Joint associations between gestational environmental chemical mixtures and child behavioral outcomes

Gestational exposure to environmental chemicals contributes to adverse neurodevelopmental outcomes in children. We aim to evaluate the joint associations between gestational chemical biomarkers and behavioral functioning in preschool-aged children.

We pooled data from 695 mother-child dyads (female, n = 353; male, n = 342) enrolled in the Health Outcomes and Measures of the Environment (HOME) & Maternal-Infant Research on Environmental Chemicals (MIREC) Studies. We assessed concentrations of 29 EDC biomarkers at gestation and assessed the child's behavior and executive functioning at 3 years using the Behavioral Assessment System for Children (BASC-2) and Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Higher scores on these instruments indicate adverse behavioral outcomes. We applied quantile g-computation to estimate joint associations, adjusting for covariates.

Every quartile increase in chemical biomarker mixture was associated with a 0.84-point higher behavior symptom index score (95% CI: -0.89, 2.57), 1.38-point higher externalizing behavior score (95% CI: -0.65, 3.41), and 1.34-point higher internalizing behavior score (95%CI: -0.97, 3.65); these associations were imprecise with confidence intervals including null. Although the interaction by child sex remained null (p = 0.69) for internalizing behavior scores, gestational chemical mixture was associated with higher internalizing behavior scores in males (Ψ: 3.59; 95%CI: 0.42, 6.75), but not in females. We found evidence of sex-specific trends for working memory scores (interaction p = 0.02), with an imprecise positive trend in males (Ψ: 3.04; 95%CI: -0.46, 6.55) and a negative trend in females.

Gestational exposure to a mixture of environmental chemicals showed suggestive but imprecise associations with internalizing problems and poorer working memory among preschool-age males, but not females. Associations were more pronounced in the HOME Study, which includes participants with higher concentrations for many chemical biomarkers, than in MIREC, raising the possibility that pooled estimates reflect cohort-specific exposure contexts. Sex-specific patterns, particularly for working memory, need further investigation, and our findings should be interpreted cautiously given the imprecision of subgroup estimates.