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Emerging Perspectives: Psychotropic Drugs During Pregnancy — New Data on Neonatal Outcomes

Both the illness and the medication can create problems for the exposed neonate.

We still know little about the neonatal risks from maternal use of psychotropic drugs during pregnancy, which limits accurate weighing of risks and benefits for expectant mothers. Three big observational studies provide new data.

Using large medical, demographic, and public drug insurance registries in Quebec, researchers focused on women with psychiatric diagnoses (mostly, mood or anxiety disorders) and antidepressant use for at least 1 month in the year before pregnancy. Researchers compared first-trimester antidepressant exposure and duration in 2140 healthy infants and 189 infants with any major congenital malformation in the year after birth. Antidepressants commonly used were paroxetine (42%), sertraline (15%), and venlafaxine (13%). The risk for congenital malformation (8%, vs. the usual population rate of 3%) was unrelated to first-trimester antidepressant use, its duration, or therapeutic class. Controlling for ethnicity and for drug, alcohol, and tobacco use, determined in 806 mothers, did not alter results.

Other researchers linked maternal and neonatal British Columbian health records to identify recipients of a serotonin reuptake inhibitor (commonly, paroxetine, 39%; fluoxetine, 25%; or sertraline, 23%) during pregnancy and compared effects of early exposure only (first and/or second trimesters; n=1575) and of continued exposure (from first or second trimester through delivery; n=1925). Late exposure was significantly associated with lower birth weight, gestational age, and birth weight for gestational age, and with risks for respiratory distress and cesarean section. Because the two groups differed in maternal illness severity, the investigators used propensity scores to create two groups (n=429 each) matched for duration of exposure and illness severity; no between-group differences were found. When illness severity was controlled for, longer duration of exposure significantly increased the risks for lower birth weight, gestational age, and weight for age, and for respiratory distress.

A third group used prospective data from the U.K. National Teratology Information Service to compare gestational age and birth weight after exposure to typical and atypical antipsychotics (45 and 25 infants, respectively) or to drugs without adverse neonatal effects (38 infants). Postdate or premature birth, maternal diabetes, and congenital malformations were exclusions. The typical-antipsychotic group had higher incidences of small size for gestational age and lower mean birth weight than the group exposed to drugs without adverse neonatal effects. The atypical-antipsychotic group had a higher incidence of large size for gestational age than both comparison groups and heavier mean birth weight than the typical-antipsychotic group, even after adjustment for maternal use of weight-altering medications. These differences were more pronounced in a subanalysis of infants exposed to olanzapine or clozapine.

Comment: The first study suggests that elevated rates of malformations are more likely related to maternal illnesses (or, possibly, to these participants’ low socioeconomic status) than to the drugs used to treat them. In addition to highlighting the importance of controlling for severity of maternal psychiatric illness, the second study echoes this neurodevelopmental theme, suggesting that neonatal effects of SRIs are more likely due to their developmental effects than to drug withdrawal at birth. Avoiding these medications during the last trimester might reduce these adverse neonatal outcomes. Use of cognitive-behavioral therapy for depression and anxiety should be considered as an alternative to antidepressants during pregnancy, although this might not be adequate treatment for some.

Findings from the last study are more ominous, as large size for gestational age increases risks for diabetes and obesity; the metabolic effects of atypical agents might transfer to infants exposed to these medications.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry July 14, 2008

Citation(s):

Ramos E et al. Duration of antidepressant use during pregnancy and risk of major congenital malformations. Br J Psychiatry 2008 May; 192:344.

• Original article (Subscription may be required)
• Medline abstract (Free)

Oberlander TF et al. Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: Population-based study. Br J Psychiatry 2008 May; 192:338.

• Original article (Subscription may be required)
• Medline abstract (Free)

Newham JJ et al. Birth weight of infants after maternal exposure to typical and atypical antipsychotics: Prospective comparison study. Br J Psychiatry 2008 May; 192:333.

• Original article (Subscription may be required)
• Medline abstract (Free)