Develop a Multi-disciplinary Approach for a Personalized Prenatal Diagnostics and Care for Twin Pregnancies (PRETWINSCREN)

Different screening modalities evaluation to develop algorithms to predict pregnancy complications in twin pregnancies, and evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.

Study Overview

• Status: Recruiting
• Conditions: Premature Birth; Twin Pregnancy With Antenatal Problem; Twin Pregnancy, Antepartum Condition or Complication; Twin Dichorionic Diamniotic Placenta; Twin Monochorionic Monoamniotic Placenta; Twin; Pregnancy, Affecting Fetus or Newborn; Prenatal Disorder
• Intervention / Treatment: Other: TTTS cases are treated by intra-uterine laser for separation.

Detailed Description

This is a multi-center study to identify biomarkers or marker combinations for early prediction of pregnancy complications in twin pregnancies in the first, second or third trimester.

In the future, the identified patients' risk will enable patients' referrals for proper prevention when such will become available

Specifically the investigators aim for

• Predicting the risk to develop preeclampsia, IUGR, preterm delivery, gestational Diabetes Melitus
• Assessment of major and minor markers for chromosomal and structural anomalies
• Identification of placenta accrete spectrum disorders and vasa previa
• Diagnosis of specific MC twin complications such as TTTS

The investigators will stratify and assess all the above according to chorionicity and delivery with complications at <32 weeks, <34 weeks, <37 weeks, and at any gestation.

Screening methods will be conducted in the first, second or third trimester or at any gestation

Also the investigators aim to Identify the risk to lose one or both twins at <32 weeks, <34 weeks, <37 weeks and at any gestation, the ability to predict fetal birth weight at <32 weeks, <34 weeks, <37 weeks and at any gestation

The investigators also aim for monitoring any of the following maternal complications including placental abruption (clinically or on placental examination), postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth) at <32 weeks, <34 weeks, <37 weeks and at any gestation.

The investigators will monitor

1. Neonatal morbidity due to intraventricular hemorrhage (IVH) grade II or above - Defined as bleeding into the ventricles, Grade II (moderate) - IVH occupies <50% of the lateral ventricle volume, Grade III (severe) - IVH occupies ≥50% of the lateral ventricle volume or Grade IV (severe) - Hemorrhagic infarction in periventricular white matter ipsilateral to a large IVH
2. Neonatal sepsis confirmed bacteremia in cultures, anemia defined as low Hemoglobin and / or hematocrit requiring blood transfusion, respiratory distress syndrome defined as need for treatment by surfactant and ventilation, necrotizing enterocolitis requiring surgical intervention, and composite of any of the above
3. Newborn admission to neonatal intensive care units (NICU), length of stay and therapies during the admission.
4. Ventilation defined as a need for a positive pressure (continuous positive airway pressure (CPAP), nasal continuous positive airway pressure (NCPAP)) or intubation and a composite of any of the above
5. Any maternal complications within the first 6-10 weeks post delivery. The investigators will recruit patients in the different sites aiming for 1200 twin pregnancy and will collect the patients' entire pregnancy data for developing an algorithm to calculate the risk to develop the complications
6. Evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

• Study Contact: Name: Ron Maymon, MD, PhD; Phone Number: +972-8-9779695; Email: Ronm@shamir.gov.il
• Study Contact Backup: Name: Hamutal Meiri; Phone Number: +972-54-7774762; Email: hamutal62@hotmail.com

