Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort

Abstract - Background: Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet with unclear etiology.

Objective: To explore the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child. Methods: We conducted a nested case-control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 US female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990-2002 with ASD (n=245), and children without ASD (n=1522) randomly selected using frequency matching for birth years. ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤2.5 μm (PM2.5) and 2.5-10 μm (PM10-2.5) were predicted from a spatiotemporal model for the continental US and linked to residential addresses.

Results: PM2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range higher PM2.5 (4.42 μg/m3) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, while the association with the 9 months of pregnancy remained (OR=1.63; 95% CI: 1.08-2.47). The association between ASD and PM2.5 was stronger for exposure during the third trimester (OR=1.42 per inter-quartile range increase in PM2.5, 95% CI: 1.09, 1.86) than other trimesters (ORs 1.06 and 1.00) when mutually adjusted. There was little association between PM10-2.5 and ASD.

Conclusions: Higher maternal exposure to PM2.5 during pregnancy, in particular the third trimester, was associated with greater odds of her child having ASD.