Oxygen Saturation Target Range Research Articles

Comparison of two different oxygen saturation target ranges for automated oxygen control in preterm infants: a randomised cross-over trial.

To compare the effect of peripheral oxygen saturation (SpO2) target range (TR) (either 91%-95% and 92%-96%) on the frequency and duration of hypoxic and hyperoxic episodes while on automated oxygen control using the OxyGenie controller. Randomised cross-over study. Tertiary-level neonatal unit in the Netherlands. Infants (n=27) with a median (IQR) gestational age of 27+0 (25+5-27+3) weeks and postnatal age of 16 (10-22) days, receiving invasive or non-invasive respiratory support. In both groups supplemental oxygen was titrated to a TR of 91%-95% (TRlow) or 92%-96% (TRhigh) by the OxyGenie controller (SLE6000 ventilator) for 24 hours each, in random sequence. After a switch in TR, a 1-hour washout period was applied to prevent carry-over bias. Frequency and duration of hypoxic (SpO2<80% for ≥1 s) and hyperoxic episodes (SpO2>98% for ≥1 s). Hypoxic episodes were less frequent when the higher range was targeted (TRhigh vs TRlow: 2.5 (0.7-6.2)/hour vs 2.4 (0.9-10.2)/hour, p=0.02), but hyperoxic episodes were more frequent (5.3 (1.8-12.3)/hour vs 2.9 (1.0-7.1)/hour, p<0.001). The duration of the out-of-range episodes was not significantly different (hypoxia: 4.7 (2.8-7.1) s vs 4.4 (3.7-6.5) s, p=0.67; hyperoxia: 4.3 (3.3-4.9) s vs 3.9 (2.8-5.5) s, p=0.89). Targeting a higher SpO2 TR with the OxyGenie controller reduced hypoxic episodes but increased hyperoxic episodes. This study highlights the feasibility of using an automated oxygen titration device to explore the effects of subtle TR adjustments on clinical outcomes in neonatal care. NL9662.

Effect of a lower target oxygen saturation range on the risk of hypoxaemia and elevated NEWS2 scores at a university hospital: a retrospective study

BackgroundThe optimal target oxygen saturation (SpO2) range for hospital inpatients not at risk of hypercapnia is unknown. The objective of this study was to assess the impact on oxygen usage...

Determining an Optimal Oxygen Saturation Target Range Based on Neonatal Maturity: Demonstration of a Decision Tree Analytic

The utility of decision tree machine learning in exploring the interactions among the SpO2 target range, neonatal maturity, and oxemic-risk is demonstrated. METHODS: This observational study used 3 years of paired age-SpO2-PaO2 data from a neonatal ICU. The CHAID decision tree method was used to explore the interaction of postmenstrual age (PMA) on the risk of extreme arterial oxygen levels at six different potential SpO2 target ranges (88–92%, 89–93%, 90–94%, 91–95%, 92–96% and 93–97%). Risk was calculated using a severity-weighted average of arterial oxygen outside the normal range for neonates (50–80 mmHg). RESULTS: In total, 7500 paired data points within the potential target range envelope were analyzed. The two lowest target ranges were associated with the highest risk, and the ranges of 91–95% and 92–96% were associated with the lowest risk. There were shifts in the risk associated with PMA. All the target ranges showed the lowest risk at ≥42 weeks PMA. The lowest risk for preterm infants was within a target range of 92–96% with a PMA of ≤34 weeks. CONCLUSIONS: This study demonstrates the utility of decision tree analytics. These results suggest that SpO2 target ranges that are different from typical range might reduce morbidity and mortality. Further research, including prospective randomized trials, is warranted.

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

Care Bundle to Improve Oxygen Maintenance and Events.

This study was completed in a 46-bed neonatal intensive care unit (NICU), involving 246 staff members and led by a quality improvement team. The change interventions included implementing new practice guidelines, reviewing daily summaries of SpO2 maintenance, daily infant wellness assessment, standardizing workflow, and responding to SpO2 alarms. In addition, we collected staff satisfaction and compliance with change interventions, resource use, and morbidity and mortality data at discharge. The mean time spent WTR increased from 65.3% to 75.3%, and the frequency of desaturation events decreased from 25.1 to 16.5 events per patient day, respectively, with a higher magnitude of benefit in infants on days with supplemental oxygen. Postimplementation, the duration of high-frequency ventilation and supplemental oxygen were lower, but morbidity and mortality rates were similar. Staff satisfaction with training workshops, coaching, use of the infant wellness assessment tool, and SpO2 alarm management algorithms were 74%, 82%, 80%, and 74%, respectively. Implementing a care bundle to improve oxygen maintenance and reduce desaturation events increased the time spent WTR and reduced the frequency of desaturation events.

