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

Study Overview
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Brief Summary
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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
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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 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 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 Newborn admission to neonatal intensive care units (NICU), length of stay and therapies during the admission. 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 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 Evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.

Official Title
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Develop a Multi-disciplinary Approach for a Personalized Prenatal Diagnostics and Care for Twin Pregnancies

Conditions
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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

Intervention / Treatment
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* Other: TTTS cases are treated by intra-uterine laser for separation.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: TTTS cases are treated by intra-uterine laser for separation.|MC twin anaestemosis separatio by laser. Vasa previa and placenta accreta are treated with steroids or other protocols, Positive trisomies by NIPS undergoes CVS or amniocentesis|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Twin pregnancy, Risk stratification algorithm,, Feto-Maternal complications (preeclampsia, IUGR, PTD, GDM),, TTTS, cfDNA, NIPT