December 18, 2018
2 min read

First-trimester use of ondansetron not linked to infant cardiac malformation

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Krista F. Huybrechts
Krista F. Huybrechts

The use of ondansetron, a 5-HT3 receptor antagonist prescribed for nausea and vomiting during pregnancy, was not associated with congenital or cardiological malformations, according to findings published in JAMA.

However, the drug conferred a small increased risk for oral clefts among mothers receiving first-trimester exposure to it.

Researchers sought to investigate the association between exposure to ondansetron during the first trimester of pregnancy and the risk for congenital malformations in offspring, with a focus on cardiac malformations and oral clefts among publicly insured pregnant women.

“Nausea and vomiting during pregnancy typically occurs during the first trimester, the most sensitive time for exposure to teratogens because of organogenesis,” Krista F. Huybrechts, PhD, of the division of pharmacoepidemiology and pharmacoeconomics at the department of medicine at Brigham and Women’s Hospital, and colleagues wrote. “The available evidence on the fetal safety of ondansetron is limited and conflicting.”

The study consisted of participants from the national Medicaid Analytic eXtract study from 2000 to 2013. Participants were required to have Medicaid coverage for at least 3 months before the date of the last menstrual period to a month after delivery.

Covariates such as treatment indication and associated conditions, including weight loss, electrolyte and laboratory abnormalities and dehydration, were considered.

The cohort consisted of 1,816,414 women (mean age, 24 years), of whom 4.9% were exposed to ondansetron during the first trimester.

Risks of exposure

For infants unexposed to ondansetron, the absolute risk for being diagnosed with a cardiac malformation was 84.4 (95% CI, 83-85.7) per 10,000 births, whereas for infants exposed to the drug, the absolute risk was 94.4 (95% CI, 88-100.8) per 10,000 births.

The absolute risk for oral clefts was 11.1 per 10,000 births in unexposed infants (95% CI, 10.6-11.6) and 14 per 10,000 births in exposed infants (95% CI, 11.6-16.5).

Researchers wrote that the risk for any congenital malformation was 313.5 per 10,000 births in 54,174 unexposed infants (95% CI, 310.9-316.1) and 370.4 per 10,000 births in 3,277 exposed infants (95% CI, 358-382.9).

According to the researchers, the adjusted RR for cardiac malformations was 0.99 (95% CI, 0.93-1.06), and the adjusted risk difference was –0.8 (95% CI, –7.3 to 5.7).

For oral clefts, the aRR was 1.24 (95% CI, 1.03-1.48), and the adjusted risk difference was 2.7 (95% CI, 0.2-5.2) per 10,000 births, Huybrechts and colleagues wrote.

A more diverse population


The researchers wrote that the study focused on participants with Medicaid, but it allowed a more diverse group of women.

“The cohort inclusion criteria resulted in the selection of a more disadvantaged subpopulation in Medicaid, mostly comprised of low-income adults, multiparae and women with disabilities,” Huybrechts and colleagues wrote. “Therefore, the results should be generalizable to the broader Medicaid population, as well as to commercially insured pregnant women in the United States, and pregnant populations in other countries.” – by Earl Holland

Disclosures: Huybrechts reports she received research grants to her institution from Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline and Pfizer. Please see the study for all other authors’ relevant financial disclosures.