Ambient Toxic Air Contaminants in the Maternal Residential Area during Pregnancy and Cerebral Palsy in the Offspring

Cerebral palsy (CP) is the most common permanent neuromotor disorder diagnosed in childhood. Although most cases have unknown etiology, emerging evidence suggests environmental risk factors of CP.

We investigated whether ambient toxic air contaminants (TACs) in the maternal residential area during pregnancy, specifically volatile organic compounds (VOCs) and metals, were associated with offspring CP risk in California.

We conducted a case-cohort study that included CP cases ($N=906$) and a 20% random sample of all live singleton births ($N=\mathrm{184,954}$) who lived within a $5\text{-mile}$ (8-km) radius of air toxics monitoring stations in California during 2005-2015 as the control comparison group. CP cases were ascertained from diagnostic records of the California Department of Developmental Services. We a priori selected TACs with suspected neurotoxicity and developmental toxicity, including 14 VOCs and 6 metals. We estimated the adjusted risk ratio (RR) and 95% confidence interval (CI) for CP and the average maternal residential exposures to each TAC over the entire pregnancy using modified Poisson regression. For air contaminant mixtures, we used quantile-based g-computation to estimate the effects of mixtures of VOCs or metals. Finally, we performed a negative control exposure analysis on exposure estimates of 36-48 months after delivery to evaluate uncontrolled confounding bias.

Maternal residential exposures to six VOCs (benzene, toluene, 1,3-butadiene, acetone, acetonitrile, and methylene chloride) and four metals (antimony, lead, nickel, and vanadium) were associated with 3%-25% higher risk of CP per interquartile range increase, and the estimated mixture effects of VOCs ($\text{RR}=1.24$; 95% CI: 1.08, 1.43) or metals ($\text{RR}=1.38$; 95% CI: 1.20, 1.58) were stronger. The observed associations were close to null for negative control exposures (36-48 months after delivery) to mixtures of VOCs or metals and CP.

In California, maternal prenatal residential exposure to VOCs and metals in the outdoor air, largely attributed to mobile traffic emission sources, was associated with an increased risk of CP in offspring. https://doi.org/10.1289/EHP14742.