Use of Ssri and Snri During Pregnancy and the Risk of Preterm Birth, Low Birth Weight, and Neonatal Adaptation Disorders: A Systematic Review

Background: Depression affects 10–15% of pregnant women and poses significant clinical management challenges. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line treatments, yet their safety profile in pregnancy remains an active area of research and clinical concern. Objective: This systematic review synthesizes evidence from 2015–2025 on associations between SSRI/SNRI use during pregnancy and risks of preterm birth (PTB), low birth weight (LBW), and poor neonatal adaptation syndrome (PNAS), with attention to confounding by maternal depression. Methods: A comprehensive search of PubMed, Cochrane Library, and related databases identified meta-analyses, systematic reviews, and large cohort studies published 2015–2025. Outcomes examined included PTB (<37 weeks), LBW (<2500g), and PNAS. Results: SSRI exposure during pregnancy is associated with modest increases in PTB risk (adjusted OR approximately 1.2–1.5) and LBW (relative risk ~1.4), with strongest effects for late-pregnancy exposure. PNAS occurs in 20–30% of infants exposed in the third trimester (adjusted OR ~2.1), typically mild and self-limited. SNRI data are more limited but show similar patterns. Confounding by indication - the underlying maternal depression - contributes substantially to observed associations. Conclusions: Both untreated maternal depression and antidepressant exposure carry risks. Clinical decision-making should involve individualized risk–benefit assessment, shared decision-making, and recognition that sertraline and escitalopram demonstrate favorable safety profiles. Absolute risk increases are modest and must be weighed against consequences of untreated illness.