长期使用别嘌醇对中等围产期窒息后神经保护作用的随访：两项随机对照试验的后续研究。
Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials.
机构信息
Perinatal Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, The Netherlands.
出版信息
Arch Dis Child Fetal Neonatal Ed. 2012 May;97(3):F162-6. doi: 10.1136/archdischild-2011-300356. Epub 2011 Nov 17.
OBJECTIVE
Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.
DESIGN
Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.
SETTING
Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.
PATIENTS
Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.
INTERVENTION
Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.
MAIN OUTCOME MEASURES
Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).
RESULTS
The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94).
CONCLUSIONS
The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.
目的
自由基诱导的再灌注损伤已被认为是出生窒息后脑组织损伤的一个重要原因。别嘌呤醇可减少自由基的形成，从而可能限制缺氧-再灌注损伤的程度。本研究旨在探讨出生窒息后新生儿别嘌呤醇治疗的长期预后。
设计
对之前进行的两项随机对照试验进行了 4 至 8 年的随访。
地点
荷兰莱顿大学医学中心、格罗宁根大学医学中心和乌得勒支大学医学中心。
患者
54 例足月婴儿在之前进行的两项试验中均患有中重度出生窒息。
干预措施
婴儿出生后 4 小时内接受 40mg/kg 别嘌呤醇（间隔 12 小时）或作为对照。
主要观察指标
存活的儿童接受韦氏学前和小学智力量表或韦氏儿童智力量表评估，并进行神经检查。在窒息婴儿的总人群中以及在中度窒息婴儿的预设亚组（基于振幅整合脑电图）中，检查别嘌呤醇对严重不良结局（定义为 4-8 岁时死亡或严重残疾）的影响。
结果
随访期间（n=23）的平均年龄为 5 岁 5 个月（标准差 1 岁 2 个月）。别嘌呤醇治疗组与对照组在长期预后方面无差异。然而，中度窒息组的亚组分析显示，别嘌呤醇治疗组严重不良结局的发生率明显低于对照组（25% vs 65%；RR 0.40，95%CI 0.17 至 0.94）。
结论
报告的数据可能提示新生儿别嘌呤醇治疗对中度窒息婴儿具有（神经）保护作用。
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