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Meta-Analysis
. 2012 Jul 11;2012(7):CD006817.
doi: 10.1002/14651858.CD006817.pub3.

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

Tejasvi Chaudhari  1 , William McGuire
Affiliations
Meta-Analysis

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

Tejasvi Chaudhari et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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.

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Conflict of interest statement

None.

Figures

1
1
Forest plot of comparison: 1 Allopurinol versus control (placebo or no drug), outcome: 1.1 Death during the neonatal period and infancy.
2
2
Forest plot of comparison: 1 Allopurinol versus control (placebo or no drug), outcome: 1.2 Death or severe neurodevelopmental disability.
3
3
Forest plot of comparison: 1 Allopurinol versus control (placebo or no drug), outcome: 1.3 Severe quadriplegia in surviving infants.
4
4
Forest plot of comparison: 1 Allopurinol versus control (placebo or no drug), outcome: 1.4 Seizures during the neonatal period.
5
5
Forest plot of comparison: 1 Allopurinol versus control (placebo or no drug), outcome: 1.5 Abnormalities on brain imaging.
6
6
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Allopurinol versus control (placebo or no drug), Outcome 1 Death during the neonatal period and infancy.
1.2
1.2. Analysis
Comparison 1 Allopurinol versus control (placebo or no drug), Outcome 2 Death or severe neurodevelopmental disability.
1.3
1.3. Analysis
Comparison 1 Allopurinol versus control (placebo or no drug), Outcome 3 Severe quadriplegia in surviving infants.
1.4
1.4. Analysis
Comparison 1 Allopurinol versus control (placebo or no drug), Outcome 4 Seizures during the neonatal period.
1.5
1.5. Analysis
Comparison 1 Allopurinol versus control (placebo or no drug), Outcome 5 Abnormalities on brain imaging.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Benders 2006 {published data only}
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Chaudhari 2008
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