9. Biomedical Risk Factors Biomedical risk factors for intellectual and develop- mental disabilities, based on the AAIDD system for classifying risk factors, are presented in Table 13.2. Involvement of factors other than biomedical ones is difficult to substantiate. Hence, it is not surpris- ing that factors identified from research studies are primarily biomedical in nature. BIOMEDICAL RISK FACTORS FOR INTELLECTUAL AND DEVELOPMENTAL DISABILITIES: GENETIC CAUSES This main section, which is divided into several sub- sections, provides details about the genetic basis of intellectual and developmental disabilities. Table 13.1. Fetal vulnerability at different stages of development [ Please contact repository@tyndale.ca for Table 13.1 details ]a Sources: Brent (2004), Dobbing (1981), Guze (2005), D. Laslo personal communication (April 25, 1999), and Rice and Barone (2000). aPregnancy is measured from the start of a woman’s last menstrual period. It usually lasts 40 weeks or about 9 calendar months. The first trimester lasts from 0 to 13 weeks, the second from 14 to 27 weeks, and the third from 28 to 40 weeks. [ Page ] 179 Table 13.2. Biomedical risk factors for intellectual and developmental disabilities [ Please contact repository@tyndale.ca for Table 13.2 details ]a (continued) [ Page ] 180 Table 13.2. (continued) [ Table 13.2 continues, please contact repository@tyndale.ca for Table 13.2 details ] Sources: American Association on Intellectual and Developmental Disabilities (2010), Percy (2007), and Percy and Brown (2011). aThe term microbiome refers to the collection of microorganisms that inhabit various places in or on one’s body, primarily in the gut. The microbiome carries out various functions which are thought to be vital for human development, health, and survival. See text of this chapter as well as Chapters 9 and 11. Overview Genetic causes of intellectual and developmental disabilities are often subdivided into a number of different categories, as shown in Table 13.2. In 2004, approximately 7,500 different genetic disorders were known. As of 2015, more than 18,000 single- gene disorders had been identified. Of these, more than 6,000 are known to be heritable (i.e., passed down through generations; R. R. McInnes, personal communication, January 18, 2015). As of 2014, 450 genes were implicated in intellectual impairments and developmental disorders, with 400 attributed to syndromic intellectual impairments and devel- opmental disorders and 50 to nonsyndromic intel- lectual impairments and developmental disorders (Srour & Shevell, 2014). Variability of Expression of Genetic Disorders Genetic disorders associated with intellectual and developmental disabilities are variable in their expression. For example, although some people with a given genetic disorder have intellectual impairments or developmental disorders, others do not. Noonan syndrome is an example of a common genetic disorder in which only approximately one third of affected children have mild intellectual dis- ability (see Chapter 21). The reason a disorder can vary so much in the way it is expressed is thought to be the result of the nature and severity of the muta- tion causing the condition, effects of background genes (i.e., genes not carrying the abnormality that causes the genetic disorder but that modify the effects of the mutant gene), and other biomedical factors and differing life experiences (see Table 13.2). The Most Common Genetic Disorders Worldwide, the most common intellectual and developmental disabilities with a genetic basis are Down syndrome, 22q11.2 deletion syndrome (which includes previously identified syndromes such as DiGeorge syndrome and velocardiofacial syndrome; see Chapter 17), and fragile X syndrome (FXS). The estimated birth incidence of Down syn- drome is between 1 in 1,000 and 1 in 100. The birth incidence of 22q11.2 deletion syndrome is approxi- mately 1 in 2,000. One in 3,600 to 1 in 4,000 males and 1 in 4,000 to 1 in 6,000 females have FXS. Down syndrome is the most common etiology for intel- lectual disability resulting from an aberration of chromosome number. It is usually caused by the presence of an additional chromosome 21 and is referred to as trisomy 21 (i.e., having three copies of chromosome 21 instead of the usual two copies). Most cases of Down syndrome are not inherited and occur spontaneously without a family history. The birth incidence of Down syndrome increases mark- edly after a maternal age of 35 years (see Chapter 14). 22q11.2 deletion syndrome is a chromosomal disor- der resulting from a missing piece of chromosome 22. Expression of this disorder is very variable and may include delayed growth and speech develop- ment and learning disabilities. Affected children are at risk of also having ADHD or ASD. Later in life, people with this syndrome are at increased risk of developing other mental health problems (see Chapter 17). FXS is the most common inherited etiology resulting in intellectual or developmental disability. FXS is an X-linked single gene disorder caused by unstable mutations in the FMR1 gene. Though both men and women can carry X chro- mosomes with FMR1 mutations, mutated FMR1 is [ Page ] 181 transmitted only by females, and the mutations tend to get larger as they are passed on from one genera- tion to the next. Males are affected more severely by FXS than females because they have only one X chromosome; females with FXS tend to be spared because they carry one normal X as well as the X with a mutation (see Chapter 15). Inborn Errors of Metabolism As of 2014, 89 potentially treatable genetic disor- ders called inborn errors of metabolism (i.e., genetic disorders in which the body cannot properly turn food into energy) had been identified (van Karne- beek, 2014). These disorders include phenylketon- uria (PKU), galactosemia, Hunter syndrome, and Lesch-Nyhan syndrome (see Chapter 21). Effects of PKU can be prevented if this disorder is identified by genetic screening at birth and a special diet lack- ing in phenylalanine is adopted. Mothers who carry a PKU gene should adhere to a strict diet during pregnancy. Effects of galactosemia can be attenuated by adherence to a diet lacking in galactose. The U.S. Food and Drug Administration approved a treat- ment for Hunter syndrome that involves intravenous administration of the enzyme that is deficient in this disorder (da Silva, Strufaldi, Andriolo, & Silva, 2016). Quite a number of different disorders, including Hunter syndrome and Lesch-Nyhan syndrome, are being treated on an experimental basis with cord blood stem cell transplants. Sex Chromosome Disorders and Imprinting Disorders Turner syndrome and Klinefelter syndrome are dis- orders involving abnormalities in the number of sex chromosomes. These syndromes are sometimes, but not always, associated with mild intellectual impair- ment and physical anomalies (see Chapter 21). Two very different but related genetic condi- tions resulting in intellectual impairment or devel- opmental disorder are Prader-Willi syndrome and Angelman syndrome. These are both caused by small deletions in exactly the same region of chro- mosome 15 or by duplication of one chromosome 15 and loss of the other. Prader-Willi syndrome is often caused by deletions in the paternal chromosome 15 or by duplication of the maternal chromosome 15. Angelman syndrome is often caused by deletions in the maternal chromosome 15 or by duplication of the paternal chromosome 15 (see Chapter 21). (This parent of origin phenomenon arises because genes on chromosome 15 are expressed only if they have not been marked by the imprinting process; maternal and paternal chromosome 15s have differ- ent imprinting patterns.) Other Disorders Congenital hypothyroidism is a disorder result- ing from thyroid hormone deficiency that is easily treated. This affects approximately 1 in 4,000 new- borns in North America. Congenital hypothyroid- ism can result from genetic mutations or from iodine deficiency (see Chapter 21). De novo single nucleotide mutations and loss of function mutations (i.e., small genetic changes not transmitted by parents that can occur in indi- viduals with intellectual and developmental dis- abilities) have emerged as possible risk factors for moderate and severe levels of intellectual impair- ment (Hamdan et al., 2014) and ASD (Gamsiz et al., 2015). Copy number variants (CNVs) also are associ- ated with intellectual disability and ASD (Kamin- sky et al., 2011). CNVs are specific types of alteration in genomic DNA that result in the cell having an abnormal number of copies of a DNA