BOSTON - In contrast to five other studies, new research from California suggests the antidepressant drug fluoxetine (Prozac), if taken during pregnancy, may cause fetal anomalies and perinatal complications.
The study, comparing 228 pregnant women who took the drug with 258 controls who did not, showed an increased incidence of three or more minor structural anomalies in babies exposed during the first trimester. It also showed an increased risk of premature delivery and poor perinatal condition in those exposed during the third trimester.
"These data suggest that if pregnant women are unable to discontinue fluoxetine therapy before the third trimester, the risk of perinatal complications is increased," said the investigators from the division of dysmorphology and teratology in the pediatrics department of the University of California-San Diego.
However, in an editorial accompanying the report in The New England Journal of Medicine, Dr. Elisabeth Robert of the Institut Européen des Génomutations in Lyon, France, said, "It seems unjustified to use these new results as a reason to withhold fluoxetine from women who require an antidepressant drug during pregnancy."
She took exception to the researchers' methods and interpretation of results, and noted the findings are "in contrast to ... five cohort studies, which included approximately 450 pregnancies and which focused on the relation between fluoxetine and developmental effects, (and) suggested that children exposed in utero, whether early or late in gestation, do not have an increased risk of birth defects, poor perinatal condition, or neurodevelopmental delay."
Those studies include two reports from the Motherisk program at Toronto's Hospital for Sick Children. Dr. Gideon Koren, director of the program and professor of pediatrics and pharmacology at the University of Toronto, discussed the group's fluoxetine studies in a recent interview with The Medical Post. (See The Medical Post, Feb. 20, 1996.)
Women in the new study were drawn from those who had called the California Teratogen Information Service and Clinical Research Program asking about the potential teratogenic effects of fluoxetine.
Controls were taken from callers not taking the drug and whose exposures were deemed not to be teratogenic.
Pregnancy outcomes of women in the fluoxetine group were analysed separately for those women who took the drug during only the first trimester and those who took it later in pregnancy.
For 97 infants born to women in the early-exposed group, there was a higher incidence of babies having three or more minor structural anomalies (15.5%) than in 153 control infants (6.5%).
The researchers, however, did not indicate what the anomalies were, but defined them as structural defects that have no cosmetic or functional importance and that are known to occur in less than 4% of the general population.
The finding, however, "indicates that fluoxetine therapy during the first trimester of pregnancy has an effect on embryonic development," they said, and "raises the possibility of an associated defect in the development of the central nervous system that may become evident when the infant is older."
The 73 infants who were exposed during the third trimester had higher rates of premature delivery, admission to special care nurseries and poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding and jitteriness, compared to either the early-exposed infants or controls.
Their birth weight was also lower and birth length was shorter, said the researchers.
In the editorial, Dr. Robert pointed out several methodological factors that could have contributed to the findings.
First, she suggested the fact that the control group was made up of women who were presumably not depressed didn't allow for the possibility that the illness itself was a confounding factor in the observations.
Several outcomes -- prematurity, admission to a special-care nursery and poor neonatal adaptation -- are known to be associated with psychiatric disorders in the mother, she said.
Maternal age was higher in the fluoxetine group, which may partly explain the observed excess of poor perinatal outcomes, she added.
In addition, 30% of the fluoxetine-treated mothers were taking other psychoactive drugs.
"It is important for physicians who take care of pregnant depressed women not be confused by these contradictory results," Dr. Robert said, referring to the other studies showing no adverse effects from taking fluoxetine in pregnancy.
"Although several hundred women have taken fluoxetine during pregnancy without obvious reproductive or developmental toxic effects, its safety for pregnant women and their fetuses has yet to be thoroughly assessed," she added.
"I do not think that fluoxetine or tricyclic antidepressant drugs have been clearly proved unsafe for pregnant women, but their use involves a calculated risk because of their uncertain side effects."
Copyright © 1996 Maclean Hunter Publishing Limited
Reprinted with permission.
Internet Mental Health (www.mentalhealth.com) copyright © 1995-2011 by Phillip W. Long, M.D.