Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

BACKGROUND: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters. OBJECTIVE: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort. METHODS: This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of [Formula: see text] ([Formula: see text])], nitrogen dioxide ([Formula: see text]), and ozone ([Formula: see text]) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season. RESULTS: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive [Formula: see text] exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative [Formula: see text] [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) ([Formula: see text]) increase]. [Formula: see text] exposure during 34–37 wk of gestation was associated with increased risk [[Formula: see text] (95% CI: 1.01, 1.11) per IQR ([Formula: see text]) increase] but with reduced risk during 20–28 wk of gestation [[Formula: see text] (95% CI: 0.89, 0.98)]. No associations were observed with [Formula: see text]. Sex-stratified early gestational [Formula: see text] associations were stronger among boys [boys [Formula: see text] (95% CI: 1.08, 1.26); girls [Formula: see text] (95% CI: 0.89, 1.26)]. [Formula: see text] associations in later gestation were observed only in boys [boys [Formula: see text] (95% CI: 1.04, 1.16); girls [Formula: see text] (95% CI: 0.84, 1.05)]. CONCLUSIONS: Exposures to [Formula: see text] in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of [Formula: see text] exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509