Krista F. Huybrechts, M.S., Ph.D. Assistant Professor of Medicine at Harvard Medical School Epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital. Boston, MA 02120

Does Zofran (ondansetron) for Nausea & Vomiting Cause Birth Defects? Interview with:

Krista F. Huybrechts, M.S., Ph.D. Assistant Professor of Medicine at Harvard Medical School Epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital. Boston, MA 02120

Dr. Krista Huybrechts

Krista F. Huybrechts, MS PhD
Associate Professor of Medicine
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA 02120 What is the background for this study? What are the main findings? 

Response: Pregnant women often experience nausea and vomiting, particularly during the first trimester.  Early treatment is recommended to relieve symptoms and prevent progression to hyperemesis gravidarum.  Although not formally approved for this indication, ondansetron is the most frequently prescribed treatment for nausea and vomiting in pregnancy in the US: 22% of pregnant women reportedly used ondansetron in the US in 2014. Despite this common use, the available evidence on the fetal safety of ondansetron is limited and conflicting, and the possibility of a doubling in risk of cleft palate and cardiac malformations has been raised.

We therefore evaluated the association between ondansetron exposure during the first trimester of pregnancy, the period of organogenesis, and the risk of congenital malformations in a cohort of 1,816,414,publicly insured pregnancies using the nationwide Medicaid Analytic eXtract data for 2000-2013.  A total of 88,467 women (4.9%) were exposed to ondansetron during the first trimester.  After adjusting for a broad range of potential confounding variables, we found no association with cardiac malformations (RR = 0.99; 95% CI, 0.93 – 1.06)  and congenital malformations overall (RR = 1.01; 95% CI, 0.98 – 1.05). For oral clefts, we found a 24% increase in risk (RR=1.24; 95% CI, 1.03 – 1.48), which corresponds to an absolute risk of 2.7 per 10,000 births (95% CI, 0.2 – 5.2 per 10,000 births).  These findings were consistent across sensitivity analyses, conducted to address potential misclassification and confounding bias. What should readers take away from your report?

Response: These results suggest that ondansetron does not meaningfully increase the risk of congenital malformations, although a small increase in the risk of oral clefts cannot be excluded. These results will hopefully provide reassurance to pregnant women who experience nausea and vomiting in pregnancy and need to make a risk-benefit trade off regarding treatment. What recommendations do you have for future research as a result of this work?

Response: It will be important to assess the safety of ondansetron with respect to other pregnancy outcomes.  Additional data regarding the comparative effectiveness of the drugs used to treat nausea and vomiting in pregnancy are also needed. 

Please see the paper for authors’ disclosures. 


Huybrechts KF, Hernández-Díaz 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. doi:10.1001/jama.2018.18307

Dec 19, 2018 @ 12:57 pm 

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1 Comment
  • Jacob-Sung Sik Keum DO
    Posted at 21:58h, 27 December Reply

    thanks for this important research and its findings.
    I do have few issues I would like to ask:
    1-this study was only conducted with medicaid recipients..Would this finding also apply to non medicaid patients? This would be a very interesting topic because we do know that quality of care could differ even though standard of care is established in prenatal care.
    Also it is important to note that higher incidence per 10000 in the exposed population constitute a 26% higher case incidence per 10000 births and that would make it pretty significant in the medicaid enrolled pregnant patients. When we consider 11.1 per 10000 vs 14 per 10000.

    thank you
    Jacob-Sung Sik Keum DO

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