Nov. 24, 2010 -- The popular over-the-counter and prescription acid-blocking drugs proton-pump inhibitors (PPIs) do not appear to increase risk of birth defects when taken during the first trimester of pregnancy, a study shows.
In the study, 2.6% of more than 840,000 live births occurring in Denmark from January 1996 through September 2008 involved major birth defects. The study showed that 3.4% of 5,082 infants whose mothers took PPIs during the four weeks before conception through first trimester were diagnosed with a major birth defect. By contrast, 2.6% of 835,886 infants whose moms did not take these acid-reducing drugs during the same time period were diagnosed with a major birth defect.
The study is published in the New England Journal of Medicine.
The researchers did an analysis of the study data on PPI use limited to the time period during the first trimester of pregnancy. Statistically speaking, there was no significant increased risk of birth defects seen among children of women who took PPIs -- including Aciphex, Nexium, Prevacid, Prilosec, and Protonix -- during their first trimester of pregnancy compared with women who did not take these drugs during the first trimester of pregnancy.
“We found no significant association between the use of PPIs during the first trimester of pregnancy and the risk of major birth defects,” conclude study researchers Björn Pasternak, MD, PhD and Anders Hviid of Statens Serum Institut in Copenhagen, Denmark.
“This is the biggest and best study to date, and it is generally reassuring about use of PPIs in pregnancy,” says Allen A. Mitchell, MD, director of the Slone Epidemiology Center at the Boston University Medical Center in Boston. Mitchell wrote an editorial accompanying the new report.
That said, more studies are needed to support the safe use of PPIs during pregnancy, he says.
An Obstetrician’s Perspective
The new study “confirms the results of previous studies that did not show an increase risk in major congenital anomalies, [but] the study is limited because they used filled prescriptions as a definition of drug exposure and the information about birth defects is acquired from a registry, which may be subject to misclassification,” says Shari Gelber, MD, PhD, an ob-gyn at Weill Medical College of Cornell University in New York City, in an email.
“Furthermore, the specific reasons for the patients to be taking the medication are not available, and certain medical conditions can independently increase the risk of birth defects,” she says. “Although this study is not definitive, it should provide reassurance to women with pregnancy exposure to this class of medications [and] given the large number of patients in the study, it is unlikely that the investigators would have missed a large increase in a major anomaly.”
Her bottom line? “Pregnant women should always discuss with their doctor any medications they are taking, including herbs and over-the-counter medications,” Gelber says. “Women should not start or stop any medications during pregnancy without a discussion with their physician [and] with any pregnancy exposure, patients and their physicians should weigh the potential benefits of a medication with the theoretical risk to the fetus.”
“My general recommendations for heartburn are lifestyle modifications first,” Gelber says. “Before I recommend PPIs for patients, I do an individualized assessment about how much discomfort they have from their heartburn, I review their history and physical to make sure there are no underlying medical illnesses other than pregnancy causing their symptoms, and discuss the fact that there is no known risk to PPIs, but that the data is limited,” she says. “This study supports that view, but again the study is not definitive.”
Robert Kimura, MD, director of neonatology at Rush University Medical Center in Chicago, is cautiously optimistic about the use of PPIs during pregnancy. He sees newborns and is not in the habit of asking new moms if they took these drugs during pregnancy, but may start doing so.
“There are certain drugs we know are associated with anomalies, but PPIs have not been that high on the radar screen,” he says.
“Some obstetricians may cite this study and tell their pregnant patients that these drugs are safe,” he says. “If a woman is really symptomatic, you can use these drugs to treat heartburn, but we shouldn’t use them like water,” he says.
Often, risks do not become apparent until millions of people take the drugs, he says.