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

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

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

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Gestational Hypertension; Hypertensive Disorders of Pregnancy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Ammar Jassim Abed, MSc; Phone Number: +9647809561105; Email: ammar.jassim11@gmail.com

Study Locations

• Iraq
  • Dhi Qar
    • Nasiriyah, Dhi Qar, Iraq, 64001
      • Recruiting
      • Bint Al Huda Maternity Hospital
      • Contact: Ammar Jassim Abed; Phone Number: 9647809561105; Email: ammar.jassim11@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

he study population will include pregnant women aged 18-45 years, between 20 and 36 weeks of gestation, attending the antenatal clinic at the study site. Participants will be divided into three groups:

Pregnant women diagnosed with preeclampsia who have not yet received antihypertensive treatment.

Pregnant women diagnosed with preeclampsia who are receiving antihypertensive treatment.

Healthy pregnant women serving as control subjects.

Exclusion criteria include pre-existing chronic hypertension, renal disease, diabetes mellitus, multiple gestations, or autoimmune disorders.

All participants will provide informed consent before enrollment. Blood samples will be collected for biomarker analysis (sFlt-1, PlGF, soluble endoglin, and osteoprotegerin). This population has been selected to allow comparison of biomarker levels in different clinical scenarios and to evaluate their

Description

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Preeclampsia - No Antihypertensive Treatment; This group includes pregnant women diagnosed with preeclampsia. Blood samples are collected at the time of diagnosis before starting any antihypertensive treatment. All participants will receive standard clinical care after sample collection. Samples will be processed, aliquoted, and stored at -80°C for biomarker analysis (sFlt-1, PlGF, soluble endoglin, and osteoprotegerin).
Preeclampsia - With Antihypertensive Treatment; is group includes pregnant women diagnosed with preeclampsia who are receiving standard antihypertensive therapy as part of their clinical care. Blood samples (5 mL) will be collected for measurement of biomarkers (sFlt-1, PlGF, sEng, OPG). Samples will be processed, aliquoted, and stored at -80°C. Clinical parameters and treatment details will also be recorded for analysi
Healthy Pregnant Controls; his group includes healthy pregnant women without preeclampsia. Blood samples (5 mL) will be collected to serve as controls for biomarker analysis. Samples will be processed, aliquoted, and stored at -80°C. Participants will receive routine prenatal care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum sFlt-1 concentration	Measurement of serum sFlt-1 levels in maternal serum using ELISA	At enrollment (20-36 weeks of gestation)
Serum PlGF concentration	Measurement of serum placental growth factor (PlGF) levels in maternal serum using ELISA.	At enrollment (20-36 weeks of gestation)
sFlt-1/PlGF ratio	Calculated ratio of serum sFlt-1 to serum PlGF concentrations	At enrollment (20-36 weeks of gestation)
Serum Osteoprotegerin (OPG) concentration	Measurement of serum osteoprotegerin (OPG) levels in maternal serum using ELISA.	At enrollment (20-36 weeks of gestation)
Serum sENG(Souble Endoglin) concentration	Measurement of serum soluble endoglin (sENG) levels in maternal serum using ELISA.	At enrollment (20-36 weeks of gestation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined biomarker panel for early detection and monitoring of preeclampsia.	Analysis of the combined levels of sFlt-1, PlGF, sEng, and OPG to assess the accuracy of a multi-biomarker panel for early detection of preeclampsia and monitoring the effectiveness of treatment interventions.	From diagnosis until delivery.

Collaborators and Investigators

• Sponsor: Ammar Jassim Abed

Publications and helpful links

General Publications

• 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.
• 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 24. No abstract available.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Angiogenesis; Preeclampsia; sFlt-1/PlGF ratio; methyldopa; Soluble Endoglin (sEng); Osteoprotegerin (OPG); Placental Dysfunction
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: 35918

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Yes - De-identified individual participant data (IPD) will be available upon reasonable request to qualified researchers. Data will include biomarker measurements (sFlt-1, PlGF, sEng, OPG) and relevant clinical parameters. Requests will be reviewed by the principal investigator, and shared under a data use agreement ensuring confidentiality. Data will be available 12 months after publication of the study results.
• IPD Sharing Time Frame: De-identified individual participant data (IPD) will be made available to qualified researchers upon reasonable request. Supporting information to be shared includes the study protocol, statistical analysis plan (SAP), and analytic code. Data will be provided in an anonymized format, with requests reviewed by the principal investigator and shared under a data use agreement ensuring confidentiality. Data will be available 12 months after publication of the study results.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No