• Cerebral palsy (CP) is the most common childhood neuromotor disorder with largely unknown etiology. • We conducted a statewide population-based study in California. • Maternal prenatal exposures to residential ambient nitrogen dioxide (NO 2 ) and ozone (O 3 ) were associated with a higher risk of overall CP in the offspring. • Certain CP subtypes may be more susceptible to different pollutants. • The negative control analysis did not suggest strong unmeasured confounding bias. Cerebral palsy (CP) is a permanent neuromotor disorder with childhood onset, and the etiology for most cases remains unexplained. We conducted a population-based case-control study in California during 2000–2015, including all identified CP cases (N = 9,343) from the California’s Department of Developmental Services and a control group of 20% random sample of live births without CP (N = 1,560,423). We employed a high-resolution (100 m) spatiotemporal model to estimate prenatal exposures to fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), ozone (O 3 ), and investigated their impacts on CP through single-pollutant, multiple-pollutant, and chemical-mixture models. Further, we examined the unmeasured confounding bias through the negative control exposure (NCE) design and assessed the potential heterogeneity across CP subtypes. Prenatal exposures throughout pregnancy to ambient NO 2 (per interquartile-range, OR = 1.14, 95% CI, 1.10–1.18) and O 3 (OR = 1.08, 95% CI, 1.05–1.11) were associated with higher odds of CP in offspring. A stronger association emerged when three pollutants were modelled as a mixture (OR = 1.23, 95% CI, 1.17–1.29), especially in the first and third trimesters. Potential interactions were noted across pollutants, with associations for NO 2 and O 3 strengthening in multiple-pollutant adjusted models or within strata of low PM 2.5 (i.e., below the median). PM 2.5 was positively associated with CP only in strata of low O 3 (OR = 1.14, 95% CI, 1.09–1.19). The 36 months post-birth NCE was not associated with CP, suggesting no strong confounding bias. CP involving ataxic and dyskinetic motor dysfunction was more sensitive to O 3 exposure. Prenatal exposure to major ambient air pollutants was associated with offspring CP. Future studies to elucidate the underlying mechanisms are recommended.
Zhuo et al. (Sun,) studied this question.