Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy

  • Review
  • Intervention




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 experimental models of perinatal asphyxia and in people with organ reperfusion injury.


To determine the effect of allopurinol on mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy.

Search methods

We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1), MEDLINE (1966 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), conference proceedings, and previous reviews.

Selection criteria

Randomised or quasi-randomised controlled trials that compared allopurinol administration versus placebo or no drug in newborn infants with hypoxic-ischaemic encephalopathy.

Data collection and analysis

We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.

Main results

We included three trials in which a total of 114 infants participated. 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 too small to exclude clinically important effects of allopurinol on mortality and morbidity. Meta-analysis did not reveal a statistically significant difference in the risk of death (typical risk ratio 0.88; 95% confidence interval (95% CI) 0.56 to 1.38; risk difference -0.04; 95% CI -0.18 to 0.10) or a composite of death or severe neurodevelopmental disability (typical risk ratio 0.78; 95% CI 0.56 to 1.08; risk difference -0.14; 95% CI -0.31 to 0.04).

Authors' conclusions

The available data are not sufficient to determine whether allopurinol has clinically important benefits for newborn infants with hypoxic-ischaemic encephalopathy. Much 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 important effects on mortality and adverse long-term neurodevelopmental outcomes.








Cochrane Neonatal Groupの標準的検索法を用いた。Cochrane Central Register of Controlled Trials(CENTRAL、コクラン・ライブラリ2012年第1号)、MEDLINE(1966~2012年3月)、EMBASE (1980~2012年3月)、CINAHL(1982~2012年3月)、学会抄録および過去のレビューを検索した。




Cochrane Neonatal Review Groupの標準的方法を用いてデータを抽出し、2名のレビューアが別々に試験の質とデータ抽出の評価を行った。


参加総数114名の新生児を対象とした3件の試験を選択した。1件の試験では、重度の脳症の新生児だけが参加していた。他の試験は、軽度から中等度の重症度の脳症の新生児を組み入れていた。これらの研究の方法論的質は全般的に良好であったが、死亡および罹病に対するアロプリノールの臨床的に重要な効果を排除するにはかなり小規模であった。メタアナリシスでは、死亡リスク[リスク比0.88、95%信頼区間(CI)0.56~1.38;リスク差 -0.04、95%CI -0.18~0.10]、死亡または重度の神経発達障害の複合(リスク比0.78、95%CI 0.56~1.08;リスク差-0.14、95%CI -0.31~0.04)に統計学的有意差は示されなかった。



Plain language summary

Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy

Newborn infants who have been deprived of oxygen before, during, or after delivery (perinatal asphyxia) are at high risk of dying or developing brain damage. Studies using animal models suggest that allopurinol (a drug commonly used for preventing gout) can reduce the level of brain damage following perinatal asphyxia. Three small randomised controlled trials that examined whether giving allopurinol to newborn infants following perinatal asphyxia affected their outcomes were identified. None of these trials provided any evidence of benefit. Larger trials are needed to exclude important effects on survival and disability.





監  訳: 江藤 宏美,2012.11.14

実施組織: 厚生労働省委託事業によりMindsが実施した。

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