Deborah A. Bilder

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012

PROBLEM/CONDITION Autism spectrum disorder (ASD). PERIOD COVERED 2012. DESCRIPTION OF SYSTEM The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence and characteristics of ASD among children aged 8 years whose parents or guardians reside in 11 ADDM Network sites in the United States (Arkansas, Arizona, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, South Carolina, Utah, and Wisconsin). Surveillance to determine ASD case status is conducted in two phases. The first phase consists of screening and abstracting comprehensive evaluations performed by professional service providers in the community. Data sources identified for record review are categorized as either 1) education source type, including developmental evaluations to determine eligibility for special education services or 2) health care source type, including diagnostic and developmental evaluations. The second phase involves the review of all abstracted evaluations by trained clinicians to determine ASD surveillance case status. A child meets the surveillance case definition for ASD if one or more comprehensive evaluations of that child completed by a qualified professional describes behaviors that are consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (including atypical autism), or Asperger disorder. This report provides ASD prevalence estimates for children aged 8 years living in catchment areas of the ADDM Network sites in 2012, overall and stratified by sex, race/ethnicity, and the type of source records (education and health records versus health records only). In addition, this report describes the proportion of children with ASD with a score consistent with intellectual disability on a standardized intellectual ability test, the age at which the earliest known comprehensive evaluation was performed, the proportion of children with a previous ASD diagnosis, the specific type of ASD diagnosis, and any special education eligibility classification. RESULTS For 2012, the combined estimated prevalence of ASD among the 11 ADDM Network sites was 14.6 per 1,000 (one in 68) children aged 8 years. Estimated prevalence was significantly higher among boys aged 8 years (23.6 per 1,000) than among girls aged 8 years (5.3 per 1,000). Estimated ASD prevalence was significantly higher among non-Hispanic white children aged 8 years (15.5 per 1,000) compared with non-Hispanic black children (13.2 per 1,000), and Hispanic (10.1 per 1,000) children aged 8 years. Estimated prevalence varied widely among the 11 ADDM Network sites, ranging from 8.2 per 1,000 children aged 8 years (in the area of the Maryland site where only health care records were reviewed) to 24.6 per 1,000 children aged 8 years (in New Jersey, where both education and health care records were reviewed). Estimated prevalence was higher in surveillance sites where education records and health records were reviewed compared with sites where health records only were reviewed (17.1 per 1,000 and 10.7 per 1,000 children aged 8 years, respectively; p<0.05). Among children identified with ASD by the ADDM Network, 82% had a previous ASD diagnosis or educational classification; this did not vary by sex or between non-Hispanic white and non-Hispanic black children. A lower percentage of Hispanic children (78%) had a previous ASD diagnosis or classification compared with non-Hispanic white children (82%) and with non-Hispanic black children (84%). The median age at earliest known comprehensive evaluation was 40 months, and 43% of children had received an earliest known comprehensive evaluation by age 36 months. The percentage of children with an earliest known comprehensive evaluation by age 36 months was similar for boys and girls, but was higher for non-Hispanic white children (45%) compared with non-Hispanic black children (40%) and Hispanic children (39%). INTERPRETATION Overall estimated ASD prevalence was 14.6 per 1,000 children aged 8 years in the ADDM Network sites in 2012. The higher estimated prevalence among sites that reviewed both education and health records suggests the role of special education systems in providing comprehensive evaluations and services to children with developmental disabilities. Disparities by race/ethnicity in estimated ASD prevalence, particularly for Hispanic children, as well as disparities in the age of earliest comprehensive evaluation and presence of a previous ASD diagnosis or classification, suggest that access to treatment and services might be lacking or delayed for some children. PUBLIC HEALTH ACTION The ADDM Network will continue to monitor the prevalence and characteristics of ASD among children aged 8 years living in selected sites across the United States. Recommendations from the ADDM Network include enhancing strategies to 1) lower the age of first evaluation of ASD by community providers in accordance with the Healthy People 2020 goal that children with ASD are evaluated by age 36 months and begin receiving community-based support and services by age 48 months; 2) reduce disparities by race/ethnicity in identified ASD prevalence, the age of first comprehensive evaluation, and presence of a previous ASD diagnosis or classification; and 3) assess the effect on ASD prevalence of the revised ASD diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders.

