Association between maternal PM2.5 exposure and congenital heart defects in offspring: a time-series study

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Background Maternal exposure to air pollutants are associated with congenital heart defects (CHDs), yet fundamental questions remain unclear: which pollutant matters most, which exposure window is most critical, and whether susceptibility differs by offspring sex. Objective To examine the association between maternal PM 2.5 exposure during periconception (from 4 weeks before conception to 28 weeks of gestation) and offspring CHD risk in urban districts of Chongqing (2018 ~ 2021), and to identify the key exposure windows. Methods Data on birth defects and air quality in urban Chongqing were utilized. The association between PM 2.5 exposure and congenital heart disease was assessed using the Distributed Lag Nonlinear Model (DLNM) time-series analysis. Results The average concentration of PM 2.5 in urban Chongqing from 2018 to 2021 was 37.27 μg/m 3 . A total of 884 cases of congenital heart disease were monitored. We observed significant increasing effects between PM 2.5 exposure during gestational weeks 6 to 27 and risk of CHDs (RR = 1.05, 95% CI: 1.01 ~ 1.09) per a 10 μg/m 3 change in PM 2.5 concentration. Sex-stratified analysis revealed that male offspring exhibited greater susceptibility from preconception week 3 to gestational week 24, with the strongest effect at gestational week 11 ~ 12 (RR = 1.10, 95% CI: 1.04 ~ 1.16). For congenital malformations of cardiac septa (Q21), the critical susceptibility windows were gestational weeks 0 ~ 26, with the strongest effect at gestational week 13 (RR = 1.06, 95% CI: 1.02 ~ 1.11). While, congenital malformations of great arteries (Q25) demonstrated susceptibility from preconception week 3 to gestational week 21, with the strongest effect at gestational week 10 (RR = 1.11, 95% CI: 1.04 ~ 1.19). Significance Maternal exposure to PM 2.5 , especially during the preconception and the first trimester, increases the risk of certain types of CHDs in offspring, and male offspring exhibited greater susceptibility. Impact Based on data from Chongqing (2018 ~ 2021), this study used DLNM method to identify that maternal exposure to PM 2.5 between gestational weeks 6 ~ 27 significantly increased the risk of CHDs, including cardiac septal defects (Q21) and great artery malformations (Q25). Male offspring showed higher susceptibility, with the strongest effect in gestational weeks 11 ~ 12. Associations were modified after adjusting for co-pollutants (SO₂, NO₂, CO, O₃) in two-pollutant models.

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