Clinical trial NCT04595214: Develop a Multi-disciplinary Approach for a Personalized Prenatal Diagnostics and Care for Twin Pregnancies
Official title: Develop a Multi-disciplinary Approach for a Personalized Prenatal Diagnostics and Care for Twin Pregnancies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Prenatal Disorder
Premature Birth
Twin Pregnancy With Antenatal Problem
Twin; Pregnancy, Affecting Fetus or Newborn
Twin Pregnancy, Antepartum Condition or Complication
Twin Dichorionic Diamniotic Placenta
Twin Monochorionic Monoamniotic Placenta
Keywords: Twin pregnancy
Risk stratification algorithm,
Feto-Maternal complications (preeclampsia, IUGR, PTD, GDM),
TTTS
cfDNA, NIPT
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-10-20
Enrollment: 1200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse pregnancy outcome
timeFrame: through study completion, an average of 1 year
measure: Adverse neonatal outcome
timeFrame: through study completion, an average of 2 year
measure: Evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.
timeFrame: through study completion, an average of 2 year including stored samples collected before vaccination was avaluable.
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann,
city: Montréal
country: Canada
facility: University of Montreal Medical Centre, Canada
city: Bonn
country: Germany
facility: University Hospital Bonn, Bonn, Germany
city: Tubingen
country: Germany
facility: Oliver Kagan
city: Zrifin
country: Israel
facility: Department of ObGyn, Assaf Harofe-Shamir Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic, Barcelona,
state: Catalonia
city: London
country: United Kingdom
facility: The Fetal Medicine Foundation
Study officials:
affiliation: Assaf-Harofeh Medical Center
name: Ron Maymon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: