Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing. Objective: A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks. Methods: MEDLINE, Web of Science, and Embase were searched from inception to January 2021. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. English-language observational studies reporting on acute postpartum outcomes following late in utero exposure to SSRIs or SSRIs/venlafaxine were evaluated. Results: Of 2,269 citations reviewed, 79 studies were assessed for eligibility; 13 were included in the qualitative analysis of the literature, which allowed us to identify 26 signs. A meta-analysis was run separately for studies on SSRI exposure (n = 3) and those on SSRI/venlafaxine exposure (n = 6). Hypoglycemia was identified as a withdrawal sign based on the SSRI studies. Tremors, hypotonia, tachycardia, rapid breathing, respiratory distress, and hypertonia were identified as withdrawal signs based on the SSRI/venlafaxine studies. Conclusions: The present work provides a framework for the identification of neonatal SSRI withdrawal syndrome. Tapering and discontinuation of antidepressant drugs before and during the early phase of pregnancy are worth attempting to prevent the occurrence of this syndrome.