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

Abstract

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 ( )], nitrogen dioxide ( ), and ozone ( ) 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 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) ( ) increase]. exposure during 34–37 wk of gestation was associated with increased risk [ (95% CI: 1.01, 1.11) per IQR ( ) increase] but with reduced risk during 20–28 wk of gestation [ (95% CI: 0.89, 0.98)]. No associations were observed with . Sex-stratified early gestational associations were stronger among boys [boys (95% CI: 1.08, 1.26); girls (95% CI: 0.89, 1.26)]. associations in later gestation were observed only in boys [boys (95% CI: 1.04, 1.16); girls (95% CI: 0.84, 1.05)]. Conclusions: Exposures to in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509

Neurodevelopmental toxicity induced by airborne particulate matter

“…There is an association between maternal prenatal exposure to PM and increased risk of developmental brain abnormalities (e.g., schizophrenia) in children (Woodward et al, 2015). Exposure to PM in early and mid‐pregnancy (1–26 weeks) increases the risk of neurodevelopmental delays and ASD in young children (Rahman et al, 2022; Su et al, 2022). Studies have shown that increased exposure to PM 2.5 during pregnancy, particularly in late pregnancy, results in greater risk for the child to develop ASD (Raz et al, 2015).…”

Social deficits induced by pervasive environmental stressors are prevented by microbial or dopaminergic modulation

“…High levels of air pollution, particularly during development, have been linked to several diseases, including autism spectrum disorder (ASD; Rahman et al, 2022; Carter et al, 2022; Volk et al, 2013). Like air pollution, maternal stress during pregnancy has been associated with an increased risk for having a child with ASD (Roberts et al, 2014; Kinney et al, 2008).…”

Invited Perspective: Air Pollution and Autism Spectrum Disorder: Are We There Yet?

“…In their study published in this issue, Rahman et al. 27 used a historical population-based cohort to analyze data for almost 300,000 children, including 5,694 diagnosed with ASD, from Kaiser Permanente Southern California hospitals. Using nonlinear distributed lag models, they found that the association of PM with an aerodynamic diameter of (i.e., ) with ASD was strongest during the earliest stages of gestation, decreasing during the last weeks of the pregnancy.…”

“…For example, live birth bias, which is very difficult to estimate or mitigate, 29 , 30 may account for the negative association that Rahman et al. 27 found with ozone during the end of the second trimester. Possible confounding structures, such as the possible association between spatiotemporally related diagnostic awareness/health care access and spatiotemporally related air pollution levels, may also limit the ability to make causal inferences about this issue.…”

“…The study by Rahman et al. 27 is notable for its robust methods, which enabled them to identify modifiable environmental factors, critical developmental windows, and susceptible populations. Accordingly, this paper adds to evidence that can support policymaking.…”