Recent Article Sets Forth A Review Of Various Medical Studies Done Over Time, Which Shows Some Conflicting Evidence For Zofran-Associated Birth Defects
It seems safe to say, now, that the use of Zofran (ondansetron) should be avoided in the first trimester of pregnancy due to the apparent increased risks of certain major birth defects.
But as set forth in this December 2015 Medscape Pharmacists article, "[Zofran] Ondansetron in Pregnancy", there is mixed evidence in the medical literature about what birth defects specifically and the extent of that danger.
To start, for an overview of the situation, we get these three basic facts (footnotes omitted) from this very informative Medscape Pharmacists article:
- Nausea and vomiting in pregnancy occurs in up to 80% of women, with about 15% requiring antiemetic medication.
- Unfortunately, nausea and vomiting peak during the first trimester of pregnancy, coinciding with greatest fetal susceptibility to teratogenic effects of medications.
- [Zofran (ondansetron)] is not recommended by current guidelines as a first-line option for nausea and vomiting in pregnancy.
The author of this article, Darren J. Hein, PharmD, then goes on to summarize the findings of several medical studies concerning Zofran-associated birth defects, as we will see below.
For his review of "The safety of ondansetron for nausea and vomiting of pregnancy: A prospective comparative study" (BJOG. 2004;111:940-943), Dr. Hein writes:
In 2004, researchers from Canada and Australia published the results of a cohort study comparing the rates of miscarriage, stillbirth, and major birth defects among pregnant women receiving [Zofran (ondansetron)], other antiemetics, or no antiemetics (n = 176 in each group). All women who received [Zofran (ondansetron)] were in the first trimester. No significant differences among the groups for all of the adverse pregnancy outcomes were observed; however, this industry-sponsored study was powered to detect only a 3.5-fold or greater increased risk in major birth defects. [footnote omitted]
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Moving next to his reading of "National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and risk of selected birth defects" (Birth Defects Res A Clin Mol Teratol. 2012;94:22-30):
A larger, case/control study associated [Zofran (ondansetron)] with a significantly increased risk for cleft palate. The odds of cleft palate were 2.4 times higher with exposure to [Zofran (ondansetron)] during the first trimester (n = 55) vs unexposed pregnancies (n = 4479); however, the risk for cleft lip, hypospadias, or neural tube defects was similar in both groups. [footnote omitted]
A third study for which Dr. Hein presents his summary of the findings is "Ondansetron use in early pregnancy and the risk of congenital malformations—a register based nationwide cohort study" (Program and abstracts of the 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 25-28, 2013; Montreal, Quebec, Canada. Abstract 25. Abstract 25, Pregnancy session 1):
Another group of Danish researchers, using the same Medical Birth Registry and National Patient Register, evaluated the teratogenic effects of [Zofran (ondansetron)] exposure during the first trimester using 1997-2010 data. Of the 897,018 births in this timeframe, prescription records suggested that 1248 women were exposed to ondansetron. The odds of fetal heart malformation were two times higher in infants of women exposed to [Zofran (ondansetron)] compared with unexposed women; the risk for major birth defects overall was similar. [footnote omitted]
And lastly, we get his take on "Use of ondansetron during pregnancy and congenital malformations in the infant" (Reprod Toxicol. 2014;50:134-137):
Swedish researchers used the Swedish Medical Birth Register and Swedish Register of Prescribed Drugs to gather data on pregnancies and exposure to [Zofran (ondansetron)] early in pregnancy. During the period between 1998 and 2012, 1349 women received [Zofran (ondansetron)] in early pregnancy. [Zofran (ondansetron)] exposure was not associated with an increased risk for severe birth defects; however, the odds of general heart defects were 1.6 times higher, and the odds of heart septum defects were 2.1 times higher. [footnote omitted]
As seen in these studies done by several different groups of international medical researchers, the fetal risks associated with the use of Zofran or ondansetron during the first trimester of pregnancy remain unclear.
We will continue to monitor this still-emerging drug safety issue and report significant developments here.