Prenatal exposure to selective serotonin reuptake inhibitors and infant outcome

The selective serotonin reuptake inhibitors are prescribed increasingly also during pregnancy. Although a number of studies have assessed their safety, data concerning congenital malformations and adverse perinatal outcome are conflicting.

Literature search in PubMed until March 31, 2012, including original research articles, meta-analyses, and reviews.

Fluoxetine and paroxetine use in early pregnancy has been associated with a small increased risk for specific cardiovascular malformations in some studies, fluoxetine with ventricular septal defects and paroxetine with right ventricular outflow tract defects. The observed absolute risk for these specific malformations is small. Data on preterm birth, low birth weight, and being small for gestational age have been conflicting; and mother's underlying depression is obviously an important confounder. Respiratory distress and neonatal adaptation problems are common in prenatally exposed infants, and an increased risk for persistent pulmonary hypertension of the newborn has been observed in several studies. Although several studies have not confirmed an increased risk for adverse neurodevelopment, a recent study observed an increased risk for autism spectrum disorders in prenatally exposed offspring.

Causality cannot be confirmed in observational study settings. However, parallel results in individual studies regarding the cardiac malformations and pulmonary hypertension of the newborn, together with an existing biologically plausible mechanism behind these events may support causality. Considering the important role of serotonin in central nervous system development, more studies are needed to assess the possible adverse effects on long-term neurodevelopment.