segment equal to or greater in size than 1,000 base pairs. A CNV can refer to the addition or deletion of such a seg- ment. These may be transmitted by parents or arise de novo. Because de novo mutations and CNVs are common in the general population, establishing that they are pathologically involved in intellectual dis- ability or ASD, and how, remains challenging. ASD has a prevalence that is an order of mag- nitude larger than Down syndrome. ASD is multi- factorial, meaning that it is thought to result from a variety of factors. Suspected risk factors include complex genetic interactions, nutritional deficiencies (e.g., vitamin D deficiency) or overloads, pre- and postnatal exposure to chemicals or viruses, errors during the embryonic neural tube closure process, dysfunctional immune systems, a dysfunctional gut microbiome, maternal diabetes in the first 26 weeks of pregnancy, and even allergies (see Chapter 16). Furthermore, a number of different genetic disor- ders associated with features similar to those seen in ASD sometimes are incorrectly diagnosed as ASD. These include PKU, FXS, tuberous sclerosis, Williams syndrome, Prader-Willi and Angelman syndromes, Rett syndrome, and 22q11.2 deletion syndrome (see Chapter 21). In a recent analysis of U.S. medical records, counties with higher rates of [ Page ] 182 genital deformities in newborn males had higher rates of ASD and intellectual disability. This high- lights the possibility of congenital exposure to harm- ful environmental factors such as pesticides in both disorders (Rzhetsky et al., 2014). Mitochondrial disorders resulting from muta- tions in mitochondrial DNA are not common. Over- all, they affect approximately 1 in 5,000 individuals across all ages. Mutations can be maternally inher- ited (see previous discussion) or occur sporadically. Mutations in mitochondrial DNA often affect mul- tiple organ systems that require a lot of energy (e.g., heart, brain, muscles). Two examples of mito- chondrial disorders that affect brain function are myoclonic epilepsy with ragged-red fibers—a dis- order affecting many parts of the body—and mito- chondrial myopathy, encephalopathy, lactic acidosis, and stroke syndrome—a progressive neurodegen- erative disorder (Nussbaum et al., 2015). Other Factors that Affect Genetic Causes of Disabilities Two other factors that affect genetic causes of intel- lectual and developmental disabilities are ethnic origin and survival advantage. Ethnic origin may influence the chances of a child being affected by, or being a carrier of, a genetic disability. Disorders that have a high prevalence in certain ethnic groups, regardless of where individuals from those groups live now, result from probable common ancestry. This explains why there are many more people in these groups who carry a gene for the disorder than in the general population. This phenomenon is sometimes referred to as a founder effect. For exam- ple, there is a high frequency of Tay-Sachs disease (a fatal genetic disorder in which harmful quantities of a fatty substance called a ganglioside accumulate in the nerve cells of the brain) among Ashkenazic (central, northern, or eastern European) Jews but not among Sephardic (Spanish, Portuguese, or Middle Eastern) Jews. In contrast, PKU is mostly found in Caucasians and is rare in people of (or descended from) African or Asian ethnic groups. FXS is reported to be particularly common in Finland and in Quebec (Percy, 2007; Percy & Brown, 2011). Con- sanguineous parentage (i.e., union of closely related kin) increases the risk for conditions with autosomal recessive inheritance. Survival advantage is a phenomenon associated with some recessive mutant genes. In such cases, mutant genes that are harmful when present in two copies have some survival advantage when only one copy has been inherited. Sickle-cell anemia (a condition in which red blood cells are sickle-shaped rather than round) and beta thalassemia (a disorder in which the body cannot make the beta chains of hemoglobin, the red cell protein that carries oxygen and carbon dioxide in the blood) are two recessive genetic disorders that are sometimes associated with intellectual and developmental disabilities and in which being the carrier of one mutant gene has an advantage. The trait for sickle-cell anemia, found in many people of African origin, is connected with a resistance to malaria; two sickle-cell genes result in the expression of anemia and resistance to malaria, whereas a carrier possessing a single sickle-cell gene is resistant to malaria and lacks the anemia. The trait of beta thalassemia, found in people of Mediterranean origin, similarly is connected with a resistance to malaria (Mount Sinai Hospital, 2013). Treatment for the anemia in both disorders requires blood transfusions, which leads to iron overload and organ failure if the body iron load is not normalized by treatment with drugs that remove iron from the body. BIOMEDICAL RISK FACTORS FOR INTELLECTUAL AND DEVELOPMENTAL DISABILITIES: HEALTH-RELATED FACTORS Numerous health-related factors are risk factors for intellectual and developmental disabilities (see Table 13.2). The following sections elaborate on some of these factors. Some of these factors are largely preventable. Malnutrition Malnutrition is suspected of being a cause of or contributing factor to intellectual impairment in a large proportion of affected individuals. Maternal malnutrition prior to conception may be the largest culprit. Although adults are remarkably resistant to the effects of malnutrition, the developing fetal brain is very susceptible. Protein-energy undernutrition and deficiencies of certain vitamins (e.g., folic acid, vitamin B12, vitamin A) and minerals (e.g., iodide, iron, zinc) are problems not only in underdeveloped countries but in developed countries, including the United States and Canada (Bailey, West, & Black, 2015). As of 2010, one quarter of the world's popula- tion younger than 5 years of age was found to be [ Page ] 183 underweight (UNICEF, 2010). About one in 12 new- borns in the United States is underweight (March of Dimes Foundation, 2016). In North America, under- weight is defined as having a birth weight of less than 2,500 grams (or 5.5 pounds). For couples planning pregnancy, there are many regional programs to address the challenge of how to prevent low birth weight infants (CDC, 2015; March of Dimes Foun- dation). The following subsections discuss several specific factors that contribute to malnutrition. Protein-Energy Undernutrition Protein- energy undernutrition refers to a reduced protein intake over an extended period of time (Scheinfeld, 2015). This reduced intake eventually leads to deple- tion of the tissue protein reserve and lowering of blood protein levels, compromising proper func- tion of nerve, muscle, and intellectual function. The latter may be irreversible if protein deprivation occurs during periods of brain development. Eco- nomic, social, and cultural factors (e.g., poor feeding habits, superstitions, belief in incorrect information about health and nutrition) all contribute to protein malnutrition in many countries. Infants and young children are very vulnerable. There are two disor- ders of protein-calorie malnutrition: marasmus and kwashiorkor (Scheinfeld, 2015). Which form devel- ops depends upon the relative availability of non- protein and protein sources of energy. In marasmus, there is severe deficiency of calories in the diet, including calories from protein. This results in severe growth failure and emaciation. Kwashiorkor results from premature abandonment from breast feeding, usually when a second child is born and replaces the first born at the mother's breast. Chil- dren with kwashiorkor have an odd reddish-orange color of the hair as well as a characteristic red skin rash. In kwashiorkor, the total calorie intake may be adequate but there is a deficiency of protein in the diet. Kwashiorkor often is associated with a maize- based diet. Protein-calorie malnutrition results in more severe infections than would occur in a state of adequate nutrition. Folic Acid and Vitamin B12 Deficiencies Folate (or folacin) is a water-soluble B vitamin that all people need in order for their bodies to make new cells. A folic acid deficiency may result from low dietary intake of folic acid (eating the wrong foods) and/or as the result of one's genetic makeup. Folic acid deficiency is a risk factor for neural tube defects such as spina bifida (a birth defect in the bony encasement of the spinal cord) and anencephaly (a birth defect characterized