Towards the Development of a Conceptual Framework of the Determinants of Pre-eclampsia: A Hierarchical Systematic Review of Biomarkers

Terteel Elawad¹, Hiten D Mistry^{1

2}, Mai-Lei Woo Kinshella³, Marianne Vidler³, Marie-Laure Volvert¹, Helen Elwell⁴, Veronique Filippi⁵, Kelly Pickerill³, Rachel Craik¹, Joel Singer⁶, Rosemary Townsend⁷, Hannah Blencowe⁵, Eleni Z Tsigas⁸, Jeffrey N Bone³, Peter von Dadelszen^{1

3}, Laura A Magee^{1

3}; PRECISE Network

Collaborators, Affiliations

Collaborators

PRECISE Network:
Umberto D'Alessandro, Anna Roca, Hawanatu Jah, Andrew Prentice, Melisa Martinez-Alvarez, Brahima Diallo, Abdul Sesay, Sambou Suso, Baboucarr Njie, Fatima Touray, Yahaya Idris, Fatoumata Kongira, Modou F S Ndure, Lawrence Gibba, Abdoulie Bah, Yorro Bah, Marleen Temmerman, Angela Koech, Patricia Okiro, Geoffrey Omuse, Grace Mwashigadi, Mary Goretti Amondi, Consolata Juma, Joseph Mutunga, Moses Mukhanya, Robin Okello, Onesmus Wanje, Isaac Mwaniki, Marvin Ochieng, Emily Mwadime, Esperança Sevene, Corssino Tchavana, Salesio Macuacua, Anifa Vala, Helena Boene, Lazaro Quimice, Sonia Maculuve, Inacio Mandomando, Peter von Dadelszen, Laura A Magee, Rachel Craik, Marie-Laure Volvert, Hiten Mistry, Thomas Mendy, Donna Russell, Prestige Tatenda Makanga, Liberty Makacha, Reason Mlambo, Lucilla Poston, Rachel Tribe, Sophie Moore, Tatiana Salisbury, Aris Papageorghiou, Alison Noble, Rachel Craik, Hannah Blencowe, Veronique Filippi, Joy Lawn, Matt Silver, Joseph Akuze, Ursula Gazeley, Judith Cartwright, Guy Whitley, Sanjeev Krishna, Marianne Vidler, Jing Li, Jeff Bone, Mai-Lei Woo Kinshella, Domena Tu, Ash Sandhu, Kelly Pickerill, Carla Carillho, Benjamin Barratt

Affiliations

¹ Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
² Department of Population Health Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
³ Department of Obstetrics and Gynaecology, BC Children's and Women's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
⁴ BMA Library, British Medical Association, London, UK.
⁵ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
⁶ School of Population and Public Health, Centre for Health Evaluation and Outcome Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
⁸ Preeclampsia Foundation, Melbourne, Florida, USA.

PMID: 40344291
DOI: 10.1111/1471-0528.18194

Review

Towards the Development of a Conceptual Framework of the Determinants of Pre-eclampsia: A Hierarchical Systematic Review of Biomarkers

Terteel Elawad et al. BJOG. 2025.

. 2025 May 8.

doi: 10.1111/1471-0528.18194. Online ahead of print.

Authors

Collaborators

PRECISE Network:
Umberto D'Alessandro, Anna Roca, Hawanatu Jah, Andrew Prentice, Melisa Martinez-Alvarez, Brahima Diallo, Abdul Sesay, Sambou Suso, Baboucarr Njie, Fatima Touray, Yahaya Idris, Fatoumata Kongira, Modou F S Ndure, Lawrence Gibba, Abdoulie Bah, Yorro Bah, Marleen Temmerman, Angela Koech, Patricia Okiro, Geoffrey Omuse, Grace Mwashigadi, Mary Goretti Amondi, Consolata Juma, Joseph Mutunga, Moses Mukhanya, Robin Okello, Onesmus Wanje, Isaac Mwaniki, Marvin Ochieng, Emily Mwadime, Esperança Sevene, Corssino Tchavana, Salesio Macuacua, Anifa Vala, Helena Boene, Lazaro Quimice, Sonia Maculuve, Inacio Mandomando, Peter von Dadelszen, Laura A Magee, Rachel Craik, Marie-Laure Volvert, Hiten Mistry, Thomas Mendy, Donna Russell, Prestige Tatenda Makanga, Liberty Makacha, Reason Mlambo, Lucilla Poston, Rachel Tribe, Sophie Moore, Tatiana Salisbury, Aris Papageorghiou, Alison Noble, Rachel Craik, Hannah Blencowe, Veronique Filippi, Joy Lawn, Matt Silver, Joseph Akuze, Ursula Gazeley, Judith Cartwright, Guy Whitley, Sanjeev Krishna, Marianne Vidler, Jing Li, Jeff Bone, Mai-Lei Woo Kinshella, Domena Tu, Ash Sandhu, Kelly Pickerill, Carla Carillho, Benjamin Barratt