OBJECTIVE. To investigate prenatal, perinatal, and neonatal risk factors for autism spectrum disorders by using participants identified through broad ascertainment and reliable classification methods. METHODS. The targeted population was 8-year-old children born in 1994 and residing in 1 of the 3 most populous counties in Utah who were identified as having an autism spectrum disorder on the basis of methodology used by the 2002 Autism and Developmental Disabilities Monitoring Network. Of those identified, 132 children (115 boys, 17 girls) had birth certificate records available. Each child was matched by gender and birth year to 100 controls (11 500 boys, 1700 girls) from the birth certificate database in a nested case-control design. Birth certificate records of participants and controls were surveyed for 23 potentially pathologic prenatal, perinatal, and neonatal factors. RESULTS. The prenatal factors that occurred significantly more frequently among children with autism spectrum disorders were advanced maternal age and parity. Increased duration of education among mothers of children with autism spectrum disorders was small but statistically significant. Significant perinatal factors were breech presentation and primary cesarean delivery. When corrected for breech presentation, a known indication for cesarean delivery, the association between primary cesarean delivery and autism spectrum disorders was eliminated. There were no significant associations found between autism spectrum disorders and neonatal factors. CONCLUSIONS. In the absence of other complications suggesting fetal distress, the association between breech presentation and autism spectrum disorders in this study suggests a shared etiology rather than causal relationship. Additional investigation focused on both genetic and environmental factors that link these autism spectrum disorder risk factors individually or collectively is needed.

Prevalence and Characteristics of Autism Spectrum Disorder Among 4-Year-Old Children in the Autism and Developmental Disabilities Monitoring Network.

Objective: Early identification of children with autism spectrum disorder (ASD) facilitates timely access to intervention services. Yet, few population-based data exist on ASD identification among preschool-aged children. The authors aimed to describe ASD prevalence and characteristics among 4-year-old children in 5 of 11 sites participating in the 2010 Autism and Developmental Disabilities Monitoring Network. Method: Children with ASD were identified through screening of health and education records for ASD indicators, data abstraction and compilation for each child, and clinician review of records. ASD prevalence estimates, ages at first evaluation and ASD diagnosis, cognitive test scores, and demographics were compared for 4-year-old children and 8-year-old children living in the same areas. Results: Among 58,467 children in these 5 sites, 4-year-old ASD prevalence was 13.4 per 1000, which was 30% lower than 8-year-old ASD prevalence. Prevalence of ASD without cognitive impairment was 40% lower among 4-year-olds compared with 8-year-olds, but prevalence of ASD with cognitive impairment was 20% higher among 4-year-olds compared with 8-year-olds. Among 4-year-olds with ASD, female and non-Hispanic white children were more likely to receive their first comprehensive evaluation by age 36 months compared with male and non-Hispanic black children, respectively. Among children diagnosed with ASD by age 48 months, median age at first comprehensive evaluation was 27 months for 4-year-olds compared with 32 months for 8-year-olds. Conclusion: Population-based ASD surveillance among 4-year-old children provides valuable information about the early identification of children with ASD and suggests progression toward lowering the age of first ASD evaluation within participating Autism and Developmental Disabilities Monitoring communities.

Phenylketonuria Scientific Review Conference: State of the science and future research needs

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Psychiatric symptoms and disorders in phenylketonuria

Psychological and psychiatric problems are well documented across the lifespan of individuals with early-treated phenylketonuria (PKU). Early-treated children and adolescents tend to display attentional problems, school problems, lower achievement motivation, decreased social competence, decreased autonomy, and low-self-esteem. As they enter adulthood, early-treated individuals may carry forward low self-esteem and lack of autonomy but also tend to develop depressed mood, generalized anxiety, phobias, decreased positive emotions, social maturity deficits, and social isolation. The correlation between level of metabolic control and severity of symptoms suggests a biological basis of psychiatric dysfunction. Additionally, psychosocial factors such as the burden of living with a chronic illness may contribute to psychological and psychiatric outcomes in PKU. The lack of a PKU-specific psychiatric phenotype combined with the observation that not everyone with PKU is affected highlights the complexity of the problem. More research on psychiatric and psychological outcomes in PKU is required. Of particular importance is the routine monitoring of emotional, behavioral, and psychosocial symptoms in individuals with this metabolic disorder. Longitudinal studies are required to evaluate the impact of new and emerging therapies on psychiatric and psychosocial functioning in PKU. Unidentified or untreated emotional and behavioral symptoms may have a significant, lifelong impact on the quality of life and social status of patients.

