The multi-modal architecture of pre-eclampsia in Sub-Saharan Africa: advancing biological understanding for enhanced risk stratification and precision care (360G-Wellcome-345729_Z_26_Z)

Pre-eclampsia is a leading cause of maternal and neonatal mortality in Sub- Saharan Africa (SSA), yet its underlying pathophysiology remains poorly understood. Consequently, no targeted treatments exist. Limited antenatal care, delayed diagnosis, and inequitable healthcare access further worsen outcomes. While epidemiological and heritability studies suggest a strong genetic component, adequately powered genomic studies are lacking. Despite the disproportionate burden, research has largely excluded women of African ancestry. Understanding the genetic basis of pre-eclampsia could uncover novel mechanisms, improving prevention, treatment, and risk stratification. However, genomic discovery studies must be integrated with scalable, affordable interventions for meaningful short-term clinical impact. This study will leverage CRADLE-SMART, a community-driven programme integrating a mobile-app- based clinical decision tool with novel point-of-care (POC) diagnostics, including the CRADLE Vital Signs Alert (Rapid), biomarker-based risk stratification, and AI-powered ultrasound. Specifically, it will: (i) Develop the CRADLE-SMART bundle as a risk stratification tool in Sub-Saharan Africa. (ii) Evaluate the predictive performance of the novel CRADLE-SMART risk stratification tool in Zambia and Sierra Leone. (iii) Investigate the genomic determinants of pre-eclampsia among women of African ancestry. Combining genomic research with practical, field-deployable diagnostics, this study aims to enhance biological understanding, improve risk stratification, and reduce maternal and neonatal mortality in SSA.