Consequences of Antiangiogenic Factors Involved in Preeclampsia on Intra-uterine Growth Restricted Preterm Newborn (ANGIODYS)

Consequences of Circulating Antiangiogenic Factors Involved in Preeclampsia on Intra-uterine Growth Restricted Preterm Newborn

Preeclampsia complicates about 2-7% of pregnancies and is a major contributor to maternal and neonatal morbidity and mortality worldwide. Imbalance between circulating angiogenic and antiangiogenic factors has emerged as a potential key pathway in the pathophysiology of preeclampsia. Patients with preeclampsia have a higher circulating concentration of antiangiogenic factors (ie, soluble vascular endothelial growth factor receptor-1 [sVEGFR- 1], also called soluble fms-like tyrosine kinase 1 [sFlt1]) and soluble endoglin (sEng)] and a lower maternal circulating concentration of free angiogenic factors (ie, vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) than patients with a normal pregnancy. Bronchopulmonary dysplasia is the main respiratory sequelae of preterm birth. Its rate increased in preterm infants born from mother with preeclampsia. Recent studies showed that bronchopulmonary dysplasia is consistently accompanied by a reduction in the number of small arteries and on abnormal distribution of vessels within the distal lungs. This is associated with reduced lung VEGF expression. The main objective of this population-based study, ie in intra uterine growth restricted preterm babies born before 30 weeks of gestational age, was to examine whether levels of sFlt1 at birth in maternal and umbilical cord blood and in the amniotic fluid is associated with an increased risk of BPD.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Bronchopulmonary Dysplasia; Intra-uterine Growth Restriction; Maternal Preeclampsia
• Intervention / Treatment: Other: Biological samples

Detailed Description

Preeclampsia complicates about 2-7% of pregnancies and is a major contributor to maternal and neonatal morbidity and mortality worldwide. Preeclampsia is the main cause of intra-uterine growth restriction and could lead to a preterm delivery for fetal or maternal indication. Imbalance between circulating angiogenic and antiangiogenic factors has emerged as a potential key pathway in the pathophysiology of preeclampsia. Patients with preeclampsia have a higher circulating concentration of antiangiogenic factors (ie, soluble vascular endothelial growth factor receptor-1 [sVEGFR- 1], also called soluble fms-like tyrosine kinase 1 [sFlt1]) and soluble endoglin (sEng)] and a lower maternal circulating concentration of free angiogenic factors (ie, vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) than patients with a normal pregnancy.

Bronchopulmonary dysplasia is the main respiratory sequelae of preterm birth. Its rate increased in preterm infants born from mother with preeclampsia. Recent studies showed that bronchopulmonary dysplasia is consistently accompanied by a reduction in the number of small arteries and on abnormal distribution of vessels within the distal lungs. This is associated with reduced lung VEGF expression. Infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF circulating levels. There was a significantly positive relationship between birth weight and cord blood sFlt-1 levels, witness of consequences of these antiangiogenic factors on fetuses. However, no study to date has shown a correlation between the level of angiogenic and antiangiogenic factors and the main complications of preterm birth.

The main objective of this population-based study, ie in 24 intra uterine growth restricted preterm babies born before 30 weeks of gestational age from mother with preeclampsia, was to examine whether levels of sFlt1 at birth in maternal and umbilical cord blood and in the amniotic fluid is associated with an increased risk of BPD at 36 weeks of gestational age. The second objectives are to explore the link between the levels of angiogenic and antiangiogenic factors and the main complications of preterm birth, ie, necrotizing enterocolitis, intra-ventricular hemorrhage, periventricular leukomalacia or infection.

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Cochin Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Intra uterine growth restricted preterm babies born before 30 weeks of gestational age from mother with preeclampsia

Description

Inclusion Criteria:

• Maternal preeclampsia
• Intra uterine growth restriction
• Preterm birth before 30 weeks of gestational age

Exclusion Criteria:

• Congenital malformation
• Eutrophic fetus
• Chorioamnionitis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Preterm babies; Intra uterine growth restricted preterm babies born before 30 weeks of gestational age from mother with preeclampsia	Other: Biological samples; To measure the levels of sFlt1, angiogenic and antiangiogenic factors at birth in maternal blood, umbilical cord blood and in the amniotic fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of sFlt1 (tyrosine kinase 1) at birth and the risk of bronchopulmonary dysplasia	The main objective of this population-based study, ie in 24 intra uterine growth restricted preterm babies born before 30 weeks of gestational age from mother with preeclampsia, was to examine whether levels of sFlt1 at birth in maternal and umbilical cord blood and in the amniotic fluid is associated with an increased risk of BPD at 36 weeks of gestational age.	at 36 weeks of gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of angiogenic and antiangiogenic factors at birth and the complications of preterm birth	The second objectives are to correlate the levels of angiogenic and antiangiogenic factors at birth, in maternal blood, cord blood and amniotic fluid, and the main complications of preterm birth, ie, necrotizing enterocolitis, intra-ventricular hemorrhage, periventricular leukomalacia or infection before 36 weeks of gestational age.	at 36 weeks of gestational age

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Elodie ZANA-TAIEB, MD, Hopital Cochin

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: July 20, 2012
• First Submitted That Met QC Criteria: July 20, 2012
• First Posted (ESTIMATE): July 24, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 24, 2016
• Last Update Submitted That Met QC Criteria: June 23, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Bronchopulmonary dysplasia; Preeclampsia; Circulating antiangiogenic factors; Developing lung
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Fetal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Lung Injury; Hypertension, Pregnancy-Induced; Infant, Premature, Diseases; Growth Disorders; Ventilator-Induced Lung Injury; Premature Birth; Pre-Eclampsia; Fetal Growth Retardation; Bronchopulmonary Dysplasia
• Other Study ID Numbers: NI 11030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO