BACKGROUND AND PURPOSE:

• Ondansteron, a 5-HT3 receptor agonist, is used to treat nausea and vomiting in pregnancy
• Safety data on the association between ondansetron and birth defects are limited
• Huybrechts et al. (JAMA., 2018) sought to evaluate whether ondansetron exposure during pregnancy is associated with risk of congenital malformations, with a focus on cardiac and oral clefting defects

METHODS:

• Retrospective cohort study
  • Data derived from the nationwide Medicaid Analytic eXtract (MAX)
  • Pregnant women registered 3 months before the last menstrual period through 1 month or longer after delivery
• Data analyzed comparing
  • Ondansetron (exposure) during the first trimester vs control group
• Primary outcomes (diagnosed during the first 90 days after delivery)
  • Cardiac malformations
  • Oral clefts
• Secondary outcomes included
  • Congenital malformations overall
  • Subgroups of cardiac malformations and oral clefts

RESULTS:

• 1,816,414 pregnancies were included
  • Mean maternal age: 24.3 years
  • 88,467 (4.9%) were exposed to ondansetron during the first trimester
• Cardiac Malformations (absolute risk)
  • Unexposed: 84.4 per 10,000 births ( 95% CI, 83.0 to 85.7)
  • Exposed: 94.4 per 10,000 births (95% CI, 88.0 to 100.8)
• Oral clefts (absolute risk)
  • Unexposed: 11.1 per 10,000 births (95% CI, 10.6 to 11.6)
  • Exposed: 14.0 per 10,000 births (95% CI, 11.6 to 16.5)
• Any congenital malformation (absolute risk)
  • Unexposed: 313.5 per 10,000 births (95% CI, 310.9 to 316.1)
  • Exposed: 370.4 per 10,000 births (95% CI, 358.0 to 382.9)
• Cardiac malformations (relative risk)
  • Adjusted relative risk (RR): 0.99 (95% CI, 0.93 to 1.06)
• Oral clefts (relative risk)
  • Adjusted RR: 1.24 (95% CI, 1.03 to 1.48)
• Congenital malformations (relative risk)
  • Adjusted RR: 1.01 (95% CI, 0.98 to 1.05)

CONCLUSION:

• First-trimester exposure to ondansetron was not associated with cardiac malformations or overall congenital malformations
• There may be a “small increased risk of oral clefts”

Learn More – Primary Sources:

Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring

Related ObG Topics:

Nausea and Vomiting in Pregnancy – Management Options for Hyperemesis Gravidarum

Ondansetron for Nausea During Pregnancy – Is There a Risk for Birth Defects?

Cleft Lip and Palate – Considerations and Discussion Points