Ondansetron use in pregnancy associated with small increased risk of oral clefts

Reference

Huybrechts KF, Hernandez-Diaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA 2018;320(23):2429-2437.

Synopsis

Ondansetron is prescribed for nausea and vomiting during pregnancy in an estimated 22% of pregnant women. These investigators analyzed data from a pregnancy cohort obtained from the US nationwide Medicaid registry for the years 2000 through 2013. Exposed cases included women who filled at least 1 ondansetron prescription during the first 3 months of pregnancy. Unexposed controls included women who did not fill a prescription for ondansetron during the 3 months prior to the start of pregnancy through the end of the first trimester. A third reference group included women who filled a prescription during the first 3 months of pregnancy for other medications aimed at reducing nausea and vomiting, including pyridoxine (with or without doxylamine), promethazine, or metoclopramide. The cohort consisted of 1,816,414 pregnancies, of which 88,467 (4.9%) were exposed to ondansetron during the first trimester. Multiple adjustments occurred for potential confounders, including weight loss, electrolyte and laboratory abnormalities, dehydration, age, race, multiple gestation, maternal health conditions (psychiatric and neurological conditions, chronic disease, illicit drug or alcohol abuse or smoking), and concomitant medication use. The adjusted overall risk of oral cleft malformations was significantly increased among exposed pregnancies (relative difference 2.7 per 10,000 births; 95% CI 0.2 - 5.2; NNTH = 3700). First-trimester exposure to ondansetron was not associated with any other congenital malformations, specifically including cardiac defects.