BACKGROUND AND PURPOSE:

• Dormuth et al (JAMA Network Open, 2021) examined the use of the antiemetic ondansetron (Zofran) during pregnancy and potential risks for spontaneous abortion, stillbirth, and major congenital malformations

METHODS:

• Cohort study with meta-analysis
• Data sources
  • Administrative data from 5 Canadian provinces | US IBM MarketScan Research Databases | UK Clinical Practice Research Datalink
• Participants
  • 12 to 55 years
  • History of: Spontaneous abortion | Induced abortion | Stillbirth | Live birth | Occurrence between April 2002 and March 2016
• Exposure
  • Ondansetron
  • Other common antiemetics
• Study design
  • Cox proportional hazards models with time-dependent drug exposures were used to estimate hazard ratio with adjusted using propensity scores (aHR)
  • For major congenital malformations, adjusted odds ratio (aOR) was estimated from logistic models
  • Site-level results were pooled using random-effects meta-analysis
• Primary outcome
  • Fetal death (spontaneous abortion or stillbirth)
• Secondary outcomes
  • Stillbirth
  • Spontaneous abortion
  • Major congenital malformation

RESULTS:

• 163,810 pregnancies exposed to ondansetron | 306,766 exposed to other antiemetics
  • 54.7% from Canada | 43.3% from US | 2.0% from UK
  • Maternal age
    • ≤24 years: 20.4%
    • 25-29 years: 32.6%
    • 30-34 years: 31.2%
    • ≥35 years: 15.8%
• Incidence of fetal death
  • Ondansetron: 7.9% of pregnancies
  • Other antiemetic exposure: 5.7%
• There was no significant association between ondansetron exposure and
  • Fetal death: aHR 0.91 (95% CI, 0.67 to 1.23)
  • Spontaneous abortion: aHR 0.82 (95% CI, 0.64 to 1.04)
  • Stillbirth: aHR 0.97 (95% CI, 0.79 to 1.20)
  • Major congenital malformations: OR 1.06 (95% CI, 0.91 to 1.22)
• Results did not change with subgroup analysis or timing of exposure during pregnancy

CONCLUSION:

• By comparing to a cohort using other antiemetics, the study was able to control for nausea and vomiting as possible confounders 
• Ondansetron exposure was not associated with increased risk for fetal death, spontaneous abortion, stillbirth, or major congenital malformations

Learn More – Primary Sources:

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort

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