Biomarkers of Inflammation and Their Association With the Severity and Onset of Preeclampsia: A Systematic Review

Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity and mortality, with systemic inflammation playing a central role in its pathogenesis. Despite extensive research on inflammatory biomarkers, inconsistencies persist regarding their associations with disease severity and onset. This systematic review synthesizes current evidence on the relationship between inflammatory biomarkers and PE, focusing on their diagnostic and prognostic potential. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, a comprehensive search was conducted across five databases (PubMed, Scopus, Web of Science, Embase, and CINAHL) to identify observational studies investigating inflammatory biomarkers in PE. Eligible studies included case-control, cross-sectional, and cohort designs with normotensive controls. Data extraction covered study characteristics, biomarker profiles, and clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. In total, 13 studies were included, predominantly from diverse geographical regions. Pro-inflammatory cytokines and acute-phase proteins (C-reactive protein) were consistently elevated in PE, with distinct profiles for early-onset (placental-driven inflammation) and late-onset (systemic inflammation) subtypes. Biomarkers such as neopterin and soluble urokinase-type plasminogen activator receptor showed promise in stratifying disease severity. Maternal-fetal inflammatory cascades were evident, with correlations between maternal biomarkers and adverse neonatal outcomes. However, heterogeneity in study designs, biomarker measurement timing, and inconsistent adjustments for confounders limited comparability. Quality assessment revealed seven low-risk and six moderate-risk studies, with no high-risk bias. Inflammatory biomarkers demonstrate significant associations with PE severity and onset, supporting their role in disease monitoring and risk stratification. However, methodological inconsistencies highlight the need for standardized protocols and larger, longitudinal studies to validate their clinical utility. Future research should integrate multi-omics approaches to refine biomarker panels and elucidate causal pathways, ultimately guiding targeted interventions.