According to data from a population-based birth cohort, prenatal exposure to elevated levels of nitric oxide (NO) is associated with increased odds for autism spectrum disorder (ASD).

Investigators linked birth records from 2004 to 2009 in the British Columbia Perinatal Data Registry with health services data, demographic data, and neighborhood data through Population Data British Columbia. Diagnosis of ASD was ascertained in the study population through the British Columbia Autism Assessment Network.

ASD was diagnosed according to a standardized assessment with the Autism Diagnostic Interview-–Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter <2.5 μm (PM2.5), NO, and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated using temporally adjusted high-resolution land regression models. These regression models were developed using neighborhood-level data and air pollution information acquired through Statistics Canada and Metro Vancouver’s Air Quality Monitoring Network, respectively.

Logistic regression was used to examine the association between prenatal air pollution exposure and the odds of ASD developing, adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018.

Of 132,256 children born in the Vancouver metropolitan area between 2004 and 2009, 1307 (1.0%) were diagnosed with ASD, among whom 83.5% were boys. The median age at ASD diagnosis was 4.2 years (interquartile range [IQR], 3.3-5.2 years). Children diagnosed with ASD were more likely to be born to slightly older mothers, multiparous mothers, and residents of lower-income neighborhoods. For mothers, the median monthly exposure during pregnancy was 3.5 μg/m3 (IQR, 2.7-4.2 μg/m3) for PM2.5, 18.3 ppb (IQR, 14.0-24.7 ppb) for NO, and 14.3 ppb (IQR, 12.2-17.0 ppb) for NO2. In the fully adjusted model, only NO was associated with significantly increased odds for ASD diagnosis (odds ratio [OR] 1.07; 95% CI, 1.01-1.13) per 10.7 ppb (IQR) increase. ORs for boys were 1.04 (95% CI, 0.98-1.10) for PM2.5, 1.09 (95% CI, 1.02-1.15) for NO, and 1.07 (95% CI, 1.00-1.13) for NO2. For girls, the OR values were 1.03 (95% CI, 0.90-1.18) for PM2.5, 0.98 (95% CI, 0.83-1.13) for NO, and 1.00 (95% CI, 0.86-1.16) for NO2. Tests of interaction between sex and exposure for all air pollutants were not statistically significant.

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An increased risk for ASD was associated with prenatal exposure to NO. These data corroborate similar findings from other studies conducted worldwide and suggest that decreasing NO exposure among pregnant women may reduce the incidence of ASD in metropolitan areas. As this study focused on exposure to single pollutants alone, further research should involve pollutant mixtures, researchers wrote.


Pagalan L, Bickford C, Weikum W, et al. Association of prenatal exposure to air pollution with autism spectrum disorder [published online November 19, 2018]. JAMA Pediatr. doi: 10.1001/jamapediatrics.2018.3101