Automated oxygen control for very preterm infants and neurodevelopmental outcome at 2 years−a retrospective cohort study

Faster resolution of hypoxaemic or hyperoxaemic events in preterm infants may reduce long-term neurodevelopmental impairment. Automatic titration of inspiratory oxygen increases time within the oxygen saturation target range and may provide a more prompt response to hypoxic and hyperoxic events. We assessed routinely performed follow-up at 2 years of age after the implementation of automated oxygen control (AOC) as standard care and compared this with a historical cohort. Neurodevelopmental outcomes at 2 years of age were compared for infants born at 24–29 weeks gestational age before (2012–2015) and after (2015–2018) the implementation of AOC as standard of care. The primary outcome was a composite outcome of either mortality or severe neurodevelopmental impairment (NDI), and other outcomes assessed were mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and CBCL problem behaviour scores. A total of 289 infants were included in the pre-AOC epoch and 292 in the post-AOC epoch. Baseline characteristics were not significantly different. Fifty-one infants were lost to follow-up (pre-AOC 6.9% (20/289), post-implementation 10.6% (31/292). The composite outcome of mortality or severe NDI was observed in 17.9% pre-AOC (41/229) vs. 24.0% (47/196) post-AOC (p = 0.12). No significant differences were found for the secondary outcomes such as mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and problem behaviour scores, with the exception of parent-reported readmissions until the moment of follow-up which was less frequent post-AOC than pre-AOC.Conclusion: In this cohort study, the implementation of automated oxygen control in our NICU as standard of care for preterm infants led to no statistically significant difference in neurodevelopmental outcome at 2 years of age. What is Known:• Neurodevelopmental outcome is linked to hypoxemia, hyperoxaemia and choice of SpO2 target range.• Automated titration of inspired oxygen may provide a faster resolution of hypoxaemic and hyperoxaemic events.What is New: • This cohort study did not find a significant difference in neurodevelopmental outcome at two years of age after implementing automated oxygen control as standard of care.

Evaluating enhanced pulse oximetry auditory displays for neonatal oxygen targeting: A randomized laboratory trial with clinicians and non-clinicians

Standard pulse oximeter auditory tones do not clearly indicate departures from the target range of oxygen saturation (SpO2) of 90%–95% in preterm neonates. We tested whether acoustically enhanced tones would improve participants' ability to identify SpO2 range. Twenty-one clinicians and 23 non-clinicians used (1) standard pulse oximetry variable-pitch tones plus alarms; (2) beacon-enhanced tones without alarms in which reference tones were inserted before standard pulse tones when SpO2 was outside target range; and (3) tremolo-enhanced tones without alarms in which pulse tones were modified with tremolo when SpO2 was outside target range. For clinicians, range identification accuracies (mean (SD)) in the standard, beacon, and tremolo conditions were 52% (16%), 73% (14%) and 76% (13%) respectively, and for non-clinicians 49% (16%), 76% (13%) and 72% (14%) respectively, with enhanced conditions always significantly more accurate than standard. Acoustic enhancements to pulse oximetry clearly indicate departures from preterm neonates’ target SpO2 range.

Determination of oxygen saturation compared to a prescribed target range using continuous pulse oximetry in acutely unwell medical patients

BackgroundBoth inadequate and excessive administration of oxygen to acutely unwell patients results in risk of harm. Guidelines recommend titration of oxygen to achieve a target oxygen saturation (SpO2) range. Information regarding whether this is being achieved is limited.MethodsIn this two-centre non-interventional study we used continuous pulse oximetry in acutely unwell medical patients over a 24-h period to determine the proportion of time spent with SpO2 within the prescribed target range and whether this is influenced by the target range, age, care in a high-dependency area and the number of oxygen adjustments.ResultsEighty participants were included in the analysis. The mean (SD) proportion of time spent in target range was 55.6% (23.6), this was lower in those with a reduced hypercapnic target range (88–92% or below) compared to those with a range of 92–96%; difference − 13.1% (95% CI − 3.0 to − 23.2), P = 0.012. The proportion of time spent above range was 16.2% (22.9); this was higher in those with a reduced hypercapnic range; difference 21.6% (31.4 to 12), P < 0.001. The proportion of time below range was 28.4% (25.2); there was no difference between target ranges. The proportion of time spent in range was higher for those in a high dependency area in the multivariate model; difference 15.5% (95% CI 2.3 to 28.7), P = 0.02.ConclusionsMedical patients receiving oxygen in a ward setting spend significant periods of time with SpO2 both above and below the prescribed target range while receiving oxygen therapy.

