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BackgroundLiterature suggests that maternal exposure to persistent organic pollutants (POPs) may influence child neurodevelopment. Evidence linking prenatal POPs and autism spectrum disorder has been inconclusive and few studies have examined the mixture effect of the POPs on autism-related traits.ObjectiveTo evaluate the associations between prenatal exposure to a mixture of POPs and autism-related traits in children from the Early Autism Risk Longitudinal Investigation study.MethodsMaternal serum concentrations of 17 POPs (11 polychlorinated biphenyls [PCBs], 4 polybrominated diphenyls [PBDEs], and 2 persistent pesticides) in 154 samples collected during pregnancy were included in this analysis. We examined the independent associations of the natural log-transformed POPs with social, cognitive, and behavioral traits at 36 months of age, including Social Responsiveness Scale (SRS), Mullen Scales of Early Learning-Early Learning Composite (MSEL-ELC), and Vineland Adaptive Behavior Scales (VABS) scores, using linear regression models. We applied Bayesian kernel machine regression and quantile g-computation to examine the joint effect and interactions of the POPs.ResultsHigher ln-PBDE47 was associated with greater deficits in social reciprocity (higher SRS score) (β = 6.39, 95% CI: 1.12, 11.65) whereas higher ln-p,p'-DDE was associated with lower social deficits (β = -8.34, 95% CI: -15.32, -1.37). Positive associations were observed between PCB180 and PCB187 and cognitive (MSEL-ELC) scores (β = 5.68, 95% CI: 0.18, 11.17; β = 4.65, 95% CI: 0.14, 9.17, respectively). Adaptive functioning (VABS) scores were positively associated with PCB170, PCB180, PCB187, PCB196/203, and p,p'-DDE. In the mixture analyses, we did not observe an overall mixture effect of POPs on the quantitative traits. Potential interactions between PBDE99 and other PBDEs were identified in association with MSEL-ELC scores.ConclusionsWe observed independent effects of PCB180, PCB187, PBDE47, and p,p' DDE with ASD-related quantitative traits and potential interactions between PBDEs. Our findings highlight the importance of assessing the effect of POPs as a mixture.

BackgroundPrenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results.MethodsTo provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS.ResultsSeparate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium.ConclusionsThis study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies.

We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; [beta] = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes.