Risk of malformations in offspring likely minimal with use of ondansetron (Zofran) in first trimester

1. In this retrospective cohort study, first trimester exposure to ondansetron (trade name Zofran) was not associated with increased risk of cardiac or congenital malformations.

2. There was a small increased risk of oral clefts in the offspring of mothers who were exposed to first trimester ondansetron.

Evidence Rating Level: 2 (Good)           

Study Rundown: Nausea is a common symptom during pregnancy, especially during the first trimester, a period of organogenesis for the developing fetus. Ondansetron is an increasingly common anti-emetic that is used for treatment during this stage, but it is unclear what how this may affect the fetus. In this retrospective cohort study of 1.8 million pregnancies, there was a small increased risk of oral clefts in those whose mothers were exposed to ondansetron. However, ondansetron exposure was not associated with increased cardiac or other congenital malformations.

Overall, the study informs our choice when discussing the risks and benefits of a commonly prescribed anti-emetic during pregnancy, and though there was an increase in oral clefts, it was very slight. A few study limitations include possible residual confounding due to retrospective study design and cohort restriction to live births.

Click to read the study, published today in JAMA 

Relevant Reading: Ondansetron Use in Pregnancy and Birth Defects: A Systematic Review

In-Depth [retrospective cohort]: Data was obtained from the nationwide Medicaid Analytic eXtract (MAX) database for the years 2000 through 2013, which has previously been used to study safety of medications during pregnancy. Pregnancies with known teratogen exposure during the first trimester and known chromosomal abnormalities were excluded. Women were considered exposed if they filled at least 1 ondansetron prescription during the first 3 months of pregnancy, and considered unexposed if they filled no prescription during the 3 months before and through the end of the first trimester. Women who filled prescription during the 3 months before start of pregnancy were excluded from the analysis. Primary outcomes included cardiac malformations and oral clefts. Secondary outcomes included specific subgroups of cardiac malformations and oral clefts, along with evaluation of congenital malformations. Sensitivity analyses were also conducted to test the primary results. Overall, adjusted relative risks for cardiac malformations was 0.99 (CI₉₅ 0.93 to 1.06), oral clefts was 1.24 (CI₉₅ 1.03 to 1.48; risk difference 2.9 per 10,000 births), and congenital malformations was 1.01 (CI₉₅ 0.98 to 10.05).

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