Results from a large meta-analysis indicate that paternal smoking during a mother’s pregnancy is a significant and independent risk factor for congenital heart defects (CHD) among offspring, as is secondhand smoke exposure in general.
Maternal smoking, maternal passive smoking and paternal smoking were all linked to greater risk for CHDs in the analysis of 125 observational studies involving more than 135,000 children with the birth defects and nearly 9 million prospective mothers and fathers.
The meta-analysis by Jiabi Qin of Central South University in Changsha, China, and colleagues, is the first to examine smoking exposure at different stages of pregnancy, they wrote in the European Journal of Preventive Cardiology.
Among women, smoking during pregnancy was associated with an increased risk of giving birth to a child with a congenital heart defect, but smoking before pregnancy was not associated with increased risk.
Qin and colleagues noted that three previous reviews of smoking and congenital heart defects examined only maternal active smoking. Results from individual studies examining maternal passive smoking and paternal active smoking and CHD risk were inconsistent, they wrote.
In addition, the previous meta-analyses were largely limited to populations living in the U.S. and Europe.
“In China, there were a large number of studies that assessed the risk of CHDs associated with paternal smoking,” the researchers wrote. “If these Chinese documents could be included in future reviews, it will inevitably increase the statistical power, which will help to find a significant statistical difference for risk of CHDs associated with parental smoking, especially for risk estimates of CHD subtypes.”
A search of seven electronic databases revealed 125 studies, with 137,574 CHD cases and 8,770,837 parents.
Summary risk estimates were calculated using either random-effects- or fixed-effects-modelling.
The researchers conducted sensitivity and subgroup analysis to identify potential heterogeneity moderators.
The analysis revealed:
Maternal active smoking (RR 1.25; 95% CI 1.16–1.34; P<0.01) and passive smoking (RR 2.24, 95% CI 1.81–2.77; P<0.01) as well as paternal active smoking (RR 1.74, 95% CI 1.48–2.06; P<0.01) were all significantly associated with CHD risk
For specific CHD subtypes, 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)
- Overall, CHD risk associated with parental smoking increased further in analyses only including Asian populations
“Our results suggest that maternal passive smoking and paternal smoking were significantly associated with increased risk of CHDs in offspring, which has not been confirmed in previous meta-analyses,” Qin and colleagues wrote.
Study limitations cited by the researchers included a lack of information on parental smoking dosage, which prevented exploration of a dose-response effect; and the possibility of residual confounding from unmeasured and uncontrolled risk factors associated with CHD.
“Many factors, including maternal dietary pattern, diabetes, obesity, metabolic syndrome, alcohol consumption, viral infections and genetic background, have been reported to be associated with risk of CHDs,” they wrote. “Therefore, these factors are likely to be confounding factors when evaluating the effect of parental smoking on fetal CHDs. However, restricting analysis to studies controlling confounding factors did not materially alter conclusions.”
The study population heterogeneity and the lack of available studies examining CHD subtypes were also mentioned as study limitations, as well as possible publication bias and the fact that most included trials were case-control studies.
“Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, our study indicated that maternal active and passive smoking, and paternal active smoking, are associated with higher risk of CHDs,” they concluded.
Funding for this research was provided by the Natural Science Foundation of Hunan Province, the National Natural Science Foundation of China and Hunan Provincial Key Research and Development Program.
The researchers declared no relevant relationships with industry related to this study.