by missing or a very reduced amount of brain tissue). Pregnant women (especially women who have diabetes, epilepsy, or a family history of neural tube defects) should take a daily folic acid supplement before and during preg- nancy to reduce the risk of having an infant with a neural tube defect. The United States, Canada, and some other countries fortify grain products, such as bread and pasta, with folic acid. As of this writing in 2016, there is concern that excessive synthetic folic acid intake may be associated with certain adverse health effects. Folic acid supplementation masks and exacerbates effects of vitamin B12 deficiency. Prenatal folic acid supplement may be associated with an increased risk of unilateral neuroblastoma in a subset of the population homozygous for a par- ticular variant of the dihydrofolate reductase gene. Finally, high maternal red cell folate in pregnancy has been associated with insulin resistance in off- spring (Selhub & Rosenberg, 2016). Vitamin B12 is a water-soluble vitamin found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 deficiency dur- ing pregnancy also is a risk factor for neural tube defects (Thompson, Cole, & Ray, 2009). Though con- firmation is needed, it is prudent for women consid- ering pregnancy to be B12 replete and have a serum value not below 300 nanograms per liter at the time of conception. Vitamin A Deficiency and Excess Vitamin A (retinol) is a fat-soluble vitamin that is found mainly in fish liver oils, liver, egg yolks, butter, and cream. Vitamin A precursors (e.g., carotene) are found in green leafy and yellow vegetables. Vita- min A is crucial for normal nervous system devel- opment and is important for proper function of the immune system. Vitamin A deficiency (VAD) is the leading cause of preventable blindness in children and raises the risk of disease and death from severe infections accompanied by diarrhea and measles. In pregnant women, VAD causes night blindness and may increase the risk of maternal mortality. For pregnant women in high-risk areas, VAD can occur during the last trimester, when demand by both the unborn child and the mother is highest. VAD may also be associated with elevated mother- to-child transmission of human immunodeficiency virus (HIV). Secondary VAD results when vitamin A precursors cannot be converted into vitamin A; from problems with absorption, storage, or trans- port of vitamin A (as in celiac disease, a disorder [ Page ] 184 resulting from intolerance to a protein called gluten that is found in wheat and many other grains); or from intestinal infections. VAD is a public health problem in 118 countries, especially in Africa and Southern and Eastern Asia. It is common in protein- energy malnutrition. More of vitamin A is not necessarily better. Too much is toxic and can result in death. Women of child-bearing age need to be very careful. Women who are pregnant should carefully check the amount of vitamin A in their multivitamins and consult with their doctor to make sure the dose is safe. Vitamin D Deficiency Vitamin D is a fat- soluble substance that is called a vitamin, although it is actually a prohormone. It is known as the “sun- shine vitamin" because it is produced in the body as the result of mild sun exposure. It also is consumed in certain foods (e.g., fatty fish, fish oil) and supple- ments. Vitamin D sufficiency is essential for pre- venting rickets in children and for good bone health (National Institutes of Health, n.d.). Vitamin D defi- ciency is unusually common in people with intellec- tual and developmental disabilities, partly because of insufficient exposure to sunlight (Frighi et al., 2014). In addition to involvement in bone health, vitamin D deficiency is suspected of contributing to abnormal fetal development (Hart et al., 2015), to ASD (Fernell et al., 2015), and to a wide range of neu- rological and neuropsychiatric disorders (Dursun, 2010; Groves, McGrath, & Burne, 2014). Furthermore, there is evidence that the vitamin D system is regu- lated by epigenetic mechanisms and is important in maintenance of the epigenome (Fetahu, Höbaus, & Kállay, 2014). These issues must be addressed in prospective research studies, and the importance of maintaining vitamin D sufficiency must be com- municated to professionals and the public. Iodine Deficiency Iodine is a trace mineral used by the thyroid gland to produce the impor- tant thyroid hormone called thyroxine. Thyroid dysfunction resulting from iodine deficiency dis- order is the single most common cause of prevent- able developmental disability and brain damage in the world; more than 54 countries are still iodine deficient (World Health Organization [WHO], 2015). In North America, salt is usually iodized. Never- theless, in the United States, mild iodine deficiency may still be problematic (Stagnaro-Green, Dogo- Isonagie, Pearce, Spencer, & Gaba, 2015). Iodine deficiency is also still problematic in some other developed countries, such as Switzerland and Germany. Iodine deficiency in children can cause stunted growth; apathy; difficulty with movement, speech, and hearing; and intellectual impairment. Iodine deficiency in pregnant women causes mis- carriages and stillbirths; if the fetus survives, severe maternal iodine deficiency retards fetal growth and brain development. Infants with iodine deficiency are usually given L-thyroxine for a week plus iodide to quickly restore a normal thyroid state. Iodide supplementation is then continued. More iodine is not necessarily better. Chronic iodine toxicity results when iodine intake is 20 times greater than the daily requirement. Paradoxically, too much iodine can lead to hypothyroidism, as can too little (Vitti, 2014). Iron Deficiency Iron, a trace metal that is essential for life, is absorbed in the intestines. It comes in two forms: heme iron (found in meats), which is well absorbed, and nonheme iron (found in leafy veg- etables-e.g., spinach), which is not as well absorbed. Most of the consumed iron goes to form hemoglo- bin, the substance that helps red blood cells transport oxygen from the lungs to the rest of the body. The rest of the iron is stored for future needs and mobilized when dietary intake is inadequate. Because iron also plays a key role in helping to prepare the immune system to do its job, a deficiency may lead to colds. Low iron levels can also cause fatigue, pallor, and listlessness—hallmarks of anemia. Iron deficiency affects more than 2 billion peo- ple in the world; 30% of the population is anemic. In developing countries, approximately 50% of preg- nant women and 40% of children are iron deficient (WHO, 2015). Iron deficiency anemia during the third trimester of fetal development affects one third of the pregnancies in the United States and has been asso- ciated with adverse postnatal behavioral outcomes. Complications of iron deficiency anemia in infants and children include developmental delays; behav- ior disturbances such as decreased motor activity, social interaction, and attention to tasks; compulsive eating of nonfood items (pica) and ice; and irrevers- ible impairment of learning ability. In adults, iron deficiency anemia can result in a low capacity to perform physically demanding labor. Iron deficiency anemia also contributes to lead poisoning in chil- dren by increasing the gastrointestinal tract's ability to absorb heavy metals, including lead. (A common source of lead overload is exposure to dust from lead- based paint in old houses.) Iron deficiency anemia is [ Page ] 185 associated with conditions that may independently affect infant and child development. Iron deficiency during pregnancy contributes to maternal mortality and fetus/infant mortality in the perinatal period. During the first two trimesters of pregnancy, it is associated with increased risk for preterm delivery and for delivering a low birth weight infant. Iron deficiency can result from poor diet (e.g., a poor vegetarian diet), parasitic diseases (e.g., from worm and malaria infections), and abnormal uterine bleeding. Iron therapy in anemic children can often, but not always, improve behavior and cognitive per- formance, lead to normal growth, and hinder infec- tions. Researchers at Guelph University in Canada created replicas of a small river fish—associated with luck in village folklore—to be put into iron cook- ing pots. When put into cooking pots in a village in Cambodia, these fish supplied up to 75% of the daily iron requirement and resulted in an enormous decrease in anemia, dizziness, and headaches in vil- lage women (Dalal, 2014). Of note, however, is that excessive iron can be damaging. Too much supple- mental iron in a malnourished child or in people from certain ethnic backgrounds promotes fatal infections, because the excess iron is available for pathogen use. Also, excessive body iron resulting from excessive iron therapy, repeated blood trans- fusions, or iron overload resulting from a genetic condition called hemochromatosis is problematic (Moalem, Weinberg, & Percy, 2004). Toxic Threats Toxic threats to a child's environment during pre- natal, neonatal, or postnatal development can have adverse outcomes ranging from severe intellectual impairment or developmental delay to more subtle changes, such as problems with attention, memory, learning, social behavior, and intellectual ability, depending on timing and dose of the toxic threat. Furthermore, infants and children have unique pat- terns of exposure and special vulnerabilities to pesti- cides (Landrigan, Kimmel, Correa, & Eskenazi, 2004). Toxic threats include exposures to methylmercury, polychlorinated biphenyls (PCBs), ethanol, lead, arsenic, toluene, manganese, fluoride, chlorpyrifos (a pesticide), tetrachloroethylene (PERC), polybro- minated diphenyl ethers (PBDEs), and dichlorodi- phenyltrichloroethane (DDT/DDE) (Grandjean & Landrigan, 2014). Additional toxic threats include exposures to aluminum, dioxins, ionizing radiation (i.e., x rays, gamma rays), and environmental tobacco smoke, as well as maternal use of alcohol, tobacco, marijuana, and cocaine. Other exposures suspected of being a threat include maternal consumption of antidepressants and antianxiety drugs and maternal exposure to dental x rays (Percy & Brown, 2011). By learning about different types of toxic threats and their sources, by taking efforts to avoid them, and by promoting hand washing and good dietary habits, parents and caregivers can play an important role in reducing exposures to toxicants present in consumer products. Many places are undertaking initiatives to reduce sources of toxic threats in the environment. (For more information, see Hamblin [2014], Mercola [2008, 2010], and Winneke [2011].) Maternal Metabolic Effects Certain metabolic abnormalities in the mother may have harmful effects on the developing fetus. Such effects are called gestational programming (Ross & Desai, 2005). Examples are described in the follow- ing subsections. Maternal Obesity and Diabetes Being over- weight during pregnancy is associated with a greatly increased risk of neural tube defects such as spina bifida and anencephaly (Stothard, Ten- nant, Bell, & Rankin, 2009). Obesity is becoming a worldwide epidemic. Associated with obesity is the occurrence of type 2 diabetes, a disorder in which the level of blood sugar is excessively high. Some women have diabetes before they become pregnant. Others develop it during pregnancy, a form called gestational diabetes. About 3% of pregnant women have problems with their blood sugar. Presently, it is not clear whether it is obesity or high blood sugar that results in the neural tube defects. Infants born to mothers with diabetes tend to be very large. This poses risks to their health and to the moth- ers, who may require delivery by caesarean section. Furthermore, infants born to diabetic mothers may have cognitive dysfunction and also develop dia- betes themselves. Maternal diabetes diagnosed at 26 weeks of gestation or earlier was recently estab- lished as a significant risk factor for ASD (Xiang et al., 2015). It is very important that pregnant women control their blood sugar levels. Abnormal Thyroid Function Abnormal thy- roid function in a pregnant mother, in the fetus, or in the newborn all have repercussions on neuropsy- chological development. There are three sets of clin- ical thyroid disorders that affect fetal development: [ Page ] 186 those that affect the infant only, those that affect only the maternal thyroid gland, and iodine defi- ciency that affects maternal and fetal thyroid func- tion. Hypothyroidism (a condition in which the thyroid does not make enough thyroid hormone) in pregnant women is associated with an increased risk of miscarriage, preeclampsia (i.e., high blood pressure sometimes with fluid retention and loss of protein in the urine), abruptio placentae (prema- ture separation of the placenta from the uterus), low birth weight infants, still births, and fetal distress in labor. Children born to mothers with untreated hypothyroidism during pregnancy score lower on IQ tests than children of healthy mothers. Thus, it is important for pregnant mothers with hypothyroid- ism to be adequately treated during their pregnan- cies. Congenital hypothyroidism of the fetus affects approximately 1 in 4,000 newborn infants, result- ing in permanent developmental delay and growth defects (see Chapter 21). In the United States, Can- ada, and other developed countries, newborns are screened for hypothyroidism and are given early thyroid replacement therapy, when necessary, to prevent severe intellectual and developmental dis- abilities. Causes of this congenital hypothyroidism can be genetic or environmental (e.g., caused by iodine deficiency). (For more information, see Grut- ers & Krude, 2012, & LaFranchi, 2016.) Maternal Stress Prospective studies have revealed that a mother's depression, anxiety, or emotional stress while preg- nant increases the risk for her child having adverse outcomes that include emotional problems, symp- toms of ADHD, ASD, or impaired cognitive develop- ment. Based upon information from animal models, the mechanisms underlying these changes are being explored (Glover, 2015). Infections Infections with various microorganisms and viruses are known to be causal or contributing factors for intellectual and developmental disabilities. This subsection provides some detail about such risk factors, including human immunodeficiency virus (HIV) and Zika virus. Intrauterine and Perinatal Infections The acronym TORCH stands for toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus, and herpesvirus infections. These infections used to cause a large percentage of intellectual impairments and developmental dis- orders in children (Stegman & Carey, 2002). How- ever, with the availability of improved vaccines, prevention methods, and early identification, these infections in many instances can now be prevented or treated early enough to prevent damage to the central nervous system of the fetus. The applica- tion of antibiotics to cut umbilical cords prevents much newborn infection. However, there has been an unfortunate resurgence of some vaccine-pre- ventable diseases in North America because some families deliberately refuse vaccination. New chal- lenges also include pediatric HIV, and perinatal bacterial infections with Group B streptococcus and Listeria monocytogenes. There is also concern that unidentified multiple organisms causing bacte- rial vaginal infections may be causing intellectual and developmental disabilities in some children (Smith, 2014). Human Immunodeficiency Virus Infection Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate fluid, or breast milk. It is spread mostly through unprotected sex- ual contact. Mother-to-child transmission of HIV occurs when an HIV-positive mother passes the virus to her child during pregnancy, labor, deliv- ery, or breastfeeding. New HIV infections among children have declined by 50% worldwide since 2010 (UNAIDS, 2016). This has resulted because of effective voluntary testing and counseling ser- vices, access to antiretroviral therapy, safer deliv- ery practices, and the widespread availability and safer use of breast milk substitutes, especially in the developed world. However, there are unique chal- lenges in the developing world—HIV infection is rampant, especially among teenagers, and many people are not aware that they are infected. Also, there are many barriers that need to be overcome with respect to HIV prevention and treatment. One is the very high cost of antiretroviral drugs; a sec- ond is lack of health infrastructure to effectively provide essential public health services (Maartens, Celum, & Lewin, 2014). Zika Virus In April, 2016, the CDC declared prenatal infection with Zika virus, carried by a par- ticular type of mosquito, to be a teratogen causing microcephaly as well as other serious neurological [ Page ] 187 diseases (Rasmussen, Jamieson, Honein, & Petersen, 2016; see also Chapter 9). First identified in Brazil early in 2015, the virus has spread rapidly through- out the Americas. Efforts are being mounted to find ways of preventing adverse outcomes especially