sFlt-1/PlGF Ratio: Impact on the Management of Patients With Suspected Pre-eclampsia

Study Overview
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Brief Summary
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Pre-eclampsia is a specific pathology of pregnancy classically associating arterial hypertension with proteinuria. Its prevalence in industrialized countries is 3 to 8% of pregnancies, which makes it a frequent pathology, and it is responsible for 30% of premature deliveries. The consequences of this pathology can be very serious for the mother:renal insufficiency, hepatic cytolysis, retro-capsular hematoma of the liver, convulsions, disseminated intravascular coagulation. Moreover, the consequences on the fetus and the pregnancy are just as serious: intrauterine growth retardation, induced prematurity, retroplacental hematoma, fetal death in utero. Pre-eclampsia therefore remains difficult to diagnose and to prognose. The diagnosis of pre-eclampsia based on blood pressure and proteinuria has a predictive value of 30% for adverse outcomes related to pre-eclampsia. In recent years, new biomarkers have been studied: PlGF, a placental growth factor, and sFlt-1, the free fraction of its membrane receptor.The pathophysiology and specificity of these biomarkers, but especially their ratio, has been widely studied and demonstrated in the diagnosis and prognosis of preeclampsia. Nevertheless, few studies have analyzed the impact of this report on the hospitalization of patients, except mainly a German study which showed a change in the decision to hospitalize in 16.9% of cases. On the other hand, no French study has been carried out on this subject. Finally, no professional recommendation fully integrates or clearly frames the use of the ratio in current practice. Its use therefore remains disparate between countries, but also within the same country, as in France, where few centers use it. The decision to hospitalize a patient with suspected preeclampsia depends on the organization of the health care system. It therefore seems interesting to analyze the precise impact on hospitalizations of the use of a diagnostic and prognostic tool such as the sFlt-1/PlGF ratio with the specificities of the French health system, which favors outpatient management.The study would evaluate the use of this promising tool in the daily management of parturients, paving the way for the development of simple recommendations applicable in the various French maternity hospitals. The hypothesis is that the use of the sFlt-1/PlGF ratio in patients with suspected pre-eclampsia would reduce the rate of hospitalization.

Official Title
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sFlt-1/PlGF Ratio: Impact on the Management of Patients With Suspected Pre-eclampsia

Conditions
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Pre-Eclampsia

Intervention / Treatment
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* Other: sFlt-1/PlGF ratio - Active Comparator: Standard
* Other: sFlt-1/PlGF ratio - Experimental: Biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant patient Affiliated to the Social Security Signature of informed consent Term > 24 week of amenorrhea and < 37 week of amenorrhea Presence of at least 2 of the following signs: de novo hypertension (Systolic Blood Pressure ≥ 140 mmHg and/or Diastolic Blood Pressure ≥ 90 mmHg) or worsening of pre-existing hypertension (increase of more than 10 mmHg in usual Systolic Blood Pressure and/or Diastolic Blood Pressure) De novo proteinuria onset (24h proteinuria ≥ 0.3 g/24h or proteinuria/creatinuria ratio ≥ 0.3) or worsening of pre-existing proteinuria Criteria for clinical suspicion of pre-eclampsia: epigastric pain, excessive edema, headache, visual disturbances, sudden weight gain (> 1kg/week in the 3rd trimester) Biological signs related to pre-eclampsia: low platelet count (thrombocytopenia < 150 G/L), liver cytolysis (AST and/or ALT AST greater than 2 times normal) Suspicion of intrauterine growth retardation on obstetrical ultrasound with no other cause found Exclusion Criteria: Minor patient Patient with poor clinical tolerance of hypertension and/or need for immediate introduction of intravenous antihypertensive therapy Patient with a specific complication of pre-eclampsia requiring immediate management at the time of inclusion: in utero fetal death, retroplacental hematoma, disseminated intravascular coagulation or emergency cesarean section. Vulnerable person requiring enhanced protection, i.e., relatively (or totally) unable to protect their own interests. Specifically, the person's power, intelligence, education, resources, strength, or other attributes necessary to protect his or her own interests may be inadequate (e.g., persons deprived of liberty, minors, persons under guardianship, persons with mental or emotional disabilities in the broadest sense of the word, illiterate persons, refugees and asylum seekers, alcoholics and drug addicts, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard<br>The monitoring criteria used will be the same as those usually used at the Nice University Hospital, according to the protocol of the department. For patients in the standard group, the biomarker results will be masked and then revealed afterwards for statistical analysis. | Other: sFlt-1/PlGF ratio - Active Comparator: Standard<br>* Blood test for biomarkers (sFlt-1/PlGF ratio) For patients in the standard group, the biomarker results will be masked and then revealed afterwards for statistical analysis. For the biomarkers group, the monitoring decision will be made based on the ratio calculation<br>|
| Experimental: Biomarkers<br>The monitoring decision will be made based on the ratio calculation: Ratio < 38: Classic monitoring with one prenatal visit per month 38 ≤ Ratio ≤ 85: Close outpatient monitoring Ratio > 85: Inpatient monitoring in Pathological Pregnancy | Other: sFlt-1/PlGF ratio - Experimental: Biomarkers<br>* Blood test for biomarkers (sFlt-1/PlGF ratio) For patients in the standard group, the biomarker results will be masked and then revealed afterwards for statistical analysis. For the biomarkers group, the monitoring decision will be made based on the ratio calculation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hospitalization rate | hospitalization rate for each group. | up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sFlt-1/PlGF ratio at inclusion and length of hospital stay | correlation between sFlt-1/PlGF ratio at inclusion and length of hospital stay | up to 4 months | 
| Complications specific to pre-eclampsia | occurrence of complications specific to pre-eclampsia (eclampsia, HELLP-syndrome, fetal death in utero...) | up to 4 months | 
| Pregnancy Outcome | Correlation of the sFlt-1/PlGF ratio at inclusion and its kinetics with pregnancy outcome (route of delivery and urgency criteria) | up to 4 months | 
| newborn health status at birth | Correlation of the sFlt-1/PlGF ratio at inclusion and its kinetics with newborn health status at birth (Apgar score and need for immediate pediatric management) | up to 4 months |