An anti-nausea medication sometimes prescribed for morning sickness may be linked to congenital heart defects and other common birth defects.

Zofran, also known by its generic name ondansetron, is a medication approved for the treatment of nausea and vomiting associated with surgery or with chemotherapy treatment. The FDA first approved Zofran in January 1991 for those specific treatments.

According to the FDA’s current Zofran label, studies in animals found no evidence of harm to the fetus attributable to Zofran. But the labeling also notes that no adequate and well-controlled studies have been conducted on human subjects. The FDA endorses use of Zofran during pregnancy only if clearly needed by the patient.

Studies Indicate Zofran Birth Defects Link

However, several studies of existing childbirth statistics point to a possible increased risk of Zofran birth defects. A study published in 2012 found that babies whose mothers took ondansetron in the first trimester of pregnancy were more than twice as likely to be born with cleft lip or cleft palate. The birth defects study stopped short of declaring a causal connection between ondansetron and birth defects, but did conclude that further investigation was warranted.

Another study published in August 2013 surveyed information from all childbirths in Denmark from 1997 to 2010. The researchers found a higher incidence of major congenital heart defects in children whose mothers used a prescription for ondansetron during their first trimester.

A more recent study from 2014 found results consistent with those of the Danish study. Researchers examined data from the Swedish Medical Birth Register, about 1,349 children born between 1998 and 2012 to mothers who had taken ondansetron early during the pregnancy. They found a statistically significant increase in cardiovascular defects, particularly cardiac septum defects, associated with early-pregnancy ondansetron treatment.

Despite these findings, the U.S. Food and Drug Administration recently rejected a petition to change Zofran’s drug category, saying in an October 2015 statement that these studies “do not support a determination that there is an increased risk of fetal adverse outcomes.”

Congenital Heart Defects

The congenital heart defects noted in these Zofran birth defects studies tend to manifest as abnormal formation of the interior structures of the heart, disrupting the normal exchange of oxygen between the lungs and blood, which can affect the function of the entire body.

Children with congenital heart defects may have inhibited breathing, reduced exercise tolerance, or they may fail to grow normally. They may also be vulnerable to life-threatening bacterial infections in their heart.  If undetected until adulthood, an atrial septal defect may result in pulmonary hypertension or heart failure, potentially shortening the patient’s life span.

Treatment of a congenital heart defect may require catheterization to open narrow blood passages. In severe cases, open-heart surgery may be necessary.

Zofran Lawsuits for Off-Label Promotion

Despite multiple subsequent FDA approvals of new formulations and label revisions over its long history, Zofran has never been approved as a treatment for morning sickness. Individual physicians are at liberty to prescribe any drug for whatever purpose they deem appropriate. However, it’s a violation of federal law for a pharmaceutical manufacturer to promote a drug for any use other than those approved by the FDA.

GlaxoSmithKline, the maker of Zofran, has already paid a high price for off-label marketing of Zofran.

In 2012, GSK settled a federal, civil false claim lawsuit alleging GSK had promoted Zofran for the treatment of morning sickness in pregnant women despite being approved only for post-operative nausea, and that GSK had paid doctors kickbacks for prescribing Zofran. In 2012, GSK settled that lawsuit along with three similar lawsuits regarding other GSK products for $1.043 billion.