Three studies published over the past week have sparked new concerns about the health risks of taking -- and not taking -- antidepressants during pregnancy.
Two of the studies point to possible dangers to the fetus, and in response to the latest study, released Wednesday by the New England Journal of Medicine, the Food and Drug Administration announced it was considering tougher warnings on the drugs' use.
Separate research, published last week in the Journal of the American Medical Assn., shows that mothers who stop taking the drugs run a high chance of slipping back into debilitating depression.
Taken together, the studies represent an increasingly difficult conundrum for mothers and doctors.
"These data make me feel all the more cautious about using antidepressants in pregnancy," said Dr. Victoria Hendrick, a professor of psychiatry at UCLA. "But it's still something I'm going to do because I see very, very depressed women."
Prozac and other antidepressants known as Selective Serotonin Reuptake Inhibitors enhance the action of the brain chemical serotonin.
Since being introduced in the late 1980s, the drugs have become the standard treatment for depression.
The range of effects of manipulating serotonin levels is not well understood. For example, serotonin can cause blood vessels to constrict. It also serves as a growth factor, helping organize neural circuitry in a maturing brain.
The FDA has begun to strengthen warnings concerning the use of the drugs by pregnant women. In December, the agency ordered a new warning label for paroxetine, sold under the brand name Paxil, after two studies linked it to heart defects in newborns.
The agency's new concern involves a lung problem known as persistent pulmonary hypertension, which normally occurs in 1 in 1,000 births.
The researchers found six times that risk in infants born to women on antidepressants.
The team interviewed 377 mothers of babies born with the condition, and found that 14 had taken antidepressants in the second half of pregnancy. In a control group of 836 mothers with healthy children, six had taken the drugs, according to the study in the New England Journal of Medicine.
The lung ailment leads to inadequate oxygen levels in the blood. Most babies recover. In severe cases it can cause deafness, neurological problems or death.
"We find the association they have reported with this very serious condition to be very worrisome," said Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs.
Christina Chambers, an epidemiologist at UC San Diego who led the research, cautioned that "even with a sixfold increase, you're still talking about a fairly low risk."
On Tuesday, a study published in the Archives of Pediatric and Adolescent Medicine bolstered previous reports that babies born to mothers on antidepressants could suffer signs of withdrawal from the drugs in the first few days of life.
Nearly a third of 60 newborns exposed to the drugs as fetuses experienced symptoms that included tremors, gastrointestinal problems and sleep disturbance, according to the study.
Two of the infants in the study suffered seizures. In most cases, the symptoms peaked in two days and then began subsiding.
When the researchers reviewed 37 cases of women taking paroxetine, they found that the symptoms did not occur at low doses.
The risks -- and the unknowns -- make it tempting for women to give up antidepressants for nine months.
The odds are against them. Researchers, led by Dr. Lee S. Cohen of Harvard Medical School, tracked 201 women who were taking antidepressants around the time they became pregnant. Sixty-eight percent of those who discontinued the medications relapsed into depression, compared with 26% of those who kept taking the drugs.
There are few studies on how a mother's depression, left untreated, affects the health of her fetus.
"These depressed women might not be eating right," Hendrick said. "They might be losing weight. Women might be suicidal. They might be more prone to smoking and drinking."
The use of antidepressants by women who are pregnant is widespread, since depression during pregnancy is fairly common. Nonetheless, it's not clear how many infants have been exposed.
The FDA said Wednesday that more research needed to be done.
The long-term effects of fetal exposure to antidepressants are particularly hard to determine. Research could require following children for a decade or more.
"There are not a lot of studies that look at these children five or 10 years down the line," said Dr. James Mills, an epidemiologist at the National Institute of Child Health and Human Development.
In recent years, the FDA has been criticized for being slow to react to evidence that the drugs can increase suicidal thoughts in some children and teenagers.
In 2004, the agency forced drug makers to include a strong warning of such risks in the information for their products.