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The Effect of Prenatal Antidepressant Exposure on Neonatal Adaptation: A Systematic Review and Meta-Analysis

Sophie Grigoriadis, MD, PhD, FRCPC; Emily H. VonderPorten, MPH; Lana Mamisashvili, MSW; Allison Eady, BA; George Tomlinson, PhD; Cindy-Lee Dennis, PhD; Gideon Koren, MD, FRCPC, FACMT; Meir Steiner, MD, PhD, FRCPC; Patricia Mousmanis, MD, CCFP, FCFP; Amy Cheung, MD, MSc, FRCPC; and Lori E. Ross, PhD

Published: April 15, 2013

Article Abstract

Objective: Conflicting reports on potential risks of antidepressant exposure during gestation for the infant have been reported in the literature. This systematic review and meta-analysis on immediate neonatal outcomes were conducted to clarify what, if any, risks are faced by infants exposed to antidepressants in utero. Subanalyses address known methodological limitations in the field.

Data Sources: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from their start dates to June 2010. Various combinations of keywords were utilized including, but not limited to, depressive/mood disorder, pregnancy/pregnancy trimesters, antidepressant drugs, and neonatal effects.

Study Selection: English language and cohort and case-control studies reporting on a cluster of signs defined as poor neonatal adaptation syndrome (PNAS) or individual clinical signs (respiratory distress and tremors) associated with pharmacologic treatment were selected. Of 3,074 abstracts reviewed, 735 articles were retrieved and 12 were included in this analysis.

Data Extraction: Two independent reviewers extracted data and assessed the quality of the articles.

Results: Twelve studies were retrieved that examined PNAS or the signs of respiratory distress and tremors in the infant. There was a significant association between exposure to antidepressants during pregnancy and overall occurrence of PNAS (odds ratio [OR] = 5.07; 95% CI, 3.25-7.90; P < .0001). Respiratory distress (OR = 2.20; 95% CI, 1.81-2.66; P < .0001) and tremors (OR = 7.89; 95% CI, 3.33-18.73; P < .0001) were also significantly associated with antidepressant exposure. For the respiratory outcome, studies using convenience samples had significantly higher ORs (Q1 = 5.4, P = .020). No differences were found in any other moderator analyses.

Conclusions: An increased risk of PNAS exists in infants exposed to antidepressant medication during pregnancy; respiratory distress and tremors also show associations. Neonatologists need to be prepared and updated in their management, and clinicians must inform their patients of this risk.

J Clin Psychiatry 2013;74(4):e309-e320

Submitted: June 21, 2012; accepted October 4, 2012 (doi:10.4088/JCP.12r07967).

Corresponding author: Sophie Grigoriadis, MD, PhD, Women’s Mood and Anxiety Clinic: Reproductive Transitions, Department of Psychiatry, FG 29, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada (

Volume: 74

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