Soluble thrombomodulin in preeclampsia: Systematic review and meta-analysis

Preeclampsia (PE) is a severe pregnancy complication associated with endothelial dysfunction. Soluble thrombomodulin (sTM) is a biomarker of endothelial injury, but its role in PE remains unclear. Although previous studies suggest elevated sTM levels in PE, inconsistencies in study designs and diagnostic criteria have led to conflicting findings. Our study addresses this gap through a systematic review and meta-analysis using standardized effect sizes and predefined severity groups to clarify the association between sTM and PE. This review followed the Cochrane Handbook and PRISMA guidelines and was registered in PROSPERO (CRD42023456919). A comprehensive search was conducted in MEDLINE/PubMed, EMBASE, and Web of Science for observational studies evaluating sTM levels in PE and normotensive controls. Eligible studies included case-control and cohort designs measuring sTM in plasma or serum. Two reviewers independently conducted data extraction and risk of bias assessment (Newcastle-Ottawa Scale). A random-effects meta-analysis estimated the Standardized Mean Difference (SMD) and 95 % confidence intervals (CI). Of 285 screened studies, 26 met inclusion criteria, and 20 were included in the meta-analysis. sTM levels were significantly higher in PE (SMD = 0.91, 95 % CI 0.3 to 1.53; I² = 94 %) with greater elevation in severe PE (SMD: 0.86, 95 % CI 0.55 to 1.16; I² = 50 %) than mild PE (SMD: 0.57, 95 % CI 0.08 to 1.06; I² = 82 %). High heterogeneity was observed, likely due to variations in inclusion criteria, measurement techniques, and diagnostic definitions. These findings support the potential of sTM as a biomarker for assessing PE severity. However, its clinical use remains limited by methodological heterogeneity and lack of standardized cutoff values. Further prospective studies are needed to validate its diagnostic and prognostic value and to enable its integration into clinical practice.