Maternal smoking during pregnancy and the risk of congenital heart defects in offspring: a systematic review and metaanalysis.

Although a previous metaanalysis indicated that maternal smoking during pregnancy increased the risk of congenital heart defects (CHD) in offspring, the effect of smoking on individual CHD subtypes was not determined. Because CHDs are anatomically, clinically, epidemiologically, and developmentally heterogeneous, the authors conducted a systematic review and metaanalysis of the association between maternal smoking during pregnancy and the risk of CHDs, including CHD subtypes among offspring. Two types of summary relative risk (RR) estimates (any smoking vs no smoking and increasing categories of smoking, i.e., light, medium, and heavy) were calculated for CHDs as a group and for a number of CHD subtypes using both fixed- and random-effects models. Random effects estimates were reported if there was evidence of heterogeneity among the studies. Consistent with the previous metaanalysis, the authors observed a positive association between maternal smoking during pregnancy and the risk of CHDs as a group (RR, 1.11; 95 % confidence interval [CI], 1.02-1.21; number of cases [n] = 18,282). Additionally, women who smoked during pregnancy were more likely to have a child with 12 (71 %) of 17 CHD subtypes analyzed compared with women who did not smoke. The highest risk was for septal defects as a group (RR, 1.44; 95 % CI, 1.16-1.79; n = 2977). The evidence of dose response was observed for septal defects as a group, atrial septal defects, and atrioventricular septal defects. This systematic review and metaanalysis suggests that maternal smoking is modestly associated with an increased risk of CHDs and some CHD subtypes.