Maternal-Fetal Endocrine Interface: A Systematic Review of the Clinicopathological Assessment of Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Pregnancy Complications
Background: The hypothalamic-pituitary-adrenal (HPA) axis played a critical role in balancing maternal stress responses during pregnancy. This systematic review aimed to evaluate the dysregulation of the HPA axis and its link to pregnancy complications. Methods: A systematic review was carried ou...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
ziauddin University
2025-04-01
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| Series: | Pakistan Journal of Medicine and Dentistry |
| Subjects: | |
| Online Access: | https://ojs.zu.edu.pk/pjmd/article/view/3641 |
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| Summary: | Background: The hypothalamic-pituitary-adrenal (HPA) axis played a critical role in balancing maternal stress responses during pregnancy. This systematic review aimed to evaluate the dysregulation of the HPA axis and its link to pregnancy complications.
Methods: A systematic review was carried out by searching PubMed, Scopus, and Web of Science while following PRISMA 2020 guidelines to analyze studies from 2010 to 2024. Studies that assessed the maternal HPA axis biomarkers (e.g., cortisol, 11β-HSD2) and their correlations with pregnancy results were included. Studies excluding direct HPA axis assessment, review articles, non-pregnant individuals, or those with insufficient sample sizes or methodological flaws were excluded. QUADAS-2 tool determined risk of bias, and GRADE criteria evaluated the evidence quality.
Results: An initial search identified 85 articles, of which 15 met the inclusion criteria. The results were synthesized through a systematic review of studies, with data extraction from cohort, observational and interventional studies. The sample size among studies ranged from 2 to 248 participants, with a total of around 912 individuals included. The study found that maternal stress and dysregulated HPA axis function were associated with altered cortisol patterns, decreased placental 11β-HSD2 expression, and increased fetal cortisol exposure. These changes were linked to pregnancy complications, including impaired fetal development and long-term neurodevelopmental effects. Furthermore, mindfulness and cognitive behavioural therapy interventions were shown to improve HPA axis regulation and reduce maternal stress.
Discussion: Maternal stress dysregulated the HPA axis, hence impacting the pregnancy outcomes and fetal-development. Standardized methodologies and future research on genetic and epigenetic influences were required to enhance intervention strategies. The evidence is limited by high variability in study designs and moderate to high risk of bias, impacting the reliability of the findings.
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| ISSN: | 2313-7371 2308-2593 |