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August 20, 2025BJOG An International Journal of Obstetrics & Gynaecology0 citations

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

GBGuro Pauck Bernhardsen MPMaiju Pesonen LKLeea Keski‐Nisula

Key Points

Higher placental weight and risk of NICU admission were observed in mothers using sustained high doses of SSRIs, indicating potential adverse effects.
No adverse perinatal outcomes associated with standard doses of SSRI were found, but further investigations are warranted based on dose-response relationships.
Longitudinal clustering identified distinct SSRI use patterns, and regression models analyzed impacts on birth and placental outcomes.
The study highlights the necessity for caution regarding SSRI prescriptions during pregnancy, particularly at higher doses.

Abstract

ABSTRACT 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.

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