Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants

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    • Additional Information
      • Reviewers:
        Askie, Lisa M 1; Darlow, Brian A 2; Davis, Peter G 3 4 5; Finer, Neil 6; Stenson, Ben 7; Vento, Maximo 8; Whyte, Robin 9
      • Review Group Information:
      • Source:
        Cochrane Database of Systematic Reviews. This document is a Academic Journal
        Review first published in Issue 4, 2017.
        Protocol first published in Issue 7, 2014.
        This version first published online: 11 April 2017 in Issue 4, 2017.
      • Update Information:
        Publication Status: Edited (no change to conclusions) in Issue 2, 2018
        Most recent changes:
        Information not supplied by reviewer.
      • Contact:
        Lisa M Askie 1; laskie@ctc.usyd.edu.au
      • Affiliations:
        1University of Sydney, NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown, NSW, Australia, 2050
        2University of Otago, Department of Paediatrics, Christchurch, New Zealand,
        3The Royal Women's Hospital, Newborn Research Centre and Neonatal Services, Melbourne, Australia,
        4Murdoch Childrens Research Institute, Melbourne, Australia,
        5University of Melbourne, Department of Obstetrics and Gynecology, Melbourne, Australia,
        6University of California San Diego, Department of Pediatrics, 200 W Arbor Dr, San Diego, California, USA, 92103‐8774
        7Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Neonatal Unit, Edinburgh, UK,
        8University & Polytechnic Hospital La Fe, Health Research Institute La Fe, Division of Neonatology, Bulevar Sur s/n, Valencia, Spain, 46026
        9Halifax Dalhousie University, IWK Health Centre, Department of Neonatal Pediatrics, 5850/5980 University Avenue, Halifax, NS, Canada, B3K 6R8
      • Sources of Support:
        Intramural sources of support: No sources of support supplied.
        Extramural sources of support: No sources of support supplied.
      • Abstract:
        Background: The use of supplemental oxygen in the care of extremely preterm infants has been common practice since the 1940s. Despite this, there is little agreement regarding which oxygen saturation (SpO₂) ranges to target to maximise short‐ or long‐term growth and development, while minimising harms. There are two opposing concerns. Lower oxygen levels (targeting SpO₂ at 90% or less) may impair neurodevelopment or result in death. Higher oxygen levels (targeting SpO₂ greater than 90%) may increase severe retinopathy of prematurity or chronic lung disease. The use of pulse oximetry to non‐invasively assess neonatal SpO₂ levels has been widespread since the 1990s. Until recently there were no randomised controlled trials (RCTs) that had assessed whether it is better to target higher or lower oxygen saturation levels in extremely preterm infants, from birth or soon thereafter. As a result, there is significant international practice variation and uncertainty remains as to the most appropriate range to target oxygen saturation levels in preterm and low birth weight infants. Objectives: 1. What are the effects of targeting lower versus higher oxygen saturation ranges on death or major neonatal and infant morbidities, or both, in extremely preterm infants? 2. Do these effects differ in different types of infants, including those born at a very early gestational age, or in those who are outborn, without antenatal corticosteroid coverage, of male sex, small for gestational age or of multiple birth, or by mode of delivery? Search methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 11 April 2016), Embase (1980 to 11 April 2016) and CINAHL (1982 to 11 April 2016). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials. Selection criteria: Randomised controlled trials that enrolled babies born at less than 28 weeks' gestation, at birth or soon thereafter, and targeted SpO₂ ranges of either 90% or below or above 90% via pulse oximetry, with the intention of maintaining such targets for at least the first two weeks of life. Data collection and analysis: We used the standard methods of Cochrane Neonatal to extract data from the published reports of the included studies. We sought some additional aggregate data from the original investigators in order to align the definitions of two key outcomes. We conducted the meta‐analyses with Review Manager 5 software, using the Mantel‐Haenszel method for estimates of typical risk ratio (RR) and risk difference (RD) and a fixed‐effect model. We assessed the included studies using the Cochrane 'Risk of bias' and GRADE criteria in order to establish the quality of the evidence. We investigated heterogeneity of effects via pre‐specified subgroup and sensitivity analyses. Main results: Five trials, which together enrolled 4965 infants, were eligible for inclusion. The investigators of these five trials had prospectively planned to combine their data as part of the NeOProM (Neonatal Oxygen Prospective Meta‐analysis) Collaboration. We graded the quality of evidence as high for the key outcomes of death, major disability, the composite of death or major disability, and necrotising enterocolitis; and as moderate for blindness and retinopathy of prematurity requiring treatment. When an aligned definition of major disability was