Teratogen update: pseudoephedrine

Pseudoephedrine is contained in decongestants such as the Sudafed line of products. It is an alpha-adrenergic receptor agonist, which causes blood vessel constriction, including the therapeutic effect of reducing airflow resistance in the nasal cavity. Pseudoephedrine is one of the most commonly used medications in pregnancy, with an estimated 25% of women exposed. It has been demonstrated that alpha-adrenergic receptor agonists slow uterine blood flow, but their effects have not been studied in relation to most reproductive outcomes in animals or humans. Two analyses of health maintenance organization pharmacy data identified 9 malformed infants among 902 first-trimester pseudoephedrine exposures, suggesting no association with birth defects overall; however, studies of such data sets often lack sufficient power to identify risks for specific birth defects. The related compounds, epinephrine, ephedrine, and phenylephrine, have been associated with hemorrhages and cardiovascular and limb malformations in animal models. Risk of ventricular septal defects was associated with decongestant use in pregnant women in 1 recent study. The vasoconstrictive effects of these drugs raise the hypothesis that their use in early pregnancy might increase the risk of vascular disruption defects. Case-control studies, which often do have power to identify risks related to specific birth defects, have explored this hypothesis. Decongestant use in the first trimester has been associated with small increases in risks of 3 defects thought to arise, at least in some instances, from vascular disruption-gastroschisis, small intestinal atresia, and hemifacial microsomia. These findings are somewhat consistent in terms of magnitude of effect and suggest that risks are even greater among women also exposed to the vasoconstrictive effects of cigarette smoking. There are, however, limitations to these studies, including the possibilities of inaccurate recall of exposures and confounding by indication. In addition, the majority of decongestant use is in oral form and the question of whether intranasal formulations carry risk has not been adequately addressed.