Which oxygen saturation level should we use for very premature infants? A randomised controlled trial (BOOST -II UK)

Lead Research Organisation: University of Oxford
Department Name: National Perinatal Epidemiology Unit

Abstract

In the UK each year over three thousand babies are born more than 12 weeks premature. Two thirds of these very premature babies now survive, but most grow poorly and many have problems breathing. A quarter have at least one major disability at age two, and many have cerebral palsy. Most of these babies require oxygen therapy for several weeks after birth, but we know that giving babies very high levels of oxygen is toxic to the developing eye which may lead to surgery on the eye in order to try and prevent blindness. We do not know whether very preterm babies should only be given enough oxygen to maintain their levels a little above what it is in if they were still in the womb, or whether we should try and keep the their oxygen levels as high as a baby born at the usual time. If oxygen levels are kept low it is likely to prevent eye damage but it may lead to more deaths and may lead to other disabilities in this group of babies. Alternatively if the oxygen levels are kept high it may cause eye damage but prevent early deaths and other later disability.

This randomised study will compare the effects of maintaining the babies oxygen level low (functional arterial oxygen saturations at 85?89%) versus high (functional arterial oxygen saturations at 91?95%) in babies born at less than 28 weeks gestation. The primary outcome for the trial is death and major disability at age 2 years. Secondary outcomes include retinal surgery for retinopathy of prematurity as well as duration of oxygen therapy, chronic lung disease, growth and health service utilisation. The trial will recruit 1,200 babies from 20 UK centres over a period of four years.

Technical Summary

In the UK each year over three thousand babies are born more than 12 weeks premature. Two thirds of these very premature babies now survive to discharge, but most grow poorly and many have respiratory problems. A quarter have at least one major disability when seen for assessment two years later, and many have cerebral palsy. Most of these babies require supplemental oxygen for several weeks after birth, but high arterial oxygen pressures are known to be toxic to the developing retina. We do not know whether very preterm babies should only be given enough oxygen to maintain arterial saturation a little above what it is in utero, or enough to achieve the saturations seen in the healthy term baby after birth. Observational studies suggest that rates of retinopathy of prematurity correlate with differing attitudes towards early oxygen use. However restricting oxygen exposure to minimise this problem risks increasing early mortality, the number of survivors with cerebral palsy, and cognitive ability in the long term survivors. This double blind randomised controlled trial will compare the effects of maintaining functional arterial oxygen saturations at levels of 85?89% versus 91?95% in babies born at less than 28 weeks gestation. The primary outcome for the trial is mortality and major disability at age 2 years. Secondary outcomes include retinal surgery for retinopathy of prematurity as well as duration of oxygen therapy, chronic lung disease, growth and health service utilisation. The trial will recruit 1,200 babies from 20 UK centres over a period of four years.

Publications

10 25 50
 
Description Changes to Oxygen Saturation Targets for extremely Pre-Term Infants at individual Neonatal Units
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Following the announcement of increased survival of infants receiving the higher saturation targets a number of hospitals have already amended their oxygen target ranges for very premature infants, to avoid targeting too low. The information given has always been that these are very early findings and that further information from the final study data is required before any clear guidance can be given. Many other neonatal units have therefore made no or only minor changes to their target ranges and are keenly awaiting further information from the forthcoming short-term results paper planned for early 2012 and the final paper due late 2013.
 
Description Major Ophthalmology Project Grant Year 1
Amount £45,000 (GBP)
Organisation The Royal College of Surgeons of Edinburgh 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2009 
End 03/2010
 
Description Major Ophthalmology Project Grant Year 2
Amount £45,000 (GBP)
Organisation The Royal College of Surgeons of Edinburgh 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2010 
End 03/2011
 
Description Major Ophthalmology Project Grant Year 3
Amount £28,000 (GBP)
Organisation The Royal College of Surgeons of Edinburgh 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2011 
End 03/2012
 
Description NeOProM: Neonatal Oxygenation Prospective Meta-analysis 
Organisation Christchurch Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution BOOST-II UK are responsible for the recruitment and follow-up of babies in the UK and Ireland. BOOST-II UK will publish their trial results independently of the NeOProM collaboration. Data from all studies will also be combined to enable a prospective meta-analysis to be performed.
Collaborator Contribution Each study will have independent responsibility for the recruitment and follow-up of babies in their country. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The methodology to be used will provide the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility.
Impact 21235822 NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol BMC Pediatrics , 11 , Article 6. 10.1186/1471-2431-11-6.
 
