Maternal ondansetron use linked to mildly increased risk of cleft-palate, renal agenesis–dysgenesis
Ondansetron has been increasingly used for treating nausea and vomiting in pregnancy, and first-trimester exposure to the drug appears to pose no increased risk of birth defects, a study has found. However, there is a modest association found for cleft palate and renal agenesis–dysgenesis.
Using data from two large studies of birth defects (National Birth Defects Prevention Study, 1997–2011; Slone Birth Defects Study, 1997–2014), researchers described time trends in ondansetron use for the treatment of first-trimester nausea and vomiting in pregnancy and its association with major birth defects.
The analysis included 23,200 mothers who reported ondansetron use for first-trimester nausea and vomiting in pregnancy and 12,624 untreated controls. Ondansetron exposure increased to 13 percent in 2013–2014 from <less 1 percent before 2000 among women in the control group.
Treatment with the study drug did not contribute to an elevated risk of most of the 51 specific birth defects analysed. There was a modest increase observed in the risk of cleft palate (adjusted odds ratio [OR], 1.6; 95 percent CI, 1.1–2.3) in the National Birth Defects Prevention Study and of renal agenesis–dysgenesis (adjusted OR, 1.8; 1.1–3.0) in the Slone Birth Defects Study.
Although the modest risk increases could be the result of chance, additional studies are needed to further examine their association with ondansetron, researchers said.
Current evidence on the risk of birth defects resulting from ondansetron use are inconsistent and sometimes conflicting. However, using the drug, particularly in cases in which other medications have failed, should always be considered, given its efficacy in the treatment of nausea and vomiting in pregnancy. [Birth Defects Res A Clin Mol Teratol 2012;94:22-30; Pharmacoepidemiol Drug Saf 2015;24:401-402; N Engl J Med 2013;368: 814-823; Reprod Toxicol 2014;50:134-137]
To minimize potential risk, ondansetron should not be given as a first-line medication for treating nausea and vomiting in pregnancy. The combination of doxylamine plus pyridoxine (the current first-line recommendation) or nonpharmacologic methods (such as ginger) should be used for initial treatment. Other antiemetics that are generally recognized as safe in pregnancy, such as metoclopramide and promethazine, can also be considered. [Obstet Gynecol 2016;127:878-883]