Selective serotonin-reuptake inhibitors in pregnancy and lactation

We explore the effects on the developing fetus and neonate of selective serotonin-reuptake inhibitors (SSRIs) during pregnancy and lactation, reviewing the relevant animal and human studies published in English from 1976 to the present. Medline was used to search the terms SSRI, fluoxetine, pregnancy, lactation, and teratogenesis. Animal studies were inconclusive: some found that fetal exposure to high doses of fluoxetine produced no congenital anomalies, while others linked the drug to abnormalities such as craniofacial malformations, alterations in serotonergic neurotransmitter systems, birth-related hematomas, and inhibition of the milk-ejection reflex. Human investigations indicated no relationship between in utero exposure to fluoxetine and teratogenic effects, although data are limited, and none have been collected regarding behavioral teratogenesis. However, we found a suggestion of an increased rate of miscarriage, an association with infants large for gestational age, one reported case of perinatal toxicity, and one case of an infant who was colicky while receiving breast milk from a mother taking fluoxetine. Based on these data, controlled prospective studies of exposure to SSRIs during pregnancy and lactation are needed, as is long-term evaluation for behavioral teratogenesis and enduring cognitive effects. Data are lacking on drug levels in breast milk and neonatal serum. Neonatal toxicity and the effect of SSRIs on labor and delivery, the mother-infant interaction, and lactation also merit further study. Clinically, a conservative approach is encouraged, minimizing the use of SSRIs in pregnancy, avoiding such drugs during the first trimester, tapering them prior to delivery, and discouraging breast-feeding during their use.