Babies whose mothers took antidepressant drugs in the second half of pregnancy are six times more likely to have a rare but dangerous lung ailment, a new study suggests.
One study isn't proof. But it's strong evidence that taking SSRI antidepressants -- such as Prozac, Zoloft, and Paxil -- carries an extra risk during pregnancy.
The risk is that the babies will have PPHN: persistent pulmonary hypertension of the newborn. Only one or two in a thousand babies get this, but it's very serious. It kills about one in 10 babies who get it. In moderately severe cases, half the survivors suffer hearing loss or brain damage.
"We find these results very concerning," Sandra L. Kweder, MD, deputy director of the FDA's office of new drugs, said in an unusual, hastily called news conference. "We find the reported association of SSRI antidepressants with this very serious condition to be very worrisome."
This does not mean that pregnant women with clinical depression should forgo treatment, says researcher Christina Chambers, PhD, MPH, of the University of California, San Diego. Chambers is program director of the California Teratogen Information Service. CTIS conducts pregnancy outcomes research and offers women information about the pregnancy risks of drugs and chemicals.
"This is a fairly low risk for women taking SSRI antidepressants," Chambers tells WebMD. "So if in fact SSRIs cause PPHN, the risk appears to be low. For 100 women taking one of these medications late in pregnancy, only one may have a child with PPHN."
"This isn't a cause for panic among pregnant women taking these medicines," the FDA's Kweder says. "This is the kind of information a woman should discuss with her doctors -- not just her obstetricians but also the doctor providing her mental health care. Stopping these medicines on your own can create more problems than it solves. The small risk that is being reported here may well be outweighed by your need for a medicine to treat your depression."
The study appears in the Feb. 9 issue of The New England Journal of Medicine.
Kweder says the FDA is taking a hard look at Chambers' findings. She says the FDA will issue a public-health advisory in the next few days.
"We are in the process of evaluating the Chambers article further," Kweder explains. "We will look at our Adverse Event Reporting System and other databases to see if we have any data to add to this."
Kweder says the FDA may ask antidepressant makers to add a warning to their labels. The agency may also ask the companies to conduct new surveys of pregnant women who use or have used their products, she notes.
The Risk of SSRIs to the Newborn
In an earlier study of pregnancy outcomes, Chambers saw two cases of PPHN. Since there were relatively few women in the study, it was an unexpected finding. Both mothers, it turned out, had taken Prozac late in their pregnancies.
So Chambers teamed up with researchers at Boston University and doctors at 97 hospitals to look for more cases of PPHN. They found 377 cases. They interviewed the mothers and compared them with 836 women who had normal babies.
Sure enough, PPHN risk was six times greater among the newborns of women who took SSRI antidepressants in the second half of pregnancy. There was no increased PPHN risk when women took the drugs in the first 20 weeks of pregnancy. And there was no PPHN risk associated with other types of antidepressants.
However, only 14 of the study's 377 cases of PPHN were linked to SSRI antidepressants. It's not clear exactly what the causes of PPHN are, but antidepressant use obviously is not the main one. In fact, it will take more studies to prove that SSRIs really are linked to PPHN.
Yet SSRI antidepressant use during pregnancy carries other risks besides PPHN, says James L. Mills, MD, chief of pediatric epidemiology at the U.S. National Institute of Child Health and Human Development. Mills' editorial accompanies the Chambers paper.
"The risk of PPHN seems to be fairly small," Mills tells WebMD. "However, there is also the consideration of infant withdrawal syndrome with maternal SSRI use. This seems to occur in 30 percent of children involved. Fortunately, the withdrawal syndrome -- also called neonatal abstinence syndrome or poor neonatal adaptation -- is limited in duration."
The Benefit of SSRIs to Babies
Having a depressed mother isn't healthy for a fetus or a baby. And a recent study showed that women who stop depression treatment during pregnancy tend to relapse -- just when their babies most need them.
There's also evidence that untreated clinical depression during pregnancy can have lead to health problems in newborns -- beyond the risk of a mother's suicide or postpartum depression.
For these reasons, Chambers and Mills strongly urge women to consider both the benefits and the risks of SSRI use during pregnancy.
"Pregnant women are just like everyone else -- they have things that need to be treated during their pregnancies," Chambers says. "They need to know the risks of their medications and to be comfortable taking them during pregnancy. So when we find a risk like PPHN, we report it as just one piece of information a woman and her doctor can use to make good decisions about what to do in her pregnancy."
Chambers notes that there are many other conditions, such as asthma and seizure disorders, that put women in a similar catch-22. Left untreated, these conditions pose a risk to the fetus. Yet drugs used to treat these conditions pose a risk, too.
"I think the key thing is when a woman is planning a pregnancy, or realizes she is pregnant, she and her health care provider should sit down together and discuss the need for therapy and make a therapy plan," Mills says. "Just telling a woman not to take her medicines is not a good option."
By Daniel J. DeNoon, reviewed by Louise Chang, MD
SOURCES: Chambers, C. D. The New England Journal of Medicine, Feb. 9, 2006; vol 354: pp 579-587. Christina Chambers, PhD, MPH, University of California, San Diego, and program director, California Teratogen Information Service, San Diego. James L. Mills, MD, chief, Pediatric Epidemiology Section, National Institute of Child Health and Human Development, Bethesda, Md. FDA news conference with Sandra L. Kweder, MD, deputy director, office of new drugs, Center for Drug Evaluation and Research, FDA.