Doctors keep prescribing Zofran as a treatment for morning sickness. But recent scientific evidence suggests a link between Zofran and severe birth defects.

Zofran, also known by its generic name ondansetron, is a type of drug known as a 5HT3 receptor antagonist. How Zofran works isn’t fully understood, but scientists believe it operates on chemoreceptors in the nerves that connect to the digestive system.

Zofran is used for the treatment of nausea and vomiting in patients undergoing chemotherapy or radiation therapy for cancer and in those recovering from surgery. In the more than 24 years Zofran has been available to consumers, the FDA hasn’t approved it for treatment of any other nausea.

That doesn’t mean Zofran can’t lawfully be prescribed for morning sickness, though. Doctors have discretion to prescribe a particular drug for uses other than those approved by the FDA, so-called “off-label” uses.

And off-label use of Zofran for morning sickness has become relatively common: doctors write an estimated 1 million such prescriptions each year. What’s against the law is for a drug’s manufacturer to promote that drug for any use other than those approved by the FDA, a practice known as “misbranding.”

GlaxoSmithKline, the maker of Zofran, denies having promoted Zofran for morning sickness or any other off-label use. However, 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.

Studies from as far back as the 1980s confirmed that ondansetron can cross the placental barrier to get from the mother to the fetus. More recent studies show the use of Zofran during pregnancy may be dangerous due to the possibility of Zofran birth defects. One study by Harvard University and the Centers for Disease Control found that mothers who took ondansetron during pregnancy had twice the risk of giving birth to a child with a cleft palate.

A review of the medical records of 900,000 Danish women revealed a doubled risk of congenital heart defects associated with taking Zofran during pregnancy. Atrial and ventral septal defects are some of the more frequently mentioned cardiac abnormalities.

These defects can result in decreased exercise tolerance and shortness of breath, and they can inhibit the whole body’s growth through childhood. Treatment may require open-heart surgery, catheterization, and antibiotic medication to prevent bacterial infections of the heart.

Other birth defects that may be associated with Zofran use include cleft lip, club foot, many different musculoskeletal deformities, and craniosynostosis, in which malformation of the skull may leave it too small or misshapen to properly contain the brain. Some studies have found increased incidences of premature birth and shorter birth length.

Despite this more recent evidence suggesting Zofran birth defects, the FDA still keeps Zofran in pregnancy category B, allowing it to be prescribed during pregnancy if it is “clearly needed.” Studies performed in animals revealed no harm to the fetus that resulted from ondansetron. The agency notes, however, that no adequate studies have been performed in humans.