Integrating Social and Clinical Determinants of Pre-Eclampsia: A Hierarchical Systematic Review and Conceptual Framework for Prevention

Background: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality, with risk factors reported across a vast literature base fragmented between social and clinical factors. Objective: To develop a comprehensive conceptual framework of the strongest risk factors and their relationships contributing to pre-eclampsia incidence. Search Strategy: Medline, Embase, Health Technology Assessments and Database of Abstracts of Reviews of Effects, Cochrane Library were searched. Selection Criteria: Reviews, randomized controlled trials and cohort studies (> 1000 participants), reporting social and clinical factors associated with pre-eclampsia were included. Data Collection and Analysis: The strongest factors, defined as those with at least moderate strength of association and quality of evidence using GRADE, were compiled from our previously published individual frameworks to create a combined conceptual framework. Indirect associations were searched and the strongest indirect factors were added. Main Results: The conceptual framework integrated 35 social and clinical determinants of pre-eclampsia. Key modifiable factors included BMI, interlinked with chronic hypertension/elevated blood pressure in early pregnancy, type 2 diabetes mellitus, and obstructive sleep apnoea, as well as antenatal care attendance, interconnected with maternal/work stress and prenatal micronutrient supplementation. Other modifiable factors included smoking, antiphospholipid syndrome, infection, exposure to occupational hazards, distance to health facility, maternal heat exposure in early gestation, and UV-B exposure. Conclusion: There are strong social factors alongside clinical factors associated with pre-eclampsia incidence. Interwoven relationships between factors highlight the multifactorial aetiology of pre-eclampsia. Many determinants were potentially modifiable, which provides actionable intervention points for clinical care and public health strategies.