Air Pollution and Autism Spectrum Disorder in Israel: A Negative Control Analysis

Hadas Magen-Molho, Marc G. Weisskopf, Daniel Nevo, Alexandra Shtein, Shimon Chen, David Broday, Itai Kloog, Hagai Levine, Ofir Pinto, Raanan Raz

Research output: Contribution to journalArticlepeer-review


Background: Residual confounding is a major concern for causal inference in observational studies on air pollution-autism spectrum disorder (ASD) associations. This study is aimed at assessing confounding in these associations using negative control exposures. Methods: This nested case-control study included all children diagnosed with ASD (detected through 31 December 2016) born during 2007-2012 in Israel and residing in the study area (N = 3,843), and matched controls of the same age (N = 38,430). We assigned individual house-level exposure estimates for each child. We estimated associations using logistic regression models, mutually adjusted for all relevant exposure periods (prepregnancy, pregnancy, and postnatal). We assessed residual confounding using postoutcome negative control exposure at age 28-36 months. Results: In mutually adjusted models, we observed positive associations with ASD for postnatal exposures to NOx (odds ratio per interquartile range, 95% confidence interval: 1.19, 1.02-1.38) and NO2(1.20, 1.00-1.43),and gestational exposure to PM2.5-10(1.08, 1.01-1.15). The result for the negative control period was 1.04, 0.99-1.10 for PM2.5,suggesting some residual confounding, but no associations for PM2.5-10(0.98, 0.81-1.18), NOx (1.02, 0.84-1.25), or NO2(0.98, 0.81-1.18), suggesting no residual confounding. Conclusions: Our results further support a hypothesized causal link with ASD that is specific to postnatal exposures to traffic-related pollution.

Original languageAmerican English
Pages (from-to)773-780
Number of pages8
Issue number6
StatePublished - 1 Nov 2021


  • ASD
  • Air pollution
  • Autism spectrum disorder
  • Negative control

All Science Journal Classification (ASJC) codes

  • Epidemiology


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