Description NeOProM: Neonatal Oxygenation Prospective Meta-analysis 
Organisation Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Department Neonatal Research Network
Country United States 
Sector Charity/Non Profit 
PI Contribution BOOST-II UK are responsible for the recruitment and follow-up of babies in the UK and Ireland. BOOST-II UK will publish their trial results independently of the NeOProM collaboration. Data from all studies will also be combined to enable a prospective meta-analysis to be performed.
Collaborator Contribution Each study will have independent responsibility for the recruitment and follow-up of babies in their country. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The methodology to be used will provide the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility.
Impact 21235822 NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol BMC Pediatrics , 11 , Article 6. 10.1186/1471-2431-11-6.
 
Description NeOProM: Neonatal Oxygenation Prospective Meta-analysis 
Organisation McMaster University
Department Canadian Oxygen Trial (COT)
Country Canada 
Sector Academic/University 
PI Contribution BOOST-II UK are responsible for the recruitment and follow-up of babies in the UK and Ireland. BOOST-II UK will publish their trial results independently of the NeOProM collaboration. Data from all studies will also be combined to enable a prospective meta-analysis to be performed.
Collaborator Contribution Each study will have independent responsibility for the recruitment and follow-up of babies in their country. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The methodology to be used will provide the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility.
Impact 21235822 NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol BMC Pediatrics , 11 , Article 6. 10.1186/1471-2431-11-6.
 
Description NeOProM: Neonatal Oxygenation Prospective Meta-analysis 
Organisation University of Sydney
Department NHMRC Clinical Trials Centre
Country Australia 
Sector Academic/University 
PI Contribution BOOST-II UK are responsible for the recruitment and follow-up of babies in the UK and Ireland. BOOST-II UK will publish their trial results independently of the NeOProM collaboration. Data from all studies will also be combined to enable a prospective meta-analysis to be performed.
Collaborator Contribution Each study will have independent responsibility for the recruitment and follow-up of babies in their country. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The methodology to be used will provide the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility.
Impact 21235822 NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol BMC Pediatrics , 11 , Article 6. 10.1186/1471-2431-11-6.
 
Description Launch of European Standards for Neonatal Care EU Parliament 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Launch of our Standards Project
Year(s) Of Engagement Activity 2018
URL https://newborn-health-standards.org/
 
Description xStudy Update to Parents & Recruiting Centres in New England Journal of Medicine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Parents and recruiting centres were sent a study update in May 2013, to notify them that Short-term Outcome results had been published in the new England Journal of Medicine. The update gave a summary of the results and details of where the full publication could be accessed.

Minimal responses from parents were received with two bereaved families requesting that no further study updates be sent.
Year(s) Of Engagement Activity 2013
 
Description xStudy Update to Parents and Hospitals in The New England Journal of Medicine 364, 17, 1680-2 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact A study update was circulated to parents of all babies enrolled onto the study and all hospitals involved in BOOST-II, in April 2011 which gave a brief summary of why recruitment was closed early and advised of the publication of the paper by Dr Ben Stenson, Increased 36-week survival with high oxygen saturation target in extremely preterm infants, in The New England journal of medicine 364, 17, 1680-2

Minimal contact was received from parents, two parents of surviving babies rang to thank us for the information and for the opportunity to take part in the study, one bereaved family rang to request no more information and a number of bereaved parents responded by post to confirm they would like further updates as they become available.
Year(s) Of Engagement Activity 2011