In Utero Exposure to Antidepressants Does Not Affect Neurodevelopment

Source: Nulman I, et al. N Engl J Med 1997;336:258-262.

Nulman et al in the motherisk program, a Toronto information and counseling service for women exposed to drugs and other potentially hazardous environmental events during pregnancy, studied mother-infant pairs from pregnancies during which the mother received tricyclic antidepressant drugs or fluoxitine (Prozac). These infants were compared to a control group in which there had been no in utero exposure to antidepressants. When studied at l6-86 months of age, no neurodevelopmental deficits were found in the exposed infants. The results were similar in children exposed to a tricyclic antidepressant or fluoxitine during the first trimester and those exposed throughout pregnancy.

Comment by John Leventhal, MD, FAAP

The authors state that 8-20% of women develop depression, most commonly during the childbearing years, and many require antidepressant therapy. A decision to initiate or continue antidepressant medications may be influenced by concerns of possible effects on the fetus, especially during the critical first trimester of pregnancy. Because discontinuation of these medications may be detrimental to the mother with high rates of relapse of serious depression, the authors conducted a study to assess prospectively cognitive and language development in large groups of children born of mothers who received tricyclic antidepressants or fluoxitine during their gestation. A previous study showed that exposure to antidepressants during pregnancy was not associated with an increased risk of major fetal malformations.1 From the population of women who came to their center for counseling, the authors recruited 80 women who received tricyclics and 59 who received fluoxitine. They also recruited pro spectively a control group of 84 women who had taken presumably innocuous drugs such as acetaminophen. No significant differences were noted in gestational age at birth, birth weight, or post-natal growth between the three groups. Neurodevelopmental status was assessed with age-appropriate testing instruments (Bayley and McCarthy Indices, and Reynell scales) at 16-86 months of age by a psychometrician who was blinded to the drug history. All three groups had virtually identical IQ scores, verbal comprehension, and language expression. Scores for mood, arousability, activity, distractibility, and behavior problems also showed no differences between the three groups.

We can stop being depressed about possible adverse effects of these widely used and effective medications on the mothers of our soon to be patients.


    1. Pastuzak A, et al. JAMA 1993;269:2246-2248.

Dr. Leventhal is Professor of Pediatrics, Child Study Center, Yale University School of Medicine.