Review articleRoom air resuscitation of the depressed newborn: A systematic review and meta-analysis☆
Introduction
In North America, newborn resuscitation protocols reflect The Neonatal Resuscitation Program guidelines created by the American Heart Association and the American Academy of Pediatrics.1 As such, resuscitation with 100% oxygen is recommended for the resuscitation of all infants who remain centrally cyanosed once regular respirations have been established. Several studies have demonstrated the safety of resuscitating asphyxiated newborns with room air.2, 3, 4, 5, 6, 7, 8 The most recent ILCOR guidelines state that initiating resuscitation with either 21% or 100% oxygen is “reasonable” and both ILCOR and the World Health Organization recommend the initial use of room air for resuscitating newborns where supplemental oxygen (O2) is not readily available.9, 10
There have been three recent meta-analyses that have examined the effects of room air resuscitation (RAR) on 30-day mortality and on the incidence of hypoxic ischemic encephalopathy (HIE).11, 12, 13 These studies demonstrated consistently that infants resuscitated with room air had a lower overall mortality rate, but similar rates of HIE, compared to infants resuscitated with 100% oxygen.
Asphyxiated newborns continue to have a high early mortality rate. RAR is a promising therapy that appears to reduce overall mortality, however, little is known about how it affects 7-day mortality. We have undertaken another systematic review and meta-analysis of the evidence for RAR in the depressed neonate. We felt that another review was necessary for two reasons. None of the previous meta analyses used the outcome of mortality in the first week of life as their main outcome measure of interest. This outcome is clinically relevant and clinically distinct from overall mortality. We contend that death in the first week of life is more likely to reflect events surrounding resuscitation at the time of birth than is death at 1 month of age or later because most of the mortality associated with asphyxia occurs in the first week after birth. In one recent study of asphyxiated term newborns, 14 of 16 deaths occurred in the first week with no deaths reported prior to 32 h of age.14 There are also several causes of late mortality (e.g., late-onset sepsis, congenital anomalies) in term infants which are not likely to be impacted by newborn resuscitation. The primary outcome in this meta-analysis is ‘death in the first week of life’. Also, a large room air resuscitation trial which examined the effect of RAR on neonatal mortality in asphyxiated infants has been published since the release of the previous meta-analyses. Our review examines separately the effect of RAR on mortality at both 1 week and 1 month. We also examine, as a secondary outcome, the incidence of moderate to severe (Grade 2 and 3) HIE.
Section snippets
Searching
The literature search was performed in August 2005 using Medline (1966-August, 2005), Embase (1980-August week 31, 2005), CINAHL (1982-July week 5, 2005) and the Cochrane Central Register of Controlled Trials (Issue 3, 2005). The following subject, text word and MeSH heading were used: “neonate(s), newborn(s) or infant(s)”; “asphyxia*” AND “resuscitat* OR room air”. The Cochrane Neonatal Group (formerly the Oxford Database of Perinatal Trials) was hand searched. The online Metaregister of
Trial flow
From the literature search, seven studies were identified as meeting the criteria for inclusion in this review.2, 3, 4, 5, 6, 7, 8 Refer to Figure 1 for a summary of the study selection process.
Study characteristics
The seven trials included were published in full and contained data on 2011 infants.2, 3, 4, 5, 6, 7, 8Table 2 presents detailed characteristics of the studies included. The Resair 2 trial was a multi-national project (Spain, Denmark, Norway, India, Egypt, Philippines and Estonia).5 The authors of this
Deaths in the first week and first month (Figures 2 and 3)
Six of the studies reported death in the first week as an outcome.3, 4, 5, 6, 7, 8 The combined sample size was 1807. Mortality in the first week of life was lower in the RAR group compared to the O×R group, odds ratio 0.70 (95% CI 0.50, 0.98). The χ2-test for heterogeneity was non-significant (P = 0.939).
The RAR group also had lower odds of death at 1 month of age compared to the O×R group, odds ratio 0.63 (95% CI 0.42,0.94). Death in the first month was reported as an outcome in five of the
Discussion
This systematic review demonstrates that room air resuscitation, when compared to resuscitation with 100% oxygen, is associated with decreased mortality at both 1 week and 1 month. These findings are not surprising in light of several studies that have demonstrated less favorable outcomes in experimentally asphyxiated animals resuscitated with hyperoxic gas mixtures.18, 19, 20, 21, 22 Vento and colleagues have shown that even a brief exposure to a hyperoxic gas mixture at the time of birth can
Conflict of interest
The authors of this paper do not have any conflicts of interest. We have no financial or personal relationships with other people or organisations that might inappropriately influence our work.
Acknowledgement
The authors wish to thank Dr. Maximo Vento for kindly providing us with unpublished details of his study results. We also appreciate the efforts of Dr. Albert Akierman and Dr. Orlando da Silva for their critical reviews of early versions of this manuscript.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at 10.1016/j.resuscitation.2006.06.134.
- 1
Present address: Heritage Medical Sciences Building, 2951 Health Sciences Centre, 330 Hospital Drive, NW, Calgary, Alberta, Canada T2N 4N1. Tel.: +1 403 210 3951; fax: +1 403 270 0979.
- 2
Present address: Rockyview General Hospital, Unit 63, 7007-14th Street, Calgary, Alberta, Canada T2V 1P9. Tel.: +1 403 943 3424; fax: +1 403 212 1243.