Torrejon-Rodriguez Laura, Pinilla-Gonzalez Alejandro, Lara Cantón Inmaculada, Albiach-Delgado Abel, Cascant-Vilaplana Mari Merce, Cernada María, Kuligowski Julia, Solves Alcaina Maria Pilar, Gómez Inés, Vento Maximo, Aguar Carrascosa Marta
Department of Neonatology, Instituto de Investigación Sanitaria La Fe (IISLAFE), Valencia, Spain.
Neonatal Research Group, Hospital Universitario y Politécnico La Fe (HULAFE), Valencia, Spain.
Front Pediatr. 2023 Oct 12;11:1269797. doi: 10.3389/fped.2023.1269797. eCollection 2023.
Currently, the treatment of anemia in preterm infants is based on packed red blood cell (RBC) transfusions from adult donors. Oxygen (O2) is mainly transported to the tissues bound to hemoglobin (Hb). In extremely low gestational age neonates (ELGANs), fetal hemoglobin (HbF), which has a higher affinity for O2, represents up to 95% of circulating hemoglobin. During the first month of life, the majority of ELGANs will require an adult-donor RBC transfusion causing HbF levels to rapidly drop. HbA releases 50% more oxygen in peripheral tissues than HbF. Increased release of O2 in the retina is one of the main factors related to the development of retinopathy of prematurity (ROP). Collecting umbilical cord blood and using autologous umbilical cord whole blood (UCB) transfusions would contribute to maintaining physiological HbF concentrations in newborns and avoid oxygen-in-excess derived damage.
This is a randomized, double-blinded, multicenter clinical trial. ELGANs ≤28 weeks of gestational age will be randomized 1:1 to receive an autologous umbilical cord blood transfusion (intervention arm) or standard transfusion of packed RBC from an adult donor (control arm) to assess ROP development. Assuming a 50% reduction in ROP incidence, 134 patients (67 per group) will be recruited. When blood transfusion is indicated, the Blook Bank will supply UCB or RCB according to the patient's group. The primary endpoint is the incidence of any ROP. Secondary endpoints are assessessment of treatment safety, results of biomarkers related to ROP and its chronology, and urine oxidative stress markers. In addition, the cellular composition of umbilical cord blood and its relationship with prematurity-related pathologies will be analyzed. All patients will be followed-up to 24 months of corrected age to evaluate their neurodevelopment.
ROP is a major cause of irreversible blindness in preterm newborns. Transfusions with adult donor blood can lead to complications, including ROP. UCB transfusions offer advantages by maintaining physiological HbF levels and potentially optimizing postnatal development. Moreover, autologous UCB transfusion could reduce risks associated with heterologous blood products, although volume collection remains challenging. UCB contains growth factors and progenitor cells that may impact ROP.
目前，早产儿贫血的治疗基于输注来自成年供血者的浓缩红细胞（RBC）。氧气（O₂）主要通过与血红蛋白（Hb）结合运输到组织。在极早早产儿（ELGANs）中，对O₂具有更高亲和力的胎儿血红蛋白（HbF）占循环血红蛋白的95%。在出生后的第一个月，大多数ELGANs需要输注成年供血者的RBC，这会导致HbF水平迅速下降。与HbF相比，HbA在外周组织中释放的氧气多50%。视网膜中氧气释放增加是与早产儿视网膜病变（ROP）发展相关的主要因素之一。采集脐带血并使用自体脐带全血（UCB）输血将有助于维持新生儿的生理HbF浓度，并避免氧过量导致的损伤。
这是一项随机、双盲、多中心临床试验。孕周≤28周的ELGANs将按1:1随机分组，接受自体脐带血输血（干预组）或成年供血者的标准浓缩RBC输血（对照组），以评估ROP的发生情况。假设ROP发生率降低50%，将招募134例患者（每组67例）。当需要输血时，血库将根据患者分组提供UCB或RCB。主要终点是任何ROP的发生率。次要终点是治疗安全性评估、与ROP及其病程相关的生物标志物结果以及尿液氧化应激标志物。此外，将分析脐带血的细胞组成及其与早产相关病理的关系。所有患者将随访至矫正年龄24个月，以评估其神经发育情况。
ROP是早产新生儿不可逆失明的主要原因。输注成年供血者的血液会导致包括ROP在内的并发症。UCB输血通过维持生理HbF水平和潜在优化出生后发育具有优势。此外，自体UCB输血可降低与异体血制品相关的风险，尽管血量采集仍然具有挑战性。UCB含有可能影响ROP的生长因子和祖细胞。
