Researchers found in a recent study that mothers who used Zofran (ondansetron) were more likely to have babies born with certain birth defects.

The research adds to growing amount of evidence indicating that Zofran can cause birth defects. There are now three major studies that note the likelihood of Zofran birth defects, with each of the studies stating that the risks are highest if the mother takes Zofran during the first trimester.

That is also the most common time mothers are likely to be prescribed Zofran, an anti-nausea drug. While Zofran has been on the market for over a decade to treat nausea in chemotherapy patients, it has been marketed for the off-label purpose of nausea treatment, for newly pregnant women suffering morning sickness.

Zofran had been popularly prescribed to women with severe to minor morning sickness soon after its release in 1991. While it is not illegal for drugs to be prescribed for off-label purposes, it is illegal for pharmaceutical companies to advertise them for such purposes.

Overview of Zofran Birth Defects Studies

The first major study was conducted by Danish researchers, who expanded an earlier study by widening the data to the years between 1997 to 2010, observing only women who were exposed to Zofran during the first trimester.

A total of 903,207 live births were analyzed, with 1,368 of the mothers being prescribed Zofran. That group was compared to women who were not prescribed the anti-nausea medication (903,207 control subjects).

While both groups did produce babies with birth defects, the Zofran group had been significantly higher, with 4.7 percent compared to 3.5 percent. The researchers calculated a 20 percent increased risk of birth defects with the use of Zofran.

In the second study, Swedish researchers had used similar methodology as the Danish researchers in collecting data, and observing the possible correlation between Zofran and birth defects. Their study was published in the December 2014 issue of Reproductive Toxicology, with the study titled “Use of Ondansetron During Pregnancy & Congenital Malformations In The Infant.”

By compiling data from Sweden’s Medical Birth Register between 1998 and 2012, researchers found a total of 1,349 children born to women prescribed Zofran. The Swedish researchers came to the same conclusions as the Danish study, with birth defects being 1.62 times more likely when fetuses are exposed to Zofran.

The last study was conducted by Australian researchers, who analyzed births between the years 2002 and 2005, with the data collected from Australia’s Pharmaceutical Benefits Scheme (PBS), Australia’s equivalent of Medicare.

A total of 96,968 live births were analyzed, with only 251 of the mothers being Zofran users. The researchers noted that the data was limited because it only included women who enrolled in the country’s benefits program, which means that the likelihood of Zofran birth defects could be much higher than observed in the study. Ultimately, the Australian researchers calculated a 20 percent  increased risk of birth defects, when women take Zofran.

In each of the studies, major birth defects such as cardiac complications, were more likely with Zofran use. So were cleft palate, skull malformations, and other physical malformations when women used Zofran.

Despite these findings, the U.S. Food and Drug Administration recently rejected a petition to change Zofran’s drug category, saying in an October 2015 statement that these studies “do not support a determination that there is an increased risk of fetal adverse outcomes.”