Open Access Highly Accessed Study protocol

NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol

Lisa M Askie1*, Peter Brocklehurst2, Brian A Darlow3, Neil Finer4, Barbara Schmidt56, William Tarnow-Mordi78 and the NeOProM Collaborative Group1

Author Affiliations

1 NHMRC Clinical Trials Centre, University of Sydney, (Parramatta Road), Camperdown, (2050), Australia

2 National Perinatal Epidemiology Unit (NPEU), University of Oxford, (Old Road Campus), Oxford, (OX3 7LF), UK

3 Christchurch School of Medicine, University of Otago, (Riccarton Avenue), Christchurch, (8140), New Zealand

4 Division of Neonatology, University of California San Diego (UCSD) Medical Center, (West Arbor Drive), San Diego, (92103), USA

5 Children's Hospital of Philadelphia, University of Pennsylvania, (Spruce Street), Philadelphia, (19104), USA

6 Neonatal Trials Group, McMaster University, (Concession Street), Hamilton, (L8V 1C3), Canada

7 Westmead Hospital, University of Sydney, (Cnr Hawkesbury and Darcy Roads), Westmead, (2145), Australia

8 Children's Hospital at Westmead, University of Sydney, (Cnr Hawkesbury Road and Hainsworth Street), Westmead, (2145), Australia

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BMC Pediatrics 2011, 11:6  doi:10.1186/1471-2431-11-6

Published: 17 January 2011

Abstract

Background

The appropriate level of oxygenation for extremely preterm neonates (<28 weeks' gestation) to maximise the greatest chance of survival, without incurring significant morbidity, remains unknown. Infants exposed to lower levels of oxygen (targeting oxygen saturations of <90%) in the first weeks of life are at increased risk of death, cerebral palsy, patent ductus arteriosus, pulmonary vascular resistance and apnoea, whilst those maintained in higher levels of oxygen (targeting oxygen saturations of >90%) have been reported to have greater rates of morbidity including retinopathy of prematurity and chronic lung disease. In order to answer this clinical dilemma reliably, large scale trial evidence is needed.

Methods/Design

To detect a small but important 4% increase in death or severe disability in survivors, over 5000 neonates would need to be recruited. As extreme prematurity affects 1% of births, such a project undertaken by one trial group would be prohibitively lengthy and expensive. Hence, the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration has been formed. A prospective meta-analysis (PMA) is one where studies are identified, evaluated, and determined to be eligible before the results of any included studies are known or published, thereby avoiding some of the potential biases inherent in standard, retrospective meta-analyses. This methodology provides the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility. The NeOProM Collaboration protocol (NCT01124331) has been agreed prior to the results of individual trials being available. This includes pre-specifying the hypotheses, inclusion criteria and outcome measures to be used. 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 primary outcome to be assessed is a composite outcome of death or major disability at 18 months - 2 years corrected age. Secondary outcomes include several measures of neonatal morbidity. The size of the combined dataset will allow the effect of the interventions to be explored more reliably with respect to pre-specified patient- and intervention-level characteristics.

Discussion

Results should be available by 2014.