Advancing Neonatal Health: Personalizing Preterm Neonatal Transfusions With Fetal Hemoglobin-Enriched Cord Blood
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- University of Parma
- Enrollment
- 200
Study Overview
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
Detailed Description
Specific AIM 1 To assess whether CB-RBC transfusions can offer a protective advantage of CB-RBC transfusions in preterm newborns by preserving HbF, reducing the risk of oxidative stress-related complications, and potentially lowering the incidence of 'free radical diseases of prematurity' .
Biomarkers of oxidative stress will be correlated with short term outcome of the newborns (diagnosis at discharge). Moreover with the aim to evaluate the social, economic, organizational implications of this intervention the investigators will perform an Health Impact Assessment (HIA).
The goal is to provide policymakers, healthcare providers, and stakeholders with evidence-based insights on the effectiveness, cost-effectiveness, safety, and potential impact of CB-RBC transfusions.
Specific AIM 2 To evaluate pathways involved in inflammatory and hypoxic-hyperoxic processes through microRNAs expression. OS cascade comprises the activation of microglia, infiltration of macrophages and release of pro-inflammatory mediators such as cytokines, chemokines, nitric oxide, free radicals. MicroRNAs, (miRs), play an important role in the regulation of OS modulated genes, with the potentiality to induce protective protein synthesis such as neuroglobin and sirtuin. Specifically, miRNA 107 e 17-5p, involved in angiogenesis and arterial remodeling are upregulated; miRNA 223-3p associated with chronic kidney disease is downregulated.
Specific AIM 3 To assess the protective role CB-RBC transfusions in newborns, by performing neurodevelopmental outcome of enrolled babies through clinical and neurobehavioral evaluations at 3-6-9-12-month of age.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 24 Weeks to 31 Weeks (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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).
Arms & Interventions
Cord Blood Red Blood Cell Transfusion (CB-RBC)
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.
Intervention: Cord Blood Red Blood Cell Transfusion (CB-RBC) (Combination Product)
Adult Donor Red Blood Cell Transfusion (A-RBC)
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
Intervention: Adult Donor Red Blood Cell Transfusion (A-RBC) (Other)
Investigators
Serafina Perrone
Professor of Pediatrics
University of Parma