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

Abstract

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. To develop a comprehensive conceptual framework of the strongest risk factors and their relationships contributing to pre-eclampsia incidence. Medline, Embase, Health Technology Assessments and Database of Abstracts of Reviews of Effects, Cochrane Library were searched. Reviews, randomized controlled trials and cohort studies (> 1000 participants), reporting social and clinical factors associated with pre-eclampsia were included. 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. 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. 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.