WEDNESDAY, Feb. 8, 2006 (HealthDay News) -- Women who use commonly prescribed antidepressants late in their pregnancies run a higher risk of delivering infants with a serious breathing problem, a new study released Wednesday shows.
The condition, called persistent pulmonary hypertension of the newborn (PPHN), occurs when a newborn's circulation system does not adapt to breathing outside the womb. It can be fatal.
The new research, published in the Feb. 9 issue of the New England Journal of Medicine, provides no clear indication of what pregnant women should or should not do when it comes to using antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which include Celexa, Paxil, Prozac and Zoloft.
But the results were disturbing enough to prompt a hastily convened U.S. Food and Drug Administration (FDA) news conference Wednesday. "This appears to be a very well-conducted study and we find the results to be very concerning," said Dr. Sandra Kweder, deputy director of the office of new drugs at the FDA's Center for Drug Evaluation and Research.
Kweder said the agency will be evaluating the data further and issuing a public health advisory in the coming days that "might or might not" include labeling changes as well as requirements for manufacturers to conduct additional post-marketing studies.
The FDA has not yet been in touch with antidepressant manufacturers, Kweder added, but it expects "that they would be paying close attention to this publication and going back to their own databases."
The new report also comes on the heels of a small study, published Monday in the Archives of Pediatrics & Adolescent Medicine, that found newborns whose mothers had used SSRIs during their pregnancy were at raised risk of symptoms indicating withdrawal from the drugs.
The PPHN findings add to the dilemma faced by women who take SSRIs to ward off depression, which carries its own risks to pregnancy.
"Pregnant women with depression or other conditions that need treatment have to make decisions, with their clinicians, about what medications they can be best treated with and which medications are the safest," said Christina Chambers, lead author of the PPHN study and assistant professor of pediatrics at the University of California, San Diego.
"These are very small numbers and it's hard to know exactly what this means," added Dr. Jennifer Wu, an obstetrician/gynecologist with Lenox Hill Hospital in New York City. "I think that there are a certain number of patients who have severe depression for whom SSRIs do work who need to continue them during pregnancy. Other patients with less severe depression may want to go off."
An estimated one to two infants per 1,000 live births develop PPHN. Some 10 percent to 20 percent of infants with PPHN will end up dying even if they receive treatment.
The issue of taking SSRIs during pregnancy is a complicated one. In September 2005, the FDA issued a warning about possible birth defects in infants born to women who took Paxil during their first trimester. A number of studies have also shown that about 20 percent to 30 percent of babies born to women taking SSRIs in late pregnancy will develop "neonatal complications," which can involve jitteriness and respiratory difficulties, Chambers said. Most of these adverse effects go away on their own.
On the other hand, a more recent study found that pregnancy did not appear to confer a protective effect on women with major depression, as many experts had previously thought. Quite the opposite, pregnant women who discontinued their antidepressant medication were found to be at a five times higher risk of relapse than women who didn't. And infants born to women suffering from untreated depression can also run risks.
The new study compared 377 women whose infants had PPHN with 836 women whose infants did not have the disorder.
In all, 14 of the infants with PPHN had been exposed to an SSRI after the 20th week of gestation, versus six of the infants in the control group.
That means that PPHN "occurred about six times more frequently in women taking SSRIs," Chambers said. "It's highly unlikely that that would have happened by chance, although this study doesn't tell you for sure that the drug caused that outcome."
Even with these odds, the researchers stressed that PPHN remains rare, and 99 percent of women taking SSRIs during pregnancy will deliver a healthy infant.
Using SSRIs before the 20th week or using non-SSRI medications at any time during pregnancy was not associated with an increased risk of PPHN.
There is some biological plausibility to the findings. PPHN occurs when the arterial pressure in the lungs remains high and low-oxygen blood circulates throughout the body. The drugs may affect this pathway, the study authors speculated.
More studies are needed "to see if there truly is a risk, what factors affect that risk, when you need to stop medication and what dosages are best," Wu said.
In the meantime, she added, the study points to the importance of "individualized patient care and weighing the risks and benefits for each patient."
Kweder added, "This isn't a cause for panic among women who are taking these medicines and they should not stop their medication on their own. Stopping these medications on your own can sometimes create more problems than it solves. Also, for many women, the small risks suggested by the study may be outweighed by their own personal need for treatment of a mental health condition."
More information
For more on PPHN, visit the Nemours Foundation.
