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

Assistance Publique - Hôpitaux de Paris

Status: Unknown

Conditions: Intrauterine Growth Restriction; Fetal Growth Restriction (FGR)

Treatments: Biological: Follow-up blood test 2 to 4 weeks after inclusion; Biological: Blood test at time of inclusion for sFlt-1/PlGF ratio; Diagnostic Test: Placenta analysis for all included patients, even in case of normal birthweight

Study type: Interventional

Funder types: Other

Identifiers

NCT05151289

APHP190472

2019-A01116-51 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 152 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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152 participants in 1 patient group

Patients consulting in one of the participating centers for intra uterine growth restriction.

Experimental group

Description:

All included patients

Treatment:

Diagnostic Test: Placenta analysis for all included patients, even in case of normal birthweight

Biological: Follow-up blood test 2 to 4 weeks after inclusion

Biological: Blood test at time of inclusion for sFlt-1/PlGF ratio