Want to take quizzes and track your credits?
Is the use of ondansetron during pregnancy associated with increased risk of cardiac malformations and oral clefts in offspring?
In this cohort study including 1.8 million pregnancies, first trimester ondansetron use was associated with an increased risk of oral clefts (3 additional cases per 10 000 women treated; adjusted relative risk, 1.24) but not cardiac malformations.
Maternal use of ondansetron in the first trimester was associated with a small increased risk of oral clefts but no increased risk of cardiac malformations.
Evidence for the fetal safety of ondansetron, a 5-HT3 receptor antagonist that is commonly prescribed for nausea and vomiting during pregnancy, is limited and conflicting.
To evaluate the association between ondansetron exposure during pregnancy and risk of congenital malformations.
Design, Setting, and Participants
A retrospective cohort study nested in the 2000-2013 nationwide Medicaid Analytic eXtract. The cohort consisted of 1 816 414 pregnancies contributed by 1 502 895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or longer after delivery; infants were enrolled in Medicaid for at least 3 months after birth. The final date of follow-up was December 31, 2013. Analyses were conducted between November 1, 2017, and June 30, 2018. Propensity score stratification was used to control for treatment indication and other confounders.
Ondansetron dispensing during the first trimester, the period of organogenesis.
Main Outcomes and Measures
Primary outcomes were cardiac malformations and oral clefts diagnosed during the first 90 days after delivery. Secondary outcomes included congenital malformations overall and subgroups of cardiac malformations and oral clefts.
Among 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, 14 577 of 1 727 947 unexposed and 835 of 88 467 exposed infants were diagnosed with a cardiac malformation, for 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 respectively. 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). 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). 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). For oral clefts, 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). 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).
Conclusions and Relevance
Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.
Sign in to take quiz and track your certificates
JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC
Corresponding Author: Krista F. Huybrechts, MS, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, 1620 Tremont St, Ste 3030, Boston, MA 02120 (firstname.lastname@example.org).
Accepted for Publication: October 26, 2018.
Author Contributions: Dr Huybrechts had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Huybrechts, Hernández-Díaz, Gray, Patorno, Desai, Bateman.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Huybrechts, Hernández-Díaz, Straub, Bateman.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Huybrechts, Hernández-Díaz, Straub, Mogun, Bateman.
Obtained funding: Huybrechts, Hernández-Díaz, Bateman.
Administrative, technical, or material support: Huybrechts, Straub, Bateman.
Supervision: Huybrechts, Hernández-Díaz, Bateman.
Conflict of Interest Disclosures: Dr Huybrechts reports receiving research grants to her institution from Eli Lilly, Pfizer, GlaxoSmithKline, and Boehringer-Ingelheim. Dr Patorno reports receiving research grants to her institution from Boehringer Ingelheim and GlaxoSmithKline. Dr Desai reports receiving grants to his institution from Merck, Bayer, and Vertex. Dr Bateman reports receiving grants to his institution from Eli Lilly, GlaxoSmithKline, Pacira, Baxalta, Pfizer, and Aetion and having served on an expert panel for a postpartum hemorrhage quality improvement project that was conducted by the Association of Women's Health, Obstetric, and Neonatal Nurses and funded by a grant from Merck for Mothers. Dr Hernández-Díaz reports receiving research grants to her institution from Eli Lilly, GlaxoSmithKline, and the National Institutes of Health and consulting fees from Roche and having served as an epidemiologist with the North America AED pregnancy registry, which is funded by multiple companies. Dr Gray reports consulting for Quest Diagnostics. No other conflicts of interest were reported.
Funding/Support: This study was supported by grant R03 HD091699 from the National Institute of Child Health and Human Development. Dr Huybrechts was supported by career development grant K01MH099141 from the National Institute of Mental Health. Dr Bateman was supported by career development grant K08HD075831 from the National Institute of Child Health and Human Development. Dr Gray was supported by career and development grant NIH K12 BIRCWH from the National Institutes of Health to Harvard Medical School. Dr Patorno was supported by career development grant K08AG055670 from the National Institute on Aging.
Role of the Funder/Sponsor: The National Institutes of Child Health and Human Development had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
You currently have no searches saved.