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Michael Monheit
Michael Monheit
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Four Studies Find Possible Link Between Zofran & Birth Defects

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In our last article, we reviewed the two primary causes of cleft lip and cleft Bottles of the prescription drug Zofranpalate: genetic abnormalities and environmental factors, or “teratogens.”

Our description ended with an overview of one prescription drug, ondansetron. Several studies have now identified a possible link between ondansetron and an increased risk of birth defects. In that post, we covered only one of these studies, an epidemiological review of more than 10,000 birth records performed by researchers at Harvard and Boston University. The team found that women who were prescribed ondansetron as an “off-label” treatment for morning sickness were more than twice as likely to deliver babies with a cleft palate.

Investigating The Potential Association Between Major Birth Defects & Ondansetron

Today, we’ll continue investigating the potential association between ondansetron, which is sold under the brand name Zofran, and congenital abnormalities.

To date, three other studies have found an increased incidence of birth defects among babies born to women who were prescribed ondansetron during the first trimester. You can find an infographic that presents the results of these studies here, and we’ll cover each in turn below.

Danish Researchers Find Risk Of Major Birth Defects

On August 27, 2013, a team of Danish researchers presented the results of a study to the International Conference on Pharmacoepidemiology in Montreal. Their paper Ondansetron Use In Early Pregnancy And The Risk Of Congenital Malformations, had been prepared in response to an earlier Danish study, one that had found no increased risk of major birth defects in children exposed to ondansetron during early pregnancy.

The first study reviewed Danish birth records filed between 2004 and 2011, but as noted pediatrician Gideon Koren has observed, half of the women included in the research had been exposed to ondansetron after ten weeks of pregnancy. According to Koren, “malformations [can] not be produced” beyond those first ten weeks. In his mind, this could have biased the earlier study toward a null hypothesis, in effect “diluting” the results by including cases that would not show ondansetron’s potential effects, even if those effects actually exist.

By widening their research to cover all Danish births between 1997 and 2010, and including only women exposed to ondansetron during the first trimester, the second team hoped to correct the earlier study’s possible problems.

Out of 903,207 live births included, 1,368 women had redeemed a prescription for ondansetron during the first trimester of pregnancy. Among the control group, the 901,839 women not exposed to the drug, 3.5% delivered a baby with a major malformation. 4.7% of the women exposed to ondansetron in the first trimester gave birth to children with major birth defects. The researchers calculated this disparity as a 20% increase in the risk for major congenital abnormalities, but noted significantly higher risks in relation to specific congenital heart defects. After exposure to ondansetron, babies were:

  • 2.1 times more likely to have atrial septal defects
  • 2.3 times more likely to have ventricular septal defects
  • 4.8 times more likely to have atrioventricular septal defects

These defects, commonly referred to as “hole in the heart” defects, involve cardiac tissues that fail to develop properly. Babies can be born with incomplete barriers between the heart’s four chambers, adversely affecting blood flow and the body’s ability to properly nourish itself with oxygen.

You can find a comprehensive overview of congenital heart defects, along with their potential causes and treatment options, here.

Swedish Study Finds Increase In Congenital Heart Defects

Using methods similar to those we discussed in our explanation of the Danish studies, a group of Swedish public health officials and researchers investigated ondansetron’s potential effects on fetal development. Their study, published in the December 2014 volume of Reproductive Toxicology, was titled “Use of Ondansetron During Pregnancy & Congenital Malformations In The Infant.”

Compiling records from Sweden’s Medical Birth Register between 1998 and 2012, the team identified a total of 1,349 children born to women who had been prescribed ondansetron during early pregnancy. They then compared the incidence of congenital malformations in that group to the incidence found among all births recorded during the 15 year period. They came to a similar conclusion as the second Danish study, finding an “increased and statistically significant” risk of cardiovascular defects.

Babies exposed to ondansetron during the first trimester were 1.62 times more likely to be born with congenital heart defects. The researchers noted that this risk specifically involved “cardiac septum defects,” a category usually considered to include atrial septal defects, ventricular septal defects and atrioventricular septal defects.

Australian Study Finds Increase In Kidney Malformations

On November 19, 2013, the journal BioMed Research International published a study called “Off-Label Use of Ondansetron in Pregnancy in Western Australia.”

According to the study’s authors, “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.” In the US, along with Australia and Canada, Zofran has never been approved as a treatment for nausea and vomiting during pregnancy. To date, the drug’s manufacturer has never studied its effects on pregnant women or developing babies in the clinical trials that would be necessary for such an approval.

With those facts in mind, the Australian researchers compiled every birth record filed in Western Australia between 2002 and 2005. They then determined how many women had been prescribed ondansetron through Australia’s Pharmaceutical Benefits Scheme (PBS), a federal program roughly equivalent to Medicare. Out of 96,968 total live births, only 251 pregnant women were prescribed ondansetron during that three year period.

The researchers note that women prescribed ondansetron were more likely to be of higher socioeconomic status, and thus have access to private health insurance. Since their study only included women logged by a public health system, they suspect that “more pregnant women were diagnosed ondansetron as a private prescription.” But the study’s data was limited to women enrolled in programs through the Pharmaceutical Benefits Scheme, so the possible effects of ondansetron were not investigated in this “quite likely” larger population of privately-insured pregnant women.

The team compared the birth outcomes of women prescribed ondansetron to those who had not taken the drug. They found a “20% increased risk of a major birth defect amongst children exposed to ondansetron in the first trimester,” while noting that their relatively small sample size (251 live births) prevented their findings from being precise. While “the study was too small to assess risks of individual birth defects,” the researchers also found a 7-fold increase in the risk for kidney malformations associated with ondansetron.

Moving Forward

While four studies may indicate that this medication could present considerable risks to pregnant women and their unborn babies, these results are a potential indication that further research should be conducted on ondansetron and its link to major birth defects.

Ondansetron has been sold in the US under the brand name Zofran since 1991. As we’ve already mentioned, neither that product, nor any of its generic equivalents, has been FDA approved for use as a treatment for morning sickness during the first trimester of pregnancy. Zofran’s manufacturer has never conducted clinical trials to investigate the drug’s possible side effects in pregnant women.

You can learn more about Zofran’s history of FDA approval by following this link.


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  1. Jason says:
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    I appreciate reading your blog for updates regarding the Zofran legal situation.

    While it’s not a confirmed relation, the wife and I believe our son’s Congenital Pseudoarthrosis of the Clavicle (born in 2014) is somehow related to this mess as she was on Zofran, well the generic form of from 12/2013 through 3/2014 (her entire first trimester).

    A total of 5 prescriptions of Ondansetron, the first two being the oral-dissolving type and the next three the oral, non-dissolving type. Maybe we should point the blame at Glenmark Pharam and Sandoz/Novartis in addition to Glaxo SmithKline, the makers of the generic forms that we (and others) have taken to cause these birth defects.

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