Postnatal Metabolic and Reproductive Consequences of Fetal and Neonatal Exposure to the Smoking Cessation Drug Bupropion

Introduction: In all, 10% to 20% of all pregnant women smoke despite intentions to quit. Smoking cessation drugs such as nicotine replacement therapy (NRT) and bupropion are recommended for pregnant women. Our observation that developmental exposure to nicotine adversely affects metabolic and reproductive outcomes in rats has raised concerns about NRT's safety during pregnancy. Conversely, the effect of bupropion has not been reported. Objective: The goal of this study was to examine the effect of fetal and neonatal exposure to bupropion on postnatal metabolic and reproductive outcomes. Methods: Dams (N = 5/group) were exposed to saline or bupropion (5 or 10 mg/kg per d) for 2 weeks prior to mating until weaning. We assessed weight, adiposity, and glucose homeostasis in all offspring until 26 weeks of age. Onset of puberty, fertility, and pregnancy outcomes in the female offspring were also assessed. Results: Fetal and neonatal exposure to bupropion did not cause metabolic derangement in the offspring despite a significant decrease in birth weight in the offspring of dams treated with 10/mg/kg per d bupropion (5.9 +/- 0.2g vs control 6.7 +/- 0.2g; P = .02). Moreover, with the exception of accelerated pubertal onset in F1 and F2 offspring, bupropion administration to pregnant dams had no impact on fertility or pregnancy outcomes for either the dam or the female offspring. Conclusion: Fetal and neonatal exposure to the smoking cessation drug bupropion, unlike NRT, does not appear to adversely affect metabolic outcomes or the fertility of the female offspring. However, bupropion does appear to alter pubertal onset through an as yet unknown mechanism.