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Not yet recruiting
    • CHU Brugmann,
    • Contact: Jacques Jani, MD; Email: jackjani@hotmail.com
• Canada
  • Montréal, Canada, H4A 3J1,
    • Not yet recruiting
    • University of Montreal Medical Centre, Canada
    • Contact: Richard N Brown, MD; Phone Number: 34074 1+ 514-9341934; Email: Richard.brown.ca@gmail.com
    • Contact: Piere Miron, MD, PhD; Phone Number: 1+ 450-934-9156
• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • University Hospital Bonn, Bonn, Germany
    • Contact: Annegrete Geipel, MD; Phone Number: +49 (0) 228-287-15942; Email: annegret.geipel@ukbonn.de
    • Contact: Brigitte Strizek; Phone Number: +49 (0) 228-287-15942
  • Tubingen, Germany, 72706
    • Recruiting
    • Oliver Kagan
    • Contact: Oliver Kagan; Phone Number: 70712984807; Email: karl.kagan@med.uni-tuebingen.de
    • Contact: Markus Hoopmann; Phone Number: 07071 298 5619; Email: markus.hooperman@med.uni-tubingen.da
• Israel
  • Zrifin, Israel, 70300
    • Recruiting
    • Department of ObGyn, Assaf Harofe-Shamir Medical Center
    • Contact: Hamutal MeiriP, PhD; Phone Number: +972-54-7774762; Email: hamutal62@hotmail.com
    • Contact: Ran Svirsky, MD; Phone Number: +972-53-7346603; Email: rsvirs@gmail.com
    • Sub-Investigator: Nadav Kugler, MD
    • Sub-Investigator: Howard Cuckle, PhD
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Not yet recruiting
      • Hospital Clinic, Barcelona,
      • Contact: Anna Gonce, MD, PhD; Phone Number: +34 664197885; Email: agnoce@clinic.cat
      • Contact: Antony Borrell, MD; Phone Number: +34 664197885; Email: ABORELL@clinic.cat
      • Sub-Investigator: Mar Benassar Sar, MD
• United Kingdom
  • London, United Kingdom, W1G 6BG
    • Not yet recruiting
    • The Fetal Medicine Foundation
    • Contact: Kypros H Nicolaides, MD; Phone Number: +44 (0)207 034 3070; Email: kypros@fetalmedicine.com
    • Contact: Argyro Syngeleki, PhD; Phone Number: +44-75109639; Email: argyro.syngelaki@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

This is prospective multi-centre study that includes a site in Israel, two sites in Germany, a site in Catalonia, Spain, a site in Quebec, Canada and a site in the UK. In the participating centres, all eligible women with DC or MC twin pregnancy attending for their routine first hospital visit in pregnancy at 11-13 weeks' gestation will be invited to participate in the trial. pregnancy characteristics will be followed and biomarkers determined. We follow ISUOG and FMF guidelines on how to undertake the appropriate measurements

Description

Inclusion Criteria:

• Age > 18 years;
• Di-chorionic (DC)or Mono-chorionic (MC) twin pregnancies;
• Both live fetuses at 11+0-13+6 weeks of gestation;
• Informed and written consent

Exclusion Criteria:

• Monoamniotic twins
• Triplet pregnancies that had undergone embryo reduction to twins or with one vanishing twin
• Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness;
• Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse pregnancy outcome	preterm delivery before 37 weeks of gestation , or hypertension of >90/140, from gestational week 24 and above throughout pregnancy , baby birth weight below the 5 lower centile for the gestation week, or shoulder dyctorcia at delivery, or newborn admission to NICU for any complication or placental position complications such as placenta accreta, or vasa previa, or intra uterine fetal death,	through study completion, an average of 1 year
Adverse neonatal outcome	Admission to neonatal intensive care unit, Sepsis, asphyxia, intraventricular hemorrhage, intrauterine growth retardation	through study completion, an average of 2 year
Evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.	Testing blood sample drawn for the study for antybody levels in conjunction to BNT162b2 Pfeizer/BioNTech vaccination	through study completion, an average of 2 year including stored samples collected before vaccination was avaluable.

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Investigators: Principal Investigator: Ron Maymon, MD,PhD, Assaf-Harofeh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: October 18, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Twin pregnancy; TTTS; Risk stratification algorithm,; Feto-Maternal complications (preeclampsia, IUGR, PTD, GDM),; cfDNA, NIPT
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 0043-20-ASF; JTC 2019-061 2019-00 (Other Grant/Funding Number: ERAPERMED)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A single database will be unified from all sites. Patents are entered after coding and personal anonymization. Level of sharing will be decided upon the policy of peer review journal. If acessible - dat be stored at the fetal medicine foundation website

Drug and device information, study documents

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