from virus infection during pregnancy. Rh Disease in the Newborn Rh factor is an inherited protein found on the sur- face of red blood cells. Most people have this protein (i.e., they are Rh positive), but some do not (i.e., they are Rh negative). Rh-negative pregnant women who carry an Rh-positive infant sometimes become sensitized to Rh protein and make antibodies to the Rh protein that destroy fetal red blood cells. Rh disease was once a leading cause of fetal and newborn death as well as of intellectual disability. Fortunately, Rh disease can be prevented by giving mothers a purified blood product called Rh immune globulin (RhIG) to prevent sensitization. These shots are given to the mother at 28 weeks of pregnancy and again within 72 hours of giving birth if a blood test shows that her infant is Rh positive (March of Dimes Foundation, 2016). Preterm Delivery and Low Birth Weight Preterm delivery (birth occurring before 36 weeks of gestation) is associated with increased risk for intellectual impairment or developmental delay. The more premature or underweight the newborn, the greater the risks of illness (e.g., infection, respiratory distress), impairments such as cerebral palsy and learning problems, hearing and vision problems, and death. Factors that predispose to prematurity are multiple births, regardless of the cause, placen- tal failure, and excess amniotic fluid. Preterm deliv- ery is known to place the immature brain at risk of hemorrhage, which can result in tissue damage. Low birth weight is also associated with increased risk for intellectual impairment or developmental delay, even if an infant is full term. The frequency of preterm and low birth weight infants is increasing in North America. This increased frequency may, in part, be related to the use of in vitro fertilization and/ or to women having children at a later age than in previous decades (Jarjour, 2015). Premature Cutting of the Umbilical Cord For more than 200 years, there has been an aware- ness that the umbilical cord should be cut after the infant has drawn its first breath and after the cord stops pulsating. However, since 1980, cords are often clamped as soon as possible after birth or following delivery of the fetal head in order to obtain cord blood samples for diagnosis of asphyxia. There is increas- ing support for delayed cord clamping because it increases the baby's hemoglobin levels and iron stores, thereby countering anemia, which can result in altered behavioral and neural development. Such consequences are considered beneficial as long as an infant does not have severe, untreated jaundice. Severe, untreated jaundice can result in permanent brain damage called kernicterus. Jaundice in new- borns is treated by phototherapy (i.e., exposure to ultraviolet light) (McDonald, Middleton, Dowswell, & Morris, 2013). Advanced Parental Age Studies of parental age are providing new infor- mation about factors that cause or contribute to intellectual and developmental disabilities and to ASD. Trisomy 21, 13, and 18 are three syndromes associated with intellectual and developmental disabilities that increase in frequency with increas- ing maternal age as the result of mistakes in cell division that occur during the time of conception. General cognitive impairment also is associated with advanced maternal age (Cohen, 2014). Evidence from multiple sources supports the hypothesis that paternal and maternal advancing age are risk factors for ASD but that different mechanisms are involved. Higher rates of de novo mutations in older fathers may account for the paternal effect, but the mecha- nism underlying the maternal effect is different (Lee & McGrath, 2015). However, it should be noted that ASD is considered to be a multifactorial and heterogeneous disorder and that factors as esoteric as the gut microbiome may be involved in affected individuals. Brain Injury As detailed in Table 13.2, brain injury can result from various factors. Brain injury resulting from head injury is a common cause of intellectual dis- ability and cerebral palsy. Many circumstances can lead to head injury, including falls; child battering; bicycle, scooter, and sports accidents; accidents with guns, and car accidents. Surveillance and interven- tion activities could prevent many cases of brain injury. [ Page ] 188 SOCIAL, BEHAVIORAL, AND EDUCATIONAL RISK FACTORS FOR INTELLECTUAL AND DEVELOPMENTAL DISABILITIES Biomedical factors are important in the etiology of intellectual and developmental disabilities; however, they do not always act alone. Various other factors can interact with such factors or independently of them over the lifetime of individuals and even act across generations (AAIDD, 2010; Emerson, 2010). By under- standing intergenerational causes, appropriate sup- ports can be used to prevent and reverse the effects of risk factors. Some examples of social, behavioral, and educational risk factors contributing to intellectual and developmental disabilities are given in Table 13.3. Table 13.3. Examples of social, behavioral, and educational risk factors for intellectual and developmental disabilities [ Please contact repository@tyndale.ca for Table 13.3 details ] Sources: American Association on Intellectual and Deveopmental Disabilities (2010) and Kaderavek (2014). [ Page ] 189 The following examples illustrate how socio- logical, behavioral, and educational factors are involved in intellectual and developmental dis- abilities. We have discussed how certain prenatal and genetic risk factors can result in the emergence of intellectual and developmental disabilities. Of importance, research has shown that the develop- mental trajectories of children with an early diag- nosis of intellectual and developmental disabilities can be altered by a favorable early environment (e.g., positive interactions with their mothers) and that such interactions can promote resilience (i.e., ability to cope with stress and adversity) (Fenning & Baker, 2012). It is known that parents do much more than ensure that their offspring are adequately nour- ished and sheltered. Deprivation and neglect from living in an orphanage can result in odd behaviors, delayed language, and various other challenges, including intellectual and developmental disabili- ties. However, children who are placed into foster care or adopted by about age 2 are more likely to grow up with “typical brains" than those who are not (Marshall, 2015; Powell, 2010; Sheridan, Drury, McLaughlin, & Almas, 2010). ASD is a neurodevelopmental disorder char- acterized by impaired social interaction, impaired verbal and nonverbal communication, and restricted and repetitive behavior that may or may not be associated with intellectual disability. There is evidence that early intensive behavior interven- tion is beneficial for some young children with ASD and has positive effects on the clinical mani- festations compared to other interventions avail- able in the community (Reichow, Bartin, Boyd, & Hume, 2014). Advanced maternal age and chromosomal nondisjunction are known risk factors for having a child with Down syndrome. Meiosis I is respon- sible for approximately 77% and meiosis II for 23% of maternal nondisjunction, but why this happens is not clear. Hunter et al. (2013) found that low socio- economic status is significantly associated with chromosome 21 nondisjunction occurring during meiosis II in mothers of children with Down syn- drome, independently of their age. Further studies are needed to explore which aspects of low mater- nal socioeconomic status, such as environmental exposures or poor nutrition, may account for these results. CO-OCCURRENCE OF SENSORY IMPAIRMENTS, CHALLENGING BEHAVIORS, AND MENTAL HEALTH DISORDERS IN PEOPLE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES Sensory impairments (impairments in vision or hearing), challenging behaviors, and mental health disorders are unusually common in people with intellectual and developmental disabilities. Because sensory impairments are underrecognized among people with intellectual and developmental disabil- ities, changes in behavior or challenging behaviors are often attributed to the intellectual impairment or to mental health disorders rather than to sen- sory impairment and resulting communication difficulties. Sensory impairments and challenging behaviors exacerbate one another. Because sen- sory impairments limit sensory stimulation, learn- ing opportunities, and social interaction, they can result in underdevelopment of learning and brain activity. In turn, this can lead to more challenging