Identifying priority pollutants NO₂, O₃, PM_2.5 and PM₁₀ for preventive strategies against birth defects in China: A...

Maternal exposure to ambient air pollution may increase fetal developmental risk, yet evidence on multi-pollutant lag effects, regional priority pollutants, and future risk burdens remains limited. We analyzed 6910,397 pregnancies from 526 prenatal screening (PS) centers across 215 Chinese cities (2019-2021), identifying 455,476 high-risk cases (6.59%) via second-trimester maternal serum triple (STMST) screening (AFP, free β-hCG, uE3). Daily NO₂, O₃, PM_2.5, and PM₁₀ concentrations were collected and aggregated regionally. Lagged and exposure-response relationships were assessed using lagged weighted quantile sum (LWQS) regression and distributed lag nonlinear models (DLNM). Future risk changes were projected with coupled model intercomparison project phase 6 (CMIP6) and ARIMA models under the SSP1-2.6 scenario, incorporating population-weighted exposures and per-capita gross domestic product (GDP) trends. High-risk rates varied regionally: Central China 6.99-8.86%, Northern China 5.61-9.21%, Southwest China 4.11-6.83%, and Southern China 4.36-6.00%. Lagged effects peaked at 6-8 weeks with relative risk (RR) increases of 1.118 (PM_2.5), 1.038 (NO₂), and 1.073 (O₃) during consecutive high-exposure weeks. PM_2.5 and O₃ showed synergistic effects, while NO₂ interactions were largely antagonistic. Projections to 2060 indicated higher risks in Northwest, Southwest, and Central China with widening spatial disparities. These findings identify region-specific priority pollutants and critical windows to inform targeted prevention strategies.