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.
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.
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)