Prenatal exposure to per- and polyfluoroalkyl substances: Association with child behavior in the environmental influences on child health outcomes (ECHO) Cohort.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact child neurodevelopment; however, epidemiologic findings remain inconclusive because of small sample sizes, limited exposure variability, and differing neurodevelopmental measures. We aimed to investigate the relationship between prenatal PFAS exposure and child behavior.

Methods: We pooled data from nine study sites in the nationwide Environmental influences on Child Health Outcomes (ECHO) Cohort. PFAS were quantified in maternal serum samples collected between 2 and 42 weeks' gestation. Behavioral and emotional problems were assessed via the Child Behavior Checklist (CBCL) in preschool-age (n = 1,723) and school-age (n = 627) children. We used age-stratified, covariate-adjusted linear mixed-effects models to estimate differences in CBCL scores by PFAS quartile, focusing on analytes detected at >75 %. We also fit quantile g-computation models to examine associations for PFAS mixtures and tested for effect modification by child sex.

Findings: Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) were the most frequently detected analytes in maternal prenatal serum, although concentrations were generally low (<5 ng/mL). Associations between PFAS concentrations and CBCL scores were mostly null, except for some suggestive findings for PFHxS in the preschool-age subset. No consistent sex differences were observed, and associations for PFAS mixtures were statistically insignificant.

Interpretation: We found little evidence of associations between prenatal PFAS exposures and child behavioral problems in the ECHO Cohort. Future studies should consider PFAS exposure during the postnatal period, which may be a more sensitive window.