Affiliations

¹ Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
² Department of Population Health Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
³ Department of Obstetrics and Gynaecology, BC Children's and Women's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
⁴ BMA Library, British Medical Association, London, UK.
⁵ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
⁶ School of Population and Public Health, Centre for Health Evaluation and Outcome Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
⁸ Preeclampsia Foundation, Melbourne, Florida, USA.

PMID: 40344291
DOI: 10.1111/1471-0528.18194

Abstract

Background: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. There are several determinants of individual pregnant women's risk of developing pre-eclampsia, including biomarkers and ultrasound markers.

Objective: A conceptual framework to collate and summarise the extensive body of literature on biomarkers (including ultrasound markers) associated with pre-eclampsia, through a hierarchical systematic literature review.

Search strategy: Medline, Embase, Health Technology Assessments, Database of Abstracts of Reviews of Effects, Cochrane Library were searched until April 2024.

Selection criteria: Reviews and cohort studies (> 100 participants) reporting biomarkers associated with pre-eclampsia were included.

Data collection and analysis: Studies were screened by title, then abstract and full text. Evidence was prioritised from umbrella reviews, followed by systematic reviews and then observational studies. Associations were assessed for strength of association and quality of evidence using GRADE.

Main results: The biomarker domain included 40 individual determinants of pre-eclampsia. Of these, there were 18 biomarkers with definite or probable associations based on moderate-strong quality evidence across markers of angiogenic imbalance, fetal-placental unit function, inflammatory and immune markers, and physiological markers. Vascular endothelial growth factor, human chorionic gonadotropin, inhibin-A, maternal serum placental protein-13, and interferon-gamma had definite associations based on high-quality evidence.

Conclusion: Biomarkers associated with the development of pre-eclampsia highlight the multi-factorial aetiology of the syndrome. The addition of biomarkers, including ultrasound, will optimise the prediction of pre-eclampsia and enable individualised risk stratification.

Keywords: Biomarkers; Conceptual framework; Pre‐eclampsia.

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References

1. M. A. Brown, L. A. Magee, L. C. Kenny, et al., “Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice,” Hypertension 72, no. 1 (2018): 24–43.
1. L. A. Magee, K. H. Nicolaides, and P. von Dadelszen, “Preeclampsia,” New England Journal of Medicine 386, no. 19 (2022): 1817–1832.
1. L. Bellamy, J. P. Casas, A. D. Hingorani, and D. J. Williams, “Pre‐Eclampsia and Risk of Cardiovascular Disease and Cancer in Later Life: Systematic Review and Meta‐Analysis,” BMJ 335, no. 7627 (2007): 974.
1. K. J. Chang, K. M. Seow, and K. H. Chen, “Preeclampsia: Recent Advances in Predicting, Preventing, and Managing the Maternal and Fetal Life‐Threatening Condition,” International Journal of Environmental Research and Public Health 20, no. 4 (2023): 2994.
1. M. Rybak‐Krzyszkowska, J. Staniczek, A. Kondracka, et al., “From Biomarkers to the Molecular Mechanism of Preeclampsia—A Comprehensive Literature Review,” International Journal of Molecular Sciences 24, no. 17 (2023): 13252.

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Towards the Development of a Conceptual Framework of the Determinants of Pre-eclampsia: A Hierarchical Systematic Review of Biomarkers

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Towards the Development of a Conceptual Framework of the Determinants of Pre-eclampsia: A Hierarchical Systematic Review of Biomarkers

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