Vaucher 2012.

Methods	Randomised, multicentre (USA) trial with a 2‐by‐2 factorial design.
Participants	1316 infants born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were enrolled prior to birth and were thus all inborn at a trial centre. Enrollment was undertaken from February 2005 until February 2009. Follow‐up assessments began in November 2006 and ended in July 2011.
Interventions	Infants were monitored with target ranges of oxygen saturation of 85% to 89% or 91% to 95% using oximeters with concealed saturation offsets of +3% in actual range 85% to 92% (low target) and ‐3% in range 88% to 95% (high target), with true readings displayed 84% and below and 96% and above (see Figure 4). Caregivers were asked to adjust the concentration of oxygen to maintain displayed saturations between 88% and 92% when the infant was receiving supplemental oxygen. Alarms were suggested to be set so that an alarm would sound at displayed saturation values of 85% and 95%, but they could be changed for individual patients. Infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. Intervention was initiated within 2 hours of birth and continued until 36 weeks of postmenstrual age or until the infant was breathing ambient air, whichever occurred first. Infants who were returned to supplemental oxygen were reassigned to the study oximeter. All infants in this trial were managed with oximeters using the original calibration software.
Outcomes	Co‐primary outcomes: survival at discharge from hospital without severe ROP (threshold ROP and/or the need for surgical intervention) assessed until diagnosis or resolution; and death or survival with neurodevelopmental impairment at 18 to 22 months corrected age. Neurodevelopmental impairment was defined as having any of the following: * BSID‐III cognitive or language score < 70 * GMFCS level 2 or higher * Moderate to severe cerebral palsy * Hearing impairment * Bilateral visual impairment Secondary outcomes: severe retinopathy of prematurity, death before discharge, death by 36 weeks postmenstrual age, BPD defined by use of supplemental oxygen at 36 weeks, BPD physiological definition at 36 weeks, intraventricular haemorrhage grade 3 or 4, periventricular leukomalacia, necrotising enterocolitis stage ≥ 2, pneumothorax, postnatal corticosteroids for BPD, death by 7 days, death by 14 days, late‐onset sepsis, patent ductus arteriosus requiring medical treatment, patent ductus arteriosus requiring surgical treatment, any air leaks in first 14 days.
Notes	Funded by: the USA Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung and Blood Institute; and the National Institutes of Health Trial registration ID: NCT00233324
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Permuted‐block randomisation was used, with stratification according to study centre and gestational age (24 weeks 0 days to 25 weeks 6 days or 26 weeks 0 days to 27 weeks 6 days). Multiple births were randomised to the same group.
Allocation concealment (selection bias)	Low risk	Sealed, sequentially numbered with central tracking opaque envelopes. Oximeter allocation was identifiable (via colour‐coded dots) to designated research staff but not to clinical staff. Bedside adjustment of supplemental oxygen was performed only by clinical staff.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding was maintained by oximeter design.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Parents and assessors were unaware of allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of the 1316 infants enrolled, 1234 (93.8%) had adequate data for the analysis of the composite primary outcome at 18 to 22 months corrected age. 35 infants were of unknown status (21 low target group, 14 high target group) and 47 had incomplete or no follow‐up (21 low target group, 26 high target group). If Bayley scores were missing, children were excluded from the primary outcome analysis. No participants were excluded after randomisation. All outcome analyses followed the principle of intention‐to‐treat. The follow‐up rate and the mean corrected age at neurodevelopmental assessment were similar for all treatment groups (in the 2‐by‐2 factorial design).
Selective reporting (reporting bias)	Low risk	The predetermined sample size of 1310 infants was achieved. The original study protocol specified a composite primary outcome of death before 36 weeks of postmenstrual age or severe ROP, but this was changed to death before discharge or severe ROP before any data analyses were performed. All other outcomes pre‐specified in the registration record were reported, including assessment of the need for oxygen at 36 weeks postmenstrual age and safety outcomes.
Other bias	Low risk	The baseline characteristics of the 2 treatment groups were similar.