Preconception, prenatal and postnatal exposure to gaseous air pollutants (NO2, O3) and neurodevelopmental disorders in children among Medicaid recipients: a national cohort study.

Although numerous etiological factors have been proposed for neurodevelopmental disorders, the contribution of environmental exposures remains insufficiently understood, particularly among socioeconomically disadvantaged populations. In this study, we evaluated the associations between exposure to nitrogen dioxide (NO2), ozone (O3), and neurodevelopmental disorders among children enrolled in Medicaid, which provides health insurance for adults and children with limited income and resources. We conducted a retrospective cohort study among 1,543,129 mother-child pairs from 2001 to 2013 from the Medicaid Analytic Extract (MAX). NO2 and O3 levels were estimated by spatial-temporal machine learning models and were aggregated to the zip code level based on maternal residence. We applied a stratified Cox model that coupled with a distributed lag model (DLM) framework to explore sensitive windows of exposure, with the adjustment for co-pollutants, meteorological factors (temperature, relative humidity), as well as individual- and zip-code level covariates over the preconception, prenatal and postnatal periods. We examined effect modifications by race, sex and population density. Associations were mostly null during the preconception and prenatal periods, while the strongest association was observed for cumulative exposure to NO2 and risk of intellectual disability (HR = 1.15, 95% CI: 1.00-1.33) with a critical window (where each consecutive week's HR was statistically significant) of exposure between 10 and 16 gestational weeks (HR = 1.04, 95% CI: 1.01 - 1.08). During the postnatal period, the strongest association was observed between NO2 and risk of learning difficulties (HR = 1.18, 95% CI: 1.00-1.41), whereas no association was found for O3 and any neurodevelopmental disorders. Yet, negative associations were also observed for several combinations between NO2/O3 and neurodevelopmental disorders. There was no evidence of effect modification by race, sex or population density. Future studies should continue to accumulate evidence for the association between NO2/O3 exposure and neurodevelopmental disorders in children.