Diagnostic Value of sFlt-1/PlGF Ratio for the Etiology of Intra Uterine Growth Restriction - ANGIOPAG (ANGIOPAG)

Diagnostic Value of sFlt-1/PlGF Ratio for the Etiology of Intra Uterine Growth Restriction

The main aim of this project is to determine the Placental Growth Factor and Vascular Endothelial Growth Factor ratio's performance (sFlt-1/PlGF) for the etiological diagnosis of vascular Intrauterine growth restriction (IUGR) compared to a non-vascular IUGR.

Study Overview

• Status: Recruiting
• Conditions: Intrauterine Growth Restriction; Fetal Growth Restriction (FGR)
• Intervention / Treatment: Biological: Blood test at time of inclusion for sFlt-1/PlGF ratio; Biological: Follow-up blood test 2 to 4 weeks after inclusion; Diagnostic test: Placenta analysis for all included patients, even in case of normal birthweight

Detailed Description

Intra-uterine growth restriction is one of the most frequent cause of consultation in prenatal diagnosis centers. Suspected Intrauterine growth restriction (IUGR) concerns 5.4% of pregnancies. Prognosis and management of IUGR depends on its etiology. It has been estimated that 80 to 90% of IUGR have a vascular cause, 5-15% an infectious cause and 2 to 5% chromosomal or genetic cause. More recently, a meta-analysis has shown that among 874 IUGR fetuses for whom amniocentesis was performed, anomaly of caryotype or comparative genomic hybridization array was reported for 6%. In case of vascular IUGR, amniocentesis is not indicated and close surveillance of mother and fetus is organized.

The diagnosis of vascular IUGR is most often confirmed after birth with placental histology. Before birth, the diagnosis of vascular IUGR is presumptive, and based on gestational age at diagnosis, quantity of amniotic fluid, end dopplers of umbilical artery and uterine arteries. The argument considered as most specific of vascular IUGR is the doppler of uterine arteries, however it has been shown that sensitivity of this test is weak : abnormal uterine arteries is reported in only 40% of fetuses with vasculat IUGR according to placenta pathology.

Biochemical markers Placental Growth Factor and Vascular Endothelial Growth Factor (sFlt1 and PlGF) have shown their prognostic value on the occurrence of preeclampsia. They are both associated to the delay until occurrence of preeclampsia and to the delay before extraction in case of IUGR. As diagnostic tool in IUGR, only two studies have investigated their value : the PlGF/sFlt-1 ratio identified 7 patients among 10 with abnormal placental pathology, and low PlGF value is associated with abnormal placental pathology among 122 cases of IUGR, however this study did not specify sensitivity and specificity values. A reliable and reproductible marker that could orient practitioners towards the need to propose amniocentesis at diagnosis of IUGR is therefore important to develop.

The main objective of ANGIOPAG is to determine the sFlt-1/PlGF ratio's performance for the etiological diagnosis of vascular IUGR compared to a non-vascular IUGR.

To reach this goal, ANGIOPAG is a diagnostic, multicenter, non-randomized study. It will be performed on 152 pregnant women over 18 with a term between 22and 34 +6 Weeks of Gestation (WG), consulting in participating centers for IUGR. For the research, a blood test will be carried, at the inclusion and 2 to 4 weeks after, to determine sFLT-1 and PlGF. All included patients'placenta will be analyzed, even in case of a child normal birth weight.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeanne Sibiude, MD, PhD; Phone Number: 01 40 60 66 11; Email: jeanne.sibiude@aphp.fr

Study Locations

• France
  • Colombes, France, 92700
    • Recruiting
    • Hopital Louis Mourier
    • Contact: Jeanne Sibiude, MD, PhD; Phone Number: 01 40 60 66 11; Email: jeanne.sibiude@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• > 18 years old
• Singleton pregnancy
• Date of conception evaluated by ultrasound < 14 WG
• Consulting in one of the 3 participating centers for IUGR
• Estimated fetal weight < 5th centile (according to Hadlock 3 et CFEF)
• Between 22+0 WG et 34+6 WG

Exclusion Criteria:

• Major birth defect diagnosed at time of inclusion
• Abnormality of caryotype known at time of inclusion
• Confirmed preeclampsia at time of inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Patients consulting in one of the participating centers for intra uterine growth restriction.; All included patients

Biological: Blood test at time of inclusion for sFlt-1/PlGF ratio; As part of the research, a blood sample is taken to measure the sFLT-1 and PlGF ratio at the inclusion visit.; Biological: Follow-up blood test 2 to 4 weeks after inclusion; As part of the research, a blood sample is taken to measure the sFLT-1 and PlGF ratio at the follow-up visit (about 2-4 weeks after inclusion). This second sample is not mandatory for the evaluation of the study's main endpoint.; Diagnostic test: Placenta analysis for all included patients, even in case of normal birthweight; After delivery, the placenta of each included patient is sent to anatomo-pathology (even in case of normal weight of the baby at birth). An anatomopathologist referent, designated for the study in each center, performs an analysis (aware of the clinic but not of the sFLT-1/PlGF ratio results), according to the benchmark criteria grid. Local analysis will classify the placenta as "vascular IUGR" or "nonvascular IUGR".

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the PlGF / sFlt-1 ratio and placental lesions to confirm the diagnosis of vascular intrauterine growth retardation	The etiological diagnosis will be confirmed as vascular if characteristic lesions are identified on placental analysis. Lesions of maternal vascular malperfusion have been described and are those used in scientific literature. These characteristics are placental infarcts, decidual arteriopathy, and villous hypoplasia.	34+6 Weeks of Gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay between inclusion and birth	Delay between inclusion and birth	21 weeks after inclusion
Occurrence of preeclampsia	Occurrence of preeclampsia	21 weeks after inclusion
Gestational age at birth	Gestational age at birth	maximum 21 weeks after inclusion
Birth weight	Birth weight	maximum 21 weeks after inclusion
Newborn evaluation (presence of birth defects)	Newborn evaluation (presence of birth defects)	maximum 21 weeks after inclusion
Rate of transfers to intensive care unit	Rate of transfers to intensive care unit	maximum 21 weeks after inclusion
Rate of death of babies	Rate of death of babies	maximum 21 weeks after inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jeanne Sibiude, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 8, 2020
• Primary Completion (ANTICIPATED): January 29, 2022
• Study Completion (ANTICIPATED): January 29, 2022

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: November 25, 2021
• First Posted (ACTUAL): December 9, 2021

Study Record Updates

• Last Update Posted (ACTUAL): December 9, 2021
• Last Update Submitted That Met QC Criteria: November 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: IUGR; fetal growth restriction; sFlt1; PlGF; intrauterine growth restriction
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation
• Other Study ID Numbers: APHP190472; 2019-A01116-51 (REGISTRY: IDRCB)

Drug and device information, study documents

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