Study examines effects of taking ondansetron during first trimester of pregnancy
- No increased risk of cardiac malformations, slight increased risk of oral clefts associated with common anti-nausea medication
Boston, MA, USA (December 18, 2018) -- Ondansetron (Zofran) is commonly and increasingly prescribed during pregnancy to relieve nausea. In 2014, an estimated 22 percent of pregnant women in the U.S. had used the drug at some point during their pregnancy. Despite its prevalence, data on the safety of the drug and any effects on the developing fetus have been limited, with small-scale studies producing conflicting results. A new study conducted by investigators at Brigham and Women's Hospital has analyzed data from more than 88,000 pregnancies in which pregnant women had taken ondansetron during the first trimester to examine risk of cardiac malformations or oral clefts. In a paper published online in JAMA, the team reports no increased risk of cardiac malformations and a very small increased risk of oral clefts.
"Use of ondansetron has increased over time, but only a handful of studies had been conducted to date and all were relatively small. We wanted to provide more robust information on two important outcomes--risk of oral clefts and cardiac malformations--for patients and clinicians," said corresponding author Krista Huybrechts, MS, PhD, epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics at the Brigham. "Our study expands the evidence available to date and represents the largest published study of tens of thousands of women and fetal outcomes with careful control for potential confounding variables."
Huybrechts and colleagues conducted a retrospective cohort study based on data from the nationwide Medicaid Analytic eXtract (MAX), a dataset that included more than 1.8 million pregnancies resulting in live births between 2000 and 2013 among publicly insured pregnant women. Records showed that patients had filled prescriptions for ondansetron in the first trimester of 88,467 (4.9 percent) pregnancies.
The team found an adjusted relative risk for cardiac malformations of 0.99 with tight confidence intervals (0.93 - 1.06)--strong evidence of no difference in risk for cardiac malformations between the group exposed to ondansetron and the control group. The researchers report a rate of 94.4 cardiac malformations per 10,000 births among ondansetron-exposed pregnancies compared to 84.4 per 10,000 among unexposed pregnancies.
The researchers found an increase in oral clefts, but this association was less precisely estimated (confidence interval 1.03 - 1.48). The researchers found an absolute risk of 14.0 cases per 10,000 births among ondansetron-exposed pregnancies compared to 11.1 cases per 10,000 births in unexposed ones. The team also examined information on congenital malformations overall, finding no increased risk among fetuses exposed to the drug during the first trimester.
"These results suggest that ondansetron does not meaningfully increase the risk of congenital malformations, although a small increase in the risk of oral clefts cannot be excluded," said Huybrechts. "These results will hopefully provide reassurance to pregnant women who experience nausea and vomiting in pregnancy and need to make a risk-benefit trade-off regarding treatment."
This study was supported by the National Institute of Child Health & Human Development (R03 HD091699, K08HD075831), the National Institute of Mental Health (K01MH099141), the National Institutes of Health (K12 BIRCWH) and the National Institute on Aging (K08AG055670). Co-authors report research funding from Eli Lilly, Pfizer, GlaxoSmithKline, Boehringer-Ingelheim, Merck, Bayer, Vertex, Pacira, and Baxalta outside the submitted work.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.
Brigham and Women's Hospital, 18.12.2018 (tB).