Elsevier

The Lancet

Volume 364, Issue 9442, 9–15 October 2004, Pages 1329-1333
The Lancet

Articles
Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis

https://doi.org/10.1016/S0140-6736(04)17189-4Get rights and content

Summary

Background

International consensus statements for resuscitation of newborn infants recommend provision of 100% oxygen with positive pressure if assisted ventilation is required. However, 100% oxygen exacerbates reperfusion injury in animals and reduces cerebral perfusion in newborn babies. We aimed to establish whether resuscitation with air decreased mortality or neurological disability in newborn infants compared with 100% oxygen.

Methods

We did a systematic review and meta-analysis of trials that compared resuscitation with air versus 100% oxygen, using the methods of the Cochrane Collaboration. We combined data for similar outcomes in the analysis where appropriate, using a fixed-effects model.

Findings

Five trials (two masked and three unmasked),consisting of 1302 newborn infants, fulfilled the inclusion criteria. Most babies were born at or near term in developing countries. In the three unmasked studies, infants resuscitated with room air who remained cyanotic and bradycardic were switched to 100% oxygen at 90 s. The masked studies allowed crossover to the other gas during the first minutes of life. Although no individual trial showed a difference in mortality, the pooled analysis showed a significant benefit for infants resuscitated with air (relative risk 0·71 [95% CI 0·54 to 0·94], risk difference –0·05 [–0·08 to –0·01]). The effect on long-term development could not be reliably determined because of methodological limitations in the one study that followed up infants beyond 12 months of age.

Interpretation

For term and near-term infants, we can reasonably conclude that air should be used initially, with oxygen as backup if initial resuscitation fails. The effect of intermediate concentrations of oxygen at resuscitation needs to be investigated. Future trials should include and stratify for premature infants.

Introduction

Rapid and complex physiological changes occur during birth. Usually, these changes are spontaneous and no intervention from health professionals is necessary. However, roughly 5–10% of newborn infants require some assistance to begin breathing in the first minutes after delivery.1 The aim of resuscitation is to prevent death and adverse long-term neurodevelopmental sequelae. International consensus statements on resuscitation of the newborn infant1, 2 state that adequate ventilation is the key to success, and that if assisted ventilation is required, 100% oxygen should be delivered by positive pressure ventilation. Others have noted3, 4 that this recommendation is based mainly on precedent rather than sound evidence.

Concerns have been raised about the potential adverse effects of 100% oxygen.5 Hyperoxia slows cerebral blood flow in term and preterm infants,6 and exposure to even brief periods of 100% oxygen at delivery causes long-term reductions in cerebral blood flow in newborn preterm infants.7 In addition, high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia.8, 9 Thus, air might be a more appropriate gas than 100% oxygen.10 We aimed to establish whether resuscitation with air reduced the occurrence of death or neurological disability in newborn infants compared with 100% oxygen.

Section snippets

Methods

We undertook a systematic review and meta-analysis using the methods and software of the Cochrane Collaboration. Three authors assessed each article according to the following criteria: masking of randomisation and intervention, completeness of follow-up, and masking of outcome assessment. Independently, these authors extracted data from every trial, then compared results and resolved differences. Four trials measured failure of resuscitation for both the 100% oxygen and air groups.13, 14, 15,

Results

Our initial search identified abstracts from about 350 potentially eligible clinical trials and 12 review articles; however most were rejected (eg, animal studies, commentaries, guidelines, or non-randomised human studies). Ten full-text articles were reviewed and five trials, totalling 1302 infants, fulfilled inclusion criteria (table 1).13, 14, 15, 16, 17 Allocation was quasi-random in three studies,13, 14, 17 which allocated babies born on even dates to resuscitation with air and those born

Discussion

One death would be prevented for every 20 babies resuscitated with air rather than 100% oxygen. No significant differences were recorded for outcomes of neurological disability. Resuscitation of adults and children is recorded as far back as biblical times,20, 21 but the use of 100% oxygen for this purpose is a recent notion.22 Providing supplemental oxygen to a patient who has had hypoxia seems logical. This biological plausibility, exemplified by the opinion that “oxygen is vital, not just

Search strategy and selection criteria

We searched PubMed from 1966–04 using the terms “resuscitation”, “oxygen”, and “infant”; and the Cochrane Controlled Trials Register using “resuscitation” and “infant”. We searched Abstracts of the Society for Pediatric Research and the European Society for Paediatric Research from 1996–04, and found full-text articles on MEDLINE by searching for authors' names. Previous reviews were cross-referenced and personal files searched for additional references. No language restrictions were

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