1. The Top 10 Studies on Zofran Use During Pregnancy
By: Tiffany Collins
Zofran, also known by its generic name ondansetron, has been used “off-label” for years to treat
morning sickness all over the world. Many women have used it throughout their entire
pregnancy, and some have just used it for a few weeks when needed. Yet, many women still
don’t know that ondansetron has been linked to a wide range of birth defects. Conflicting
research and stories about the safety of Zofran use by pregnant women has been confusing to
say the least. So, to clear up some of that confusion, let's take a look at this simple breakdown
of the top 10 studies on Zofran use during pregnancy.
1. September 2004- Toronto, Canada
Where it all began; there were no studies that examined the use of ondansetron (Zofran) by
pregnant women before this study. Researchers had small sample size of just 176 pregnant
women who took ondansetron to observe in comparison to pregnant women who did not take
it. There were 5 miscarriages and 6 major birth defects among the 176 women. Researchers
concluded that ondansetron use did not appear to increase the risk of birth defects, but a larger
sample size would be needed in future studies to better understand ondansetron’s impact on
pregnancies.
2. December 2005- Stockholm & Lund, Sweden
The second study to observe ondansetron use in pregnancies used data from the Swedish
Medical Birth Register from July 1, 1995 to 2002. Researchers from this study concluded there
wasn’t an increased risk of birth defects. Yet, again, the number of women included in their
study was low.
3. January 2012- Boston, MA

2. Seven years later, the data available for ondansetron’s effects on infants was still lacking. So, in
a multi-state population-based case control study, researchers sought the answers the public
needed. Based in Boston, MA, and Atlanta, GA, this team examined if morning sickness or its
treatments were associated with an increased risk of birth defects. Using data from the National
Birth Defects Study from September 24, 1997 through December 31, 2004, they discovered
good and bad news. Good news: morning sickness was not associated with birth defects. Bad
news: the use of ondansetron during pregnancy proved to double the odds of an infant having a
cleft palate.
4. January 2013- Shatin, Hong Kong
Researchers set out to simply see if ondansetron transferred to the fetus during the first
trimester. In all of their samples, they found ondansetron and concluded that further
investigation was needed to see if this exposure affects the development of a fetus. This study is
important, for during the first trimester, the most sensitive developments of the fetus take place.
5. February 2013- Copenhagen, Denmark
The start of confusion. Danish researchers set out to investigate the risk of adverse fetal
outcomes from ondansetron. They defined the adverse fetal outcomes as: spontaneous
abortion, stillbirth, any major defect, preterm delivery, and delivery of a low-birth-weight infant.
They analyzed data taken from the Danish Birth Registry collected between 2004 and 2011.
Around half of the pregnancies in this study showed that ondansetron was prescribed after the
10th
week, when malformations could not be produced anymore. With that in mind, they
unsurprisingly concluded that ondansetron was not linked to an increased risk of any of those
adverse fetal outcomes.

3. 6. August 2013- Copenhagen, Denmark
Just months later, at the International Society of Pharmacoepodemiology conference in
Montreal, a second Danish study, using data from the Danish Birth Registry from 1997-2010 was
presented. Along with covering more years and women for their research, this study concluded
the very opposite of the February 2013 study. These researchers concluded that there was a
30% increase in the prevalence of major congenital heart defects when women took
ondansetron in the first trimester. And here’s a funny fact for you: both of these studies’
opposing results were presented on the same day in Montreal. It was clear that even more
research was needed.
7. December 2013- Western Australia
Researchers took on the challenge to gain some clarity from those conflicting results from the
conference in Montreal. Using the data from all births in Western Australia in 2002-2005, they
saw that there was a small, (20%) but not significantly increased risk of major birth defects.
Since there were only 251 women in their database that took ondansetron, they concluded that
they did not detect any adverse outcomes from ondansetron use, but still could not state that it
was safe for pregnant women to use.
8. February 2014- Ther Drug Monit
Dr. Gideon Koren, director of the Motherisk resource centre at Toronto’s Hospital for Sick
Children, wrote a critical review of the two Denmark studies from 2013. He has experience on
this topic; he was one of the authors of the September 2004 study. His observations on the
designs of the Denmark studies pointed out that neither one was “designed to specifically
address fetal drug safety and there may be flaws in the quality and completeness of the data.“
He also noted the risks of the mother’s safety when using ondansetron in regards to her
developing abnormal heart rhythms and serotonin syndrome. Overall, he advised that
ondansetron should be “used cautiously only after drugs with better safety record, which have
been labeled to use in pregnancy (e.g. doxylamine-pyridoxine) have been tried.”
9. June 2014- The Toronto Star
Canada’s largest daily newspaper, The Toronto Star, published the findings of their investigation
on the effects of ondansetron use by pregnant women. They analyzed the data of Canadian
women who took ondansetron in the FDA’s public side-effect report database and saw that
there were 20 incidents of birth defects and two deaths of infants. When The Star contacted
GlaxoSmithKline, the maker of Zofran, for a comment, Glaxo said, “the safety of ondansetron for
use in human pregnancy has not been established.” And just how we have noted in an earlier
blog post, The Star noted that is illegal for drug companies to promote off-label uses of drugs to
doctors. Yet, GlaxoSmithKline did exactly that for years with many of their drugs, including
Zofran.

4. 10. October 2014- Stockholm, Sweden
Researchers again sought out the presence of major birth defects from ondansetron use by
pregnant women. In this study they used data from the Swedish Medical Birth Register from
1998 through 2012. They concluded that the risk of major birth defects was low, but there was a
significant increased risk of cardiac septum defects, holes in the heart, for infants.
From these studies it is clear that more extensive studies need to be done before Zofran is ever
considered as the first, second, or third option for preventing morning sickness. The risks simply
do not outweigh the benefits when it comes to your and your baby’s health. So what should you
do with all of this information? Take it straight to your doctor to learn about other options for
avoiding morning sickness. If there aren’t any non-pharmaceutical options you can take, ask
your doctor about Diclegis, the only drug that the FDA has approved for morning sickness. It has
not been studied for women suffering from hyperemesis gravidarum (HG), so ask your doctor for
his or her opinion on using Diclegis “off-label” for HG.
If you think that your baby has been affected by Zofran use, contact our offices today. We will
confidentially and promptly review your case. Helping those babies affected and preventing
future birth defects from occurring from Zofran is our main objective.