If your morning sickness is lasting all day and negatively affecting your life, you may have hyperemesis gravidarum (HG). Even if you haven’t been diagnosed with HG, it’s possible that your doctor or midwife will prescribe Zofran for severe nausea and vomiting of pregnancy. Read on for an overview of what researchers know about the safety of Zofran during pregnancy.
Now sold under the generic name ondansetron, Zofran first became available in 1991 and was approved by the US Food and Drug Administration (FDA) for the treatment of nausea and vomiting related to chemotherapy for cancer. When it’s prescribed to pregnant people with nausea and vomiting, it’s a so-called “off label” use, meaning that regulatory bodies, such as the FDA, have not officially approved prescribing it to pregnant people. Despite its lack of official approval, many clinicians prescribe it for pregnant people because the impacts of nausea and vomiting during pregnancy can be dire. Because plenty of people have taken this medication during pregnancy, there’s been lots of research on the outcomes of Zofran use during pregnancy on both the pregnant person and the fetus.
The most recent study—and one of the largest—to look at pregnancy outcomes after ondansetron use was published in April 2021 in JAMA Network Open.  In this paper, Colin Dormuth, a drug safety researcher at The University of British Columbia in Canada, and colleagues combined data from Canada, the United States, and the United Kingdom about pregnancy outcomes when the pregnant person took Zofran or another medication to prevent nausea and vomiting. The researchers found that there was not a significant association with ondansetron use and adverse pregnancy outcomes, including stillbirth or fetal malformations.
In a study that came out in the journal Reproductive Toxicology in 2019, Debra Kennedy, a researcher in women’s and children’s health at the University of New South Wales in Australia, and colleagues did a similar analysis of previously published data from three databases.  They looked specifically at whether taking Zofran increases the risk of fetal malformations, including cleft palate and heart defects. The researchers found that taking the drug during pregnancy was not associated with an increased risk of major malformations in babies, findings they write may be reassuring for pregnant people who take Zofran. They did recommend that further research be done on a possible link between oral clefts and taking the drug.
A 2018 study published in the Journal of the American Medical Association specifically addressed ondansetron use during the first trimester of pregnancy and the link to oral clefts.  Krista Huybrechts, an epidemiologist at Harvard Medical School, and her colleagues found “exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall . . . but was associated with a small increased risk of oral clefts.” That means that there was a slightly increased risk of oral clefts in the dataset they looked at; however, the risk of oral clefts overall is very low (11 in 10,000 births), so even the slightly increased risk still makes the chance of an oral cleft still very low (14 in 10,000 births).
So what does this mean for you? If you’re sick and miserable, talk to your doctor or midwife about Zofran. The research indicates that it is very likely to be safe, but your individual care provider knows you and your specific situation and can help you make an informed decision. The risks of complications from hyperemesis gravidarum are also not to be minimized, particularly the mental health and long term health implications for you. You can also speak with your doctor or midwife about other pharmaceutical options: vitamin B6 and doxylamine, an antihistamine, combined can help. You can take them separately (get the correct dosing information from your care provider), and there is a commercial combination of those two drugs available called Diclegis.
- Dormuth CR et al., “Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort,” JAMA Network Open,
- Kaplan YC et al., “Use of ondansetron during pregnancy and the risk of major congenital malformations: A systematic review and meta-analysis,” Reproductive Toxicology,
- Huybrechts KF et al., “Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring,” JAMA,