In Denmark, researchers from Copenhagen University found an increase in congenital heart defects among babies born to women prescribed Zofran during early pregnancy. Using birth records from their own country, a Swedish team found a statistically significant increase in heart defects as well. American researchers from Harvard and Boston University found that women prescribed Zofran during the first trimester were 2.37 times more likely to deliver children with a cleft palate. The results of these studies have been widely-publicized, and you may have seen descriptions on the web, in television advertisements or on our own site.
Australian Study: Increase In Kidney Defects After Zofran Exposure
But the findings of an Australian study have received less attention.
Conducted by researchers from the University of Western Australia, the study found evidence that women prescribed Zofran during early pregnancy may be up to 7 times more likely to have babies with kidney defects.
These results, however, have been highly-contested. The study was very small, and included only 263 babies who were exposed to Zofran during the first trimester. Generally, the smaller a study’s group of subjects, the less reliable are its results.
Boston University Analysis Reveals Potential Kidney Defect
February 22, 2016 – New data from an ongoing birth defect surveillance program in the US has revived fears that Zofran may be linked to kidney defects.
Analyzing recent information from two birth defect registries, a group of researchers from Boston University say women who were prescribed Zofran appeared to be 2.3 times more likely to deliver babies with renal atresia. In this condition, also referred to as “renal agenesis,” children are born missing either one or both kidneys.
Much like the Australian study, these new results are “unstable,” according to the authors. The findings were based on a relatively small sample of Zofran-exposed pregnancies.
Over 200 families have filed lawsuits against GlaxoSmithKline, claiming the company failed to warn parents of Zofran’s potential pregnancy risks. Several of these lawsuits have been filed in relation to kidney defects, including this July 2015 complaint, in which a family from North Dakota says their son was born missing one of his kidneys.
In Australia & Worldwide, Zofran Commonly Used During Pregnancy
The Australian study was published in the journal Biomed Research International, under the title: “Off-Label Use of Ondansetron in Pregnancy in Western Australia.” In its opening paragraph, researchers noted the troubling trend in Zofran’s “off-label” use as a morning sickness treatment:
“Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. There is an increasing trend to prescribe ondansetron although its safety for use in pregnancy has not been established.”
The researchers note that ondansetron is not approved in Australia for the treatment of nausea and vomiting of pregnancy (NVP). Further, the Australian Pharmaceutical Benefits Scheme (a governmental program subsidizing prescription purchases) makes ondansetron available to patients as a subsidized drug only for the “management of nausea and vomiting associated with radiotherapy [or] cytotoxic chemotherapy.”
Despite this, “a recent survey of the management of NVP by obstetricians in Australia found that off-label use of ondansetron in NVP is clearly widespread.” You can read an abstract of that survey, which found that around 75% of pregnant women suffering from hyperemesis gravidarum in Australia had been prescribed ondansetron, here.
Zofran has quickly become one of America’s most commonly prescribed drugs during early pregnancy, too. This is true despite the fact that GlaxoSmithKline never sought Zofran’s approval as a treatment for morning sickness, and has never conducted clinical trials to determine the drug’s effects on pregnant women or their developing babies.
How Was This Zofran Study Designed?
The study itself was designed as a slightly-modified version of the classic “case-control” model. This type of study seeks to determine whether a certain outcome (such as congenital defects) is linked to a certain exposure (like taking Zofran during the first trimester).
What Is A Case-Control Study?
Case-control studies are the foundation of epidemiological research, a field that endeavors to investigate the causes and effects of health conditions in defined populations.
In classic case-control studies, two groups are identified: individuals who experienced an outcome, and those who did not. The group of people identified as experiencing the outcome are considered the study’s “case” group, while those who did not are its “control” group.
Then researchers look back in time, attempting to identify members in each group who were exposed to whichever medication or chemical is under investigation. If a significantly higher proportion of the individuals who experienced the outcome were exposed to the medication or chemical beforehand, researchers may be able to conclude that the outcome is associated with the exposure.
For the vast majority of outcomes and exposures, singular studies are not sufficient to establish an association. Instead, multiple independent studies will be conducted. In the event that additional research finds similar results, the case for the association’s reality becomes stronger and stronger.
There are currently four studies, including the Australian paper, that have found an increased incidence of congenital defects among babies born to women who were prescribed ondansetron during the first trimester.
Did The Australian Study Fit The Case-Control Model?
While the Australian team employed a “case” and “control” group comparison, their study actually flipped the classic model’s order.
First, they identified women who had been exposed to ondansetron during pregnancy, and contrasted that “case” group to a similar group of “controls”: pregnant women who had not been prescribed ondansetron.
After defining these exposure groups, the researchers determined whether or not women who had been prescribed ondansetron were more likely than women in the “control” group to experience adverse outcomes.
Details From The Australian Zofran / Ondansetron Study
Using records from the Australian Pharmaceutical Benefits Scheme, a public program that subsidizes prescription purchases, the team identified every pregnancy in Western Australia between 2002 and 2005 in which a mother was prescribed ondansetron as a morning sickness treatment.
As its control group, the study included every pregnancy during the same period in which mothers were not prescribed ondansetron.
Ultimately, the control group (women not exposed) included 96,717 pregnancies. The case group, those women prescribed ondansetron, came to only 251 pregnancies in which a total of 263 babies were delivered.
Kidney Defects May Be Associated With Zofran
The study’s most significant finding was that women prescribed ondansetron during the first trimester were 7 times more likely to deliver babies with “obstructive defects of renal pelvis and ureter.”
This category of congenital abnormalities occurs when the ureters, tubes that carry urine from the kidneys to the bladder, are blocked. Urine is prevented from draining properly, and can back up in the kidneys.
When left untreated, obstructive kidney abnormalities can result in chronic urinary tract infections. Kidney failure and impaired growth are other possible complications.
What Were The Australian Study’s Other Results?
While the researchers make clear that these results were not statistically significant, they also found an increased risk of stillbirth (1.8 times more likely) and an increased risk of delivering a baby with a low APGAR score (2 times more likely) in Australian women prescribed ondansetron during the first trimester.
A finding is statistically significant when researchers are very certain that it is reliable, that it accurately reflects circumstances in reality. It’s likely that the Australian team did not consider these findings statistically significant because their results were based on a relatively small case group, 251 pregnancies.
In addition, they found “a 20% nonsignificant increased risk of […] major birth defect[s] with first trimester exposure.”
Potential Zofran Kidney Abnormalities Identified In Canada
An investigative report published in Canada’s Toronto Star newspaper also found evidence of kidney defects that may be linked to Zofran and its active ingredient.
Reviewing adverse event reports submitted to the US Food & Drug Administration, journalists at the Star found accounts filed by “at least 20 Canadian women treated with ondansetron for vomiting in pregnancy [who] experienced serious suspected side-effects, including two infant deaths and multiple cases of newborns with heart defects and kidney malformations.”
Only time, and further research, will be able to confirm or contradict the Australian study’s findings. For now, in the words of distinguished Canadian pediatrician Gideon Koren, cases of women taking Zofran and giving birth to children with congenital defects are a “signal that should be looked into.”