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

Author:

Zusman Enav ZORCID,Lavu AlekhyaORCID,Pawliuk ColleenORCID,Pawluski JodiORCID,Hutchison Sarah MORCID,Platt Robert WORCID,Oberlander Tim FORCID

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.

CLINICALTRIAL

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

INTERNATIONAL REGISTERED REPORT

PRR1-10.2196/33363

Publisher

JMIR Publications Inc.

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