WHAT'S KNOWN ON THIS SUBJECT:Virtually all persons in industrialized countries are exposed to bisphenol A (BPA), and early-life BPA exposure might be associated with behavior problems. Few human studies have been conducted, and the impact of gestational versus childhood BPA exposures is unclear. WHAT THIS STUDY ADDS:BPA exposure during pregnancy, but not childhood, was associated with worse behavior at 3 years of age, especially among girls. Domains related to behavioral and emotional regulation were most affected by gestational BPA exposure. abstract OBJECTIVES:To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations. METHODS:We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). RESULTS:BPA was detected in Ͼ97% of the gestational (median: 2.0 g/L) and childhood (median: 4.1 g/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender. CONCLUSIONS:In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear. Pediatrics 2011;128:873-882 AUTHORS:

BackgroundPrenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy.ObjectiveOur goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy.MethodsWe measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models.ResultsGeometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations.ConclusionsThese results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.

Background: Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult.Objective: Our goal was to identify gestational EDC exposures associated with autistic behaviors.Methods: We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs.Results: Most of the EDCs were associated with negligible absolute differences in SRS scores (≤ 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (β = 2.5; 95% CI: –0.6, 5.6) or trans-nonachlor (β = 4.1; 95% CI: 0.8–7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (β = –3.0; 95% CI: –6.3, 0.2), β-hexachlorocyclohexane (β = –3.3; 95% CI: –6.1, –0.5), or PBDE-85 (β = –3.2; 95% CI: –5.9, –0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (β = –2.0; 95% CI: –4.4, 0.4).Conclusions: Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, β-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors.Citation: Braun JM, Kalkbrenner AE, Just AC, Yolton K, Calafat AM, Sjödin A, Hauser R, Webster GM, Chen A, Lanphear BP. 2014. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the HOME Study. Environ Health Perspect 122:513–520; http://dx.doi.org/10.1289/ehp.1307261

In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.

Background Hazardous air pollutants are plausible candidate exposures for autism spectrum disorders. They have been explored in recent studies for their role in the development of these disorders. Methods We used a prevalent case-control design to screen perinatal exposure to 35 hazardous air pollutants for further investigation in autism etiology. We included 383 children with autism spectrum disorders and, as controls, 2829 children with speech and language impairment. All participants were identified from the records-based surveillance of 8-year-old children conducted by the Autism and Developmental Disabilities Monitoring Network in North Carolina (for children born in 1994 and 1996) and West Virginia (born in 1992 and 1994). Exposures to ambient concentrations of metal, particulate, and volatile organic air pollutants in the census tract of the child’s birth residence were assigned from the 1996 National Air Toxics Assessment annual-average model. We estimated odds ratios (ORs) for autism spectrum disorders and corresponding 95% confidence intervals (CIs), comparing across the 20th and 80th percentiles of log-transformed hazardous air pollutant concentration among the selected controls, using semi-Bayes logistic models and adjusting for sampling variables (surveillance year and state), a priori demographic confounders from the birth certificate and census, and covarying air pollutants. Results We estimated many near-null ORs, including those for metals, established human neurodevelopmental toxicants, and several pollutants that were elevated in a similar study in California. Hazardous air pollutants with more precise and elevated OR estimates included methylene chloride, 1.4 (95% CI = 0.7–2.5), quinoline, 1.4 (1.0–2.2), and styrene, 1.8 (1.0–3.1). Conclusions Our screening design was limited by exposure misclassification of air pollutants and the use of an alternate developmental disorder as the control group, both of which may have biased results toward the null. Despite these limitations, methylene chloride, quinoline, and styrene emerged (based on this analysis and prior epidemiologic evidence) as candidates that warrant further investigation for a possible role in autism etiology.