ONDANSETRON NOT LINKED TO FETAL HARM 

The antiemetic drug ondansetron, taken by pregnant women for nausea and vomiting, is not associated with an increased risk for adverse fetal events, according to a study published online February 27 in the New England Journal of Medicine.

Björn Pasternak, MD, PhD, from the Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark, and colleagues analyzed the records of 608,385 singleton pregnancies and associated prescriptions recorded in Danish registries between January 1, 2004, and March 31, 2011.

The researchers used Cox proportional-hazards regression models to estimate hazard ratios. They accounted for the gestational age at which adverse events occurred by using gestational age in days as a time scale in the models. They estimated propensity scores for the probability of exposure to ondansetron according to baseline characteristics of the women at pregnancy onset. They then adjusted for nausea and vomiting severity and exposure to other antiemetics.

The investigators identified 1970 (0.3%) women who received ondansetron during pregnancy. They matched the ondansetron-exposed women in a ratio of 1:4 to unexposed women for the propensity-score-matched analysis. Among ondansetron-exposed women, more than half were hospitalized for nausea and vomiting during pregnancy, and almost half took another antiemetic.

Ondansetron-exposed women were not at increased risk for spontaneous abortion after adjustment for hospitalization and use of other antiemetics. The rate was 1.1% in ondansetron-exposed women and 3.7% in unexposed women (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.27 - 0.91) in gestational weeks 7 to 12 and 1.0% and 2.1%, respectively (HR, 0.60; 95% CI, 0.29 - 1.21), in weeks 13 to 22.

For 1915 exposed women, 6 stillbirths (0.3%) occurred compared with 27 stillbirths 0.4% among 7660 women not exposed (adjusted hazard ratio, 0.42; 95% CI, 0.10 - 1.73).

For 1233 ondansetron-exposed women, 36 infants (2.9%) had a major birth defect during the first year of life compared with 141 (2.9%) of 4932 infants delivered by unexposed women (adjusted prevalence odds ratio [OR], 1.12; 95% CI, 0.69 - 1.82).

For 1792 ondansetron-exposed women, 111 (6.2%) had preterm deliveries compared with 374 (5.2%) among 7168 unexposed women (adjusted prevalence OR, 0.90, 95% CI, 0.66 - 1.25).

Ondansetron exposure was not associated with low birth weight (4.1% among exposed women vs 3.7% unexposed; adjusted prevalence OR, 0.76; 95% CI, 0.51 - 1.13) or with infants who were small for gestational age at birth (10.4% exposed vs 9.2% unexposed; adjusted prevalence OR, 1.13; 95% CI, 0.89 - 1.44).

"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," the researchers write.

A limitation is whether an unmeasured confounder may have "masked a true risk associated with ondansetron," they write.

They conclude that although their results don't "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."

This research was supported by a grant from the Danish Medical Research Council. The authors have disclosed no relevant financial relationships.

N Eng J Med. 2013;386:814-823.