sFlt-1:PlGF Ratio in Diagnosing Superimposed Preeclampsia

November 11, 2020 updated by: University of Tennessee

The Utility of the sFlt-1/PlGF Ratio in Diagnosing Superimposed Preeclampsia and Predicting Adverse Outcomes in Subjects With Chronic Hypertension

Preeclampsia: associated with poor placentation, incomplete uteroplacental spiral arteries remodeling. Result: ischemia, re-perfusion injury, oxidative stress.

A low-grade systemic inflammatory response is more pronounced in preeclampsia. This results in an imbalance between maternal circulating pro-angiogenic (PlGF & VEGF) & anti-angiogenic factors (sFlt-1).

PlGF & VEGF function as vasodilators & preserve structure & function of glomerular endothelium. sFlt-1 blocks these actions, resulting in hypertension, endothelial dysfunction & nephropathy.

Various stressors, including hypoxia, villous crowding, angiotensin II, & oxidative stress are associated with preeclampsia & mediate secretion of soluble vascular growth factor 1 (sVEGFR-1 or sFlt-1) by GADD45 (Growth Arrest and DNA Damage-45). GADD45 is one of a family of stress-induced genes sFlt-1 releases into maternal circulation. Excess sFlt-1 leads to endothelial dysfunction, hypertension & proteinuria.

Exogenously administered sFlt-1 results in syndrome of nephrotic range proteinuria, hypertension, and glomerular endotheliosis in animal models.

Women with preeclampsia tend to have higher sFlt-1 & lower PlGF, resulting in an increased ratio (sFlt-1:PlGF). The difference is greater in women who develop early-onset preeclampsia (before 34 wks gestation).

Verlohren, et al., showed an increased sFlt-1/PlGF ratio in patients with preeclampsia as compared to controls & patients with chronic/gestational hypertension.

Other work has examined the longitudinal changes in the individual values of sFlt-1 & PlGF over the course of the pregnancy, as well as the ratio.

Given the low prevalence of preeclampsia in the population, the positive predictive value remained low, however the negative predictive value approached 97% late in gestation. This suggests that the utility of the sFlt-1/PlGF may be in its ability to rule out preeclampsia.

More recently the PROGNOSIS study was designed to investigate the value of the sFlt-1/PlGF ratio for the prediction of the presence or absence of preeclampsia in the short term & found that a cutoff point of 38 for the sFlt-1/PlGF ratio is useful for predicting the short-term absence of preeclampsia in women with suspected disease (Negative predictive value 99.3% for ruling out preeclampsia within 1 week).

Hypothesis: In women with chronic hypertension, the sFlt-1/PlGF ratio will better predict the development of superimposed preeclampsia than clinical criteria alone.

Study Overview

Status

Completed

Conditions

Detailed Description

Subjects with a diagnosis of chronic hypertension made prenatally or in the first 20 weeks of pregnancy (+/- medical therapy). The clinical diagnosis of preeclampsia will follow the current criteria outlined by ACOG (American College of Obstetricians & Gynecologists) 10.

Study/Project Procedures:

  • Blood draw at the time of initial presentation at the time of a clinically indicated blood draw (10cc maternal blood via venipuncture)
  • Blood draw at 2-7 days after initial presentation if undelivered at the time of a clinically indicated blood draw(10 cc maternal blood via venipuncture)
  • Laboratory analysis will be performed in batches after all clinical history, clinically indicated laboratory information, delivery information, and clinical outcomes recorded for sFlt-1 level, PlGF level, and the sFlt-1/PlGF ratio (not part of routine care and will be performed for research purposes only at the cost of the investigators).
  • Urine protein creatinine ratio performed as clinically indicated (will not be altered for research purposes)
  • Maternal CBC (Complete Blood Count), CMP (Complete Metabolic Profile), LDH (Lactate dehydrogenase), Uric acid as indicated clinically (will not be altered for research purposes)
  • Ultrasound performed by the investigators for research purposes only evaluating the uterine artery Doppler, middle cerebral artery Doppler, umbilical artery Doppler, estimated fetal weight, and amniotic fluid volume on a weekly basis from the time of enrollment until delivery.
  • Medical record abstraction of medical history, laboratory and clinical findings for both the mother and fetus.

Study Type

Observational

Enrollment (Actual)

87

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Regional One Health Center for High Risk Pregnancies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

150 pregnant subjects and their respective fetuses (total 300 subjects)

Prospective cohort:

  • Group 1: elevated sFlt-1/PlGF ratio;
  • Group 2: normal sFlt-1/PlGF ratio.

Description

Inclusion Criteria:

  • Gestational age at enrollment: 20 0/7 weeks to 38 6/7 weeks gestation Pregnant women aged 14 to 45 years
  • Presenting for admission for suspected superimposed preeclampsia
  • Diagnosis of chronic hypertension made prenatally or in the first 20 weeks of pregnancy (+/- medical therapy)
  • The clinical diagnosis of preeclampsia will follow the current criteria outlined by ACOG 10.

Exclusion Criteria:

  • Age 45 years;
  • Gestational age 19 6/7 weeks or less or 39 weeks or more ;
  • Multiple gestations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Group 1
elevated sFlt-1/PlGF ratio
Group 2
normal sFlt-1/PlGF ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The diagnosis rate of superimposed preeclampsia for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: From 20 0/7 weeks through 38 6/7 weeks.
result at the point of enrollment; compared to the ratio result at 2-7 days post enrollment
From 20 0/7 weeks through 38 6/7 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The diagnosis rate of Maternal morbidity HELLP syndrome for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of Eclampsia for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of Pulmonary edema for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of DIC (Disseminated Intravascular Coagulation) for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of Liver hematoma/rupture for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of Stroke for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation
The diagnosis rate of Death for gestations of 20 0/7 weeks through 38 6/7 as evidenced by the degree of change in the 'sFlt-1/PlGF ratio'
Time Frame: between 20 0/7 weeks to 38 6/7 weeks gestation
result at the point of enrollment; compared to the ratio result at 2-7 days post
between 20 0/7 weeks to 38 6/7 weeks gestation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Giancarlo Mari, M.D., OB/GYN, MFM

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

June 30, 2020

Study Completion (Actual)

June 30, 2020

Study Registration Dates

First Submitted

February 6, 2018

First Submitted That Met QC Criteria

February 20, 2018

First Posted (Actual)

February 22, 2018

Study Record Updates

Last Update Posted (Actual)

November 13, 2020

Last Update Submitted That Met QC Criteria

November 11, 2020

Last Verified

January 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • 16-04377-XP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Preeclampsia

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