Associations Between Prenatal Exposure to Serotonergic Medications and Biobehavioral Stress Regulation: Protocol for a Systematic Review and Meta-analysis

Enav Z Zusman; Alekhya Lavu; Colleen Pawliuk; Jodi Pawluski; Sarah M Hutchison; Robert W Platt; Tim F Oberlander

doi:10.2196/33363

Associations Between Prenatal Exposure to Serotonergic Medications and Biobehavioral Stress Regulation: Protocol for a Systematic Review and Meta-analysis

JMIR Res Protoc. 2022 Mar 28;11(3):e33363. doi: 10.2196/33363.

Authors

Enav Z Zusman^{1

2

3}, Alekhya Lavu⁴, Colleen Pawliuk¹, Jodi Pawluski⁵, Sarah M Hutchison^{1

3}, Robert W Platt^{6

7

8}, Tim F Oberlander^{1

9}

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
² Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada.
³ British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
⁴ College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
⁵ Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, F-35000, Rennes, France.
⁶ Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.
⁷ Department of Pediatrics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
⁸ Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
⁹ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.

PMID: 35343913
PMCID: PMC9002587
DOI: 10.2196/33363

Abstract

Background: Up to 20% of mothers experience antenatal depression and approximately 30% of these women are treated with serotonergic psychotropic pharmacological therapy during pregnancy. Serotonergic antidepressants readily cross the placenta and the fetal blood-brain barrier, altering central synaptic serotonin signaling and potentially altering serotonin levels in the developing fetal brain.

Objective: The aim of this study is to assess the impact of prenatal exposure to serotonergic antidepressants, accounting for maternal mood disturbances, on markers of stress regulation during childhood.

Methods: We will follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and will search MEDLINE, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov for full-length studies that assessed physiological (eg, cortisol level, heart rate variability, salivary amylase, pupillary size, C-reactive protein) indices of stress regulation in children of pregnant people who were treated with a serotonergic antidepressant at any point during pregnancy. We will assess the quality of observational studies using the Newcastle-Ottawa Scale and the quality of experimental studies using the Cochrane risk-of-bias tool. When possible, we will conduct a random-effects meta-analysis. If meta-analysis is not possible, we will conduct a narrative review. If a sufficient number of studies are found, we will perform subgroup analysis and assess outcomes measured by drug class, dose, trimester of exposure, and child's age and gender.

Results: We registered our review protocol with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021275750), completed the literature search, and initiated title and abstract review in August 2021. We expect to finalize this review by April 2022.

Conclusions: Findings should identify the impact of prenatal antidepressant effects on stress regulation and distinguish it from the impact of prenatal exposure to maternal mood disturbances. This review should inform decisions about serotonergic antidepressant use during pregnancy.

Trial registration: PROSPERO CRD42021275750; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=275750.

International registered report identifier (irrid): PRR1-10.2196/33363.

Keywords: antidepressants; meta-analysis; pregnancy; serotonergic medications; stress regulation; systematic review.

©Enav Z Zusman, Alekhya Lavu, Colleen Pawliuk, Jodi Pawluski, Sarah M Hutchison, Robert W Platt, Tim F Oberlander. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.03.2022.