Resuscitation of newborn infants with 21% or 100% oxygen: an updated meta-analysis

The optimal oxygen concentration for newborn resuscitation has been a matter of intense debate during the past years.
Experimental and clinical trials have suggested that resuscitation in room air is at least as effective as resuscitation in 100% oxygen. Some systematic reviews have addressed this issue. Overall, these analyses suggested a decreased risk of neonatal mortality and a trend toward a reduced risk of hypoxic ischemic encephalopathy (HIE) in infants resuscitated in room air. Despite these findings, international guidelines recommend use of 100% oxygen during initial resuscitation. This suggestion may be based, at least in part, on the belief that the trials available in clinical literature were not methodologically rigorous.
In the last years, new randomized trials of room air versus 100% oxygen have been published. Therefore, a new meta-analysis has been recently conducted. This meta-analysis has updated and analyzed all the available information from randomized or quasi-randomized trials of resuscitation in room air compared to 100% oxygen. Moreover, a separate analysis of the data from strictly randomized studies was conducted, in order to address concerns regarding the impact of methodology on the estimates of effect.
In particular, randomized or quasi-randomized studies of depressed newborn infants resuscitated with 21 or 100% oxygen with or without masking of treatment were considered for inclusion. Neonatal mortality and the incidence of HIE stage 2-3 were among the outcomes of interest. The studies included newborn infants regardless of gestational age and birth weight.
Ten studies fulfilled the inclusion criteria; among these, 6 were identified as being strictly randomized. In total, 1,082 infants were allocated to resuscitation with 21% oxygen and 1,051 infants with 100% oxygen. The risk of neonatal mortality was reduced in the 21% oxygen group when compared to the 100% oxygen group both in the analysis of all studies (typical relative risk [RR] = 0.69, 95% confidence interval [CI] 0.54-0.88) and in the analysis of strictly randomized studies (typical RR 0.32, 95% CI 0.12-0.84). A trend toward a decrease in the risk of HIE stage 2 and 3 was noted with resuscitation in 21% oxygen in the analysis of all studies (typical RR 0.88, 95% CI 0.72-1.08).
This meta-analysis indicates that resuscitation of term or near-term newborn infants with room air seems to be safe and may be of great benefit, leading to a reduction of neonatal mortality by 30-40%. Moreover, the use of this technique could also reduce severe HIE when compared to 100% oxygen. Overall, these results are in good agreement with those of the previous meta-analyses, and are consistent when considering only strictly randomized trials. A possible alternative to resuscitation in room air may be represented by resuscitation with 40% oxygen, which showed promising results in an observational trial; however, this technique has not been tested in a randomized study.
In conclusion, the results of this meta-analysis might suggest that pure oxygen should be avoided for resuscitation of depressed newly born term or near-term infants, until new data are available.

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