Multi-biomarker approaches to assessing preeclampsia risk and severity: The roles of vitamin d, inflammation, and oxidative stress

Preeclampsia is a complex pregnancy-related disorder characterized by heterogeneous clinical manifestations, making early risk identification and severity assessment challenging. Vitamin D dysregulation, systemic inflammation, and oxidative stress are implicated in its pathophysiology, but their combined clinical relevance remains uncertain. This narrative review aims to examine the roles of vitamin D, inflammatory biomarkers, and oxidative stress markers in assessing preeclampsia risk and severity, emphasizing the potential of multi-biomarker approaches. The review considers evidence concerning maternal vitamin D status, proinflammatory and anti-inflammatory mediators, oxidative damage, and antioxidant defenses. These interconnected pathways contribute to placental dysfunction, impaired vascular adaptation, and endothelial injury. Although individual biomarkers have been associated with preeclampsia occurrence, their relationships with disease severity and clinical deterioration remain inconsistent. Combining biomarkers representing distinct biological mechanisms may provide complementary information and improve risk stratification compared with single-marker assessment. However, evidence supporting their incremental predictive value beyond established clinical parameters and angiogenic biomarkers remains insufficient. Differences in study populations, gestational age, sampling procedures, and biomarker measurement methods further complicate clinical interpretation. Future prospective studies should incorporate longitudinal measurements, standardized severity definitions, and external validation of integrated prediction models. Multi-biomarker approaches offer a promising framework for comprehensive preeclampsia assessment, but their predictive accuracy and clinical utility require further validation before routine implementation.