On April 30, 2015, Monheit Law sent a Freedom of Information Act (FOIA) request to the US Food & Drug Administration. We asked for every adverse event report submitted in relation to GlaxoSmithKline’s Zofran, along with generic equivalents using the same active ingredient, ondansetron.
Eventually, the FDA responded with two massive files of data, spanning from January of 1991 to April of 2015. In total, we received over 3,800 pages of reports comprising almost 8,700 individual adverse events. We’ve made these files publicly available; you can download .PDF versions at Zofran.Monheit.com.
Then we sifted through the data, searching for any adverse event reports in which maternal or fetal exposure to Zofran had been listed as a suspected cause of birth defects, congenital abnormalities or other adverse fetal outcomes.
On our website, you’ll find an infographic presenting the highlights of our analysis in visual form and a thorough breakdown of every birth defect and abnormality mentioned in the adverse event reports we received from the FDA. You can find our complete report here.
Zofran Suspected Cause Of Over 400 Birth Defects & Adverse Fetal Events, Monheit Law’s FOIA Request Reveals
Between January 1, 1991 and April 30, 2015, Monheit Law identified 475 reports of birth defects and adverse fetal outcomes in which Zofran or its active ingredient ondansetron were believed to be the cause.
In many instances, the FDA received multiple adverse fetal event reports naming Zofran as a suspected cause in a single day. On February 4, 2015, the agency logged 38 individual reports of birth defects linked to Zofran. These reports were submitted by a drug company in regard to Swedish patients. While health care professionals are allowed to submit adverse event reports directly to the FDA, the vast majority of AERs we received had been submitted by pharmaceutical manufacturers, including many from GlaxoSmithKline.
Below, you’ll find a more detailed rundown of specific congenital abnormalities that were linked to prenatal Zofran exposure. This list is far from complete; a comprehensive look can be found on Monheit Law’s website.
Congenital Heart Defects
Out of 475 total reports, there were 170 references to congenital heart defects and other cardiovascular anomalies.
Cardiac septal defects, or “hole in the heart” anomalies, were reported most often with:
- 21 references to ventricular septal defects
- 16 references to atrial septal defects
- 6 references to atrioventricular septal defects
One reference to an unspecified cardiac septal defect brought the total to 44 references.
Has Zofran Been Linked To Heart Defects Before?
Yes. It’s crucial to note that a series of major epidemiological studies have found an association between Zofran’s active ingredient and an increased risk for congenital heart defects. In fact, a team of Danish researchers linked prenatal exposure to Zofran and cardiac septal defects specifically.
Reviewing more than 900,000 pregnancies logged in Denmark’s Medical Birth Registry, the researchers found that women prescribed ondansetron in the first trimester were:
- 2.1 times more likely to deliver babies with an atrial septal defect
- 2.3 times more likely to deliver babies with a ventricular septal defect
- 4.8 times more likely to deliver babies with an atrioventricular septal defect
Swedish public health officials conducted a similar study in 2014. Reviewing every birth record filed in Sweden between 1998 and 2012, the team concluded that Zofran’s active ingredient was associated with a 62% increase in the risk for cardiovascular defects, and a more than two-fold increase in the risk for cardiac septal defects.
Craniofacial Birth Defects & Anomalies
We found 52 references to craniofacial congenital defects and associated anomalies, including:
- 7 references to cleft lip and palate
- 4 references to isolated cleft palate
- 7 references to microcephaly, a condition in which a baby’s head is abnormally small, generally due to insufficient brain growth
- 3 references to Pierre Robin syndrome
Pierre Robin syndrome is a sequence, a series of associated anomalies that generally occur together. In sequences, one abnormality causes another, which causes another, like a trail of dominoes. Pierre Robin includes a cleft palate, as well as:
- micrognathia – an abnormally small lower jaw
- retrognathia – a lower jaw that is set further back than normal, relative to facial skeleton and muscles
- glossoptis – a tongue that sits far back in the throat, obstructing the airway
We also noted 5 references to congenital deafness and 4 references to “otitis media,” or middle ear infection, a common symptom of cleft palate.
Have Craniofacial Defects Been Linked To Zofran Before?
Yes. In 2012, a group of researchers from Harvard, Boston University and the US Centers for Disease Control & Prevention published a study that included more than 10,000 pregnancies.
Women prescribed Zofran or a generic equivalent were 2.37 times more likely to deliver babies with a cleft palate.
Congenital Respiratory Defects & Adverse Fetal Events
Monheit Law found a total of 86 references to congenital respiratory defects and associated conditions, including:
- 24 references to neonatal respiratory distress syndrome, in which inadequately developed lungs lead to severe breathing difficulties
- 5 references to pulmonary hypoplasia, a condition in which the lungs develop only partially
Other Adverse Fetal Outcomes
While we attempted to categorize each congenital anomaly according to the body region that was affected, there were numerous adverse events implicating fetal exposure to Zofran that did not fit into our classification.
We’ve called these events “adverse fetal outcomes,” and the results of our FOIA request included 382 such conditions.
- 55 references to fetal death, stillbirth, spontaneous abortion or missed abortion
- 73 references to premature babies
- 63 references to fetal growth restriction, in which fetal weight is below the 10th percentile for gestational age.
What Is An Adverse Event Report (AER)?
Adverse event reports are reports of adverse health outcomes that health care professionals believe may be linked to a pharmaceutical drug. The FDA maintains a database of these reports and uses the data to identify potential safety issues.
Do Adverse Event Reports Present An Accurate Picture?
The first report involving fetal exposure to Zofran, submitted on December 29, 1992, listed only “congenital anomaly.” Many reports followed suit. In total, we received 21 reports of unspecified congenital anomalies, or birth defects, that had been linked to prenatal Zofran exposure. Even within specific categories of defect, many reports were vague. For example, we identified 20 reports filed in relation to unspecified congenital heart defects and 9 reports of unspecified congenital kidney malformations.
According to QuarterWatch, a publication of the Institute for Safe Medication Practices, the FDA’s Adverse Event Reporting System (FAERS) “works worst […] for events in newborns and children.” In fact, the FDA itself has stated that reports of adverse events in children are “too few for effective postmarket surveillance.” In QuarterWatch’s words: “for birth defects, reporting is even more limited, compounded by poor quality reporting.”
FAERS was created to monitor emerging health risks, dangers that may be posed by previously-approved pharmaceutical products. It seems that for infant and adolescent patients, especially those born with congenital abnormalities, reporting is so inconsistent that FAERS is almost totally ineffective.