Prenatal Ozone Exposure and Reduced Brain Volume in Infants: A Nationwide Population-Based Study

Ozone (O₃) pollution is increasingly recognized as a serious environmental threat associated with elevated dementia risks. However, evidence regarding the impact of prenatal exposure to O₃ on the morphological development of the brain remains limited. This nationwide population-based study investigated associations between prenatal O₃ exposure and brain volume in 3294 infants aged 0-1 year without major anomalies, who underwent magnetic resonance imaging for non-neurological indications at hospitals within the China Neonatal Neuro-Critical Care Network group. Prenatal O₃ exposure was estimated using geocoded residential addresses linked to 1 km × 1 km air pollution datasets. Linear mixed-effects models revealed that each 10 μg/m³ increase in prenatal O₃ exposure was associated with a decrease of 1.14% (95% CI: 0.38-1.88) in total brain volume, 1.15% (95% CI: 0.40-1.89) in gray matter volume, 1.13% (95% CI: 0.37-1.88) in white matter volume, 1.11% (95% CI: 0.35-1.87) in cerebral blood volume, and 1.12% (95% CI: 0.36-1.88) in cerebrospinal fluid. No significant association was observed for the apparent diffusion coefficient [-0.08% (95% CI: -0.43-0.27)]. The associations remained significant in dual-pollutant models that additionally adjusted for prenatal PM_2.5 exposure. Mediation analysis confirmed a direct effect of prenatal O₃ exposure on brain morphology, as birth weight accounted for only 3.47% to 3.54% of the total effect. Our findings underscore the imperative for stricter air quality regulations to protect pregnant individuals and mitigate potential neurodevelopmental impairment originating as early as the fetal stage.