Association between gestational environmental chemical mixtures and folate exposures with autistic behaviors in a Canadian birth cohort

Background: Prenatal exposure to environmental chemicals may be associated with autism or autistic-like behaviors. Previous studies suggest that these associations are stronger when folic acid (FA) supplementation is lower. Methods: We used data from the Maternal-Infant Research on Environmental Chemicals study, a Canadian pregnancy and birth cohort (2008-2011). We considered five separate chemical mixtures (measured during the first trimester of pregnancy): metals, organochlorine pesticides, per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and persistent organic pollutants (POPs; including organochlorine pesticides, PFAS, PCBs, and one polybrominated diphenyl ether congener). Autistic-like behaviors were documented in 601 3-4-year-old children with the social responsiveness scale-2 (SRS-2), where higher T-scores denote more behaviors. We used quantile g-computation to estimate the mixture-SRS-2 associations and assessed whether gestational FA supplementation and plasma total folate concentrations modified these associations. Results: The PFAS mixture was associated with decreased SRS-2 T-scores (Psi = -0.5; 95% confidence interval [CI] = -1.1, 0.1). The metal-SRS-2 associations were stronger in the positive direction among participants with high (>1,000 mu g/d) FA supplementation (Psi = 2.4; 95% CI = 0.8, 3.9) versus those with adequate (400-1,000 mu g/d) supplementation (Psi = -0.2; 95% CI = -1.1, 0.7) (p-interaction = 0.003). Plasma total folate concentrations similarly modified these associations (p-interaction = 0.01). The associations between the PFAS, PCB, and POP mixtures and SRS-2 T-scores were stronger in the positive direction among participants with low (<400 mu g/d) versus adequate FA supplementation. This was not observed when assessing modification by plasma total folate concentrations. Conclusion: Our results suggest that the metal mixture is more strongly associated with autistic-like behaviors among participants with higher folate exposure, and the PFAS, PCB, and POP mixtures are more strongly associated with autistic-like behaviors among participants with low FA supplementation.