早产儿红细胞生成素神经保护的随机试验。
A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.
机构信息
From the University of Washington, Seattle (S.E.J., B.A.C., D.E.M., P.T.V., P.J.H.); Florida Hospital Orlando, Orlando (R.W.), the University of Florida, Gainesville (M.W.), South Miami Hospital, South Miami (J.E.P.), and Johns Hopkins All Children's Hospital, St. Petersburg (V.M.) - all in Florida; the University of Arkansas for Medical Sciences, Little Rock (S.E.C.); the University of Louisville, Louisville, KY (T.R.); Methodist Children's Hospital, San Antonio, TX (K.A.A.); Children's Hospital and Clinics of Minnesota (E.B.-S.) and University of Minnesota Masonic Children's Hospital (R.R., N.F.), Minneapolis, and Children's Minnesota, St. Paul (A.L.) - all in Minnesota; the University of Utah, Salt Lake City (M.B.); Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY (E.F.L.); Wake Forest School of Medicine, Winston-Salem (L.C.D.), and the University of North Carolina, Chapel Hill (T.M.O.) - both in North Carolina; Beth Israel Deaconess Medical Center (I.D.F.) and Boston University (K.K.) - both in Boston; Prentice Women's Hospital (J.Y.K.) and Children's Hospital of the University of Illinois (N.S.) - both in Chicago; Johns Hopkins University, Baltimore (M.M.G.), and the National Institute of Neurological Disorders and Stroke, Bethesda (A.L.H.) - both in Maryland; and the University of New Mexico, Albuquerque (R.K.O., J.L.).
出版信息
N Engl J Med. 2020 Jan 16;382(3):233-243. doi: 10.1056/NEJMoa1907423.
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.).
背景
高剂量促红细胞生成素已在新生儿脑损伤的临床前模型中显示出神经保护作用，并且 2 期试验表明其可能有效；然而，这种疗法在极早产儿中的益处和安全性尚未得到证实。
方法
在这项多中心、随机、双盲的高剂量促红细胞生成素试验中，我们将 941 名胎龄 24 周零 0 天至 27 周零 6 天的婴儿随机分为出生后 24 小时内接受促红细胞生成素或安慰剂治疗的两组。促红细胞生成素以 1000 单位/千克体重的剂量静脉内给药，每 48 小时给药一次，共给药 6 次，然后通过皮下注射每周 3 次给予 400 单位/千克的维持剂量，直至完成 32 周的校正胎龄。安慰剂通过静脉内生理盐水给药，然后进行假注射。主要结局是出生后 22 至 26 个月时死亡或严重神经发育障碍。严重神经发育障碍定义为严重脑瘫，或婴儿和幼儿发育第三版贝利量表的综合运动或综合认知评分低于 70（低于平均值 2 个标准差，得分越高表示表现越好）。
结果
共有 741 名婴儿被纳入方案疗效分析：376 名接受促红细胞生成素治疗，365 名接受安慰剂治疗。在 2 岁时死亡或严重神经发育障碍的发生率方面，促红细胞生成素组与安慰剂组之间无显著差异（97 名儿童[26%] vs. 94 名儿童[26%]；相对风险，1.03；95%置信区间，0.81 至 1.32；P=0.80）。两组间早产儿视网膜病变、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以及严重不良事件的频率均无显著差异。
结论
出生后 24 小时至 32 周校正胎龄期间给予极早产儿高剂量促红细胞生成素治疗并未降低 2 岁时严重神经发育障碍或死亡的风险。（由国家神经病学和中风研究所资助；PENUT ClinicalTrials.gov 编号，NCT01378273。）
Zotero 插件