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

Abstract

BACKGROUND AND AIM: Emerging animal and human data demonstrate sexual dimorphism in the developmental neurotoxicity of PM2.5 exposure. However, little is known about the sensitive gestational windows of prenatal PM2.5 exposure associated with increased ASD risk. METHODS: This population-based retrospective birth cohort study included 294,937 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals between 2001 and 2014. Children were followed using electronic medical records (EMR) until a clinical diagnosis of ASD, non-KPSC membership, death, or December 31, 2019, whichever came first. Weekly mean PM2.5, NO2, and O3 exposures during pregnancy were estimated using spatiotemporal (1km x 1km) prediction models. Cox proportional-hazard models with distributed lags were used to estimate the independent associations between weekly pollutant exposures with ASD risk, separately for boys and girls. RESULTS:5,694 children (4,636 boys, 1,058 girls) had ASD diagnosis. Significant sensitive windows of exposure associated with PM2.5 exposure were found throughout the first two trimesters [1-27 weeks, cumulative HR=1.20 (95%CI=1.09–1.32) per 10 µg/m3 increase], adjusting for maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, median household income, birth year, and season. The cumulative hazard ratio (HR) during the entire pregnancy was 1.24 per 10 µg/m3 increase in PM2.5 (95%CI=1.10 –1.39). O3 exposure during 34-37 gestational weeks was also associated with increased ASD risk [cumulative HR=1.03 (1.01–1.06) per 10 ppb increase]. No associations were observed with NO2. When stratified by sex, early gestational (1-28 weeks) associations of PM2.5 were stronger for boys [cumulative HR=1.23 (1.10 –1.36) for boys and 1.10 (0.81 –1.38) for girls]; O3 associations in later gestation (33-37 weeks) were observed only in boys [boys=1.05 (1.02 –1.08); girls= 0.97 (0.9 –1.03)]. CONCLUSIONS:Exposures to higher levels of PM2.5 in the first two trimesters and O3 in the late 3rd trimester was associated with increased ASD risk, especially among boys. KEYWORDS: Autism Spectrum Disorder, Air Pollution, Sex Differences, Sensitive Windows