Automatic versus manual oxygen titration using a novel nasal high-flow device in medical inpatients with an acute illness: a randomised controlled trial

BackgroundGuideline recommendations state oxygen should be administered to acutely unwell patients to achieve a target oxygen saturation (SpO2) range. The current practice of manual oxygen titration frequently results in SpO2...

Impact of higher oxygen saturation levels on postnatal weight gain to predict retinopathy of prematurity.

Retinopathy of prematurity (ROP) is the leading cause of vision loss in children. A well-known risk factor for the development of ROP is duration of oxygen supplementation. Other postnatal factors have also been associated with ROP risk, including poor post-natal weight gain. The weight, insulin-like growth factor, neonatal retinopathy of prematurity (WINROP) algorithm predicts severe ROP based on postnatal weight gain and has been validated in several studies,1,2 including a high sensitivity for prediction of severe ROP in our local NICU populations. However, target oxygen saturation levels were subsequently increased in many NICUs based on results from the Neonatal Oxygen Prospective Meta-analysis (NeOProM) Collaboration, which showed statistically higher death and disability rates among preterm infants randomized to a lower oxygen-saturation target range (85 - 89%) versus a higher target range (91 - 95%),3 which may affect the incidence and severity of ROP4 as well as the validity of the WINROP algorithm. In 2018, Lundgren et al reported that the WINROP algorithm was no longer able to predict ROP requiring treatment at their institution after the implementation of higher target oxygen saturation levels, with a sensitivity of only 50%.5 The objective of this review was to evaluate WINROP's ability to identify infants at risk for severe ROP at our institution after target oxygen saturation levels were increased in 2014.

Audit of oxygen administration to achieve a target oxygen saturation range in acutely unwell medical patients

Purpose of the studyTo evaluate documentation of a target oxygen saturation (SpO2) range and ability to achieve this range in acutely unwell inpatients.Study designIn this single-centre audit, patients with discharge...

Survival rate dependent variations in retinopathy of prematurity treatment rates in very low birth weight infants

As increased oxidative stress causes increased mortality and morbidities like bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in very low birth weight infants (VLBWIs), the conundrum of improved survival but increased ROP observed with the high oxygen saturation target range of 91–95% is difficult to explain. To determine the survival rate-dependent variation in ROP treatment rate, 6292 surviving eligible VLBWIs registered in the Korean Neonatal Network were arbitrarily grouped according to the survival rate of infants at 23–24 weeks’ gestation as group I (> 70%, n = 1626), group II (40–70%, n = 2984) and group III (< 40%, n = 1682). Despite significantly higher survival and lower BPD rates in group I than in groups II and III, the ROP treatment rate was higher in group I than in groups II and III. However, the adjusted odds ratios for ROP treatment were not significantly different between the study groups, and the ROP treatment rate in the infants at 23–24 weeks’ gestation was 21-fold higher than the infants at ≥ 27 weeks’ gestation. The controversial association between improved survival and reduced BPD reflecting quality improvement of neonatal intensive care but increased ROP treatment rate might be primarily attributed to the improved survival of the most immature infants.

Acute oxygen therapy: a cross-sectional study of prescribing practices at an English hospital immediately before COVID-19 pandemic

ABSTRACT Background Approximately 14% of UK hospital in-patients receive supplemental oxygen therapy, only 57% have valid prescriptions. Oxygen must be optimally prescribed to ensure maximal therapeutic response whilst minimizing adverse outcomes (including fatality). This study investigates prescription compliance. Methods All adults admitted to medical wards (18 February to 3 March 2020) were included. Analyses present proportions, descriptive statistics, and hypothesis testing. Ethical approval was unnecessary for this audit. Results Of the 636 patients admitted, 66 (10%) were receiving oxygen therapy. Ages ranged from 34 to 100 years with 36 (54.5%) males and 30 (45.5%) females. The prescription was not documented in the oxygen section of the drug chart (n = 37, 56.1%, p = 0.389), nor did it have the physicians signature (n = 40, 60.6%, p = 0.110) nor date (n = 46, 69.7%, p = 0.002). Thirteen chronic obstructive pulmonary disease (COPD) patients (19.7%) were at risk of hypercapnic failure (p = 1.582x10−6). Target oxygen saturation (SpO2) range had been documented for 30 (45.5%) patients. A target SpO2 range of 88–92% was documented for 9 patients (13.6%), a 94–98% range documented for 11 patients (16.7%). All patients had an invalid prescription. Conclusion We present real-world practice in naturalistic settings, immediately before pandemic-lockdown. Enhanced compliance is advocated to reduce risks of harm and mortality.

Nonpharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-Analysis

ObjectiveTo evaluate the effectiveness and adverse events of nonpharmacologic interventions in patients with exacerbation of chronic obstructive pulmonary disease (COPD). Patients and MethodsWe searched Embase, MEDLINE, Cochrane databases, Scopus, and clinicaltrials.gov from database inception to January 2, 2019, for randomized controlled trials that enrolled adults with exacerbation of COPD and evaluated the effect of nonpharmacologic interventions on clinical outcomes and/or lung function. ResultsWe included 30 randomized controlled trials with 2643 participants. Improvement in 6-minute walking test distance was associated with resistance training (weighted mean difference [WMD], 74.42; 95% CI, 46.85 to 101.99), pulmonary rehabilitation (WMD, 20.02; 95% CI, 12.06 to 28.67), whole body vibration (WMD, 89.42; 95% CI, 45.18 to 133.66), and transcutaneous electrical nerve stimulation (WMD, 64.54; 95% CI, 53.76 to 75.32). Improvement in quality of life was associated with resistance training (WMD, 18.7; 95% CI, 5.06 to 32.34), combined breathing technique and range of motion exercises (WMD, 14.89; 95% CI, 5.30 to 24.50), whole body vibration (WMD, -12.02; 95% CI, -21.41 to -2.63), and intramuscular vitamin D (WMD, -4.67; 95% CI, -6.00 to -3.35 at the longest follow-up). Oxygen titration with a target oxygen saturation range of 88% to 92% was associated with reduced mortality compared with high flow oxygen (odds ratio, 0.36; 95% CI, 0.14 to 0.88). All findings were based on low strength of evidence. ConclusionIn patients hospitalized for exacerbation of COPD, exercise interventions and pulmonary rehabilitation programs may ameliorate functional decline. Oxygen should be titrated with a target oxygen saturation of 88% to 92% in these patients. Trial RegistrationPROSPERO Identifier: CRD42018111609.

Designing a Remote Closed-Loop Automatic Oxygen Control in Preterm Infants

Background: Different automated systems have been developed to improve the maintenance of target range of arterial oxygen saturation (SPO2) in premature infants with respiratory distress. Objectives: This study aimed to develop a remote closed-loop automatic oxygen control (RCLAC) as an efficient monitoring device. Then the means of the fraction of inspired oxygen (FIO2) and SPO2 by routine manual control (RMC) and RCLAC were compared. Methods: A developmental-descriptive study was carried out in an Iranian hospital (Tehran, Iran; 2015 - 2017). Twenty-two preterm infants with gestational age 24 - 28 weeks entered the study. A database was prepared based on pulse oximeter parameters. A Wi-Fi module was implemented to receive data from a pulse oximeter and send inputs to the user’s mobile. Vibrate alarm was implemented for high or low FIO2. After receiving notifications associated with an increase or decrease of FIO2 levels and user’s confirmation; the alterations were applied on the ventilator. Results: The mean FIO2 in the RMC system was significantly higher than the RCLAC system (98.1 ± 2.67 vs 79.5 ± 16.03; P = 0.0001). According to the results, when the SPO2 reached close to target SPO2 range and consequently FIO2 changed (decreased or increased based on target SPO2), heart rate showed a regular beating with a decrease in the numbers. Conclusions: Remote closed-loop automatic oxygen control system as a simple device could prevent preterm neonates from sustained hypo-hyperoxemic and arrhythmia episodes. Moreover, by using RCLAC, there was no need for continuous monitoring that may reduce the workload of NICU medical staff. Collecting reliable data and recording information in digital forms were also other benefits. Further studies with larger sample size are strongly suggested.

Strategies to Prevent Severe Retinopathy of Prematurity: A 2020 Update and Meta-analysis.

The incidence of retinopathy of prematurity (ROP) is showing an increasing trend in the United States. This may be because of increasing survival rates among extremely preterm infants (<25 weeks' gestation) and targeting higher oxygen saturation. Five randomized clinical trials of low versus high oxygen saturation target ranges found increased mortality in the low oxygen saturation target group and an increased incidence of ROP in the high oxygen saturation target group. The American Academy of Pediatrics recommends using an oxygen saturation target range of 90% to 95% in extremely low-birthweight infants. The change of practice to target this higher oxygen saturation range, from admission until discharge, may be contributing to the increasing incidence of ROP in extremely preterm infants. To decrease the incidence of ROP without increasing mortality, 2 new cohort trials suggest gradually increasing oxygen saturation targets as preterm infants mature. There is evidence that human milk, vitamin A, and omega-3 fatty acids can help, in addition to continuous oxygen saturation monitoring, to decrease the risk of ROP. We review this literature and provide a meta-analysis to evaluate the evidence.

