Neonatal Outcomes Following Selective Serotonin Reuptake Inhibitor Use During Pregnancy

Evaluating the safety of selective serotonin reuptake inhibitors (SSRIs) during pregnancy is challenging due to ethical barriers to randomized trials and potential confounding in observational studies.

To compare neonatal outcomes for pregnancies with SSRI continuation vs those with SSRI discontinuation using a target trial framework.

This cohort study comprised target trials using electronic health records of linked mothers and neonates from a single academic center. The periconception trial examined congenital anomalies with first-trimester exposure, and the early-pregnancy trial evaluated nonanomaly outcomes with first- or second-trimester exposure. Participants were women with singleton pregnancies (2006 to 2022) with SSRI use within the 2 years before conception and at least 1 prenatal visit during the first trimester (periconception trial) or during the first or second trimester (early-pregnancy trial). Data were analyzed from May 2022 to December 2023.

SSRI continuation vs discontinuation during pregnancy.

Apgar scores, meconium in amniotic fluid, neonatal intensive care unit (NICU) admission, preterm birth, birth weight, respiratory distress, feeding problems, hypoglycemia, hypothermia, pulmonary hypertension, cesarean delivery, and congenital anomalies.

The early-pregnancy trial included 1014 pregnancies (mean [SD] maternal age, 30.3 [5.4] years). The periconception trial included 807 pregnancies (mean [SD] maternal age, 30.4 [5.5] years). SSRI continuation was associated with lower Apgar scores at 1 minute (mean difference [MD], -0.39; 95% CI, -0.60 to -0.18) and 5 minutes (MD, -0.28; 95% CI, -0.42 to -0.13), and increased risk of meconium in amniotic fluid (odds ratio [OR], 1.73; 95% CI, 1.22 to 2.45). No significant associations were found for congenital anomalies (OR, 1.09; 95% CI, 0.63 to 1.90), though this result should be interpreted with caution given limited sample size. No differences were found for neonatal intensive care unit admission (OR, 1.23; 95% CI, 0.82 to 1.83) or other outcomes.

In this cohort study, SSRI continuation during pregnancy was associated with impaired neonatal adaptation but not with severe complications or NICU admission. These findings highlight the importance of appropriate comparator selection to minimize confounding and illustrate how target trial emulation can improve causal inference in studies of medication safety during pregnancy.