摘要Background Evidence remains limited on the association between maternal ozone(O3)exposure and congenital heart defects(CHDs)in offspring,and few studies have investigated the interaction and modification of paternal smoking on this association.Methods Using a sample including pregnant women at high risk of fetal CHD(with metabolic disease,first-trimester viral infection,family history of CHD,etc.)from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021,we examined the associations between maternal O3 exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association.CHD was diagnosed by fetal echocardiograms,maximum daily 8-hour average O3 exposure data at a 10 km ×10 km spatial resolution came from the Tracking Air Pollution in China dataset,and paternal smoking was collected using questionnaires.Logistic regression models were used to estimate adjusted odds ratios(ORs)and 95％confidence intervals(CIs).Results Among 27,834 pregnant women at high risk of fetal CHD,17.4％of fetuses were diagnosed with CHD.Each 10μg/m3 increase in maternal O3 exposure was associated with a 17％increased risk of CHD in offspring(OR=1.17,95％CI=1.14-1.20).Compared with paternal nonsmoking and maternal low O3 exposure,the ORs(95％CI)of CHD for smoking and low O3 exposure,nonsmoking and high O3 exposure,and smoking and high O3 exposure were 1.25(1.08-1.45),1.81(1.56-2.08),and 2.23(1.84-2.71),respectively.Paternal smoking cessation seemingly mitigated the increased risk of CHD.Conclusions Maternal O3 exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring,which calls for effective measures to decrease maternal exposure to O3 pollution and secondhand smoke for CHD prevention.