Fetal exposure to ondansetron showed no association with adverse pregnancy outcomes in a nationwide Danish cohort study that included more than 608,000 pregnancies, according to a report published online Feb. 28 in the New England Journal of Medicine.
Ondansetron, an antiemetic often prescribed for nausea and vomiting during pregnancy, was not associated with an increased rate of spontaneous abortion, stillbirth, any major birth defect, preterm delivery, low-birth-weight (LBW) infants, or small-for-gestational-age (SGA) infants, reported Björn Pasternak, M.D., Ph.D., of the department of epidemiology research at Statens Serum Institut, Copenhagen, and his associates.
Dr. Bjorn Pasternak
"Although these 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," the investigators noted.
To date, only two controlled studies have assessed the fetal safety of the drug, which nevertheless is the most frequently prescribed antiemetic in the United States.
Dr. Pasternak and his colleagues used data from Danish national registries to construct a nationwide historical cohort of all pregnancies that resulted in a singleton birth, stillbirth, or any abortive outcome between 2004 and March 31, 2011. (Ondansetron was rarely used during pregnancy before 2004 in Denmark.)
The investigators assessed outcomes in 608,385 pregnancies. Mothers took ondansetron in 1,970 of these pregnancies. The median number of doses dispensed was 30 per pregnancy.
In an initial unadjusted analysis, exposure to ondansetron did not increase the risk of stillbirth, major birth defects, LBW infants, or SGA infants.
The researchers then conducted several propensity-matched analyses for six possible adverse outcomes.
For the 1,233 pregnancies in this analysis in which the mother took ondansetron during the first trimester, 36 infants (2.9%) had a major birth defect. In comparison, 141 of 4,932 infants (also 2.9%) not exposed to the drug had a major birth defect. This study was not powered to assess the risks of individual birth defects.
The rate of preterm birth was 6.2% among women who took ondansetron and 5.2% among women who did not, a difference that was not significant. Similarly, the rates of stillbirth were 0.3% and 0.4%, respectively, also a nonsignificant difference.
The rates of LBW infants were 4.1% with exposure to ondansetron and 3.7% without exposure, also a nonsignificant difference. And the rates of SGA infants were 10.4% and 9.2%, another nonsignificant difference, Dr. Pasternak and his associates reported (New Engl. J. Med. 2013;368:814-23).
These results remained robust in several sensitivity analyses, including one that compared rates of adverse fetal outcomes between women who filled only one prescription for ondansetron and women who filled two or more such prescriptions.
Previously, a case-control study found an increase in the risk of cleft palate with in utero exposure to ondansetron. In this cohort, there were no cases of cleft palate, Dr. Pasternak and his associates said.
This study was funded by the Danish Medical Research Council. No financial conflicts of interest were reported.