Changes in the administrative prevalence of autism spectrum disorders: contribution of special education and health from 2002-2008.

This study examined changes in the administrative prevalence of autism spectrum disorders (ASD) in Utah children from 2002 to 2008 by record source (school and health), age (four, six, and eight), and special education classification. Prevalence increased 100% with 1 in 77 children aged eight identified with ASD by 2008. Across study years and age groups rates were higher when health and school data were combined with a greater proportion of cases ascertained from health. The proportion of children with both a health ASD diagnosis and a special education autism classification did not significantly change. Most children with an ASD health diagnosis did not have an autism special education classification. Findings highlight the growing health and educational impact of ASD.

Maternal Prenatal Weight Gain and Autism Spectrum Disorders

BACKGROUND: The rising population of individuals identified with an autism spectrum disorder (ASD) calls for further investigation of its underlying etiology. A disturbance in the fetal steroid hormone environment may be a mechanism in which environmental and genetic risk factors interact. The mother, fetus, and placenta collectively create the fetal steroid environment. Prepregnancy BMI and pregnancy weight gain have served as markers for fetal steroid hormone exposure in other disease states. This study’s objective is to determine whether prepregnancy BMI and pregnancy weight gain are associated with increased ASD risk across study designs and cohorts while controlling for important confounding variables. METHODS: A population-based Utah ASD cohort (n = 128) was ascertained in a 3-county surveillance area and gender- and age-matched to 10 920 control subjects. A second, research-based ASD cohort of Utah children (n = 288) and their unaffected siblings (n = 493) were ascertained through participation in an ASD genetics study. Prenatal variables were obtained from birth certificate records. RESULTS: ASD risk was significantly associated with pregnancy weight gain (adjusted odds ratio = 1.10, 95% confidence interval: 1.03 to 1.17; adjusted odds ratio = 1.17, 95% confidence interval: 1.01 to 1.35 for each 5 pounds of weight gained), but not prepregnancy BMI, in population and research-based cohorts, respectively. When analyses were restricted to ASD cases with normal IQ, these associations remained significant. CONCLUSIONS: ASD risk associated with a modest yet consistent increase in pregnancy weight gain suggests that pregnancy weight gain may serve as an important marker for autism’s underlying gestational etiology. This justifies an investigation into phenomena that link pregnancy weight gain and ASD independent of prepregnancy BMI.

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury

Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

Prenatal and Perinatal Factors Associated with Intellectual Disability.

Prenatal and perinatal risk factors associated with intellectual disability (ID) were studied in 8-year-old Utah children from a 1994 birth cohort (N  =  26,108) using broad ascertainment methods and birth records following the most current recording guidelines. Risk factor analyses were performed inclusive and exclusive of children with a known or suspected underlying genetic disorder. Risk factors identified were poly/oligohydramnios, advanced paternal/maternal age, prematurity, fetal distress, premature rupture of membranes, primary/repeat cesarean sections, low birth weight, assisted ventilation greater than 30 min, small-for-gestational age, low Apgar scores, and congenital infection. Although several risk factors lost significance once children with underlying genetic disorders were excluded, socioeconomic variables were among those that maintained a prominent association with increased ID risk.

A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980s Utah/UCLA Autism Epidemiologic Study

This study describes medical conditions experienced by a population-based cohort of adults with autism spectrum disorder whose significant developmental concerns were apparent during childhood. As part of a 25-year outcome study of autism spectrum disorder in adulthood, medical histories were collected on 92 participants (N = 69 males) who were first ascertained as children in the mid-1980s, 11 of whom were deceased at the time of follow-up. Questionnaires queried medical symptoms, disorders, hospitalizations, surgeries, and medication use. Median age at follow-up was 36 years (range: 23.5–50.5 years), and intellectual disability co-occurred in 62%. The most common medical conditions were seizures, obesity, insomnia, and constipation. The median number of medical conditions per person was 11. Increased medical comorbidity was associated with female gender (p = 0.01) and obesity (p = 0.03), but not intellectual disability (p = 0.79). Adults in this cohort of autism spectrum disorder first ascertained in the 1980s experience a high number of chronic medical conditions, regardless of intellectual ability. Understanding of these conditions commonly experienced should direct community-based and medical primary care for this population.