EVERREST Developing a Therapy for Fetal Growth Restriction

NCT02097667 | Completed

• 1 other identifier: 13/0289
• Study Type: observational
• Target: 142
• Locations: 4 countries
• Sites: 4

Brief Summary

Fetal Growth Restriction (FGR) is a major obstetric problem, affecting 1.46 million fetuses worldwide each year and contributing to 50% of stillbirths. Severe early onset FGR affects 1 in 500 pregnancies, leading to stillbirth or the need for delivery before 28 weeks gestation. The combination of FGR and prematurity is associated with a significant risk of neonatal mortality and short and long-term complications. Even modest increases in birthweight (e.g from 500 to 600g) and gestation at delivery (e.g from 26 to 27 weeks) are associated with significantly better outcomes but there are currently no treatments. The EVERREST Clinical Trial, funded by the European Commission, aims to develop a treatment which will increase fetal growth in severe early onset FGR. It will use gene therapy injected into the uterine arteries of the mother to increase the levels of vascular endothelial growth factor (VEGF) and so increase uterine artery blood flow and fetal growth. The EVERREST prospective study aims to form a clinical database and biobank of pregnancies affected by severe early onset FGR to improve understanding of the condition and serve as a comparison to assess the safety and efficacy of this intervention. The prospective study will take place across four European centers who will later take part in the EVERREST Clinical Trial. Women with singleton fetuses with early onset FGR will be approached to take part in the study. Participating women will provide blood samples, details of their clinical condition, samples of umbilical cord blood, placenta and myometrial and placental bed biopsies at the time of Caesarean section (if needed). Data on short and long-term outcomes of the babies will be collected. All data will be entered onto a central database for eventual use as a comparator for treated women on the EVERREST Clinical Trial, for which separate ethical approval will be sought.

Conditions

Fetal Growth Retardation

Keywords

Severe early onset Fetal Growth Restriction

Outcome Measures

Primary Outcomes (1)

• data collection from pregnancies affected by severe early onset FGR.

  As the study will be purely descriptive there are no defined primary outcome measures. Data will be collected on the following: * Parental demographics * Maternal past medical history and obstetric history * Antenatal ultrasound findings including growth and Doppler measurements * Maternal antenatal, perinatal and postnatal complications and treatment * Stillbirth * Delivery and immediate neonatal condition * Neonatal progress including complications, treatment and neonatal death * Infant growth and development up to 2 years corrected age * Maternal and neonatal service use

  each hospital visit and up to 2 years follow up for babies

Other Outcomes (2)

• Model validation 1

  2021

• Model validation 2

  2021

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with FGR

You may qualify if:

• Live singleton fetus
• Estimated fetal weight \<600g and \<3rd centile for gestational age as defined by local criteria
• Gestational age at diagnosis 20+0-26+6 weeks, based on ultrasound and/or last menstrual period
• Informed consent given by the participant and signed consent form completed

You may not qualify if:

• Multiple pregnancy
• Maternal age under 18 years
• Known abnormal karyotype at enrolment
• Known structural abnormality at enrolment defined as a lethal, incurable serve abnormality with a high risk of residual handicap.
• Indication for immediate delivery
• Participants who lack the capacity to give informed consent
• Any medical or psychiatric condition which compromises the participant's ability to participate
• Maternal HIV or hepatitis B or C infection
• Premature preterm rupture of membranes before enrolment

Sponsors & Collaborators

• University College, London: lead
• University College London Hospitals: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Hospital Clinic of Barcelona: collaborator
• Lund University: collaborator

Study Sites (4)

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

Location

Maternal-Fetal Unit Hospital Clinic de Barcelona

Barcelona, Spain

Location

Lund University Hospital and University Hospital Malmö

Malmo, Sweden

Location

University College London Hospital

London, United Kingdom

Location

Related Publications (4)

• Spencer R, Ambler G, Brodszki J, Diemert A, Figueras F, Gratacos E, Hansson SR, Hecher K, Huertas-Ceballos A, Marlow N, Marsal K, Morsing E, Peebles D, Rossi C, Sebire NJ, Timms JF, David AL; EVERREST Consortium. EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction. BMC Pregnancy Childbirth. 2017 Jan 23;17(1):43. doi: 10.1186/s12884-017-1226-7.

  PMID: 28114884 BACKGROUND

• Bray G, Maksym K, Dilipkumar M, Spencer RN, Ginsberg Y, Weissbach T, Peebles DM, Marlow N, Huertas-Ceballos A, Buquis G, Okell J, Hecher K, Diemert A, Singer D, Hansson SR, Ley D, Figueras F, Gratacos E, Crispi F, David AL, Hunter R. Economic Impact of Severe Early-Onset Foetal Growth Restriction: A Multicentre Prospective Cohort Study. BJOG. 2026 Jan;133(1):61-70. doi: 10.1111/1471-0528.18266. Epub 2025 Jun 24.

  PMID: 40552422 DERIVED

• Spencer R, Maksym K, Hecher K, Marsal K, Figueras F, Ambler G, Whitwell H, Nene NR, Sebire NJ, Hansson SR, Diemert A, Brodszki J, Gratacos E, Ginsberg Y, Weissbach T, Peebles DM, Zachary I, Marlow N, Huertas-Ceballos A, David AL. Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction. J Clin Invest. 2023 Sep 15;133(18):e169199. doi: 10.1172/JCI169199.

  PMID: 37712421 DERIVED

• Lingam I, Okell J, Maksym K, Spencer R, Peebles D, Buquis G, Ambler G, Morsing E, Ley D, Singer D, Tenorio V, Dyer J, Ginsberg Y, Weissbach T, Huertas-Ceballos A, Marlow N, David A; EVERREST consortium. Neonatal outcomes following early fetal growth restriction: a subgroup analysis of the EVERREST study. Arch Dis Child Fetal Neonatal Ed. 2023 Nov;108(6):599-606. doi: 10.1136/archdischild-2022-325285. Epub 2023 Apr 26.

  PMID: 37185272 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, whole blood, fixed placenta, frozen placenta, fixed placenta bed.

MeSH Terms

Conditions

Fetal Growth Retardation

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anna David, Dr

  Institute of Women's Health, UCL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: March 27, 2014
• Study Start: March 1, 2014
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

ES (1); SE (1); GB (1); DE (1)