Maternal and Paternal Infertility Disorders and Treatments and Autism Spectrum Disorder: Findings from the Study to Explore Early Development

Previous studies of associations between ASD and conception using assisted reproductive technology (ART) are inconsistent and few studies have examined associations with other infertility treatments or infertility disorders. We examined associations between ASD and maternal/paternal infertility disorders and numerous maternal treatments among 1538 mother–child pairs in the Study to Explore Early Development, a population-based case-control study. ASD was associated with any female infertility diagnosis and several specific diagnoses: blocked tubes, endometriosis, uterine-factor infertility, and polycystic ovarian syndrome. Stratified analyses suggested associations were limited to/much stronger among second or later births. The findings were not explained by sociodemographic factors such as maternal age or education or multiple or preterm birth. ASD was not associated with ART or non-ART infertility treatments

Reasons for participation in a child development study: Are cases with developmental diagnoses different from controls?

Background: Current knowledge about parental reasons for allowing child participation in research comes mainly from clinical trials. Fewer data exist on parents’ motivations to enrol children in observational studies. Objectives: Describe reasons parents of preschoolers gave for participating in the Study to Explore Early Development (SEED), a US multi-site study of autism spectrum disorder (ASD) and other developmental delays or disorders (DD), and explore reasons given by child diagnostic and behavioural characteristics at enrolment. Methods: We included families of children, age 2–5 years, participating in SEED (n = 5696) during 2007–2016. We assigned children to groups based on characteristics at enrolment: previously diagnosed ASD; suspected ASD; non-ASD DD; and population controls (POP). During a study interview, we asked parents their reasons for participating. Two coders independently coded responses and resolved discrepancies via consensus. We fit binary mixed-effects models to evaluate associations of each reason with group and demographics, using POP as reference. Results: Participants gave 1–5 reasons for participation (mean = 1.7, SD = 0.7). Altruism (48.3%), ASD research interest (47.4%) and perceived personal benefit (26.9%) were most common. Two novel reasons were knowing someone outside the household with the study conditions (peripheral relationship; 14.1%) and desire to contribute to a specified result (1.4%). Odds of reporting interest in ASD research were higher among diagnosed ASD participants (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.49–3.35). Perceived personal benefit had higher odds among diagnosed (OR 1.92, 95% CI 1.61–2.29) or suspected ASD (OR 3.67, 95% CI 2.99–4.50) and non-ASD DD (OR 1.80, 95% CI 1.50–2.16) participants. Peripheral relationship with ASD/DD had lower odds among all case groups. Conclusions: We identified meaningful differences between groups in parent-reported reasons for participation. Differences demonstrate an opportunity for future studies to tailor recruitment materials and increase the perceived benefit for specific prospective participants

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to ‘over-’ or ‘under-report’ child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD

Prenatal Alcohol Exposure in Relation to Autism Spectrum Disorder: Findings from the Study to Explore Early Development (SEED)

Background: Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). Methods: We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case–control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report. Results: Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk. Conclusions: These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment

Demographic and Operational Factors Predicting Study Completion in a Multisite Case-Control Study of Preschool Children

Participant attrition can limit inferences drawn from study results and inflate research costs. We examined factors associated with completion of the Study to Explore Early Development (2007-2011), a multiple-component, case-control study of risk factors for autism spectrum disorder in preschoolers, conducted in California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania. Participants (n = 3,769) were asked to complete phone interviews, questionnaires, an in-person evaluation, and biologic sampling. We examined whether participant demographic and administrative factors predicted completion using mixed-effects logistic regression models. Completion of individual key study components was generally 70% or higher. However, 58% of families completed all per-protocol data elements (defined a priori as key study components). Per-protocol completion differed according to mother's age, race, educational level, driving distance to clinic, number of contact attempts to enroll, and number of telephone numbers provided (all P < 0.05). Case status was not associated with completion, despite additional data collection for case-confirmation. Analysis of a subset that completed an early interview revealed no differences in completion by household factors of income, primary language spoken, number of adults, or number of children with chronic conditions. Differences in completion by race and education were notable and need to be carefully considered in developing future recruitment and completion strategies

The Changing Epidemiology of Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction. Epidemiologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potential risk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals. We discuss future challenges and goals for ASD epidemiology as well as public health implications

The epidemiology of autism spectrum disorders

Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. They are much more common than previously believed, second in frequency only to mental retardation among the serious developmental disorders. Although a heritable component has been demonstrated in ASD etiology, putative risk genes have yet to be identified. Environmental risk factors may also play a role, perhaps via complex gene-environment interactions, but no specific exposures with significant population effects are known. A number of endogenous biomarkers associated with autism risk have been investigated, and these may help identify significant biologic pathways that, in turn, will aid in the discovery of specific genes and exposures. Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes

Early Life Exposure to Air Pollution and Autism Spectrum Disorder: Findings from a Multisite Case-Control Study

BACKGROUND: Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. OBJECTIVES: We examined associations between early life exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone in association with ASD across multiple US regions. METHODS: Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. RESULTS: The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life (OR = 1.3 [95% CI: 1.0, 1.6] per 1.6 µg/m increase in PM2.5). CONCLUSIONS: Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods

Cleft lip and palate in family members of cancer survivors

The presence of cleft lip with or without cleft palate (CL/P) in family members of cancer patients was investigated. An epidemiological questionnaire including family history of cancer and congenital oral cleft malformations was administered to 168 cancer survivors and a population-based sample of 170 healthy subjects. In the control group, 1.2% reported a family member with CL/P; among cancer survivors the figure was 4.2% (odds ratio: 3.7; 95% confidence interval: 0.75-17.8; p = .07). Among cancer survivors with a family member with CL/P, there was an apparent excess of testicular cancer and melanoma in comparison with the cancer survivors with no family history of CL/P. These preliminary results suggest a common etiologic background for cancer and CL/P. © 2010 Informa Healthcare USA, Inc