Advancing Neonatal Health: Personalizing Preterm Neonatal Transfusions With Fetal Hemoglobin-Enriched Cord Blood
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 200
- 主要终点
- Incidence of free radical-related morbidities in preterm neonates receiving CB-RBC transfusions
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 24 Weeks 至 31 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: 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
干预措施: Adult Donor Red Blood Cell Transfusion (A-RBC) (Other)
结局指标
主要结局
Incidence of free radical-related morbidities in preterm neonates receiving CB-RBC transfusions
时间窗: From birth until hospital discharge or 36 weeks postmenstrual age
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
次要结局
- 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)
- Transfusion-associated complications(From enrollment until hospital discharge (up to 6 months))
- Expression levels of oxidative stress-related microRNAs(Baseline and after first transfusion assessment during hospitalization (up to 6 months))
- Changes in neuroprotective and antioxidant protein expression(Baseline and within 72 hours after transfusion)
- 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))
研究者
Serafina Perrone
Professor of Pediatrics
University of Parma