Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder

BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000–2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case–control study at age 2–5 y, were clinically confirmed to have ASD ([Formula: see text]) or typical development ([Formula: see text]), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003–2011. High vs. low daily FA intake was dichotomized at [Formula: see text] (median). Mothers’ addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake ([Formula: see text]) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with [Formula: see text] and any indoor pesticide exposure {adjusted odds ratio [Formula: see text] [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [[Formula: see text] (95% CI: 0.7, 2.2)] or indoor pesticides [[Formula: see text] (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure ([Formula: see text]) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604