behavior. To provide the best quality of life, it is imperative that hearing and vision be evaluated at as early an age as possible and at regular intervals throughout life and that appropriate supports are provided. Co-occurring Sensory Impairments and Intellectual and Developmental Disabilities The prevalence of sensory impairments (visual and hearing) is much greater in adults with intel- lectual and developmental disabilities than in the general population. The prevalence of hearing loss is approximately 1 in 1,000 in the general population and is about 40 times higher in people with intellec- tual and developmental disabilities. The prevalence of visual impairment is approximately 0.5%-2% in the general population and at least 8.5 times higher in people with intellectual and developmental dis- abilities. Comorbidity (i.e., the presence of both) of hearing and vision impairment also is more com- mon in people with intellectual and developmental disabilities. The frequency of sensory impairments increases with severity of intellectual impairment and increasing age (Kiani & Miller, 2010). Vision loss in people with intellectual and developmental disabilities may be congenital, arise [ Page ] 190 Table 13.4. Factors resulting in vision loss in people with intellectual and developmental disabilities [ Please contact repository@tyndale.ca for Table 13.4 details ] From the Rehabilitation Research and Training Center on Developmental Disabilities and Health (RRTCDD). (2015b). Visual Impairment. Retrieved from http://www.rrtcadd.org/resources/Resources/Topics-of-Interest/Health-Promotion/visual-imp.PDF, p. V7; adapted by permission. For additional resources, please visit the Rehabilitation Research and Training Center on Developmental Disabilities and Health (www.RRTCDD.org). during pregnancy or birth, or stem from later onset ophthalmological problems or cerebral conditions (Table 13.4). Similarly, hearing loss may be congeni- tal, arise during pregnancy or birth, or be of later onset (Rehabilitation Research and Training Center on Developmental Disabilities and Health, 2015a). At least 50% of cases of congenital hearing loss are caused by genetic disorders, which are primarily a result of inheriting recessive genes (Kiani & Miller, 2010). Congenital hearing loss is associated with pro- creation within a close family network, poverty, and inadequate access to health care and immunization in the general population. Cytomegalovirus infec- tion plays a major role in acquired hearing loss (Del- tenre & Van Maldergem, 2013). In Down syndrome, structural anomalies of sensory organs are common (e.g., narrow ear canals, keratoconus—a degenera- tive disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than the more normal gradual curve), and sensory impairments may occur sev- eral decades earlier than in the general popula- tion (Kiani & Miller, 2010; see also Chapters 14 and 49). Certain syndromes or conditions are associ- ated with intellectual and developmental disabili- ties and combined hearing and vision loss. These include prematurity, congenital rubella syndrome, meningoencephalitis, and Usher syndrome, among others. (For information about Usher syndrome, see Mathur & Yang, 2015.) Many individuals with con- genital deafblindness have some degree of intellec- tual impairment. Co-occurring Challenging Behaviors, Mental Health Disorders, and Intellectual and Developmental Disabilities The prevalence of challenging behaviors, including mental health disorders, is three to four times more common in people with intellectual and develop- mental disabilities than in the general population. People with ASD, severe disabilities, and sensory impairments and communication disorders are more likely to demonstrate these behaviors. More- over, as mentioned earlier, quite a number of genetic disorders are associated with behaviors resembling those seen in individuals with ASD. People with intellectual and developmental disabilities also are at increased risk of having comorbid mental health disorders, including ADHD, schizophre- nia, depression, and bipolar disorder. As already noted, sensory impairments can exacerbate chal- lenging behaviors and mental health disorders. Because challenging behaviors often serve as a form of communication, efforts should be made to identify the cause of these and implement supports [ Page ] 191 to subdue them (see Chapter 23). Ideally, a sensory impairment team, care pathway, and clinical net- work should be developed within every disability support service to work across the professional and organizational boundaries and in close collabora- tion with audiology and ophthalmology services (Kiani & Miller, 2010). INTELLECTUAL AND DEVELOPMENTAL DISABILITIES AND PREVENTION Since the mid-1980s, advances in research and pub- lic education endeavors have reduced the incidence of intellectual and developmental disabilities (The Arc, n.d.). In particular, newborn screening pro- grams have prevented the development of intel- lectual impairment and developmental disorder from PKU, congenital hypothyroidism, and other causes by early and appropriate therapy. Rh dis- ease resulting in severe jaundice in the newborn has been prevented by the use of anti-RhIG in the mother. Immunization programs can reduce intel- lectual impairment or developmental delay result- ing from infectious causes. For example, vaccination programs in young children have prevented many cases of Haemophilus influenzae type b, measles, encephalitis, and rubella (German measles). Other interventions also reduce occurrences of intellectual impairment or developmental disorders (Percy & Brown, 2011); examples follow. • Having access to early comprehensive prenatal care and preventive measures prior to and dur- ing pregnancy increases a woman's chances of not having a child with intellectual impairment or developmental disorders. • Counseling women with PKU to use a restricted phenylalanine diet for 3 months prior to preg- nancy and during pregnancy prevents intellec- tual impairment or developmental disorders in their infants. • Removal of lead from the environment reduces the chances of brain damage in children. • Safe storage of toxins prevents accidental expo- sures. • Use of child safety seats, bicycle helmets, and sports helmets reduces occurrences of head trauma in children. • Installation of pool fencing prevents asphyxia from near drowning. • Measures to avoid drunk driving help prevent accidents that result in brain injury and intel- lectual impairment. • Enrolling high-risk infants and toddlers into early intervention programs has positive effects on intellectual functioning. • Identifying children's special educational needs and providing appropriate supports and ser- vices helps enable them to develop to their full potential. For more information, see chapters for specific dis- orders (e.g., Chapters 14-20) as well as ones with broader perspectives (e.g., Chapters 21, 33, and 34). SUMMARY Since 2000, tremendous technical advances have been made with respect to the ability and feasibility of detecting abnormalities in DNA of individuals. In particular, complete sequencing of genomic DNA is becoming economically as well as practically fea- sible. This latter technique is leading to new infor- mation about the involvement of genetic mutations in intellectual and developmental disabilities and ASD and to new strategies for obtaining a genetic diagnosis (Ellison, Rosenfeld, & Shaffer, 2013). New approaches are being developed to determine whether new mutations are pathologically associ- ated with particular disorders (Xiong et al., 2015). The recognition that life experiences and different bacteria in the gut (i.e., the microbiome), via epigen- etic mechanisms, can modify brain function as well as infant development in positive and negative ways has created awareness of the probable complexity of the mechanisms that cause variation in intellec- tual and developmental disability phenotypes (see Chapters 11 and 23). The potential involvement of vitamin D deficiency in intellectual and develop- mental disabilities and associated mental disorders warrants particular attention. Also, insights about what aspects of cognitive function and behavior are genetic and what are not also are coming from comparison studies of “identical" twins (who were once thought to be exact genetic photocopies of one another but are not) and of fraternal twins (whose genes are different but upbringings are very simi- lar). Because epigenetic processes are potentially [ Page ] 192 reversible and theoretically amenable to manipula- tion, there is optimism that changes in lifestyle and environment (including physical exercise, social activity, and exercises to develop brain function), and also new forms of pharmacological intervention directed at modification of epigenetic processes, may be fruitful avenues for intervention in intellectual and developmental disorders and certain disorders of mental health. Finally, much can be learned about risk factors for intellectual and developmental dis- abilities from detailed longitudinal studies of indi- viduals in families including the prenatal, neonatal, and postnatal stages of development as well as the transition to adulthood and aging. FOR FURTHER THOUGHT AND DISCUSSION 1. What can be done to target and educate prospec- tive mothers about the dangers of folic acid and vitamin B12 deficiencies, drinking, smoking, pre- term birth, low birth weight infants, as well as other preventable causes of developmental disabilities? 