(A-294) Ondansetron in the First Trimester of Pregnancy and Risk of Congenital Malformations: a Study using the New Zealand Pregnancy Cohort

Background: In Aotearoa New Zealand, ondansetron use during Trimester 1 increased from 0.1% to ≈10% of pregnancies between 2005 and 2020. Some studies have found associations between Trimester 1 ondansetron exposure and congenital anomalies, particularly cardiac defects and orofacial clefts.

Objectives: To examine the potential association between Trimester 1 ondansetron exposure and congenital anomalies.

Methods: A retrospective cohort study was undertaken using the New Zealand Pregnancy Cohort, a cohort generated from national maternity, hospitalisation, laboratory claims, and mortality databases. Pregnancies were eligible if they ended in delivery, linked to an infant record, and the last menstrual period was between 1 January 2007 and 12 March 2020. Exclusion criteria included an antiemetic dispensing in the 90 days before conception, dispensing of a teratogen in the 90 days before conception or in Trimester 1, TORCH infection in pregnancy, and infants with a chromosomal abnormality or malformation syndrome of known cause.
Information about maternal use of antiemetics was obtained from national dispensing data. Exposure was defined as ≥1 antiemetic dispensing in Trimester 1, with three categories: ondansetron monotherapy, ondansetron with another antiemetic (ondansetron polytherapy), and other antiemetics only. Pregnancies with no dispensing of an antiemetic in Trimester 1 were the comparator. Primary outcomes were major cardiac malformations and orofacial clefts, identified using ICD-10-AM codes in national hospitalisation and mortality databases.
Analysis was undertaken using log-linear regression with Poisson errors, an independence working correlation and robust standard errors within a generalised estimating equation framework, adjusted for maternal and pregnancy characteristics, and clustering by mother.

Results: The study included 783,830 infants; 5,652 (0.72%) had a cardiac anomaly and 1,062 (0.14%) had an orofacial cleft. Compared to unexposed infants, those exposed to ondansetron monotherapy (0.72% vs 0.82%, aRR 1.09 [95% CI 0.91–1.31]) and ondansetron polytherapy (0.72% vs 0.82%, aRR 1.07 [95% CI 0.93–1.24]) had similar risks of a cardiac anomaly. Prevalence of orofacial clefts was similar in unexposed infants and those exposed to ondansetron monotherapy (0.14% vs 0.14%, aRR 1.04 [95% CI 0.68–1.60]) and ondansetron polytherapy (0.14% vs 0.15%, aRR 1.14 [95% CI 0.81–1.61]).

Conclusions: Ondansetron exposure was not associated with an increased risk of cardiac anomalies or orofacial clefts, although the confidence intervals did not rule out small increases in risk.