Molecular Subtypes of Preeclampsia and the Emergence of Precision Obstetric Phenotyping: A Systematic Review of Transcriptomic, Multiomic, and Clinical Integration Frameworks

Abstract The last decade has brought an unexpected shift in how preeclampsia is understood, and yet the literature remains scattered across narrow molecular silos. This review arose from the sense that the field was, paradoxically, rich in data but poor in synthesis. We searched major biomedical databases without date limits and assessed eligible studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidance, retaining 33 investigations that offered transcriptomic, proteomic, metabolomic, or epigenomic insight into the condition. Although these studies varied widely in design and intent, a surprisingly coherent picture emerged when their findings were allowed to speak to one another rather than remain isolated. Distinct molecular constellations – metabolic, inflammatory–immune, vascular–angiogenic, mitochondrial–oxidative, and endocrine–trophoblast – recaptured the clinical heterogeneity that has long troubled conventional classifications. Several multiomic studies pushed this further, showing that integrated models can anticipate disease weeks before symptoms arise, especially when computational clustering is paired with maternal clinical data. The evidence, while uneven in places and occasionally limited by cohort size or analytical inconsistency, consistently pointed toward a more precise taxonomy of preeclampsia than current diagnostic criteria allow. This review attempts to articulate that emerging structure and to outline how these molecular signatures might inform individualized prevention strategies – aspirin responsiveness, metabolic modulation, or mitochondrial support – rather than one-size-fits-all management. The outlook is cautiously optimistic: with stronger cross-study harmonization and prospective validation, molecular subtyping could reshape both antenatal risk assessment and the broader philosophy of obstetric care.