Int J Hyg Environ Health. 2025 Jul 19;269:114624. doi: 10.1016/j.ijheh.2025.114624. Online ahead of print.
ABSTRACT
While prenatal PM2.5 exposure constitutes an established risk factor for congenital heart defects (CHDs), the modifying role of greenness exposure in this association remains underexplored. We conducted a retrospective cohort study analyzed 1,356,420 birth records (11,803 CHD cases) from Zhejiang Province, China (2018-2023). Prenatal exposure to PM2.5 and its major constituents was estimated using satellite-derived speciation models, and greenness was assessed via the normalized difference vegetation index (NDVI). Generalized additive models (GAMs) with a quasibinomial logit link and restricted maximum likelihood were used to model non-linear associations and interactions. Mixture effects and joint exposure-response surfaces were estimated using fast Bayesian kernel machine regression (fbKMR). Causal mediation analysis under a counterfactual framework was used to assess indirect effects of PM2.5 in the greenness-CHD relationship. We identified predominantly J-shaped exposure-response relationships between key PM2.5 constituents and CHD risk, with organic matter (OM) and black carbon (BC) exhibiting the steepest risk increases. Mixture modeling via fbKMR revealed a monotonic increase in CHD risk with joint pollutant exposure. NDVI showed a robust U-shaped association with CHDs, with lowest risk at moderate greenness. Seasonal analysis highlighted strong BC and OM effects in autumn and winter, sulfate in spring and winter, and a threshold pattern for ammonium in summer. Spatial heterogeneity was evident, with eastern coastal cities (e.g., Ningbo, Jiaxing) showing pronounced risk increases above 35 μg/m3. Septal-type CHDs exhibited consistent positive associations with PM2.5, while complex subtypes showed weaker patterns. Mediation analysis indicated that PM2.5 accounted for 5.6-15.7 % of the greenness-CHD association, with BC showing the strongest mediation effect. Our findings underscore the cumulative toxicity of PM2.5 mixtures and the protective yet nonlinear role of greenness. Region- and season-specific strategies that integrate pollution control and green infrastructure may help mitigate CHD risk.
PMID:40684539 | DOI:10.1016/j.ijheh.2025.114624
