Zofran® Birth Defects

Zofran Birth Defects

Zofran is known to cross the placenta and expose the fetus to significant levels of the drug.

Information about Zofran birth defects resulting from prenatal exposure to Zofran has come to light via three major sources:

  • Studies by researchers who have reported their results in medical journals.
  • Charges made by individuals who are now suing the maker of Zofran, GlaxoSmithKline (GSK).
  • Reports received by GSK and uncovered in the course of fact-finding related to Zofran birth defects lawsuits.

All three sources point to two major areas of concern related to fetal exposure to Zofran during the first trimester: cardiovascular defects and malformations of the face, including cleft palate.

Zofran® Heart Defects

Ventricular Septal Defect (VSD)

The most common Zofran birth defects associated with the heart are known as septal defects. The two upper chambers of the heart (atria) and the two lower chambers (ventricles) are separated by muscular walls. The medical term for such a wall is “septum.” A hole in the septum dividing the left and right atria is called an atrial septal defect (ASD). A hole in the septum dividing the two ventricles is known as a ventricular septal defect (VSD). A third category is the atrioventricular septal defect (AVSD), where there are holes in the walls between the atria and ventricles, as well as defects in the valves that separate the atria and ventricles.

These defects have been reported in research studies. Plaintiffs have described septal defects in their lawsuits and court filings suggest that these defects have been reported directly to GlaxoSmithKline.

Zofran® Cleft Palate

Cleft Palate

In 2011, scientists from Sloan Epidemiology Center at Boston University and the Centers for Disease Control and Prevention (CDC) investigated a variety of medications used to treat nausea and vomiting in pregnancy. They found that Zofran exposure during the first trimester increased the risk of cleft palate by nearly two and a half times. Significantly, of the several drugs that were tested, only Zofran and other drugs in its class were associated with an increased risk of this defect.

In cleft palate Zofran birth defects lawsuits, several plaintiffs have complained of facial malformations in their children exposed to the drug prenatally. Plaintiffs also allege that orofacial anomalies are among the hundreds of defects reported to GSK since Zofran received FDA approval.

Zofran® Kidney Defects

An Australian study published in December 2012 in BioMed Research International reported a six-fold increased risk of kidney obstructions associated with Zofran birth defects. Although the sample of women who took Zofran (ondansetron) was small (251), which lessens the significance of the finding, it is nevertheless concerning. In some cases of kidney obstruction, surgery is required to prevent serious damage. On average, the women who took ondansetron began at a relatively late gestational age (11.9 weeks), after the primary period of organ development (organogenesis).

Reports from the FDA Database – Toronto Star Investigation

On June 25, 2014, the Toronto Star published the results of their investigation into Canadian women who had taken ondansetron. Using the database of the U.S. Food and Drug Administration (FDA), they found 20 Canadian women whose babies had suffered from a number of Zofran birth defects, including:

  • Fetal death
  • Fetal growth restriction
  • Heart defects
  • Heart murmur
  • Jaundice
  • Kidney defects
  • Mouth deformity
  • Musculoskeletal anomaly

Zofran Birth Defects Studies

In February of 2013, a Danish study of over 600,000 women was widely publicized, with media claims that it provided convincing evidence that Zofran did not cause birth defects. The headline in the Huffington Post stated: “Zofran, Pregnancy Nausea Drug, Won’t Harm Fetus.” Six months later another Danish researcher Jon T. Andersen, presented the results of an even larger study (nearly 900,000 women) which found babies were twice as likely to be born with cardiac malformations associated with Zofran. A large Swedish study published in 2014 also found that infants were twice as likely to be born with cardiac septal defects if their mother took Zofran during the first trimester of pregnancy.

The first Danish study did report septal defects (in a supplement to the published paper) in a number of women who took Zofran. Though the findings were not statistically significant, they suggested a possible effect of Zofran on septal defects that could not be ruled out.

In essence, two of the three studies show a significant increase in the risk of cardiovascular malformations and the third, at best, failed to rule out such defects. And all three may be biased in the direction of no effect: the actual risk may be higher than any of these studies found.

Zofran Birth Defects

Drugs pass to the baby from the placenta. After birth, baby suffers from withdrawal.

A plausible biological pathway underlying Zofran birth defects has been established in both animal and human studies. Animal studies conducted by GSK in the 1980’s demonstrated that Zofran crossed the placenta and exposed rat and rabbit fetuses to the drug. In a 2006 study, 41 human subjects who were given the drug also found that “ondansetron readily passed through the human placenta in the first trimester. A significant amount of ondansetron was also found in fetal tissue and amniotic fluid.” In the study, authors reported that on average the concentration of ondansetron in the fetal tissue was 41% of the concentration in maternal plasma.

