Teofili Luciana, Papacci Patrizia, Dani Carlo, Cresi Francesco, Remaschi Giulia, Pellegrino Claudio, Bianchi Maria, Ansaldi Giulia, Campagnoli Maria Francesca, Vania Barbara, Lepore Domenico, Franco Fabrizio Gaetano Saverio, Fabbri Marco, de Vera d' Aragona Roberta Penta, Molisso Anna, Beccastrini Enrico, Dragonetti Antonella, Orazi Lorenzo, Pasciuto Tina, Mozzetta Iolanda, Baldascino Antonio, Locatelli Emanuela, Valentini Caterina Giovanna, Giannantonio Carmen, Carducci Brigida, Gabbriellini Sabrina, Albiani Roberto, Ciabatti Elena, Nicolotti Nicola, Baroni Silvia, Mazzoni Alessandro, Besso Federico Genzano, Serrao Francesca, Purcaro Velia, Coscia Alessandra, Pizzolo Roberta, Raffaeli Genny, Villa Stefania, Mondello Isabella, Trimarchi Alfonso, Beccia Flavia, Ghirardello Stefano, Vento Giovanni
Fondazione Policlinico A. Gemelli IRCCS, Largo Gemelli 8, 00168, Roma, Italy.
Università Cattolica del Sacro Cuore, Roma, Italy.
Ital J Pediatr. 2024 Aug 7;50(1):142. doi: 10.1186/s13052-024-01714-w.
Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP.
BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions.
Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk.
The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.
Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.
早产儿发生早产儿视网膜病变（ROP）的风险很高，可能导致终身视力损害。胎儿血红蛋白（HbF）水平低可预测ROP。目前尚不清楚阻止HbF下降是否也能降低ROP的发生率。
BORN是一项正在进行的多中心双盲随机对照试验，旨在研究输注富含HbF的脐血红细胞（CB-RBCs）而非成人供体红细胞（A-RBCs）是否能降低严重ROP的发生率（NCT05100212）。纳入妊娠24至27⁺⁶周出生的新生儿，并按1:1随机分组，从出生至孕龄（PMA）31⁺⁶周接受成人供体红细胞（A-RBCs，A组）或同种异体CB-RBCs（B组）。主要结局是PMA 40周或出院时严重ROP的发生率，样本量为146例患者。在首批58例患者入组后进行了预先设定的中期分析，主要目的是评估CB-RBC输血的安全性。
报告了意向性分析和符合方案分析的结果。A组28例患者，B组30例患者。总体而言，共输注了104个A-RBC单位和49个CB-RBC单位，方案偏离率较高。共记录到336例不良事件，两组的发生率和严重程度相似。根据符合方案分析，接受A-RBCs或两种红细胞类型的患者比未输血患者或仅接受CB-RBCs输血的患者发生更多不良事件，且患有更严重形式的心动过缓、肺动脉高压和血流动力学显著的动脉导管未闭。输注CB-RBCs或A-RBCs后血清钾、乳酸和pH值相似。14例患者死亡，44例接受ROP评估。其中10例发生严重ROP，两组之间无差异。在符合方案分析中，与CB-RBCs相比，每次A-RBC输血发生严重ROP的相对风险为1.66（95%CI 1.06-2.20）。HbF曲线下面积表明，PMA 30周前HbF下降对严重ROP的发生至关重要。随后输注CB-RBCs并不能降低ROP风险。
中期分析表明，早产儿输注CB-RBC的策略是安全的，且如果早期采用，可能使他们免受严重ROP的影响。
2021年10月29日在ClinicalTrials.gov上进行前瞻性注册。标识符编号NCT05100212。
