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Impact of Antenatal Corticosteroids on Brain Function and Underlying Mechanisms in Preclinical Studies: Protocol for
Mauritz F Herselman1,2, Tara Hislop1,2, Sebastian D McBride3
1School of Pharmacy and Biomedical Science, University of Adelaide, Adelaide Health & Medical Sciences building, corner George St and North Terrace, Adelaide, SA, 5005, Australia, +61 883134158.
Insights
Antenatal corticosteroids (ACS) aid fetal lung development but may harm the brain. This review synthesizes preclinical evidence on how in utero ACS exposure impacts brain function and stress systems in mammals.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Antenatal corticosteroids (ACS) mature fetal lungs, reducing preterm birth complications.
- However, ACS exposure in utero has been linked to adverse long-term neurodevelopmental and stress regulatory impacts.
- Preclinical studies are crucial for understanding the mechanisms behind these effects.
Purpose of the Study:
- To systematically review evidence on how in utero ACS exposure affects brain function in nonhuman mammals.
- To investigate the underlying mechanisms, including impacts on the hypothalamic-pituitary-adrenal axis.
- To synthesize findings from preclinical mammalian models.
Main Methods:
- Systematic review of peer-reviewed primary studies.
- Inclusion of studies on nonhuman mammals exposed in utero to ACS in the second half of pregnancy.
- Analysis of brain function measures (e.g., learning, behavior) and neurobiological mechanisms (e.g., brain size, myelination, HPA axis).
Main Results:
- Over 56,000 records were initially screened, with over 40,000 excluded after title/abstract review.
- Data synthesis will include narrative review and potential dose-response meta-analysis.
- Searches will be updated to include literature up to the end of 2025, with publication planned for 2027.
Conclusions:
- This review will consolidate current knowledge on the neurodevelopmental effects of antenatal corticosteroids.
- Findings will guide future research, including the development of interventions to mitigate adverse brain impacts.
- Informs strategies to optimize the use of ACS in high-risk pregnancies.
Background:
Antenatal corticosteroid (ACS) treatment matures the fetal lung and reduces risks of neonatal morbidity and mortality in babies born preterm. However, ACS treatment also impacts the brain and stress regulatory systems, with increasing clinical evidence for adverse long-term impacts. Preclinical studies are important to investigate the mechanisms for these impacts.
Objective:
This systematic review aims to synthesize the best available evidence describing how in utero exposure to ACS affects brain function, the underlying mechanisms, and the hypothalamic-pituitary-adrenal axis in nonhuman mammalian species.
Methods:
This review will include peer-reviewed, primary studies that report measures of brain function (eg, learning, behavior) and the underlying mechanisms (eg, brain size, neuron number, myelination, hypothalamic-pituitary-adrenal axis function) in nonhuman mammals exposed in utero to ACS 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 searched PubMed, Embase, MEDLINE (Ovid), Web of Science, Scopus, and ProQuest for English language publications without date restrictions. Two independent reviewers will perform abstract screening, data extraction, and quality assessment. 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-analysis will be performed where at least three studies report the same outcome following in utero exposure to the same steroid. As of February 21, 2026, title and abstract screening were completed for 42,024 of 56,493 records, with 40,795 records excluded. Searches will be updated in June-July 2026 to include sources published to the end of 2025. Publication is planned for 2027.
Conclusions:
This review will inform future research including intervention studies to reduce the adverse effects of antenatal corticosteroids on the brain.
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