# Cortisol as a Mediator of Prenatal Distress and Difficult Infant Temperament: A Systematic Review and Meta‐Analysis Protocol

**Authors:** Ferdinand Sörensen, Emma Fransson, Alkistis Skalkidou, Ingeborg Krägeloh‐Mann, Birgit Derntl

PMC · DOI: 10.1002/hsr2.71309 · Health Science Reports · 2025-10-24

## TL;DR

This study aims to explore how cortisol might link prenatal maternal distress to difficult infant temperament, using a systematic review and meta-analysis.

## Contribution

The study introduces a systematic review protocol to investigate cortisol's mediating role in prenatal distress and infant temperament.

## Key findings

- Prenatal distress is linked to difficult infant temperament, but the biological mechanisms are unclear.
- Cortisol is a potential mediator, but evidence remains inconsistent.
- Subgroup analyses will help identify vulnerable populations affected by this association.

## Abstract

Exposure to prenatal distress is associated with a risk of developing difficult temperament in infants, an indicator for a higher likelihood of later adverse developmental outcomes, including behavioral and mental health problems. The underlying biological mechanisms of this association are still unclear, but many support the idea of fetal programming, which postulates the influence of environmental factors on the fetus during pregnancy. Evidence points to the role of cortisol as a mediator of stress, but the results are inconsistent. In this systematic review and meta‐analysis, the association between prenatal distress and difficult infant temperament will be assessed, focusing on cortisol exposure as a possible mediator and including subgroup analyses.

Literature research will be performed in PubMed, Web of Science, MEDLINE, PSYNDEX, APA PsycArticles, APA PsycInfo, and CINAHL. Inclusion criteria are the availability of (self‐) assessment of maternal prenatal distress, maternal prenatal cortisol levels, and (parental) assessment of difficult infant temperament up to the age of 2 years. Screening and selection of peer‐reviewed English (or German) articles and assessment of article quality will be done by two independent reviewers, with a third one included in the case of disagreement. Effect sizes will be extracted and subgroup analyses will be performed not only for covariables but also for the methods of assessing prenatal distress, cortisol, and temperament. This protocol follows the PRISMA‐P checklist.

This systematic review and meta‐analysis will contribute to the ongoing discussion of whether and how cortisol mediates the association between prenatal maternal distress and difficult infant temperament. Identifying sensitive subgroups is an integral part of this study, as results might guide further research to vulnerable population groups.

## Linked entities

- **Chemicals:** cortisol (PubChem CID 5754)

## Full-text entities

- **Diseases:** maternal distress (MESH:D012128), behavioral and mental health problems (MESH:D000076082)
- **Chemicals:** Cortisol (MESH:D006854)

## Full text

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## Figures

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## References

77 references — full list in the complete paper: https://tomesphere.com/paper/PMC12550403/full.md

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Source: https://tomesphere.com/paper/PMC12550403