Neonatal Outcomes After Prenatal Exposure to Selective Serotonin Reuptake Inhibitor Antidepressants and Maternal Depression Using Population-Based Linked Health Data

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Abstract
Depression occurs in an estimated 7% to 15% of all pregnancies1 and is widely recognized as a perinatal factor that alters birth outcomes and neonatal behaviors.2,3 However, pharmacologic management of perinatal depression is not without risk to the neonate.4 Soon after the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants in 1988 and their use to manage mood disorders during pregnancy, studies emerged reporting adverse neonatal effects.4-6 Some early studies suggested that SSRI use was safe,7 with little or no risk of adverse outcomes,8-10 while others reported neurobehavioral disturbances and increased risks of lower birth weight and preterm birth.5,11,12 While exposure has not been associated with major anomalies,13,14 recent scientific and public attention has focused on a cluster of symptoms often referred to as “poor neonatal adaptation,” which includes respiratory distress, hypoglycemia, temperature instability, and irritability5,15-17 that may reflect pharmacologic neurotoxic12,16 or behavioral teratogenic18,19 effects. An increased risk of these symptoms, including convulsions, has also been found through the use of large population-based birth registries or World Health Organization data sets.17,20 Two previous prospective population-based studies matching maternal prescription data with birth data yielded conflicting evidence of adverse outcomes. Using the Swedish Medical Birth Registry, Ericson et al21 reported that prenatal exposure was not associated with an increased risk of adverse birth outcomes among 546 neonates of mothers receiving an SSRI during their pregnancy. In contrast, using US health maintenance organization data, Simon et al22 reported that prenatal SSRI exposure was associated with earlier delivery and lower birth weight, and third-trimester SSRI exposure was particularly associated with lower Apgar scores.

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