PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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: 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.
CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.
BACKGROUND: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.
METHODS: 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: 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.
CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.
BACKGROUND: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.
摘要：
背景：早产儿视网膜病变（ROP）的风险很高，有潜在的终身视力障碍。低胎儿血红蛋白(HbF)水平预测ROP。尚不清楚防止HbF降低是否也降低ROP。
方法：BORN是一项正在进行的多中心双盲随机对照试验，研究输注富含HbF的脐带血红细胞（CB-RBC）而不是成人供体红细胞单位（A-RBC）是否可以降低严重ROP的发生率（NCT05100212）。出生在妊娠24至27+6周之间的新生儿被招募，并以1：1的比例随机分配接受成人供体RBC（A-RBC，A组）或从出生到月经后年龄（PMA）为31+6周的同种异体CB-RBC（B组）。主要结果是PMA或出院40周时严重ROP的发生率，样本量为146名患者。在纳入前58名患者后，安排了预先指定的中期分析，主要目的是评价CB-RBC输血的安全性。
结果：报告了意向治疗和符合方案分析的结果。28名患者在A臂，30名患者在B臂。输注104个A-RBC单位和49个CB-RBC单位，协议偏差率很高。共记录了336起不良事件，两组的发病率和严重程度相似。通过符合协议的分析，接受A-RBC或两种类型的RBC的患者比未输血患者或仅输注CB-RBC的患者经历了更多的不良事件，患有更严重的心动过缓，肺动脉高压,和血流动力学显著动脉导管未闭。血清钾，乳酸，CB-RBC或A-RBC后的pH值相似。14例患者死亡，44例接受ROP评估。其中十个发生了严重的ROP，武器之间没有区别。在符合方案分析中，与CB-RBC相比，每次A-RBC输血的严重ROP相对风险为1.66（95％CI1.06-2.20）。HbF曲线下面积表明，PMA前30周HbF下降对严重的ROP发展至关重要。随后的CB-RBC输血不会降低ROP风险。
结论：中期分析表明，早产新生儿的CB-RBC输血策略是安全的，如果早期采用，可以保护他们免受严重的ROP。
背景：于2021年10月29日在ClinicalTrials.gov进行了前瞻性注册。标识符号NCT05100212。
方法：BORN是一项正在进行的多中心双盲随机对照试验，研究输注富含HbF的脐带血红细胞（CB-RBC）而不是成人供体红细胞单位（A-RBC）是否可以降低严重ROP的发生率（NCT05100212）。出生在妊娠24至27+6周之间的新生儿被招募，并以1：1的比例随机分配接受成人供体RBC（A-RBC，A组）或从出生到月经后年龄（PMA）为31+6周的同种异体CB-RBC（B组）。主要结果是PMA或出院40周时严重ROP的发生率，样本量为146名患者。在纳入前58名患者后，安排了预先指定的中期分析，主要目的是评价CB-RBC输血的安全性。
结果：报告了意向治疗和符合方案分析的结果。28名患者在A臂，30名患者在B臂。输注104个A-RBC单位和49个CB-RBC单位，协议偏差率很高。共记录了336起不良事件，两组的发病率和严重程度相似。通过符合协议的分析，接受A-RBC或两种类型的RBC的患者比未输血患者或仅输注CB-RBC的患者经历了更多的不良事件，患有更严重的心动过缓，肺动脉高压,和血流动力学显著动脉导管未闭。血清钾，乳酸，CB-RBC或A-RBC后的pH值相似。14例患者死亡，44例接受ROP评估。其中十个发生了严重的ROP，武器之间没有区别。在符合方案分析中，与CB-RBC相比，每次A-RBC输血的严重ROP相对风险为1.66（95％CI1.06-2.20）。HbF曲线下面积表明，PMA前30周HbF下降对严重的ROP发展至关重要。随后的CB-RBC输血不会降低ROP风险。
结论：中期分析表明，早产新生儿的CB-RBC输血策略是安全的，如果早期采用，可以保护他们免受严重的ROP。
背景：于2021年10月29日在ClinicalTrials.gov进行了前瞻性注册。标识符号NCT05100212。
