Joint effects of PM2.5 components during periconception on offspring congenital heart disease risk in Chongqing, China

Although the association between particulate matter(PM_2.5) exposure and congenital heart disease (CHD) has been widely reported, the component-specific effects, critical exposure window period, and multicomponent synergistic effects remain unknown. This study used a case-control design. In our study, we assessed PM_2.5 and its components exposure concentrations during preconception and first trimester of 9152 pregnancies collected from the Chongqing Municipal Birth Defects Surveillance System. Multivariate logistic regression was used to analyse the effect of PM_2.5 and its components on offspring CHD prevalence. A quantile-based g-computation was also used to analyse the risk of mixed exposure to the components. For all participants, mean daily PM_2.5 exposure was 31.26 and 32.59 μg/m³ during preconception and first trimester, respectively. Black carbon (BC),and unspeciated matter (UM) were significantly associated with overall CHD, Septal Defects (SPD), and Patent Ductus Arteriosus (PDA) risk in the single-pollution model. Sulfates(SO₄^2-), and organic matter (OM) specifically increased the risk of PDA during preconception and first-trimester, respectively. During the first trimester, co-exposure to PM_2.5 components was associated with a 17 % increase (OR = 1.17, 95 % CI: 1.03-1.33) in the overall risk of CHD, a 22 % increase (OR = 1.22, 95 % CI: 1.00-1.50) in SPD, a 29 % increase (OR = 1.29, 95 % CI: 1.05-1.59) in PDA, and a 33 % increase (OR = 1.33, 95 % CI: 1.03-1.72) in other CHD subtypes. In the preconception period, the risk of PDA increased by 38 % (OR = 1.38, 95 % CI: 1.07-1.78). The Marginal Mixture Odds Ratios (MM-ORs) for the combined effects of components during both the preconception and first-trimester periods were higher than those for PM_2.5 alone, highlighting the importance of considering component mixtures. This study suggests that the toxicity of PM_2.5 may be driven by the synergistic effects of its components. BC, SO₄^2-, OM, and UM may interfere with offspring cardiac development through distinct mechanisms during both preconception and the first trimester of pregnancy. These results advocate for component-specific air quality regulations to mitigate CHD risk.