Trajectories of Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Perinatal Outcomes: A Longitudinal Register Study.

Objective: We examined the possible impact of selective serotonin reuptake inhibitor (SSRI)-trajectories describing the timing of different SSRI dosages on adverse perinatal outcomes.

Design: Longitudinal register study.

Setting: Study from Kuopio University Hospital Birth Register.

Population Or Sample: Altogether 553 mothers who reported using SSRIs in pregnancy were matched to a five-fold comparison group (n = 2765), based on depression, psychiatric diagnoses and age.

Methods: We applied unsupervised k-Means longitudinal clustering to identify four distinct patterns of SSRI use, and propensity score adjusted regression models based on generalised estimating equations to examine the associations between the exposure groups and the perinatal outcomes, using the unexposed group as reference. Secondary analyses assessed linear associations between average SSRI dose and outcomes.

Main Outcome Measures: Birth weight, placental weight, placental-to-birth-weight ratio (PBWR), umbilical cord length, gestational length, preterm birth (< 37 gestational weeks), low 5-min Apgar score, neonatal intensive care unit (NICU) admission.

Results: Compared to the no SSRI group, we found no associations between the use of SSRI up to standard doses and the perinatal outcomes. However, the sustained high dose group (~twice the standard dose) displayed higher placental weight (B = 36.9, 95% CI = 3.2, 70.7) and PBWR (B = 1.54, 95% CI = 0.70, 2.38), and the risk of NICU admission was 2-fold (95% CI = 1.05, 3.76), compared with the no SSRI group. The average SSRI dose was linearly associated with placental weight, PBWR, and umbilical cord length.

Conclusions: SSRI use up to standard doses was not associated with adverse perinatal outcomes. However, linear dose-response associations and sustained higher doses suggest potentially reduced placental efficacy and increased risk of adverse perinatal health, warranting caution.