Chaudhari Tejasvi, McGuire William
Centre for Newborn Care, Canberra Hospital, Canberra, ACT, Australia, 2605.
Cochrane Database Syst Rev. 2008 Apr 16(2):CD006817. doi: 10.1002/14651858.CD006817.pub2.
Delayed neuronal death following a perinatal hypoxic insult is due partly to xanthine oxidase-mediated production of cytotoxic free radicals. Evidence exists that allopurinol, a xanthine-oxidase inhibitor, reduces delayed cell death in animal models of perinatal asphyxia and in human patients with other forms of organ reperfusion injury.
To determine the effect of allopurinol on mortality and morbidity in newborn infants with suspected hypoxic-ischaemic encephalopathy.
The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007), MEDLINE (1966 - December 2007), EMBASE (1980 - December 2007), conference proceedings, and previous reviews.
Randomised or quasi-randomised controlled trials that compared allopurinol administration vs. placebo or no drug in newborn infants with suspected hypoxic-ischaemic encephalopathy.
The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two authors. Data were synthesised using a fixed effects model and reported using typical relative risk, typical risk difference and weighted mean difference.
Three trials in which a total of 114 infants participated were identified. In one trial, participants were exclusively infants with severe encephalopathy. The other trials also included infants with mild and moderately-severe encephalopathy. These studies were generally of good methodological quality, but were underpowered to detect clinically important effects of allopurinol on mortality and morbidity. Meta-analysis did not reveal a statistically significant difference in the risk of death during infancy [typical relative risk 0.92 (95% confidence interval 0.59 to 1.45); typical risk difference -0.03 (95% confidence interval -0.16 to 0.11)], nor in the incidence of neonatal seizures [typical relative risk 0.93 (95% confidence interval 0.75 to 1.16); typical risk difference -0.05 (95% confidence interval -0.21 to 0.11)]. Only one trial assessed neurodevelopment in surviving children and did not find a statistically significant effect.
AUTHORS' CONCLUSIONS: The available data are not sufficient to determine whether allopurinol has clinically important benefits for newborn infants with hypoxic-ischaemic encephalopathy and, therefore, larger trials are needed. Such trials could assess allopurinol as an adjunct to therapeutic hypothermia in infants with moderate and severe encephalopathy and should be designed to exclude clinically important effects on mortality and adverse long-term neurodevelopmental outcomes.
围产期缺氧性损伤后迟发性神经元死亡部分归因于黄嘌呤氧化酶介导的细胞毒性自由基生成。有证据表明，黄嘌呤氧化酶抑制剂别嘌醇可减少围产期窒息动物模型以及患有其他形式器官再灌注损伤的人类患者的迟发性细胞死亡。
确定别嘌醇对疑似缺氧缺血性脑病新生儿死亡率和发病率的影响。
采用Cochrane新生儿综述小组的标准检索策略。这包括检索Cochrane对照试验中央注册库（CENTRAL，《Cochrane图书馆》，2007年第4期）、MEDLINE（1966年 - 2007年12月）、EMBASE（1980年 - 2007年12月）、会议论文集以及以往的综述。
比较别嘌醇给药与安慰剂或不给药对疑似缺氧缺血性脑病新生儿影响的随机或半随机对照试验。
采用Cochrane新生儿综述小组的标准方法，由两位作者分别评估试验质量并提取数据。数据采用固定效应模型进行综合分析，并使用典型相对风险、典型风险差值和加权平均差值进行报告。
共确定了三项试验，总计114名婴儿参与。在一项试验中，参与者均为患有严重脑病的婴儿。其他试验还包括患有轻度和中度 - 重度脑病的婴儿。这些研究总体方法学质量良好，但检测别嘌醇对死亡率和发病率的临床重要影响的能力不足。荟萃分析未发现婴儿期死亡风险存在统计学显著差异[典型相对风险0.92（95%置信区间0.59至1.45）；典型风险差值 -0.03（95%置信区间 -0.16至0.11）]，新生儿惊厥发生率也无差异[典型相对风险0.93（95%置信区间0.75至1.16）；典型风险差值 -0.05（95%置信区间 -0.21至0.11）]。仅有一项试验评估了存活儿童的神经发育情况，未发现统计学显著影响。
现有数据不足以确定别嘌醇对缺氧缺血性脑病新生儿是否具有临床重要益处，因此需要进行更大规模的试验。此类试验可评估别嘌醇作为中度和重度脑病婴儿治疗性低温的辅助药物，并且应设计为排除对死亡率和长期不良神经发育结局的临床重要影响。
