Maternal treatment with selective serotonin reuptake inhibitors during pregnancy and delayed neonatal adaptation: a population-based cohort study

Abstract

ObjectiveSelective serotonin reuptake inhibitor (SSRI) use is common in pregnancy. It is associated with delayed neonatal adaptation. Most previous studies have not adjusted for the severity of maternal mental health disorders or examined the impact of SSRI type and dosage. We examined whether treatment with SSRIs in late pregnancy (after 20 weeks) is associated with delayed neonatal adaptation independent of maternal depression and anxiety.Design, setting and patientsRetrospective population-based birth cohort of 280 090 term infants born at 15 Kaiser Permanente Northern California hospitals, 2011–2019. Individual-level pharmacy, maternal, pregnancy and neonatal data were obtained from electronic medical records.ExposureDispensed maternal SSRI prescription after 20 weeks of pregnancy.Main outcome measuresDelayed neonatal adaptation defined as a 5 min Apgar score ≤5, resuscitation at birth or admission to a neonatal intensive care unit for respiratory support. Secondary outcomes included each individual component of the primary outcome and more severe neonatal outcomes (pulmonary hypertension, hypoxic-ischaemic encephalopathy and seizures).Results7573 (2.7%) infants were exposed to SSRIs in late pregnancy. Delayed neonatal adaptation occurred in 11.2% of exposed vs 4.4% of unexposed infants (relative risk 2.52 (95% CI 2.36 to 2.70)). After multivariable adjustment, there was an association between SSRI exposure and delayed neonatal adaptation (adjusted OR 2.14 (95% CI 1.96 to 2.32)). This association was dose dependent. Escitalopram and fluoxetine were associated with the highest risk of delayed neonatal adaptation.ConclusionsInfants exposed to SSRIs have increased risks of delayed adaptation in a type and dose-dependent relationship, pointing toward a causal relationship.