Exposure to Particulate Matter Air Pollution during Pregnancy Is Associated with Increased Risk of Autism Spectrum Disorder: A Nested Case-Control Study from the Nurses' Health Study II

Background:  Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Airborne particles are covered with biocontaminants, penetrate the subcellular environment and induce oxidative stress and mitochondrial damage in vitro. In rodents, they also stimulate inflammatory cytokine release systemically and in the brain, and alter the neonatal immune system – processes that are implicated in autism spectrum disorder (ASD). Several studies have explored associations of air pollution with ASD, using the US Environmental Protection Agency hazardous air pollutants models, distance to freeway or local models for specific pollutants. These studies suggest increased risk of ASD with higher exposures to diesel particulate matter (PM), several metals and some organic pollutants as well as closer proximity to a freeway.

Objectives:  To explore the association between maternal exposure to PM air pollution and risk of ASD.

Methods:  This is a nested case-control study of participants in the Nurses' Health Study II (NHS II), a prospective cohort of 116,430 United States female nurses aged 25-43 when recruited in 1989, followed by biennial mailed questionnaires. Study participants 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. Monthly averages of airborne particulate matter with diameters ≤2.5µm (PM2.5) and between 2.5µm and 10µm (PM10-2.5) were predicted from a spatiotemporal model for the continental US and linked to residential addresses updated every two years.

Results:  PM_2.5 exposure during pregnancy was significantly associated with increased odds of ASD, with the 4^th quartile having an adjusted odds ratio of 1.71 (95% CI: 1.10–2.66) in comparison to the 1^st quartile. The association was stronger when limiting the sample to those who did not change residences around the time of pregnancy (odds ratio = 2.02, 95% CI: 1.15-3.54). Associations with PM_2.5 exposure 9 months before or after the pregnancy were substantially lower. There was no association of ASD risk with PM_10-2.5.

Conclusions:  Higher exposure to PM_2.5 during pregnancy is associated with risk of ASD. This association is specific to PM_2.5 and to the pregnancy period.