Soluble thrombomodulin in preeclampsia: Systematic review and meta-analysis

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-05-02 DOI:10.1016/j.cca.2025.120323

Jesiel Francisco de Jesus Fernandes Martins Lima , Thaíse Emilia Moreira da Silva , Ana Cristina dos Santos Lopes , Victor Antonio Ferreira Freire , Melina Barros-Pinheiro , Patrícia Nessralla Alpoim

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引用次数: 0

Abstract

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.

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可溶性血栓调节素在子痫前期：系统回顾和荟萃分析

子痫前期（PE）是一种与内皮功能障碍相关的严重妊娠并发症。可溶性血栓调节蛋白（sTM）是内皮损伤的生物标志物，但其在PE中的作用尚不清楚。尽管先前的研究表明PE中sTM水平升高，但研究设计和诊断标准的不一致导致了相互矛盾的结果。我们的研究通过系统回顾和荟萃分析解决了这一差距，使用标准化效应大小和预定义的严重程度组来澄清sTM和PE之间的关联。本综述遵循Cochrane手册和PRISMA指南，并在PROSPERO注册（CRD42023456919）。在MEDLINE/PubMed， EMBASE和Web of Science中进行了全面的搜索，以评估PE和正常对照组中sTM水平的观察性研究。符合条件的研究包括病例对照和队列设计，测量血浆或血清中的sTM。两名审稿人独立进行数据提取和偏倚风险评估（纽卡斯尔-渥太华量表）。随机效应荟萃分析估计标准化平均差（SMD）和95%置信区间（CI）。在285项筛选研究中，26项符合纳入标准，20项纳入meta分析。sTM水平显著高于PE (SMD = 0.91, 95% CI 0.3 ~ 1.53；I2 = 94%)，重度PE升高幅度更大(SMD: 0.86, 95% CI 0.55 ~ 1.16；I2 = 50%)比轻度PE (SMD: 0.57, 95% CI 0.08 ~ 1.06；i2 = 82%)。观察到高度异质性，可能是由于纳入标准、测量技术和诊断定义的差异。这些发现支持sTM作为评估PE严重程度的生物标志物的潜力。然而，其临床应用仍然受到方法学异质性和缺乏标准化临界值的限制。需要进一步的前瞻性研究来验证其诊断和预后价值，并使其融入临床实践。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.