Ondansetron in Early Pregnancy Seen Not to Promote Cardiac Birth Defects Overall

Megan Brooks

December 18, 2018

A new report provides some reassurance regarding the safety of the antiemetic ondansetron when taken for nausea and vomiting in early pregnancy, researchers say.

In the large retrospective cohort study, use of ondansetron in the first trimester of pregnancy was not associated with an increased risk for cardiac malformations overall.

In a secondary finding, use of the drug was associated with increased risk for oral clefts, although the absolute risk was low.

"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," Krista F. Huybrechts, Brigham and Women's Hospital and Harvard Medical School, Boston, told theheart.org | Medscape Cardiology.

"These results will hopefully provide reassurance to women who experience nausea and vomiting in pregnancy and need to make a risk–benefit trade off regarding treatment," said Huybrechts, lead author on the study published December 18 in JAMA.

Evidence for the fetal safety of ondansetron, which is often prescribed for nausea and vomiting during pregnancy, is "limited and conflicting," the researchers note in their article.

They looked at data from the Medicaid Analytic eXtrract (MAX) database of more than 1.8 million pregnancies, including 88,467 (4.9%) with exposure to ondansetron during the first trimester. They focused on cardiac malformations and oral clefts, the main congenital anomalies identified with any consistency in previous studies.

There were 14,577 cardiac abnormalities in 1,727,947 unexposed infants and 835 in 88,467 exposed infants. The adjusted risk difference was −0.8 (95% confidence interval [CI], −7.3 to 5.7 per 10,000 births) and the adjusted relative risk was 0.99 (95% CI, 0.93 to 1.06).

There was a small but statistically significant increased risk for oral clefts with first-trimester exposure to ondansetron (1912 cases in unexposed infants and 124 in exposed infants). The adjusted risk difference was 2.7 (95% CI, 0.2 - 5.2 per 10,000 births) and the adjusted relative risk was 1.24 (95% CI, 1.03 - 1.48).

After multiple adjustments, there was no difference in the risk for cardiac or overall congenital anomalies in infants born to women exposed to ondansetron. The adjusted risk difference was 5.4 (95% CI, −7.3 to 18.2 per 10,000 births) and the adjusted relative risk was 1.01 (95% CI, 0.98 to 1.05).

"The findings were consistent across a broad range of sensitivity analyses," the authors report.

Although not formally approved for the treatment nausea and vomiting during pregnancy, the drug's use for this purpose increased from 0.01% in 2000 to 12% in 2013, they point out.

In an accompanying editorial, David M. Haas, MD, Indiana University School of Medicine, Indianapolis, says early and effective safe treatment of nausea and vomiting in pregnancy is "crucial."

This study provides "important and helpful" information for physicians to use when counseling women about the safety of treatment options, Haas writes.

The study shows clearly that although the adjusted relative risk for oral clefts was "elevated, the absolute risk increase is very low. The multiple adjustments and comparison groups presented, including accounting for the potential baseline risk of nausea and vomiting, demonstrate the robustness of the authors' conclusions," he adds.

The study was supported by the National Institute of Child Health and Human Development. Huybrechts reports that her institution has received research grants from Eli Lilly, Pfizer, GlaxoSmithKline, and Boehringer-Ingelheim. Disclosures for the other authors are detailed in the report. Haas discloses no relevant conflicts of interest.

JAMA. Published online December 18, 2018. Abstract, Editorial

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