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Background: Oxygen has long been implicated in the pathogenesis of retinopathy of prematurity (ROP) and is rigorously monitored in today's neonatal intensive care units. Recent research using a feline model has shown an improvement in ROP outcome of kittens treated with supplemental oxygen. Current treatment for ROP by retinal ablation is not without complications so a non-invasive method of treatment is preferred. The possible effects of long term oxygen supplementation on chronic lung disease, length of hospital stay and growth and development are, however, unknown., Objectives: To determine whether, in preterm or low birth weight infants with prethreshold ROP, targeting higher as compared to normal transcutaneous oxygen levels or pulse oximetry levels when using supplemental oxygen reduces the progression of ROP to threshold disease and improves visual outcome without any adverse effects., Search Strategy: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching. An additional literature search of the MEDLINE (1966-June 2002), EMBASE (1980-April 2002), and CINAHL (1982-April 2002) databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR, The Cochrane Library Issue 2, 2002)., Selection Criteria: All randomised or quasi randomised studies comparing higher versus normal target oxygen levels in preterm or low birthweight infants with prethreshold ROP were eligible for inclusion., Data Collection and Analysis: The methodological quality of the one eligible trial was assessed independently by two authors for the degree of selection, performance, attrition and detection bias. Data regarding clinical outcomes including progression to threshold ROP, blindness or severe visual impairment, mortality, respiratory morbidities and long term growth were extracted and reviewed independently by two authors. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group., Main Results: The one trial included in this review enrolled 649 infants. There was a trend for supplemental oxygen to reduce the progression to threshold ROP, however this did not reach statistical significance (RR 0.84, 95% CI 0.70, 1.02). A subgroup analysis of those infants without plus disease showed significantly fewer infants progressing to threshold ROP in infants treated with supplemental oxygen. However this analysis was not pre-specified so these results should be interpreted with caution. No significant effects were detected on blindness or severe visual function at three months corrected age, mortality, pneumonia, chronic lung disease or weight gain. Adverse pulmonary events were more common in the higher oxygen saturation group and these infants were in hospital and on supplemental oxygen for longer. Longer term visual outcomes were not reported., Reviewer's Conclusions: The results of this systematic review do not show a statistically significant reduction in the rate of progression to threshold ROP with supplemental oxygen treatment, but reveal increased adverse pulmonary sequelae with higher oxygen targeting in this group of preterm infants. Future research needs to be directed towards the question of whether infants without plus disease are more likely to respond to supplemental oxygen therapy than those with plus disease.

Background: It has been hypothesized that the duration of supplemental oxygen administration, independent of the oxygen concentration, gestational age and/or birth weight, is influential in the development of severe retinopathy of prematurity. Concern regarding the possible deleterious effects of prolonged oxygen supplementation has lead many clinicians to wean infants from oxygen therapy as early as possible in their neonatal course. However recent work in feline models has suggested that visual outcomes may be improved by continuing oxygen supplementation during the recovery phase of ROP. The effect of duration of oxygen supplementation on the long term growth and development of preterm or low birth weight infants remains unclear., Objectives: In preterm or low birth weight infants, does early versus late weaning from supplementary oxygen influence mortality, retinopathy of prematurity, lung function, growth or development?, Search Strategy: The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR)., Selection Criteria: All trials utilising random or quasi-random patient allocation, in which early weaning was compared with late discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion., Data Collection and Analysis: The methodological quality of the one eligible trial was assessed independently by each author for the degree of selection, performance, attrition and detection bias. Data regarding clinical outcomes including mortality, retinopathy of prematurity, and long term growth and development were extracted and reviewed independently by each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group., Main Results: In the single eligible trial of 99 infants with birthweights less than 1650g, there were no significant differences in neonatal death rates or retrolental fibroplasia (any grade or severe) for all infants, or among infants with birth weights of less than 1000g. No other outcome measures specified a priori as clinically meaningful were reported in enough detail or with satisfactory follow-up rates to include in the analysis (early death; chronic lung disease; and long term growth, development, lung or visual function)., Reviewer's Conclusions: The results of this systematic review do not provide strong evidence for either the benefits or harms of early oxygen weaning in preterm/LBW infants. Future research should be directed toward addressing the question of what are the most appropriate target levels of oxygenation, in both the early and late neonatal periods, rather than whether oxygen should be weaned early or late.

Background: Whilst the use of supplemental oxygen has a long history in neonatal care, resulting in both significant health care benefits and harms, uncertainty remains as to the most appropriate range to target blood oxygen levels in preterm and low birth weight infants. Potential benefits of higher oxygen targeting include more stable sleep patterns and improved long term growth and development. However, there may be significant deleterious pulmonary effects and health service use implications resulting from such a policy., Objectives: In preterm or low birth weight infants, does targeting ambient oxygen concentration to achieve a lower versus higher blood oxygen range, or administering restricted versus liberal supplemental oxygen, influence mortality, retinopathy of prematurity, lung function, growth or development?, Search Strategy: The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR)., Selection Criteria: All trials in preterm or low birth weight infants utilising random or quasi-random patient allocation, in which ambient oxygen concentrations were targeted to achieve a lower versus higher blood oxygen range, or restricted versus liberal oxygen was administered, were eligible for inclusion., Data Collection and Analysis: The methodological quality of the eligible trials was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group., Main Results: The restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates in the meta-analysis of the five trials included in this review. The one trial that specifically addressed the question of lower versus higher PaO2 found no effect on death, but did not report (in sufficient detail to warrant inclusion) the effect of this intervention on eye or other outcomes. The effects of either of these oxygen administration policies on other clinically meaningful outcomes including chronic lung disease and long term growth, neurodevelopment, lung or visual function were not reported in any of the available trials., Reviewer's Conclusions: The results of this systematic review confirm the commonly held view of today's clinicians that a policy of unrestricted, unmonitored oxygen therapy has potential harms, without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.

Background: The issue of whether to abruptly or gradually discontinue supplemental oxygen is a contentious one. There have been mixed results in studies of both humans and animal models on the effects of either method of oxygen cessation on important infant outcomes., Objectives: In preterm or low birth weight infants, does gradual versus abrupt discontinuation of supplemental oxygen influence mortality, retinopathy of prematurity, lung function, growth or development?, Search Strategy: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR)., Selection Criteria: All trials utilising random or quasi-random patient allocation, in which gradual weaning was compared with abrupt discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion., Data Collection and Analysis: The methodological quality of the eligible trial was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group., Main Results: The results of the one small trial of 51 infants included in this systematic review indicate a significant reduction in vascular retrolental fibroplasia (i.e. severe ROP) for infants weaned gradually from high oxygen concentrations compared with abrupt discontinuation (RR 0.22, 95% CI 0.07-0.68). This finding was independent of the duration of oxygen therapy., Reviewer's Conclusions: The results of this systematic review provide additional evidence linking routine exposure to high ambient oxygen in the early neonatal period to the development of ROP in preterm/LBW infants. However, due to small numbers and historical oxygen monitoring techniques, they provide little assistance to clinicians with regard to the most appropriate method of oxygen weaning, gradual or abrupt, in modern neonatal care settings.