First-trimester exposure to bupropion and risk of cardiac malformations

Bupropion is a drug uniquely used both to treat depression and as an aid to smoking cessation. We investigated previously reported associations between first-trimester exposure to bupropion and cardiac defects.

Using data gathered since 2003 by the Slone Epidemiology Center's Case-control Birth Defects Study, we classified subjects with cardiac defects into subgroups. Exposure categories included first-trimester bupropion alone or in combination with other antidepressants, first-trimester antidepressants other than bupropion, and no exposure to any antidepressant at any time from 2 months prior to pregnancy through delivery. We calculated odds ratios and 95% confidence intervals, controlling for confounding using logistic regression.

There were 8611 non-malformed infants and 7913 infants with cardiac defects. Eight cardiac subgroups had sufficient subjects (two or more exposed cases) for analysis. The adjusted odds ratio (aOR) for first-trimester bupropion use in relation to ventricular septal defect (VSD) was slightly elevated (1.6, 95% confidence interval 1.0-2.8); for exposure to bupropion alone, the aOR was 2.5 (95% confidence interval 1.3-5.0). Risks were not materially elevated for bupropion in relation to the other seven cardiac subgroups.

We did not confirm previously reported associations for left-sided defects overall but had too few exposed cases to evaluate specific defects in this category. We did observe an elevated risk of VSD following first-trimester bupropion use, particularly when used without other antidepressants. This pattern for bupropion alone was observed in all our risk comparisons and was not explained by higher doses or gestational timing.