Accepted for/Published in: JMIR Research Protocols
Date Submitted: Sep 21, 2025
Open Peer Review Period: Sep 21, 2025 - Nov 16, 2025
Date Accepted: Feb 26, 2026
(closed for review but you can still tweet)
Impact of antenatal corticosteroids on brain function and underlying mechanisms in preclinical studies: a systematic review protocol.
ABSTRACT
Background:
Antenatal treatment with corticosteroids (ACS) matures the fetal lung and reduces risks of neonatal morbidity and mortality in babies born preterm. However, ACS also impact the brain, with increasing clinical evidence for adverse long-term impacts. Preclinical studies are important to determine the mechanistic basis for impacts of ACS on the brain.
Objective:
The primary objective of this systematic review is to synthesize the best available evidence describing how in utero exposure to exogenous corticosteroids affect brain function and the underlying mechanisms in non-human mammalian species.
Methods:
This review will include peer-reviewed, primary studies that report measures of brain function (e.g. learning, behavior) and the underlying mechanisms (e.g. brain size, neuron number, myelination, hypothalamic-pituitary-adrenal axis function) in non-human mammalian individuals exposed in utero to exogenous corticosteroids in the second half of pregnancy, in comparison to unexposed individuals. Initial search terms include (corticosteroid* OR glucocorticoid*) AND (antenatal OR fetal* OR pregnan*) AND (brain OR neurodevelopment*). We will search PubMed, EMBASE, Medline (Ovid), Web of Science, Scopus and ProQuest. There will be no restrictions on publication date, and language will be restricted to English. Abstract screening, data extraction and quality assessment will be conducted by two independent reviewers. Antenatal corticosteroid treatment information, study design, methods and outcomes will be reported for each study.
Results:
A narrative synthesis will be presented following standard guidelines. A dose-response meta-analyses will be performed where at least three studies report the same outcome following in utero exposure to the same steroid.
Conclusions:
This review will inform future research including intervention studies to reduce the adverse effects of antenatal corticosteroids on the brain. Clinical Trial: PROSPERO 2025 CRD420251116681; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251116681
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