BACKGROUND AND AIM: Previous studies have reported associations between {in-utero} exposure to regional air pollution and autism spectrum disorders (ASD). {In-utero} nitrogen oxide (NOx) exposure has been linked to adverse neurodevelopment in animals and cardiovascular conditions in humans, but few studies have investigated pregnancy exposure to near-roadway air pollution (NRAP) and ASD risk. METHODS: This retrospective birth cohort included 311,617 mother-child pairs of singletons born between 2001-2014 at Kaiser Permanente Southern California (KPSC) hospitals. Maternal and child data were extracted from KPSC electronic medical records. Children were followed until: clinical diagnosis of ASD, non-KPSC membership, death, or December 31, 2019, whichever came first. Exposure to the complex NRAP mixture during pregnancy was estimated by monthly California line-source dispersion models (CALINE4) for both near-roadway (freeway; non-freeway) and total NOx, using maternal addresses during pregnancy. Cox proportional-hazard models were used to estimate hazard ratios (HR) of ASD associated with NRAP during pregnancy, adjusted for covariates. Nonfreeway NRAP was analyzed using quintile distribution due to nonlinear associations with ASD. RESULTS:A total of 6,291 children (5,114 boys, 1,177 girls) were diagnosed with ASD. Prenatal exposure to total NRAP was associated with ASD diagnosis [HR (95% CI): 1.03 (1.00,1.06) per 10 ppb increase in NOx]. Nonfreeway NRAP was associated with ASD diagnosis; however, freeway NRAP was not. The HR (95% CI) comparing the highest quintile of nonfreeway NRAP exposure (3.8 ppb NOx) to the lowest quintile (0.89 ppb) or to the lower 4 quintiles (≤3.8 ppb) were 1.20 (1.08, 1.33) and 1.20 (1.13, 1.27) respectively. The HR (95% CI) associated with high nonfreeway NOx (3.8 vs ≤3.8 ppb) were significant in boys [1.20 (1.10, 1.26)] and girls [1.23 (1.06,1.39)], and robust to adjustment for PM2.5. CONCLUSIONS:Prenatal exposure to near-roadway air pollution, particularly from nonfreeway sources, may be associated with ASD risk in boys and girls KEYWORDS: oxides of nitrogen, neurodevelopmental, children's environmental health
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