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Use of the antiemetic ondansetron during pregnancy was not associated with any adverse fetal outcomes, an observational study showed.

After accounting for differences between women who had taken the drug and those who had not, there were no significant relationships between ondansetron and spontaneous abortion, stillbirth, any major birth defect, preterm delivery, infants with a low birth weight or small-for-gestational-age size, according to Björn Pasternak, MD, PhD, of the Statens Serum Institut in Copenhagen, and colleagues.

Although the results "cannot definitively rule out the possibility of adverse effects in association with ondansetron, the results do provide reassurance regarding the use of this agent for nausea and vomiting in pregnancy," they wrote in the Feb. 28 issue of the New England Journal of Medicine.

There is not much concern about adverse fetal effects with the drug, but some women are hesitant to use it, according to Loralei Thornburg, MD, of the University of Rochester Medical Center in New York, who specializes in treating high-risk pregnancies.

What the current study "gives women is a confidence that the medications that we're giving them to make them feel better, to help them get through that first trimester feeling better and able to keep things down and function in their daily lives are, in fact, safe for their fetuses," she said in an interview.

Ondansetron is the most common drug used in the U.S. to treat nausea and vomiting during pregnancy, which occurs in more than half of all pregnant women, typically during early pregnancy when the risk of teratogenic effects is highest, according to Pasternak and colleagues.

Yet despite the widespread use of ondansetron, there are relatively few data on safety for the fetus. A prior case-control study showed a significant association between ondansetron and an increased risk of cleft palate.

To explore the safety of the drug, the researchers looked at data from Danish national registries covering January 2004 through March 2011. The analysis included 608,385 pregnancies, of which 0.3% included exposure to ondansetron, mostly in the second half of the first trimester. Women who had a spontaneous abortion before 6 completed weeks of gestation were excluded.

The researchers used propensity scoring to account for the differences between women who took ondansetron during pregnancy and those who did not, yielding 1,233 to 1,915 exposed women and 4,932 to 7,660 unexposed women for the analyses of the various outcomes.

The mean age of the women in the matched analyses was 30. Of those who took ondansetron, more than half were hospitalized for hyperemesis or nausea and vomiting and roughly 40% received an antiemetic other than ondansetron, including metoclopramide, antihistamines, scopolamine, or domperidone.

After adjustment for hospitalization for hyperemesis or nausea and vomiting and for exposure to other antiemetics, ondansetron exposure was not associated with an increased risk of any of the outcomes examined:

• Spontaneous abortion from 7 to 12 weeks of gestation (1.1% with ondansetron versus 3.7% without; HR 0.49, 95% CI 0.27 to 0.91)
• Spontaneous abortion from 13 to 22 weeks of gestation (1% versus 2.1%; HR 0.60, 95% CI 0.29 to 1.21)
• Stillbirth (0.3% versus 0.4%; HR 0.42, 95% CI 0.10 to 1.73)
• Any major birth defect (2.9% in each group; prevalence odds ratio 1.12, 95% CI 0.69 to 1.82)
• Preterm delivery (6.2% versus 5.2%; prevalence odds ratio 0.90, 95% CI 0.66 to 1.25)
• Having an infant with low birth weight (4.1% versus 3.7%; prevalence odds ratio 0.76, 95% CI 0.51 to 1.13)
• Having an infant small for gestational age (10.4% versus 9.2%; prevalence odds ratio 1.13, 95% CI 0.89 to 1.44)

The significantly lower rate of spontaneous abortion in the women exposed to ondansetron should not be interpreted as a protective effect of the drug, according to the researchers.

"Our findings that pregnant women who were exposed to ondansetron were at a significantly lower risk for spontaneous abortion as compared with unexposed women, but at a similar risk as compared with women exposed to an antihistamine, support the conclusions that nausea and vomiting, rather than the treatment of these conditions with ondansetron, are associated with a lower risk of spontaneous abortion," they wrote.

The findings were consistent in various sensitivity analyses looking at different exposure time windows, birth defects among induced abortions and stillbirths, antihistamine use, and the number of ondansetron prescriptions filled.

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