BACKGROUND High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).

中文翻译：

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促红细胞生成素对早产儿神经保护作用的随机试验。

背景 大剂量促红细胞生成素已被证明在新生儿脑损伤的临床前模型中具有神经保护作用，并且 2 期试验表明可能有效；然而，这种疗法对极度早产儿的益处和安全性尚未确定。方法 在这项大剂量促红细胞生成素的多中心、随机、双盲试验中，我们分配了 941 名出生于妊娠 24 周 0 天至 27 周 6 天的婴儿在出生后 24 小时内接受促红细胞生成素或安慰剂。促红细胞生成素以每 48 小时 1000 U/kg 体重的剂量静脉内给药，共 6 剂，随后通过皮下注射维持剂量 400 U/kg，每周 3 次，直至停经后整整 32 周。安慰剂以静脉注射盐水的形式给药，然后进行假注射。主要结局是停经后 22 至 26 个月时的死亡或严重的神经发育障碍。严重的神经发育障碍被定义为严重的脑瘫或综合运动或复合认知评分低于 70（相当于低于平均值 2 标准差，分数越高表示表现越好）贝利婴幼儿发育量表第三版. 结果 共有 741 名婴儿被纳入符合方案疗效分析：376 名接受促红细胞生成素治疗，365 名接受安慰剂治疗。促红细胞生成素组和安慰剂组在 2 岁时死亡或严重神经发育障碍的发生率上没有显着差异（97 名儿童 [26%] 对 94 名儿童 [26%]；相对风险，1.03；95% 置信区间，0.81 至 1.32；P = 0.80）。早产儿视网膜病变、颅内出血、败血症、坏死性小肠结肠炎、支气管肺发育不良或死亡的发生率或严重不良事件的发生率在两组之间没有显着差异。结论 从出生后 24 小时到绝经后 32 周，对极早产儿进行大剂量促红细胞生成素治疗并没有降低严重神经发育障碍或 2 岁时死亡的风险。（由国家神经疾病和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）。颅内出血、败血症、坏死性小肠结肠炎、支气管肺发育不良或死亡或严重不良事件的发生频率。结论 从出生后 24 小时到绝经后 32 周，对极早产儿进行大剂量促红细胞生成素治疗并没有降低严重神经发育障碍或 2 岁时死亡的风险。（由国家神经疾病和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）。颅内出血、败血症、坏死性小肠结肠炎、支气管肺发育不良或死亡或严重不良事件的发生频率。结论 从出生后 24 小时到绝经后 32 周，对极早产儿进行大剂量促红细胞生成素治疗并没有降低严重神经发育障碍或 2 岁时死亡的风险。（由国家神经疾病和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）。结论 从出生后 24 小时到绝经后 32 周，对极早产儿进行大剂量促红细胞生成素治疗并没有降低严重神经发育障碍或 2 岁时死亡的风险。（由国家神经疾病和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）。结论 从出生后 24 小时到绝经后 32 周，对极早产儿进行大剂量促红细胞生成素治疗并没有降低严重神经发育障碍或 2 岁时死亡的风险。（由国家神经疾病和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）。