PICO Summary: Does a lower targeted range of blood oxygen levels or restricted oxygen administration lead to a decreased risk of retinopathy of prematurity (ROP) without increased risk of mortality or neurodevelopmental problems in preterm and low birth weight infants requiring supplemental oxygen?


BackgroundThe use of oxygen in preterm and low birth weight infants suffering respiratory insufficiency has resulted in health care benefits such as reduced mortality and spastic diplegia as well as deleterious effects like retinopathy of prematurity and lung toxicity. Despite the frequent use of supplemental oxygen, there is little consensus as to the optimal mode of administration and appropriate levels of oxygen. Therefore, there is a need to determine the effects of using restricted vs liberal supplemental oxygen or targeting lower vs higher oxygen levels.
ParticipantsPreterm (<37 weeks gestation) or low birth weight (<2500 g) infants receiving supplemental oxygen.
InterventionRestricted administration of supplemental oxygen or targeting lower range of blood oxygen levels.
ComparisonLiberal administration of supplemental oxygen or targeting higher range of blood oxygen levels.
Outcome(s)Retinopathy of prematurity (ROP)—any, severe (≥ stage 3), mortality (early or later neonatal period), combined ROP (severe) or death (any), apnea of prematurity, Chronic lung disease/bronchopulmonary dysplasia, growth during the neonatal period and long-term, long-term neurodevelopment, long-term visual function
StudiesRandomized or quasi-randomized controlled trials.
Study description and settingAskie and coworkers (Askie 2008) identified six trials addressing the question of targeting oxygen administration in preterm/LBW infants. Five of them were done in the ‘pre-1990s era’, one in the ‘post 1990s era’. The studies from the ‘pre-1990s era’ with practices and therapies different from modern intensive care, included only a small number of survivors with birth weights under 1000 g. Due to variation in measurement methods values of restricted and liberal oxygen varied in the different studies. Only one study reported the longer term (i.e. 12 months corrected age) effects on the intervention on growth, neurodevelopment, lung function, or chronic lung disease. Also, only one study reported eye outcome data using the international classification of Retinopathy of Prematurity grading system. The five ‘pre-1990s’ trials gave an ascertainment of retrolental fibroplasias (RLF), visualizing the posterior pole only.
ResultsRestricted oxygen administration when started during the early neonatal period did not have any significant effect on the incidence of death (Typical RR 1.23, 95% CI 0.80–1.90), but reduced the incidence of all forms of retrolental fibroplasia (RLF) in survivors (Typical RR 0.26, 95% CI 0.11–0.58, NNT 6(4–12)). Comparison of lower vs higher oxygen saturation targeting when started in the later neonatal period revealed no statistically significant difference in the incidence of death, ROP stage 3 or 4, nor in the incidence of blindness. Higher blood oxygen levels, however, showed an increase in the risk of chronic lung disease (typical RR 1.52, 95% CI 1.19–1.93, NNH 5(3–12)).
Confidence in resultsHigh quality evidence for all primary outcomes reported.
Key figure(s)Thumbnail image of
Figure captionRestricted vs liberal oxygen therapy (all preterm/LBW infants) in early neonatal period, outcome 3 vascular RLF (any stage) in survivors
Search for eligible studiesCENTRAL, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert information, journal hand searching mainly in the English language; additional literature search, using OVID software, in Medline and CINHAL; search updated July 2008.
ConclusionsRestricted oxygen administration when started during the early neonatal period did not have any significant effect on the incidence of death, but reduced the incidence of all forms of retrolental fibroplasia (RLF) in survivors. Comparison of lower vs higher oxygen saturation targeting when started in the later neonatal period revealed no statistically significant difference in the incidence of death, ROP stage 3 or 4, nor in the incidence of blindness. Higher blood oxygen levels, however, showed increase risk of chronic lung disease. Unrestricted, unmonitored oxygen therapy has potential harms without clear benefits. The answer to the question of what is the optimal therapeutic range of blood oxygen level for preterm/LBW infants remains uncertain. Several large international multicentre trials are underway to address this important question.
CitationAskie LM, Henderson-Smart DJ, Ko H. Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001077. DOI: 10.1002/14651858.CD001077.pub2.
Date completed18 February 2010
People who helped prepare this Cochrane PICO:Sabine Beuger, MD, Fellow Neonatology, Emma Children's Hospital AMC, Amsterdam, The Netherlands

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