Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.
Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.
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DOI：
10.1056/nejmoa2119660
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发表时间：
2022-07-14
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新生儿缺氧缺血性脑病是幸存者死亡和长期残疾的重要原因。据推测，促红细胞生成素对患有缺氧缺血性脑病的婴儿具有神经保护作用，但当与治疗性低温联合使用时，其对神经发育结果的影响尚不清楚。在一项多中心、双盲、随机、安慰剂对照试验中，我们分配了501名妊娠36周或以上伴有中度或重度缺氧缺血性脑病的婴儿接受促红细胞生成素或安慰剂治疗，并结合标准治疗性低温治疗。在出生后26小时内以及2、3、4和7天龄时静脉注射促红细胞生成素（每公斤体重1000 U）或生理盐水安慰剂。主要结局是22至36月龄时死亡或神经发育障碍。神经发育障碍的定义为脑瘫、大运动功能分类系统水平至少为1（在0[正常]到5[最受损]的范围内），或者在第三版Bayley婴幼儿发育量表中认知评分低于90（相当于比平均值低0.67 SD，得分越高表现越好）。在修改意向治疗分析的500名婴儿中，257名接受促红细胞生成素治疗，243名接受安慰剂治疗。红细胞生成素组的死亡或神经发育障碍发生率为52.5%，安慰剂组为49.5%（相对危险度为1.03；95%可信区间[CI]， 0.86 ~ 1.24; P = 0.74）。红细胞生成素组每个儿童严重不良事件的平均数量高于安慰剂组（0.86 vs 0.67；相对危险度，1.26;95% CI, 1.01 ~ 1.57）。对因缺氧缺血性脑病而接受治疗性低温治疗的新生儿给予促红细胞生成素并不会导致比安慰剂更低的死亡或神经发育障碍风险，而且与更高的严重不良事件发生率相关。（由国家神经疾病和中风研究所资助；ClinicalTrials.gov编号：NCT02811263。）
Neonatal hypoxic–ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic–ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic–ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic–ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.)