2. What actions might be taken to curb brain injury due to drunk driving, accidental falls, and child battering? 3. What actions might policy makers take to ensure that health professionals are appropriately paid for providing services to people with intellectual and developmental disabilities? 4. What strategies should be undertaken to create awareness of toxic threats to the health of infants and children? REFERENCES American Association on Intellectual and Developmental Disabilities. (2010). Intellectual disability: Definition, clas- sification, and systems of supports (11th ed.). Washington, DC: Author. American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.). Washington, DC: Author. American Psychiatric Association. (2013). Diagnos- tic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. The Arc. (n.d.). Causes and prevention of intellectual disabilities. Retrieved from http://www.thearc.org/page .aspx?pid=2453 Bailey, R.L., West, K.P., Jr., & Black, R.E. (2015). The epide- miology of global micronutrient deficiencies. Annals of Nutrition and Metabolism, 66(Suppl. 2), 22-33. Boyle, C.A., Boulet, S., Schieve, L.A., Cohen, R.A., Blumberg, S.J., Yeargin-Allsopp, M.,.Kogan, M.D. (2011). Trends in the prevalence of developmental disabilities in US children, 1997-2008. Pediatrics, 127(6), 1034-1042. Brent, R.L. (2004). Environmental causes of human con- genital malformations: The pediatrician’s role in deal- ing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics, 113(Suppl. 4), 957-968. Centers for Disease Control and Prevention (CDC). (2015). Preterm birth. Retrieved from http://www.cdc .gov/reproductivehealth/maternalinfanthealth /pretermbirth.htm Cohen, P.N. (2014, April 4). Parental age and cognitive dis- ability among children in the United States. Sociological Science. Retrieved from https://www.sociologicalscience .com/parental-age-cognitive-disability/ da Silva, E.M., Strufaldi, M.W., Andriolo, R.B., & Silva, L.A. (2016). Enzyme replacement therapy with idur- sulfase for mucopolysaccharidosis type II (Hunter syn- drome). Cochrane Database of Systematic Reviews, Feb 5(2), CD008185. doi:10.1002/14651858.CD008185.pub4 Dalal, M. (2014, May 29). Lucky iron fish in cooking pots tackle anemia. Retrieved from http://www.cbc.ca /news/health/lucky-iron-fish-in-cooking-pots-tackle -anemia-1.2658632 Deltenre, P., & Van Maldergem, L. (2013). Hearing loss and deafness in the pediatric population: Causes, diag- nosis, and rehabilitation. Handbook of Clinical Neurology, 113, 1527-1538. Dobbing, J. (1981). The later development of the brain and its vulnerability. Journal of Inherited Metabolic Disease, 5(2), 88. Dursun, S. (2010). Vitamin D for mental health and cogni- tion. Canadian Medical Association Journal, 182(17), 1886. doi: 10.1503/cmaj.110-2125 Ellison, J.W., Rosenfeld, J.A., & Shaffer, L.G. (2013). Genetic basis of intellectual disability. Annual Review of Medicine, 64, 441-450. Emerson, E. (2010). Socio-economic position. In J.H. Stone & M. Blouin (Eds.), International encyclopedia of rehabilitation. Retrieved from http://cirrie.buffalo.edu /encyclopedia/en/article/313/ Fenning, R.M., & Baker, J.K. (2012). Mother-child interac- tion and resilience in children with early developmen- tal risk. Journal of Family Psychology, 26(3), 411-420. Fernell, E., Bejerot, S., Westerlund, J., Miniscalco, C., Simila, H., Eyles, D.,...Humble, M.B. (2015). Autism spectrum disorder and low vitamin D at birth: A sibling control study. Molecular Autism, 6, 3. Retrieved from http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4396835 Fetahu, I.S., Höbaus, J., & Kállay, E. (2014).Vitamin D and the epigenome. Frontiers in Physiology, 29(5), 164. Frighi, V., Morovat, A., Stephenson, M.T., White, S.J., Hammond, C.V., & Goodwin, G.M. (2014). Vitamin D deficiency in patients with intellectual disabilities: Prevalence, risk factors and management strategies. British Journal of Psychiatry, 205(6), 458-464. Gamsiz, E.D., Sciarra, L.N., Maguire, A.M., Pescosolido, M.F., van Dyck, L.I., & Morrow, E.M. (2015). Discovery of rare mutations in autism: Elucidating neurodevelop- mental mechanisms. Neurotherapeutics, 12(3), 553-571. [ Page ] 193 Glover, V. (2015). Prenatal stress and its effects on the fetus and the child: Possible underlying biological mechanisms. Advances in Neurobiology, 10, 269-283. Grandjean, P., & Landrigan, PJ. (2014). Neurobehavioural effects of developmental toxicity. Lancet Neurology, 13(3), 330-338. Groves, N.J., McGrath, J.J., & Burne, T.H. (2014). Vitamin D as a neurosteroid affecting the developing and adult brain. Annual Review of Nutrition, 34, 117-141. Gruters, A., & Krude, H. (2012, February). Detection and treatment of congenital hypothyroidism. Nature Reviews Endocrinology, 8(2), 104-113. Guze, C. (2005). Teratogens. Retrieved July 15, 2005, from http://www.carolguze.com/text/442-13-teratogens.shtml Hamblin, J. (2014, March 18). The toxins that threaten our brains. The Atlantic. Retrieved from http://www .theatlantic.com/features/archive/2014/03/the-toxins -that-threaten-our-brains/284466/ Hamdan, F.F., Srour, M., Capo-Chichi, J.M., Daoud, H., Nassif, C., Patry. L, ..Michaud, J.L. (2014). De novo mutations in moderate or severe intellectual disabil- ity. PLOS Genetics, 10(10), e1004772. doi:10.1371/journal .pgen.1004772 Hart, PH., Lucas, R.M., Walsh, J.P., Zosky, G.R., White- house, A.J., Zhu, K.,.Mountain, J.A. (2015). Vitamin D in fetal development: Findings from a birth cohort study. Pediatrics, 135(1), e167-173. doi:10.1542/peds.2014-1860 Hunter, J.E., Allen, E.G., Shin, M., Bean, L.J., Correa, A., Druschel, C.,.Sherman, S.L. (2013). The association of low socioeconomic status and the risk of having a child with Down syndrome: A report from the National Down Syndrome Project. Genetics in Medicine, 15(9), 698-705. Jarjour, I.T. (2015). Neurodevelopmental outcome after extreme prematurity: A review of the literature. Pediat- ric Neurology, 52(2), 143-152. Kaderavek, J.N. (2014). Children with intellectual disabil- ity. In J.N. Kaderavek, Language disorders in children (2nd ed., pp. 82-92). New York, NY: Pearson Education. Kaminsky, E.B., Kaul, V., Paschall, J., Church, D.M., Bunke, B., Kunig, D.,.Martin, C.L. (2011). An evidence-based approach to establish the functional and clinical sig- nificance of copy number variants in intellectual and developmental disabilities. Genetics in Medicine,13(9), 777-784. Karam, S.M., Riegel, M., Segal, S.L., Félix, T.M., Barros, A.J., Santos, I.S.,...Black, M. (2015). Genetic causes of intellectual disability in a birth cohort: A population- based study. American Journal of Medical Genetics Series A, 167(6), 1204-1214. Kaufman, L., Ayub, M., & Vincent, J.B. (2010). The genetic basis of non-syndromic intellectual disability: A review. Journal of Neurodevelopmental Disorders, 2(4), 182-209. Kiani, R., & Miller, H. (2010). Sensory impairment and intel- lectual disability. Advances in Psychiatric Treatment, 16(3), 228-235. LaFranchi, S. (2016). Clinical features and detection of congenital hypothyroidism. Retrieved from http://www .uptodate.com/contents/clinical-features-and-detection -of-congenital-hypothyroidism Lai, M. C., Lombardo, M.V., Auyeung, B., Chakrabarti, B., & Baron-Cohen, S. (2015). Sex/gender differences and autism: Setting the scene for future research. Journal of the American Academy of Child and Adolescent Psychiatry, 54(1), 11-24. Landrigan, P.J., Kimmel, C.A., Correa, A., & Eskenazi, B. (2004). Children’s health and the environment: Pub- lic health issues and challenges for risk assessment. Environmental Health Perspectives, 112, 257-265. Laslo, D. (1999, April 