Evaluation of sFlt-1/PlGF Ratio ,OPG and sEng as Predictive Biomarkers in the Diagnosis and Treatment Evaluation of Preeclampsia

Официальное название

Evaluation of sFlt-1/PlGF Ratio, Osteoprotegerin (OPG) and Soluble Endoglin (sEng) as Predictive Biomarkers in the Diagnosis and Treatment Evaluation of Preeclampsia

Обзор

his study investigates the effectiveness of three specific biological markers (biomarkers) in the blood-the sFlt-1/PlGF ratio, soluble endoglin (sEng), and osteoprotegerin (OPG)-to better diagnose and monitor preeclampsia. Preeclampsia is a serious pregnancy complication characterized by high blood pressure and potential organ damage that affects 2-8% of pregnancies worldwide

Подробное описание

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by newonset hypertension and proteinuria or other maternal organ dysfunction after 20 weeks of gestation. It affects 2-8% of pregnancies globally and remains a major contributor to maternal and perinatal morbidity and mortality The etiology is multifactorial, but placental dysfunction and abnormal angiogenesis are central to its pathogenesis. Given the limitations of current clinical indicators (e.g., blood pressure, proteinuria), there is growing interest in identifying predictive and diagnostic biomarkers to improve early detection, prognosis, and monitoring of therapeutic response. This study proposes to investigate three biomarkers: the sFlt-1/PlGF ratio, soluble endoglin (sEng), and osteoprotegerin (OPG), based on their roles in angiogenesis and endothelial dysfunction, which are hallmarks of preeclampsia

sFlt-1/PlGF Ratio Soluble fms-like tyrosine kinase-1 (sFlt-1) is an anti-angiogenic protein that binds to vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), preventing their interaction with endothelial receptors. The imbalance, especially elevated sFlt-1 and decreased PlGF, is characteristic of preeclampsia. Numerous studies, including the multicenter PROGNOSIS trial, have validated the sFlt-1/PlGF ratio as a strong predictor of preeclampsia. A ratio ≥85 is associated with a high risk of developing preeclampsia within two weeks, while ≤38 effectively rules it out .

Soluble Endoglin (sEng) Endoglin is a co-receptor for transforming growth factor-beta (TGF-β), involved in vascular development. Its soluble form (sEng) acts as a decoy receptor, inhibiting TGF-β signaling, contributing to endothelial dysfunction, a key feature of preeclampsia. sEng levels are elevated in the maternal circulation prior to clinical onset and correlate with disease severity.

Osteoprotegerin (OPG) OPG, a member of the TNF receptor superfamily, is primarily involved in bone metabolism but also plays a role in vascular biology. Some studies have reported altered OPG levels in preeclampsia, potentially reflecting vascular damage or endothelial activation . Its role remains less defined, but it may complement other angiogenic markers in profiling disease status.

Первичные конечные точки

• Serum sFlt-1 concentration [Срок оценки: At enrollment (20-36 weeks of gestation)]
• Serum PlGF concentration [Срок оценки: At enrollment (20-36 weeks of gestation)]
• sFlt-1/PlGF ratio [Срок оценки: At enrollment (20-36 weeks of gestation)]
• Serum Osteoprotegerin (OPG) concentration [Срок оценки: At enrollment (20-36 weeks of gestation)]
• Serum sENG(Souble Endoglin) concentration [Срок оценки: At enrollment (20-36 weeks of gestation)]

Критерии участия

IInclusion Criteria:

• Pregnant women between 20 and 36 weeks of gestation
• Age between 18 and 45 years
• Attending the antenatal clinic at the study site

Критерии исключения

• Chronic hypertension
• Renal disease
• Diabetes mellitus
• Multiple gestations
• Autoimmune disorders

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Ирак · 1 центр

• Bint Al Huda Maternity Hospital — Nasiriyah

Публикации

• Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S; International Society for the Study of Hypertension in Pregnancy (ISSHP). The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018 Jul;13:291-310. doi: 10.1016/j.preghy.2018.05.004. Epub 2018 May PMID 29803330
• Miller JJ, Higgins V, Melamed N, Hladunewich M, Ma L, Yip PM, Fu L. Clinical Validation of the sFlt-1:PlGF Ratio as a Biomarker for Preeclampsia Diagnosis in a High-Risk Obstetrics Unit. J Appl Lab Med. 2023 May 4;8(3):457-468. doi: 10.1093/jalm/jfad003. PMID 36869760
• Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838. PMID 26735990
• Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D'Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006 Jun;12(6):642-9. doi: 10.1038/nm1429. Epub 2006 Jun 4. PMID 16751767

Идентификаторы

NCT: NCT07349277 · 35918

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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