These findings are important because the formation of organs during embryonic development is known to take place during the first trimester of pregnancy. This is the time period during which fetal exposure to toxic agents is most likely to cause major congenital malformations. In addition, serotonin, the chemical in the body whose action is blocked by Zofran, is thought to play an important role in the development of the embryo, particularly in the formation of the skull and heart.

Swedish researcher Bengt Danielssion and his colleagues offer a compelling case for one possible mechanism behind Zofran birth defects in their recent study (see Zofran Heart Defects). Zofran and all the drugs in its class, known as 5-HT3 receptor antagonists, affect the electrical activity of the heart and may cause significant disruption of the normal heart rhythm, including a condition known as QT prolongation (Q and T refer to two electrical waves seen on an electrocardiogram.)

In 2011, the FDA warned, “Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm.”

Danielsson offers the following evidence:

  • The “embryonic heart of all studied species, including humans” is even more susceptible than the adult heart to develop cardiac arrhythmia in organogenesis (the early development of organs) when exposed to QT prolonging drugs.
  • In animal studies, several QT prolonging drugs produce dose dependent birth defects, particularly ventricular septal defects.
  • “Mechanistic studies show that the teratogenicity [the capability of producing fetal malformations] is a consequence of drug induced embryonic cardiac arrhythmia, interrupted blood and oxygen supply to the embryo and reperfusion (the restoration of blood flow) damage.
  • Other QT prolonging drugs have been associated with an increase in cardiac ventricular defects in humans.

Danielsson’s argument is ultimately quite simple: a drug which can produce potentially fatal heart arrhythmias in an adult, might well be expected to produce unwanted effects in a developing fetus.

Danielsson Study

In 2014, Swedish researchers led by Bengt Danielsson reported the results of their investigation of 1,349 infants born to women who had taken ondansetron in early pregnancy between 1998 and 2012. There were 17 cases of septal defects, mainly ventricular septal defects, in babies who had been exposed to ondansetron in early pregnancy. In three cases, both VSD and ASD were reported. Exposure of the fetus to ondansetron in early pregnancy was associated with a 62% increased risk of overall cardiovascular defects and a doubling of the risk of septal defects. In addition to the 17 cases of septal defects, Danielsson reported one case of coarctation (narrowing) of the aorta and one case of tetralogy of Fallot. In one of the patients, the ventricular septal defect was accompanied by pulmonary valve stenosis.

Andersen Study

A 2013 Danish study led by Jon T. Andersen investigated over 900,000 births in that country and also reported a significantly increased risk of septal defects. Exposure to ondansetron during the first trimester more than doubled the risk of VSD and ASD. The risk of a third category of heart defects, atrioventricular septal defects (AVSD), which involves defects of the ventricular and atrial walls, as well as defects in the valves that join the atria and ventricles, was increased four-fold.

Danielsson and Andersen have both come out against the use of Zofran in pregnant women, based on the strength of their findings. As stated in the Danielsson study,

“…the drug should not be used off label for nausea and vomiting in early pregnancy until further large prospective studies are available.”

– Bengt Danielsson et al., Reproductive Toxicology (January 2014)

Dr. Andersen is a researcher in the Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Copenhagen. He discussed his findings at an August 2013 presentation to the International Society of Pharmacoepidemiology in Montreal, Canada. At the conclusion of his talk (available for viewing at Motherisk.org), Dr. Anderson stated that Zofran should not be used for the treatment of morning sickness in pregnant women.

In both the Danielsson and Andersen studies, information on which women who took ondansetron was based on prescription registries. However, as Danielsson and Andersen have pointed out, registry-based studies tend to underestimate risk, because they cannot confirm with certainty that the women actually took the drug. If any of the women in the ondansetron group failed to take the drug, the results would be biased in the direction of no drug effect. This means the actual risk of heart defects associated with fetal exposure to ondansetron in early pregnancy may be significantly greater than either study reported.

Please contact our law firm if you took Zofran while pregnant and your child has any of the following Zofran birth defects:

  • Abdominal Birth Defects / Omphalocele
  • Anal atresia (complete or partial closure of the anus
  • Cardiac (heart) defects
  • Cleft palate or cleft lip
  • Clubfoot (one or both feet turn downward and inward)
  • Craniosynostosis (skull defect)
  • Limb Defects
  • Neural-tube defects (brain and spinal cord, spina bifida)
  • PPHN (Persistent Pulmonary Hypertension of the Newborn)