EG-VEGF : Potential Marker of Pre-eclampsia and / or Intrauterine Growth Restriction (EGEVE)

EG-VEGF (Endocrine Gland-derived Vascular Endothelial Growth Factor) in Normal and Pathological Pregnancies: Potential Marker of Pre-eclampsia and / or Intrauterine Growth Restriction

The purpose of this study is to assess the potential prognostic value of seric concentrations of EG-VEGF for Pre-eclampsia and/or intrauterine growth restriction and will allow checking whether plasma levels of EG-VEGF at 14-18 weeks of gestation could be proposed as prognostic marker for preeclampsia.

Study Overview

• Status: Completed
• Conditions: Pre-eclampsia; Intra-uterine Growth Retardation
• Intervention / Treatment: Other: blood sample and doppler Ultrasound of uterine arteries

Detailed Description

Successful human placentation depends on adequate transformation of the uteroplacental vasculature by extravillous trophoblast (EVT) following proliferation, migration, and invasion of these cells into the maternal decidua. This process of vascular remodelling rises to a peak by the end of the first trimester and declines rapidly thereafter. Poor invasion can lead to the development of pathological condition such as Pre-eclampsia (PE) and intrauterine growth restriction (IUGR). PE affects 5-6 % of pregnancies in France and causes the death of ten or so women per year. Our research project is dedicated to the comprehension of the mechanisms underlying the development of PE and to the search of gold prognostic marker of this pathology. We were particularly interested in the study of the new angiogenic factor, EG-VEGF, recently reported as new factor specific to endocrine glands including the placenta. In recent results obtained by our team, we have shown that i) placental EG-VEGF showed a peak of expression just before the establishment of the foeto-maternal circulation ii) EG-VEGF receptors, PKR1 and PKR2 were also expressed during the first trimester of pregnancy and iii) EG-VEGF expression and that of its receptor PKR1 were up-regulated by hypoxia. In our last publication "under press in JCMM" we have shown that EG-VEGF inhibits EVT migration and invasion. More importantly, we have succeeded to measure EG-VEGF circulating levels in non pregnant and in pregnant women at the three trimesters of pregnancy and showed that its highest levels (5 times the non pregnant levels) were found during the first trimester of pregnancy with a significant decrease thereafter. Furthermore, on a cohort of 19 PE patient and 21 age matched controls, we have observed a significant increase in EG-VEGF levels in the PE group. Therefore we hypothesize that EG-VEGF could play an important role in human placentation and that a persistence in its expression over the first trimester of pregnancy may contribute to the development of PE.

Based on the Doppler analysis method for the assessment of uterine artery transformation by the end of 1st trimester, we propose to search for a correlation between the circulating levels of the new angiogenic factor EG-VEGF in the sera of pregnant woman between 14 to 18 WG, and the development of PE and/or IUGR. Doppler ultrasonography is a predictive method of the pregnancy outcome at the time of the development of the disease (1st to 2nd trimester), before threatening symptoms launch (end of the 2nd to the 3rd trimester). In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation as result of trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels by the end of first trimester of pregnancy. Therefore, the present study will also allow the search for a negative correlation between the level of uterine artery transformation and the level of EG-VEGF. The study will be conducted in collaboration with the Clinical centre of the Grenoble CHU Hospital (Dr JL. Cracowski). In this study we plan to include 500 pregnant pregnant women. Patients will be recruited at the time of their first ultrasonography between 11 and 13 WG and included in the study between 14 and 18 WG. For each patient a blood sample will be taken for the measurement of circulating EG-VEGF and Doppler analysis for uterine artery transformation will be performed. These results will provide information concerning the potential prognostic value of seric concentrations of EG-VEGF for PE and/or IUGR and will allow checking whether plasma levels of EG-VEGF at 14-18 weeks of gestation could be proposed as prognostic marker for preeclampsia.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Isere
    • Grenoble, Isere, France, 38043
      • Clinical investigation center of the Grenoble University Hospital

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:

• Women older than 17 years old
• All pregnant patients enrolled before 14 SG and with singleton, irrespectively of their parity
• Pregnant woman living in the Grenoble area
• Women accepting, the participation to the study.

Exclusion Criteria:

• Inability to understand the project
• Persons deprived of their liberty by judicial or administrative decisions
• Person under legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pregnent women with blood sample	Other: blood sample and doppler Ultrasound of uterine arteries; 36 ml of blood samples (serum and plasma) will be collected; After a bed rest supine for 15 minutes, ultrasound Doppler from each of the uterine arteries will be performed to search for Notch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of the circulating levels of EG-VEGF in the sera of pregnant woman between 14 and 18 WG	Measure the circulating levels of the new angiogenic factor EG-VEGF in the sera of pregnant woman between 14 and 18 WG to determine whether EG-VEGF could represent a prognostic marker for the development of PE and/or IUGR	Between 14 and 18 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the level of uterine artery transformation and the level of EG-VEGF.	Correlation between the level of EG-VEGF and the level of uterine artery transformation evaluated by Doppler ultrasound.	Between 14 and 18 week of gestation
Measure the circulating levels of other pro and/or anti-angiogenic factors	Measure the circulating levels of other pro and/or anti-angiogenic factors that could represent alternative biomarkers in the development of placental pathologies of vascular origin. As candidates, we will measure the soluble receptor of VEGF (s-flt) and Bone morphogenetic protein-9 (BMP9)	Between 14 and 18 week of gestation
Measure the circulating levels of the new angiogenic factor EG-VEGF	Measure the circulating levels of the new angiogenic factor EG-VEGF in the sera of pregnant woman between 14 and 18 WG to determine whether EG-VEGF could represent a prognostic marker for the development of PE.	Between 14 and 18 weeks of gestation
Measure the circulating levels of the new angiogenic factor EG-VEGF in the sera	Measure the circulating levels of the new angiogenic factor EG-VEGF in the sera of pregnant woman between 14 and 18 WG to determine whether EG-VEGF could represent a prognostic marker for the development of IUGR	Between 14 and 18 weeks of gestation

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Pascale Hoffmann, MD/PHD, University Hospital, Grenoble; Study Director: Nadia ALFAIDI, PHD, inserm U878

Publications and helpful links

General Publications

• Hoffmann P, Feige JJ, Alfaidy N. Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation. Placenta. 2007 Oct;28(10):1049-58. doi: 10.1016/j.placenta.2007.03.008. Epub 2007 May 25.
• Hoffmann P, Feige JJ, Alfaidy N. Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Endocrinology. 2006 Apr;147(4):1675-84. doi: 10.1210/en.2005-0912. Epub 2005 Dec 29.
• Hoffmann P, Saoudi Y, Benharouga M, Graham CH, Schaal JP, Mazouni C, Feige JJ, Alfaidy N. Role of EG-VEGF in human placentation: Physiological and pathological implications. J Cell Mol Med. 2009 Aug;13(8B):2224-2235. doi: 10.1111/j.1582-4934.2008.00554.x.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 13, 2015

Study Registration Dates

• First Submitted: December 8, 2011
• First Submitted That Met QC Criteria: December 9, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: prognosis; Pre-eclampsia; intra-uterine growth retardation; EG-VEGF; Endocrine Gland-derived Vascular Endothelial Growth Factor
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Hypertension, Pregnancy-Induced; Growth Disorders; Eclampsia; Pre-Eclampsia; Fetal Growth Retardation
• Other Study ID Numbers: C09-43; 2009-A01304-53 (Registry Identifier: IDRCB)