umBilical Or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN)

Study Overview
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Brief Summary
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Extremely low gestational age neonates (ELGAN, i.e., born before 28 gestation weeks) are among the most heavily transfused pediatric patients. In this clinical setting, repeated red blood cell (RBC) transfusions independently predict a poor outcome, with a higher risk for mortality and morbidity. Recent studies from our own and other groups highlighted a close association between low levels of fetal hemoglobin (HbF) and severity of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), two disabilities that frequently complicate preterm birth. This association is not surprising, considering that 1) preterm neonates have a highly immature antioxidant reserve and both ROP and BPD rely on the oxidative damage as underlying mechanism; 2) in comparison with HbA, HbF is endowed with higher oxygen affinity, greater redox potential, higher tetrameric stability, and higher ability to generate unbound nitric oxide, all functions potentially protective in presence of an oxidative challenge; 3) in normal prenatal life, developing organ and tissues are exposed exclusively to HbF until last weeks of gestation; 4) in preterm neonates, the switch of the synthesis from HbF to HbA occurs around their due date, i.e., several weeks after the premature birth; 5) when preterm neonates receive transfusions, their tissues are abruptly exposed to high levels of HbA. We have recently run a pilot trial demonstrating as a proof-of-concept that transfusing cord blood red blood cell concentrates (CB-RBC) effectively prevents or restrains the HbF loss consequent to adult donor standard transfusions (A-RBC). This study explores the hypothesis that transfusing CB-RBCs instead of A-RBC may lower the incidence of severe ROP in ELGANs needing transfusions.

Official Title
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Umbilical or Adult Donor Red Blood Cells to Transfuse Extremely Low Gestational Age Neonates. A Randomized Trial to Assess the Effect on Retinopathy of Prematurity Severity.

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Biological: cord blood-RBC concentrates
* Biological: adult donor RBC concentrates


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational age (GA) at birth between 24+0 and 27+6 weeks signed informed consent of parents. Exclusion Criteria: One or more of the following: maternal-fetal immunization hydrops fetalis major congenital malformations associated or not with genetic syndromes previous transfusions hemorrhage at birth congenital infections health care team deeming it inappropriate to approach the infant's family for informed consent.

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 27 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Interventional, randomized, controlled, double-blind, with an adaptive design to evaluate safety and efficacy of allogeneic CB-RBC transfusions.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adult-RBC transfusions<br>Adult-red blood cell concentrate transfusions | Biological: adult donor RBC concentrates<br>* Patients in the comparator arm are candidates to receive adult donor-RBC units<br>* Other names: adult donor packed RBC;|
| Experimental: CB-RBC transfusions<br>Cord blood-red blood cell concentrate transfusions | Biological: cord blood-RBC concentrates<br>* Patients in the experimental arm are candidates to receive CB-RBC units until the completion of 31 weeks of postmenstrual age (31+6). In case of unavailability of an ABO/Rh matched CB-RBC unit, patients receive adult -RBC (standard transfusions).<br>* Other names: cord blood packed RBC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinopathy of prematurity | Incidence of severe ROP (stage 3 and higher) in CB-RBC and A-RBC arms | up to the age of 40 weeks |