Accuracy of pulse oximetry in preterm and term infants is insufficient to determine arterial oxygen saturation and tension.

Oxygen saturation is frequently monitored with pulse oximetry to assess vital signs in critically ill patients. Optimally, pulse oximetry closely tracks arterial oxygen tension (PaO2 ), which provides guidance in oxygen titration. We investigated whether monitoring peripheral oxygen saturation (SpO2 ) could accurately guide oxygen titration in newborn infants. Twenty seven thousand two hundred thirty seven SpO2 readings were retrospectively paired with arterial oxygen saturation (SaO2 ) and PaO2 results from blood gas analyses performed in infants with arterial catheters in place. SpO2 overestimated SaO2 readings by 2.9±5.8%. When pulse oximetry readings were within the defined oxygen saturation target range, 7809 (20.9%) SaO2 values were below and 2830 (7.6%) exceeded the target range. In 57% of patients, PaO2 levels<6kPa was diagnosed while SpO2 readings were>90%. PaO2 >11kPa was recorded in 19% of cases, when SpO2 readings were<95%. Infants treated with supplemental oxygen showed a threefold increased risk of hypoxaemia compared to infants breathing room air. Sensitivity and specificity for detecting upper and lower target range limits were fair to good. For SpO2 values below 91%, ISO quality criteria were no longer fulfilled. Based on arterial blood gas analyses as reference, pulse oximetry readings did not fulfil the performance requirements for titrating oxygen in neonatal patients.

Implementing target range oxygen in critical care: A quality improvement pilot study.

Iatrogenic hyperoxaemia is common on critical care units and has been associated with increased mortality. We commenced a quality improvement pilot study to analyse the views and practice of critical care staff regarding oxygen therapy and to change practice to ensure that all patients have a prescribed target oxygen saturation range. A baseline measurement of oxygen target range prescribing was undertaken alongside a survey of staff attitudes. We then commenced a programme of change, widely promoting an agreed oxygen target range prescribing policy. The analyses of target range prescribing and staff survey were repeated four to five months later. Thirty-three staff members completed the baseline survey, compared to 29 in the follow-up survey. There was no discernible change in staff attitudes towards oxygen target range prescribing. Fifty-four patients were included in the baseline survey and 124 patients were assessed post implementation of changes. The proportion of patients with an oxygen prescription with a target range improved from 85% to 95% (χ2 = 5.17, p = 0.02) and the proportion of patients with an appropriate prescribed target saturation range increased from 85% to 91% (χ2 = 1.4, p = 0.24). The improvement in target range prescribing was maintained at 96% 12 months later. The introduction and promotion of a structured protocol for oxygen prescribing were associated with a sustained increase in the proportion of patients with a prescribed oxygen target range on this unit.

Closed loop automated oxygen control in neonates-A review.

Neonates frequently require supplementary oxygen but may develop complications if the oxygen saturation is outside the target range. This review aimed to determine whether the algorithms used in closed loop automated oxygen control systems influenced their efficacy and whether use of the systems reduced relevant, long-term neonatal complications. A literature search was conducted using PubMed and Google Scholar. The search terms were 'closed loop' or 'automat*', 'oxygen' and 'neonat*'. Eighteen studies were identified: sixteen comparison clinical studies, an observational study and an animal study. Overall, closed loop automated oxygen control was associated with an increased percentage of time spent within the target oxygen saturation range and there were fewer manual adjustments to the inspired oxygen concentration when compared with manual oxygen control. The systems were effective in infants on non-invasive respiratory support or mechanically ventilated, but no study included term-born infants. No long-term data were available to determine if complications of oxygen toxicity were reduced. Closed loop automated oxygen control has been shown in short term trials including preterm and low birth weight infants to improve target saturation achievement. Whether long-term outcomes will be improved with their use requires investigation.

Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants \u2013 study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy

BackgroundMost extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA.Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the hemoglobin oxygen saturation (SpO2) target range, number and duration of hypo- and hyperoxemic episodes and caregivers’ workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.MethodsAn outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO2-C (in addition to routine manual control (RMC) of FiO2), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO2-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks).FiO2-C is provided by commercially available and CE-marked ventilators with an FiO2-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.DiscussionShort-term studies on FiO2-C showed improved time ELGANs spent within their assigned SpO2 target range, but effects of FiO2-C on clinical outcomes are yet unknown and will be addressed in the FiO2-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO2-C may be implemented as standard therapy.Trial registrationThe study is registered at www.ClinicalTrials.gov: NCT03168516, May 30, 2017.