Infants born to women taking commonly prescribed antidepressants during the first trimester of their pregnancies have an increased risk of serious birth defects, though the danger remains tiny, according to two studies published today.
The reports in the New England Journal of Medicine found a higher risk of developmental problems affecting the intestines, brain and skull. Although life-threatening, all of the defects are rare and normally occur in no more than one in 2,500 births.
"The take-home message is that we are talking about very small risks," said UC San Diego epidemiologist Christina Chambers, who has studied the effects of antidepressants but wasn't involved in the new research.
The studies are the latest to raise concerns about the effects of antidepressants on fetuses.
Babies born to women on antidepressants have been shown to experience signs of withdrawal, including tremors and sleep disturbances, during the first days of life.
Others studies have linked a mother's antidepressant use later in pregnancy to an increased risk of lung problems in newborns. Two reports have tied the drug Paxil, in particular, to a higher rate of congenital heart malformation. The drug carries a warning about heart defects.
The latest studies were the largest yet to analyze the association between antidepressants and birth defects.
The findings could complicate decisions by pregnant women about whether to use or continue taking antidepressants, because untreated depression also carries risks and can lead to smoking, drinking and other harmful behaviors. An estimated 10% of pregnant women have depression, according to previous research.
Women should not discontinue antidepressants without first talking with their doctors, the researchers said.
The studies focused on antidepressants known as selective serotonin reuptake inhibitors, a class that includes Paxil, Prozac, Zoloft and Celexa. The medications work by enhancing the activity of the brain chemical serotonin. They have become the standard treatment for depression since their introduction in the 1980s.
In addition to acting on the brain to improve mood, serotonin constricts blood vessels and performs other functions. The full impact of manipulating serotonin levels within the body isn't completely understood, although animal studies have detected a role for serotonin in prenatal development of the heart and head.
Taken together, the two studies looked at 19,471 infants with birth defects and compared them with 9,952 normal babies. Researchers examined which antidepressants mothers had taken during the first trimester and searched for patterns among dozens of different birth defects reported.
The studies found that Paxil tripled the risk of a heart defect that reduces blood flow to the lungs, though the chance of developing such a defect was less than 1%, according to an editorial published with the reports. No other antidepressants were linked to cardiac problems.
Dr. Victoria Hendrick, a UCLA psychiatrist who was not involved in the research, said it was reassuring that cardiac malformations weren't found with most of the drugs.
But the findings "add to our concern about Paxil in pregnancy," said Hendrick, who has received speaking fees from Zoloft manufacturer Pfizer Inc.
The two studies differed in other respects.
One of the reports, funded in part by Paxil maker GlaxoSmithKline, associated Zoloft with a nearly sixfold increase in cases of omphalocele, in which intestines or other abdominal organs protrude from the navel. The birth defect is very rare, occurring in one of every 5,000 births, according to federal statistics.
The finding was based on three cases in which infants with the intestinal defect had been exposed to Zoloft -- not enough to draw firm conclusions, said Carol Louik, a Boston University epidemiologist and lead author of the study.
The other study linked antidepressant use to a doubling of the risk of three congenital problems: anenecephaly, a defect in which a large portion of the brain and skull is missing; craniosynostosis, in which connections between skull bones close prematurely; and intestinal defects.
The researchers, from the Centers for Disease Control and Prevention and the University of British Columbia in Vancouver, Canada, cautioned that their findings were based on only a handful of cases.
The risks appeared greater for obese women who used antidepressants, said Dr. Sonja A. Rasmussen of the CDC, a coauthor of the study.
Although obesity itself is a risk factor for some kinds of birth defects, antidepressants appeared to increase that risk. One possible reasons is that antidepressants dissolve in fats and so they may work differently in women who are obese, she said.