By Dennis Thompson
More than 40,000 women exposed to metoclopramide while pregnant did not face any increased risk of birth defects or miscarriage, according to a study published Oct. 16 in the Journal of the American Medical Association.
"This is by far the largest study on metoclopramide safety in pregnancy, and as such it expands substantially on the published evidence," said co-author Dr. Bjorn Pasternak of the Statens Serum Institute in Copenhagen. "It found that metoclopramide use in pregnancy was not associated with increased risk of major adverse outcomes, including major malformations and fetal death, and as such supports what is known about the safety profile of this drug."
More than half of pregnant women experience nausea and vomiting, usually early in their pregnancy, the study authors noted.
Most women deal with these symptoms with little treatment, but about 10 percent to 15 percent eventually will require medication because they face more serious complications such as dehydration or weight loss.
But many pregnant women have grave concerns regarding any sort of nausea medication because of the horrific birth defects associated with the drug thalidomide, which was used to treat morning sickness in the late 1950s and early 1960s. Thalidomide's tragic history led to the strengthening of the U.S. Food and Drug Administration (FDA) and the development of regulations regarding medication use during pregnancy.
"There's a general feeling to take no medications during pregnancy," said Dr. Siobhan Dolan, associate professor of obstetrics and gynecology at Montefiore Medical Center in New York City and medical adviser to the March of Dimes. "The truth is in the first trimester when the organs are forming we're cautious about any medication the women take. But there's a growing appreciation that there can be risks to not treating symptoms like nausea and vomiting."
The drug has FDA approval for use as a treatment for patients suffering heartburn and esophagitis due to acid reflux. It's also used to treat nausea caused by surgery or chemotherapy, and is often recommended as a treatment for morning sickness if other therapies have failed.
Pasternak said there aren't many alternatives for the treatment of nausea and vomiting in pregnancy. "There appears to be some degree of individual variation in response to drug treatment, so some women may be helped by one drug and others by another. Therefore, different treatment alternatives are needed," he said.
In this study, researchers reviewed more than 1.2 million pregnancies in Denmark from 1997 to 2011 and compared outcomes between women who used metoclopramide and those who did not.
The investigators compared 28,486 infants exposed to metoclopramide in the first trimester of pregnancy to 113,698 unexposed infants, and found no associations between the nausea drug and any major malformations.
The study also found no increased risk of miscarriage, stillbirth, preterm birth, low birth weight or fetal growth restriction associated with metoclopramide use in pregnancy.
Because birth defects are rare, it can be difficult to assess a drug's safety in small-scale studies, Dolan said. A study looking at tens of thousands of pregnancies is more likely to find patterns and associations between a medication and the risk of birth defects, if such risk exists.
"We can take from this some reassurance" of metoclopramide's safety, Dolan said. "What's powerful about a study like this is they looked at all the births in Denmark between 1997 and 2011. That's a lot of births."
Regardless, Dolan said further study into the safety of this and other medications used during pregnancy will always be needed.
"We need good data to have good understanding so women can be cared for, and their symptoms can be treated and they can have successful pregnancy outcomes," she said. "Women need to understand the risks of any medication they choose to take."