Gestational exposure to environmental chemical mixtures and cognitive abilities in children: A pooled analysis of two North American birth cohorts.

BACKGROUND: Gestational exposures to single toxic chemicals have been associated with cognitive deficits in children, but few studies have explored chemical mixtures. OBJECTIVES: To evaluate the associations between gestational chemical biomarker mixtures and cognitive abilities in children from two prospective cohorts. METHODS: This study includes 617 birthing parent-child pairs from the Health Outcomes and Measures of the Environment (HOME) and Maternal-Infant Research on Environmental Chemicals (MIREC) Studies. We measured 29 chemical biomarkers (metals, persistent organic pollutants, perfluoroalkyl substances, organophosphate esters, phenols, phthalates, organophosphate pesticides, and parabens) in pregnant individuals during early pregnancy and their children's cognitive abilities at ages 3 to 5 years using Wechsler Intelligence Scales. We assessed linear associations using quantile g-computation and non-linear associations using Bayesian Kernel Machine Regression (BKMR) methods, adjusted for covariates. RESULTS: Using quantile g-computation, we observed overall null associations between the chemical biomarker mixture and cognitive outcomes among preschool-age children. Although statistical significance was not attained for child sex as an effect modifier, our stratified analysis unveiled a moderate divergence in association trends. We noted a marginal inverse trend between the chemical biomarker mixture and cognitive scores [Full-Scale Intelligence Quotient (FSIQ) & Performance Intelligence Quotient (PIQ)] among males. Using quantile g-computation and BKMR methods, we observed that PBDE47, PFHxS, and di-ethyl organophosphates commonly contributed towards a decline in FSIQ scores in males. Among males, a quartile increase in the chemical biomarker mixture was associated with a 0.64-point decrease (95% CI: -2.59, 1.31) in the FSIQ score and a 1.59-point decrease (95% CI: -3.72, 0.54) in the PIQ score. CONCLUSION: In this study, we observed a weak negative trend between the gestational chemical biomarker mixture and cognitive scores (FSIQ/PIQ) among males. Further studies are needed to confirm the findings between the longitudinal chemical biomarkers and child cognitive scores at school ages.