Personalizing Preterm Neonatal Transfusions With Fetal Hemoglobin-Enriched Cord Blood

NCT07636473 | Not Yet Recruiting DMC

• 2 other identifiers: AOUPRRF-2024-12380404 - ER
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Long-term morbidities among very low birth weight infants remain a significant challenge. Oxidative stress is a key factor in the pathogenesis of 'free radical (FR) diseases of prematurity,' including retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage. Red blood cell (RBC) transfusions are recognized as a contributing factor to FR-related diseases. RBCs contain adult hemoglobin (HbA), which has a lower affinity for oxygen. This characteristic increases oxygen delivery and tissue uptake, leading to a potentially harmful state of hyperoxia and over-generation of FRs. The strategy employs a multidisciplinary approach to evaluate the impact of cord blood transfusions in anemic newborns. Results will be assessed in relation to short- and long-term neonatal outcomes to determine the effectiveness of this new preventive strategy. Improving the current data are critical for setting action priorities for and monitoring progress

Conditions

Prematurity Complications; Anemia

Keywords

Cord Blood red blood cells; transfusion; preterm newborns

Outcome Measures

Primary Outcomes (1)

• Incidence of free radical-related morbidities in preterm neonates receiving CB-RBC transfusions

  Composite incidence of: Retinopathy of prematurity (ROP) Bronchopulmonary dysplasia (BPD) Necrotizing enterocolitis (NEC) Intraventricular hemorrhage (IVH) diagnosed according to standard neonatal criteria. Metric / Unit Number (%) of infants with at least one morbidity

  From birth until hospital discharge or 36 weeks postmenstrual age

Secondary Outcomes (7)

• Severity of retinopathy of prematurity

  Until hospital discharge or 44 weeks postmenstrual age

• Severity of bronchopulmonary dysplasia

  At 36 weeks postmenstrual age

• Bayley Scales of Infant Development score (Bayley-III)

  At 12 months corrected age

• Incidence of acute and delayed transfusion-related adverse events following CB-RBC transfusions

  From the first CB-RBC transfusion to hospital discharge (up to 6 months)

• Transfusion-associated complications

  From enrollment until hospital discharge (up to 6 months)

Study Arms (2)

Cord Blood Red Blood Cell Transfusion (CB-RBC)

EXPERIMENTAL

The experimental intervention consists of transfusion of cord blood red blood cell concentrates (CB-RBC), prepared from cord blood units donated to public cord blood banks. The units are processed as follows: * Leukodepletion using BioR Flex filters; * Fractionation using Compomat G5 cell separators; * Suspension in SAG-M additive solution; * Storage in DEHP-free pediatric blood bags. All units are irradiated with gamma rays prior to administration and transfused within 24 hours after irradiation. Safety is ensured through screening for infectious diseases (HIV, HBV, HCV, syphilis, bacterial and fungal cultures). The dose, volume, and frequency of transfusion follow the same guidelines as adult red blood cell concentrates (A-RBC), according to current Italian neonatal standards. Transfusion is performed by the clinical staff of the Neonatology Unit according to the standard protocol.

Combination Product: Cord Blood Red Blood Cell Transfusion (CB-RBC)

Adult Donor Red Blood Cell Transfusion (A-RBC)

ACTIVE COMPARATOR

The control arm receives transfusions of adult donor red blood cell concentrates (A-RBC), leukodepleted and irradiated according to the same thresholds and doses as the experimental arm, representing the Italian standard of care for anemic preterm neonates and ensuring that the only difference between the two arms is the source of the transfusion product - and therefore the HbF content - with respect to which CB-RBC is expected to demonstrate superiority

Other: Adult Donor Red Blood Cell Transfusion (A-RBC)

Interventions

Cord Blood Red Blood Cell Transfusion (CB-RBC) COMBINATION_PRODUCT

Transfusion of leukodepleted, gamma-irradiated cord blood-derived red blood cell concentrates (CB-RBC), prepared from donated public cord blood bank units, characterized by high fetal hemoglobin (HbF) content and administered according to standard neonatal transfusion thresholds

Cord Blood Red Blood Cell Transfusion (CB-RBC)

Adult Donor Red Blood Cell Transfusion (A-RBC) OTHER

Transfusion of leukodepleted, gamma-irradiated adult-donor derived red blood cell concentrates (A-RBC) administered according to standard neonatal transfusion thresholds.

Adult Donor Red Blood Cell Transfusion (A-RBC)

Eligibility Criteria

• Age: 24 Weeks - 31 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm neonates born between 24+0 and 31+6 weeks of gestational age;
• Requirement for at least one red blood cell transfusion during hospitalization, according to current Italian transfusion thresholds;
• Written informed consent obtained from parents or legal guardians prior to any study procedure.

You may not qualify if:

• Gestational age \> 32+0 weeks;
• Pregnancy complicated by maternal-fetal alloimmunization (e.g., hemolytic disease of the newborn);
• Pregnancy complicated by fetal hydrops;
• Major congenital anomalies or genetic syndromes;
• Previous red blood cell transfusions (prior to enrollment);
• Perinatal hemorrhage at delivery;
• Documented congenital infections (TORCH).

Sponsors & Collaborators

• University of Parma: lead

MeSH Terms

Conditions

Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: June 9, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: June 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At the end of the sudy
• Access Criteria: Access to de-identified individual participant data will be provided to qualified researchers upon reasonable request, subject to approval by the study investigators and institutional ethics requirements. Data sharing will be permitted only for scientifically sound research purposes and after execution of a data access agreement