Prenatal and postnatal exposure to heavy metals in PM_2.5 and autism spectrum disorder

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders, and its incidence is increasing over time. Although several environmental factors have been suspected to be risk factors for ASD, studies on the effects of airborne heavy metals on newly developed ASD are still limited. We conducted a large birth cohort study of 168,062 live term births in Taichung during 2004-2011 to assess the association of heavy metals in particulate matter with an aerodynamic diameter less than 2.5 μm (PM_2.5) with ASD, and identify sensitive time windows during prenatal and postnatal periods. Heavy metals, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in PM_2.5, were estimated using the Weather Research and Forecasting/Chem (WRF/Chem), inserted from the top 75 emission sources for the module. The association between childhood ASD and 4 metals were analyzed from pregnancy to 9 months after birth. The Cox proportional hazard model with a distributed lag nonlinear model (DLNM) was used to estimate the association between heavy metals in PM_2.5 and ASD. We identified 666 incident ASD cases in 168,062 participants. A positive association between Hg and ASD was found at 9 months after birth (Hazard Ratio: 1.63; 95% CI: 1.13-2.36). According to the DLNM, there was an increased risk of exposure to Hg during 10-25 weeks after birth, and decreased risk of exposure to Hg during gestational weeks 4-6. Exposure to As and Hg on the risk of ASD were significantly stronger in low birth weight infants (<2500 g) than in those of birth weight ≥2500 g during postnatal period. Postnatal exposure to Hg in PM_2.5 may associate with increased ASD incidence. Infants with low birth weight and exposure to As and Hg in PM_2.5 are more likely to develop ASD.