Objectives: In a population-based case-control study, we investigated the association between congenital heart defects and maternal smoking.

Methods: The National Birth Defects Prevention Study enrolled 3067 infants with nonsyndromic congenital heart defects and their parents and 3947 infants without birth defects and their parents. Affected infants had > or = 1 of the following defects: conotruncal, septal, anomalous pulmonary venous return, atrioventricular septal defects, and left-sided or right-sided obstructive heart defects. Mothers of case and control infants were asked if they smoked during the periconceptional period, defined as 1 month before pregnancy through the first trimester. Maternal home and workplace exposure to tobacco smoke during the same period was also determined. Logistic regression was used to compute odds ratios and 95% confidence intervals while controlling for potential confounders.

Results: Case infants were more likely to be premature and have lower birth weight than control infants. Women who smoked anytime during the month before pregnancy to the end of the first trimester were more likely to have infants with septal heart defects than women who did not smoke during this time period. This association was stronger for mothers who reported heavier smoking during this period. This relation was independent of potential confounding factors, including prenatal vitamin use, alcohol intake, maternal age, and race or ethnicity. Women who smoked > or = 25 cigarettes per day were more likely than nonsmoking mothers to have infants with right-sided obstructive defects. There was no increased risk of congenital heart defects with maternal exposure to environmental tobacco smoke.

Conclusions: Maternal smoking during pregnancy was associated with septal and right-sided obstructive defects. Additional investigation into the timing of tobacco exposure and genetic susceptibilities that could modify this risk will provide a more precise evidence base on which to build clinical and public health primary prevention strategies.