Differential Impacts of Fine Particulate Matter Constituents on Congenital Heart Disease across Critical Periconceptional Windows.

The effect of specific chemical constituents of fine particulate matter (PM2.5) on congenital heart disease (CHD) remains unknown and urgently needed. This study aimed to quantify the associations between PM2.5 constituents and CHD risk, identify critical exposure windows, and explore potential effect modifiers. We included 12,680 CHD cases and 10,266 controls from the Guangdong Registry of CHD (2004-2022). Multilevel logistic regression found that PM2.5 total mass and its constituents were significantly associated with CHD, particularly during the preconception period, with each interquartile range (IQR) increase corresponding to a 9-16% elevated risk. The associations were generally attenuated in later exposure windows, whereas BC and nitrate showed significant associations during pregnancy. Conotruncal defects showed the strongest association with PM2.5 constituents (ORs ranged from 1.14 to 1.36 per IQR increase). Mixture analyses indicated that sulfate and BC dominated the effects during preconception, while BC and nitrate prevailed subsequently. Subgroup and interaction analyses showed that higher socioeconomic status significantly amplified PM2.5 constituent-related CHD risk during the preconception period, whereas multiparity and lack of folic acid supplementation significantly modified risk during later windows (P for interaction <0.05). These findings underscore that periconceptional exposure to PM2.5 is associated with increased CHD risk, with effects varying by constituent and exposure window. Targeting emissions of BC, sulfate, and nitrate may help mitigate PM2.5-related CHD burden.