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The presence of multiple dysmorphic features in some children with autism spectrum disorder (ASD) might identify distinct ASD phenotypes and serve as potential markers for understanding causes and prognoses. To evaluate dysmorphology in ASD, children aged 3-6 years with ASD and non-ASD population controls (POP) from the Study to Explore Early Development were evaluated using a novel, systematic dysmorphology review approach. Separate analyses were conducted for non-Hispanic White, non-Hispanic Black, and Hispanic children. In each racial/ethnic group, ~ 17% of ASD cases were Dysmorphic compared with ~ 5% of POP controls. The ASD-POP differential was not explained by known genetic disorders or birth defects. In future epidemiologic studies, subgrouping ASD cases as Dysmorphic vs. Non-dysmorphic might help delineate risk factors for ASD.

The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.

Background: Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use. Objective: To evaluate the association between prenatal ultrasound use and ASD. Methods: We used data from the Study to Explore Early Development, a multisite case‐control study of preschool‐aged children with ASD implemented during 2007–2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in‐person standardised assessments. We stratified analyses by pre‐existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure. Results: Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester‐specific analyses using medical record data showed no association in any individual trimester. Conclusions: We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold‐standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the relationship between congenital gastrointestinal anomalies requiring neonatal surgery and neurodevelopmental outcome. Among the children born in metropolitan Atlanta during 1982-2001 who survived to age 1 year (N = 762,824), we identified children with congenital gastrointestinal anomalies via linkage with the Metropolitan Atlanta Congenital Defects Program and children who received special education services via linkage with the Special Education Database of Metropolitan Atlanta. Several modest increases in special education service use were observed among children with isolated congenital gastrointestinal anomalies; no association was statistically significant. Among children with Hirschsprung disease, gastroschisis, esophageal atresia, intestinal malrotation, bowel atresia, or imperforate anus who had multiple anomalies, we observed statistically significant increases in special education service use.

DNA rearrangements have been found on both chromosome 17 homologues in a mildly delayed person whose family has a history of autosomal dominant carpal tunnel syndrome. A patient with mild distal neuropathy, multifocal mononeuropathies, growth hormone deficiency, and mild mental retardation has a duplication of the Smith-Magenis syndrome (SMS) region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22 (ital)) gene in 17p12 on the homologous chromosome. The dup(17)(p11.2p11.2) is a de novo change. The PMP22 deletion is familial and family members with it have abnormalities that indicate carpal tunnel syndrome. The two rearrangements were likely found together because of high frequency of the abnormalities and underlying molecular characteristics of the genome in the region. Familial entrapment neuropathies, among them focal ulnar neuropathy syndrome and carpal tunnel syndrome, can be caused by PMP22 deletions.

Objective: The objective of this study was to examine the prevalence of, and maternal characteristics associated with, ADHD medication use before and during pregnancy, and associations between early pregnancy ADHD medication use and risk for 12 selected birth defects. Method: We used data from the National Birth Defects Prevention Study (1998-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects. Results: There was an increase in ADHD medication use from 1998-1999 (0.2%) to 2010-2011 (0.5%; p < .001). Early pregnancy ADHD medication use was more commonly reported by mothers of infants/fetuses with gastroschisis (crude odds ratio [cOR]: 2.9, 95% confidence interval [CI] = [1.2, 6.9]), omphalocele (cOR: 4.0, 95% CI = [1.2, 13.6]), and transverse limb deficiency (cOR: 3.3, 95% CI = [1.1, 9.6]). Conclusion: ADHD medication use before and during pregnancy was rare, but the prevalence of use has increased over time. In this analysis, early pregnancy ADHD medication use was associated with three of 12 selected birth defects. [ABSTRACT FROM AUTHOR]

Background: The National Birth Defects Prevention Study (NBDPS) is a multisite, population‐based, case–control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens. Methods: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA. Results: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol. Conclusions: This proof‐of‐principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well‐characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene–environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers. [ABSTRACT FROM AUTHOR]

Background The National Birth Defects Prevention Study (NBDPS) is a large population-based multicenter case-control study of major birth defects in the United States. Methods Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn, or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases by means of either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father, and infant (if living). Results There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%), respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. Conclusion The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. Birth Defects Research (Part A) 103:656-669, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]