Maternal pre-pregnancy/early-pregnancy smoking and risk of congenital heart diseases in offspring: A prospective cohort study in Central China

Background Prior studies suggested that maternal smoking before and during pregnan-cy could be associated with increased risks of congenital heart diseases (CHDs) in off-spring. However, the results were inconsistent, and the existence of a causal relationship was not confirmed. Our study aimed to estimate the associations of maternal active and passive smoking during the pre-pregnancy/early-pregnancy period with CHDs as well as its common phenotypes in offspring. Methods This study was based on data from a prospective cohort study conducted in Central China. A total of 49 158 eligible pregnant women between the 8th and 14th weeks of gestation were invited to join the cohort and were planned to be followed up until 3 months postpartum. The exposure of interest was maternal smoking status, including active and passive smoking status in 3 months before pregnancy as well as in early preg-nancy. Self-reported maternal smoking status was ascertained via an in-person interview after recruitment. CHDs were diagnosed by pediatric cardiologists and classified accord-ing to ICD-10. Multivariable Poisson regression models were used to estimate the relative risks (RRs) with 95% confidence intervals (CIs) of all CHDs and their common pheno-types associated with maternal smoking status, adjusting for potential confounding fac-tors identified by directed acyclic graphs. Results CHDs were diagnosed in 564 children. After adjusting for potential confounding factors and comparing with the unexposed groups, CHDs incidence was 165% higher (adjusted RR = 2.65; 95% CI = 1.76-3.98) in offspring exposed to maternal active smok-ing in 3 months before pregnancy, 69% higher (adjusted-RR = 1.69; 95% CI = 1.39-2.05) in offspring exposed to maternal passive smoking in 3 months before pregnancy, 133% higher (adjusted RR = 2.33; 95% CI = 1.46-3.70) for offspring exposed to maternal active smoking in early pregnancy, and 98% higher (adjusted-RR = 1.98; 95% CI = 1.56-2.51) for offspring exposed to maternal passive smoking in early pregnancy. More specifically, the offspring exposed to maternal active smoking in early pregnancy had the highest risk of Tetralogy of Fallot (adjusted RR = 9.84; 95% CI = 2.49-38.84). These findings were re-capitulated in analyses that further adjusted for other behaviour variables apart from the characteristic being assessed and were also confirmed by sensitivity analyses. Conclusions Our findings add to the existing body of evidence that implicates maternal pre-pregnancy/early-pregnancy smoking as a significant risk factor for CHDs and their select phenotypes.