New study contradicts earlier findings about ondansetron teratogenicity

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Although prior research indicated that intravenous (IV) ondansetron in pregnancy could increase risk for congenital malformations, a recently published follow-up study has refuted those findings. The new study was published in JAMAPsychiatry.

The original study found no significant association with congenital malformations overall or cardiac malformations but found a small but not insignificant risk of oral clefts after accounting for potential confounding variables. Subsequent research suggested that IV administration may be associated with greater risk of cardiac malformations and oral clefts. To provide further clarification, the authors conducted a follow-up study to examine the association between IV ondansetron and congenital malformations.

Methods
For the present study, the researchers used a mother-infant-linked cohort from the Medicaid Analytic eXtract, which ranged from 2000 to 2014. Women were considered exposed if a claim for Healthcare Common Procedure Coding System code J2405 indicating ondansetron injection was recorded during the first trimester of pregnancy. The authors also created a reference group consisting of women without exposure to either oral or IV ondansetron from 3 months prior to the start of the pregnancy through the end of the first trimester. Study outcomes included cardiac malformations, oral clefts, and congenital malformations overall. The authors also estimated relative risks (RRs) and risk differences (RDs).

Findings
The cohort included more than 1.8 million pregnancies, in 1.3% of which at least one ondansetron injection was given during the first trimester. The adjusted RR for cardiac malformations was 0.97 (95% CI 0.86 to 1.10) and the adjusted RD was -2.9 (95% CI -15.7 to 9.8) per 10,000 births. For oral clefts, the adjusted RR was 0.95 (95% CI, 0.63 to 1.43) and the adjusted RD was -0.5 (95% CI, -4.5 to 3.5) per 10,000 births. In regard to malformations overall, the RR was 1.02 (95% CI, 0.96 to 1.08) and the RD was 7.1 (95% CI, -17.9 to 32.2) per 10,000 births.

Conclusions
The authors believe these findings suggest that IV ondansetron was not associated with an increased risk of cardiac malformations, oral clefts, or congenital malformations overall, and that it is not a major teratogen.