Objective: To investigate the association between maternal smoking during pregnancy and risk of congenital heart defects (CHDs) among offspring.
Methods: PubMed, EMBASE, and Web of Science were searched for eligible studies. The outcomes of interest included risk of any CHD and nine subtypes. We summarized study characteristics and used a random-effects model in meta-analysis, and a two-stage dose-response model was utilized to assess the association between smoking consumption and risk. Statistical heterogeneity was assessed by a chi-squared test of the Cochrane Q statistic and I-squared value. Publication bias was assessed by funnel plots and Egger's test, and trim and fill method was utilized when publication bias existed.
Results: Forty-three observational epidemiologic studies were included. The pooled risk ratio (RR) of any CHD was 1.11 (95% CI: 1.04, 1.18), but it exhibited substantial statistical heterogeneity (p < 0.001, I2 = 69.0%). In sensitivity analysis, we observed significant associations for atrial septal defect (ASD) and marginally significant associations for septal defects (SPD). The two-stage dose-response analysis showed evidence to support that higher levels of tobacco smoke was associated with an increased risk of septal defects, particularly for ASD and VSD (ventricular septal defect).
Conclusion: Our study presents evidence to support the cardiovascular teratogenic effect of maternal smoking during pregnancy, and their offspring may suffer from approximately a 10% relative increase in the risk of CHDs on average.
Keywords: Cardiovascular disease; child health; smoking; systematic review.