23). Embryonic neurodevelopment, neural tube defects, and folic acid. Presentation in Neuroscience of Developmental Disabilities: PSL1062S [Seminar], Depart- ment of Physiology, University of Toronto, Canada. Laufer, B.I., Kapalanga, J., Castellani, C.A., Diehl, E.J., Yan, L., & Singh, S.M. (2015). Associative DNA methylation changes in children with prenatal alcohol exposure. Epigenomics, 7(8), 1259-1274. Lee, B.K., & McGrath, J.J. (2015). Advancing parental age and autism: Multifactorial pathways. Trends in Molecular Medicine, 21(2), 118-125. Maartens, G., Celum, C., & Lewin, S.R. (2014). HIV infection: Epidemiology, pathogenesis, treatment, and prevention. Lancet, 384(9939), 258-271. March of Dimes Foundation. (2016). Rh disease. Retrieved from http://www.marchofdimes.org/complications/rh -disease.aspx Marshall, E. (2015, January 26). Childhood neglect erodes the brain. Retrieved from http://news.sciencemag.org /brain-behavior/2015/01/childhood-neglect-erodes -brain Mathur, P., & Yang, J. (2015). Usher syndrome: Hearing loss, retinal degeneration and associated abnormali- ties. Biochimica et Biophysica Acta, 1852(3), 406-420. McDonald, S.J., Middleton, P., Dowswell, T., & Morris, P.S. (2013, July 11). Effect of timing of umbilical cord clamping of term infants on mother and baby out- comes. Cochrane Database System Review, 7, CD0040747. Retrieved from http://www.cochrane.org/CD004074 /PREG_effect-of-timing-of-umbilical-cord-clamping -of-term-infants-on-mother-and-baby-outcomes McLaren, J., & Bryson, S.E. (1987). Review of recent epi- demiological studies of mental retardation: Prevalence, associated disorders, and etiology. American Journal of Mental Retardation, 92(3), 243-254. Mercola, J. (2008, December 23). How to avoid the top ten most common toxins. Retrieved from http://articles.mercola .com/sites/articles/archive/2005/02/19/common-toxins .aspx Mercola, J. (2010, April 13). BPA toxins puts newborns, mothers at risk. Retrieved from http://www.huffingtonpost.com /dr-mercola/bpa-toxins-puts-newborns_b_457590.html Miller, C., & Sweatt, J.D. (2007). Covalent modification of DNA regulates memory formation. Neuron, 53(6), 857-869. Moalem, S., Weinberg, E.D., & Percy, M.E, (2004). Hemo- chromatosis and the enigma of misplaced iron: Impli- cations for infectious disease and survival. Biometals, 17(2), 135-139. Mount Sinai Hospital. (2013). Ethnicity-based conditions. Retrieved from http://www.mountsinai.on.ca/care/pdmg /genetics/ethnicity-based-conditions [ Page ] 194 National Institutes of Health, Office of Dietary Supple- ments. (n.d.). Nutrient recommendations: Dietary reference intakes (DRI). Retrieved from https://ods.od.nih.gov /Health_Information/Dietary_Reference_Intakes.aspx Nussbaum, R.L., McInnes, R.R., & Willard, H.F. (2015). Thompson & Thompson genetics in medicine (8th ed.). Philadelphia, PA: Elsevier. Percy, M. (2007). Factors that cause or contribute to devel- opmental disabilities. In I. Brown & M. Percy (Eds.), A comprehensive guide to intellectual and developmental dis- abilities (pp. 125-148). Baltimore, MD: Paul H. Brookes Publishing Co. Percy, M., & Brown, I. (2011). Factors that cause or contrib- ute to intellectual and developmental disabilities. In I. Brown & M. Percy (Eds.), Developmental disabilities in Ontario (3rd ed., pp. 207-226). Toronto, Canada: Ontario Association on Developmental Disabilities. Powell, A. (2010, October 10). Breathtakingly awful. Harvard Gazette. Retrieved from http://news.harvard .edu/gazette/story/2010/10/breathtakingly-awful/ Rasmussen, S.A., Jamieson, D.J., Honein, M.A., & Petersen, L.R. (2016). Zika virus and birth defects: Reviewing the evidence for causality. The New England Journal of Medicine, 374, 1981-1987. doi: 10.1056/NEJMsr1604338 Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T.,..Strom, T. M. (2012). Range of genetic mutations associated with severe non-syndromic spo- radic intellectual disability: An exome sequencing study. Lancet, 380(9854), 1674-1682. Rehabilitation Research and Training Center on Devel- opmental Disabilities and Health. (2015a). Guidelines on hearing impairment in ID. Retrieved from http://www .rrtcadd.org/resources/Resources/Topics-of-Interest /Health-Promotion/hearing-imp.PDF Rehabilitation Research and Training Center on Devel- opmental Disabilities and Health. (2015b). Guidelines on vision impairment in ID. Retrieved from http://www .rrtcadd.org/resources/Resources/Topics-of-Interest /Health-Promotion/visual-imp.PDF Reichow, B., Bartin, E.E., Boyd, B.A., & Hume, K. (2014, November 3). Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD): A systematic review [Monograph]. Campbell Systematic Reviews, Issue 9. Retrieved from http://www.campbellcollaboration.org /lib/?go=monograph&year=2014 Rice, D., & Barone, S., Jr. (2000). Critical periods of vul- nerability for the developing nervous system: Evidence from humans and animal models. Environmental Health Perspectives, 108 (Suppl. 3), 511-533. Ross, M.G., & Desai, M. (2005). Gestational programming: Population survival effects of drought and famine dur- ing pregnancy. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 288, R25-R33. Rzhetsky, A., Bagley, S.C., Wang, K., Lyttle, C.S., Cook, E.H., Jr., Altman, R.B., & Gibbons, R.D. (2014). Environmental and state-level regulatory factors affect the incidence of autism and intellectual disability. PLOS Computational- Biology, 10 (3), e1003518. doi:10.1371/journal.pcbi.1003518 Scheinfeld, N.S. (2015). Protein-energy malnutrition. Re- trieved from http://emedicine.medscape.com/article /1104623-overview Selhub, J., & Rosenberg, I.H. (2016). Excessive folic acid intake and relation to adverse health outcome. Biochimie, 126, 71-78. Sheridan, M., Drury, S., McLaughlin, K., & Almas, A. (2010). Early institutionalization: Neurobiological consequences and genetic modifiers. Neuropsychology Review, 20(4), 414-429. Smith, D.C. (2014). Bacterial infections and pregnancy. Retrieved from http://emedicine.medscape.com/article /235054-overview#a3 Srour, M., & Shevell, M. (2014). Genetics and the inves- tigation of developmental delay/intellectual disability. Archives of Disease in Childhood, 99(4), 386-389. Stagnaro-Green, A., Dogo-Isonagie, E., Pearce, E.N., Spencer, C.A., & Gaba, N. (2015). Marginal iodine status and high rate of subclinical hypothyroidism in Washington DC in women planning conception. Thyroid, 25(10), 1151-1154. Stegman, B.J., & Carey, J.C. (2002). TORCH Infections. Toxoplasmosis, other (syphilis, varicella-zoster, par- vovirus B19), rubella, cytomegalovirus (CMV), and herpes infections. Current Women’s Health Reports, 2, 253-258. Stothard, K.J., Tennant, P.W., Bell, R., & Rankin, J. (2009). Maternal overweight and obesity and the risk of congenital anomalies: A systematic review and meta- analysis. JAMA: The Journal of the American Medical Association, 301(6), 636-650. Susser, M.W. (2002). Causality, causes, and causal inference. Retrieved from http://www.encyclopedia.com Thompson, M.D., Cole, D.E., & Ray, J.G. (2009). Vitamin B-12 and neural tube defects: The Canadian expe- rience. American Journal of Clinical Nutrition, 89(2), 697S-701S. UNAIDS. (2016). Fact sheet 2016. Retrieved from http:// www.unaids.org/en/resources/fact-sheet UNICEF. (2010). Nutrition. Retrieved from http://www .unicef.org/nutrition/ van Karnebeek, C.D. (2014). [Inborn errors of metabo- lism are not hopeless; early identification of treatable conditions in children with intellectual disability]. Nederlands Tijdschrft voor Geneeskunde, 158, A8042. Vitti, P. (2014). Iodine deficiency disorders. Retrieved from http://www.uptodate.com/contents/iodine-deficiency -disorders Winneke, G. (2011). Developmental aspects of envi- ronmental neurotoxicology: Lessons from lead and polychlorinated biphenyls. Journal of the Neurological Sciences, 308(1-2), 9-15. World Health Organization. (2015). Micronutrient defi- ciencies. Retrieved from http://www.who.int/nutrition /topics/ida/en/ Xiang, A.H., Wang, X., Martinez, M.P., Walthall, J.C., Curry, E.S., Page, K.,.Getahunm, D. (2015). Asso- ciation of maternal diabetes with autism in offspring. JAMA: The Journal of the American Medical Association, 313(14), 1425-1434. Xiong, H.Y., Alipanahi, B., Lee, L.J., Bretschneider, H., Merico, D., Yuen, R.K.,.Frey, B.J. (2015). RNA splic- ing. The human splicing code reveals new insights into the genetic determinants of disease. Science, 347(6218), 1254806. doi:10.1126/science.1254806. ***** This is the end of the e-text. This e-text was brought to you by Tyndale University, J. William Horsey Library - Tyndale Digital Collections *****