Use of Ondansetron for Nausea and Vomiting During Pregnancy and Adverse Pregnancy Outcomes [thesis]

Elizabeth A Suarez
2019
Ondansetron, a 5-HT3-receptor antagonist, is commonly used off-label in the United States to treat nausea and vomiting in pregnancy. Previous studies of adverse pregnancy outcomes offer an incomplete picture of the safety of ondansetron because they use methods that increase the potential for unmeasured confounding or fail to appropriately account for events occurring along the gestational age time scale. The objective of this project was to compare the risk of various adverse pregnancy
more » ... between women exposed to ondansetron during the first 20 weeks pregnancy and women exposed to alternative antiemetic medications, including promethazine and metoclopramide. Adverse outcomes included miscarriage, stillbirth, preterm birth, gestational hypertensive disorders, small for gestational age, and mean birth weight. A pregnancy cohort was created using electronic health record data from the UNC Health Care system in North Carolina. Women were classified as exposed to either ondansetron or comparator antiemetics (metoclopramide or promethazine) based on the first prescription received in the first 20 weeks of gestation. The cumulative incidence of each outcome was estimated using methods that account for the gestational age of antiemetic exposure and competing events in pregnancy, and risk ratios (RR) and risk differences (RD) were calculated. Measured confounding by was controlled using stabilized inverse probability of treatment weights. We identified 2677 eligible pregnancies with antiemetic orders, 66% of which first received ondansetron. After adjustment for measured covariates, there was no difference in risk of miscarriage (RR 1.23, 95% CI 0.23, 8.51; RD 2.3%, 95% CI -25.4, 24.1). No association was observed between ondansetron and stillbirth (odds ratio=1.32; 95% CI 0.39, 4.53), preterm birth (RR=0.91; 95% CI 0.40, 2.54), or gestational hypertensive disorders (RR=0.90; 95% CI 0.47, 1.89). Similarly, no association was observed for small for gestational age (RR=1.19; 95% CI 0.52, 3.38) and the [...]
doi:10.17615/nzyf-xc13 fatcat:pxudjiyjpzgm5bvjnnrzjfv5km