Prenatal Selective Serotonin Reuptake Inhibitor Exposure and Its Impact on Neonatal Gastrointestinal and Urinary System: A Retrospective Matched Cohort Study

Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal SSRI use during pregnancy and time to first stool and time to first void in healthy neonates. Methods: In this retrospective matched cohort study, neonates exposed to SSRIs in utero were matched 1:1 with unexposed controls by gestational age (GA) and weight-for-gestational-age category. The primary outcomes were time to first void and time to first stool. Multivariable linear regression was performed using log10-transformed time to first stool, adjusting for maternal age, GA, and neonatal sex. Sensitivity analyses included size-for-gestational-age and time to first feeding. Results: A total of 266 neonates were included (133 SSRI-exposed, 133 unexposed). Time to first stool was shorter in SSRI-exposed neonates compared with unexposed neonates (median 7.4 vs. 8.6 h, p = 0.023), while the time to first void did not differ. In adjusted analysis, SSRI exposure remained associated with shorter time to first stool (β = −0.08, 95% CI −0.16 to −0.001, p = 0.035), corresponding to an approximate 17% reduction. The association was consistent across sensitivity analyses. Meconium-stained amniotic fluid was associated with shorter time to first stool among SSRI-exposed neonates but not in unexposed neonates. The overall model explained a limited proportion of variance. Conclusions Prenatal SSRI exposure was associated with modest but consistent reduction in time to first stool, without affecting time to first void. While the clinical significance remains uncertain, these findings suggest a potential influence of in utero SSRI exposure on early neonatal gastrointestinal adaptation, which may be influenced by intrapartum conditions.