Risk of Congenital Heart Defects in the Offspring of Smoking Mothers: A Population-Based Study

Objectives To conduct a population-based study examining the occurrence of congenital heart defects (CHDs) in relation to maternal smoking during the first trimester of pregnancy. Study design This retrospective case-control study used Washington State birth certificates from 1989 to 2011 and linked hospital discharge International Classification of Diseases, 9th revision, codes to identify singleton non-syndromic CHD cases and determine maternal prenatal smoking status. We calculated ORs from multivariate logistic regression models to compare maternal first-trimester smoking status (any and daily number of cigarettes) among 14 128 cases, both overall and by phenotype, and 60 938 randomly selected controls frequency matched on birth year. Results Offspring of mothers reporting cigarette use in the first trimester of pregnancy were more likely to be born with a CHD (aOR 1.16 [1.08-1.24]) independent of demographic characteristics and other prenatal risk factors for CHDs. Maternal smoking was most strongly associated with pulmonary valve anomalies (aOR 1.48 [95% CI: 1.15-1.90]), pulmonary artery anomalies (aOR 1.71 [1.40-2.09]), and isolated atrial septal defects (aOR 1.22 [1.08-1.38]). The association between maternal smoking and CHDs was stronger with increasing number of daily cigarettes and among older (35+ years) mothers compared with younger mothers. Conclusions We provide evidence that maternal smoking during pregnancy is a risk factor for select CHD phenotypes. Maternal smoking may account for 1.4% of all CHDs. New findings include a strong dose-dependence of the association and augmented risk in older mothers.