Huybrechts KF, et al. - In this cohort study, including 1,8 million pregnancies, researchers assessed the relationship between exposure to ondansetron during pregnancy and the risk of congenital malformations. Findings suggested no association of first-trimester exposure to ondansetron with cardiac malformations or congenital malformations overall after accounting for measured confounders but with a small increased risk of oral clefts among offspring of mothers enrolled in Medicaid.

Methods

• A retrospective cohort study was conducted at the nationwide Medicaid Analytic eXtract from 2000 to 2013.
• The cohort consisted of 1,816,414 pregnancies of 1,502,895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or more after delivery.
At least 3 months after birth, infants were registered with Medicaid.
• December 31, 2013 was the final date of follow-up.
• Between November 1, 2017, and June 30, 2018, analyses were conducted.
• To control for treatment indication and other confounders, propensity score stratification was used.
• Exposures included ondansetron dispensing during the first trimester, the period of organogenesis.
• Cardiac malformations and oral clefts diagnosed during the first 90 days after delivery were primary outcomes.
• Congenital malformations overall and subgroups of cardiac malformations and oral clefts were included secondary outcomes.

Results

• Of the 1,816,414 pregnancies (mean age of mothers, 24.3 [5.8] years), 88,467 (4.9%) were exposed to ondansetron during the first trimester.
• Overall, an absolute risk of 84.4 (95% CI, 83.0 to 85.7) and 94.4 (95% CI, 88.0 to 100.8) per 10,000 births was diagnosed with 14,577 out of 1,727,947 unexposed and 835 out of 88,467 exposed infants with cardiac malformation.
• Findings revealed that the absolute risk of oral clefts was 11.1 per 10 000 births (95% CI, 10.6 to 11.6; 1921 unexposed infants) and was 14.0 per 10 000 births (95% CI, 11.6 to 16.5; 124 exposed infants).
• It was noted that the risk of any congenital malformation was 313.5 per 10 000 births (95% CI, 310.9 to 316.1; 54 174 unexposed infants) and was 370.4 (95% CI, 358.0 to 382.9; 3277 exposed infants).
• Data reported that the adjusted relative risk (RR) for cardiac malformations was 0.99 (95% CI, 0.93 to 1.06) and the adjusted risk difference (RD) was −0.8 (95% CI, −7.3 to 5.7 per 10,000 births).
• The adjusted RR was 1.24 (95% CI, 1.03 to 1.48) and the RD was 2.7 (95% CI, 0.2 to 5.2 per 10 000 births) for oral clefts.
• According to the findings obtained, the adjusted estimate for congenital malformations overall was an RR of 1.01 (95% CI, 0.98 to 1.05) and an RD of 5.4 (95% CI, −7.3 to 18.2 per 10,000 births).