Parental smoking and the risk of congenital heart defects in offspring: An updated meta-analysis of observational studies

Objective Although previous reviews confirmed maternal active smoking was significantly associated with risk of fetal congenital heart defects (CHDs), association between maternal passive smoking and paternal smoking and risk of CHDs is inconclusive nowadays; furthermore, a complete overview is lacking. A meta-analysis of observational studies was conducted to assess the risk of CHDs associated with maternal active and passive smoking and paternal smoking. Methods Seven electronic databases were searched for qualified research up to June 2018. We summarized study characteristics and the summary risk estimates were calculated using either the random-effect model or fixed-effect model. Sensitivity and subgroup analysis were carried out to identify the potential heterogeneity moderators. Results One hundred and twenty-five studies involving 137,574 CHDs cases in 8,770,837 study participants were included. Overall, maternal active (risk ratio (RR) = 1.25; 95% confidence interval (CI): 1.16-1.34;p < 0.01) and passive (RR = 2.24, 95% CI: 1.81-2.77;p < 0.01) smoking as well as paternal active smoking (RR = 1.74, 95% CI: 1.48-2.06;p < 0.01) were significantly associated with CHDs risk. For specific CHD subtypes, our study showed that maternal active smoking was significantly associated with risk of atrial septal defect (RR = 1.27, 95% CI: 1.02-1.59;p = 0.03) and right ventricular outflow tract obstruction (RR = 1.43, 95% CI: 1.04-1.97;p = 0.03). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. Conclusion Maternal active smoking, maternal passive smoking as well as paternal smoking all increased the risk of CHDs in offspring. Preventing parental smoking during peri-pregnancy is a priority for CHDs prevention.