Clinical PaperOutcomes of preterm infants following the introduction of room air resuscitation☆
Introduction
Guidelines for oxygen use during newborn resuscitation have changed repeatedly over the past 10 years as new evidence regarding the perils of excessive oxygen exposure became available. In 2005, the International Liaison Committee on Resuscitation (ILCOR) published recommendations stating there was “insufficient evidence to specify the concentration of oxygen to be used at initiation of resuscitation”, which implied that it was reasonable to continue the standard practice of giving 100% oxygen at the start of resuscitation.1 Given mounting concerns about the dangers of hyperoxemia at birth, the Canadian Neonatal Resuscitation Program (NRP) Committee issued an amendment in 2006 to recommend that newborn resuscitation should begin with room air, regardless of gestational age.2 The latest ILCOR recommendation, published in 2010, was updated to state that resuscitation of term infants should start with room air and that blended oxygen may be used for preterm infants.3 However, the recommendation also specifies that, where blended oxygen is not available, resuscitation should be initiated with room air. The most recent Canadian addendum to the 6th edition of the NRP textbook states that resuscitation should be started with room air for infants born at ≥32 weeks gestation, while oxygen concentrations for infants born at <32 weeks gestation should be guided by local protocols.4, 5
There is convincing evidence that 100% oxygen use in the delivery room can have far-reaching, clinically significant detrimental effects on outcomes for term infants.6, 7, 8 Several smaller studies comparing low versus high oxygen concentrations for the resuscitation of preterm infants have been published.6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 These studies failed to show differences in clinically meaningful outcomes, perhaps due to small sample sizes, and as a result there are still many unanswered questions about the safety of using different oxygen concentrations during resuscitation of very preterm infants. Nearly all infants in the low oxygen groups in these studies required an increase in the inspired concentration of oxygen (FiO2). While none of the studies showed differences in survival or severe injury, they did demonstrate high treatment failure rates for preterm infants initially resuscitated with 21–30% oxygen.
Following publication of the Canadian NRP amendment in 2006, most neonatal intensive care units (NICUs) in Canada changed their local resuscitation practices for preterm infants and began using either room air or an intermediate concentration of oxygen (e.g., 30–40% oxygen) at the start of resuscitation. Our study objective was to determine if neonatal outcomes for infants born at ≤27 weeks gestation changed following this modification in practice.
Section snippets
Study design and population
In this retrospective cohort study, we included infants born at a gestational age of 23–27 weeks between 2004 and 2009 who were inborn at participating Canadian Neonatal Network (CNN) NICUs that stopped using a static concentration of 100% oxygen during resuscitation. To be included in the study, inborn infants must have been admitted to the NICU, or died prior to NICU admission despite resuscitation efforts. Infants were excluded from the study if they had severe congenital anomalies, were
Results
Of the 27 participating CNN centers during the period of interest, 17 centers contributed data: 6 NICUs were not eligible as they continued resuscitation with 100% oxygen and 4 NICUs did not respond to the questionnaire. Data collection for the OX100 (n = 1082 infants) and OXtitrate (n = 1244 infants) groups spanned 2004–2007 and 2006–2009, respectively. Details of the eligible infants and study flow are reported in Fig. 1. Of the 17 NICUs included in the study, 12 NICUs switched to initiating
Discussion
In this retrospective cohort study, the risk of severe neurologic injury or death increased in infants born at ≤27 weeks gestation following a change in local policies to begin resuscitation using less than 100% oxygen. This increased risk was observed both in infants that received 21% oxygen (room air) and those that received between 22 and 100% oxygen. If the magnitude of the observed change in our primary outcome is accurate, we estimate that following the change in policy we observed
Conclusions
This study reports a significant increase in severe neurologic injury or death for infants born ≤27 weeks gestation following changes to local policies in Canadian NICUs recommending the use of less than 100% oxygen during newborn resuscitation. Our results should not be interpreted as treatment recommendations. Rather, this study highlights an observed association between a change in policy at several institutions and various outcomes, which raises potential concerns about the use of room air
Funding source
No external funding was secured for this study. Organizational support to the Canadian Neonatal Network™ was provided by the Canadian Institutes of Health Research-funded Team in Maternal-Infant Care. Dr. Prakesh Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the Canadian Institutes of Health Research.
Conflict of interest statement
None of the authors have conflicts of interest to disclose.
Clinical trial registration
Not applicable.
Contributors’ statement
Yacov Rabi and Prakesh S Shah: Drs. Rabi and Shah conceptualized and designed the study, coordinated and supervised the acquisition of data, carried out the statistical analysis, reviewed and interpreted the data, drafted the initial manuscript, critically reviewed and revised the manuscript, and approved the final manuscript as submitted.
Abhay Lodha: Dr. Lodha conceptualized and designed the study, coordinated and supervised the acquisition of data, carried out the statistical analysis,
Acknowledgements
We would like to thank the staff of the CNN Coordinating Centre for providing organizational support to the CNN and Ruth Warre for editorial assistance with this article. The CNN Coordinating Centre and Dr. Warre are based at the Maternal-Infant Care Research Centre at Mount Sinai Hospital, Toronto, Ontario, Canada, which is supported by funding from the Canadian Institutes for Health Research and Mount Sinai Hospital, Toronto. Prakesh Shah is supported by an Applied Research Chair in
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2015.08.012.
- 1
Department of Paediatrics, Section of Neonatal-Perinatal Medicine, Foothills Medical Centre, Room C211, 1403 29 Street NW, Calgary, Alberta, Canada T2N 2T9.
- 2
Department of Paediatrics, Section of Neonatal-Perinatal Medicine, Alberta Children's Hospital, 2888 Shaganappi Trail Northwest, Calgary, Alberta, Canada T3B 6A8.
- 3
Department of Paediatrics, Section of Neonatal-Perinatal Medicine, Sainte Justine University Health Center, 2900, boul. Édouard-Montpetit, Montréal, Québec, Canada H3T 1J4.
- 4
Department of Paediatrics, Section of Neonatal-Perinatal Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.