Traffic-Related Air Pollution and Autism Spectrum Disorder: A Population-Based Nested Case-Control Study in Israel

Abstract

Accumulating evidence suggests that perinatal air pollutant exposures are associated with increased risk of autism spectrum disorder (ASD), but evidence for traffic pollutants outside the United States is inconclusive. We assessed the association between nitrogen dioxide, a traffic pollution tracer, and risk of ASD. We conducted a nested case-control study among the entire population of children born during 2005-2009 in the central coastal area of Israel. Cases were identified through the National Insurance Institute of Israel (n = 2,098). Controls were a 20% random sample of the remaining children (n = 54,191). Exposure was based on an optimized dispersion model. We estimated adjusted odds ratios and 95% confidence intervals using logistic regression and a distributed-lag model. In models mutually adjusted for the 2 periods, the odds ratio per 5.85-parts per billion (ppb) increment of nitrogen dioxide exposure during pregnancy (median, 16.8 ppb; range, 7.5-31.2 ppb) was 0.77 (95% confidence interval: 0.59, 1.00), and the odds ratio for exposure during the 9 months after birth was 1.40 (95% confidence interval: 1.09, 1.80). A distributed-lag model revealed reduced risk around week 13 of pregnancy and elevated risk around week 26 after birth. These findings suggest that postnatal exposure to nitrogen dioxide in Israel is associated with increased odds of ASD, and prenatal exposure with lower odds. The latter may relate to selection effects.

Figure 1.

Associations between exposure to nitrogen dioxide during pregnancy and during the 9 months after birth and risk of autism spectrum disorder among children born in central coastal Israel during 2005–2009. Odds ratios show the risk of autism spectrum disorder per interquartile-range increment (5.85 ppb) in nitrogen dioxide exposure. A) Results from 2 separate models, each adjusted for year of birth, calendar month of birth, population group, paternal age, and census poverty index. B) Results from 1 model, with mutual adjustment for both exposure periods in addition to all of the covariates listed above. Bars, 95% confidence intervals.

Figure 2.

Results from a distributed-lag model representing polynomial time-dependent associations between weekly nitrogen dioxide exposure and risk of autism spectrum disorder among children born in central coastal Israel during 2005–2009. The black line represents the time-varying function estimating risk of autism spectrum disorder with weekly exposures during 38 weeks of pregnancy (left) and the first 38 weeks of life (right), and the gray area around it represents its 95% confidence interval. These results are from a nonlinear distributed-lag model with 7 degrees of freedom. A linear association was assumed between the exposure and the outcome at each time point. Results were adjusted for year of birth, calendar month of birth, population group, paternal age, and census poverty index.