used, there was no significant difference in the composite primary outcome of death or major disability in extremely preterm infants when targeting a lower (SpO₂ 85% to 89%) versus a higher (SpO₂ 91% to 95%) oxygen saturation range (typical RR 1.04, 95% confidence interval (CI) 0.98 to 1.10; typical RD 0.02, 95% CI ‐0.01 to 0.05; 5 trials, 4754 infants) (high‐quality evidence). Compared with a higher target range, a lower target range significantly increased the incidence of death at 18 to 24 months corrected age (typical RR 1.16, 95% CI 1.03 to 1.31; typical RD 0.03, 95% CI 0.01 to 0.05; 5 trials, 4873 infants) (high‐quality evidence) and necrotising enterocolitis (typical RR 1.24, 95% 1.05 to 1.47; typical RD 0.02, 95% CI 0.01 to 0.04; 5 trials, 4929 infants; I² = 0%) (high‐quality evidence). Targeting the lower range significantly decreased the incidence of retinopathy of prematurity requiring treatment (typical RR 0.72, 95% CI 0.61 to 0.85; typical RD ‐0.04, 95% CI ‐0.06 to ‐0.02; 5 trials, 4089 infants; I² = 69%) (moderate‐quality evidence). There were no significant differences between the two treatment groups for major disability including blindness, severe hearing loss, cerebral palsy, or other important neonatal morbidities. A subgroup analysis of major outcomes by type of oximeter calibration software (original versus revised) found a significant difference in the treatment effect between the two software types for death (interaction P = 0.03), with a significantly larger treatment effect seen for those infants using the revised algorithm (typical RR 1.38, 95% CI 1.13 to 1.68; typical RD 0.06, 95% CI 0.01 to 0.10; 3 trials, 1716 infants). There were no other important differences in treatment effect shown by the subgroup analyses using the currently available data. Authors' conclusions: In extremely preterm infants, targeting lower (85% to 89%) SpO₂ compared to higher (91% to 95%) SpO₂ had no significant effect on the composite outcome of death or major disability or on major disability alone, including blindness, but increased the average risk of mortality by 28 per 1000 infants treated. The trade‐offs between the benefits and harms of the different oxygen saturation target ranges may need to be assessed within local settings (e.g. alarm limit settings, staffing, baseline outcome risks) when deciding on oxygen saturation targeting policies.
      • ISSN:
        14651858
      • Rights:
        Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
      • Medical Subject Headings(MeSH):
        Infant Mortality*
        Infant, Extremely Premature*
        Oxygen /*administration & dosage
        Oxygen /*blood
        Humans
        Infant
        Infant, Newborn
        Age Factors
        Arteries
        Blindness /epidemiology
        Blindness /etiology
        Cerebral Palsy /epidemiology
        Enterocolitis, Necrotizing /epidemiology
        Enterocolitis, Necrotizing /etiology
        Incidence
        Oximetry
        Oxygen /adverse effects
        Publication Bias
        Randomized Controlled Trials as Topic
        Retinopathy of Prematurity /epidemiology
        Retinopathy of Prematurity /etiology
        Retinopathy of Prematurity /prevention & control
        Selection Bias
        Software
      • Source:
        This record should be cited as: Askie, Lisa M, Darlow, Brian A, Davis, Peter G, Finer, Neil, Stenson, Ben, Vento, Maximo, Whyte, Robin. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. (Protocol) Cochrane Database of Systematic Reviews 2017, Issue 4. Art. No.: CD011190. DOI: 10.1002/14651858.CD011190.pub2.
      • Accession Number:
        edschh.CD011190
    • Citations
      • ABNT:
        ASKIE, L. M. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Cochrane Database of Systematic Reviews, [s. l.], n. 2, [s. d.]. Disponível em: http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912. Acesso em: 27 set. 2020.
      • AMA:
        Askie LM. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Darlow BA, Davis PG, Finer N, Stenson B, Vento M, Whyte R, eds. Cochrane Database of Systematic Reviews. (2). Accessed September 27, 2020. http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912
      • APA:
        Askie, L. M. (n.d.). Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Cochrane Database of Systematic Reviews, 2.
      • Chicago/Turabian: Author-Date:
        Askie, Lisa M. 2020. “Effects of Targeting Lower versus Higher Arterial Oxygen Saturations on Death or Disability in Preterm Infants.” Edited by Brian A Darlow, Peter G Davis, Neil Finer, Ben Stenson, Maximo Vento, and Robin Whyte. Cochrane Database of Systematic Reviews, no. 2. Accessed September 27. http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912.
      • Harvard:
        Askie, L. M. (no date) ‘Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants’, Cochrane Database of Systematic Reviews. Edited by B. A. Darlow et al., (2). Available at: http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912 (Accessed: 27 September 2020).
      • Harvard: Australian:
        Askie, LM n.d., ‘Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants’, in BA Darlow, PG Davis, N Finer, B Stenson, M Vento & R Whyte (eds), Cochrane Database of Systematic Reviews, no. 2, viewed 27 September 2020, .
      • MLA:
        Askie, Lisa M. “Effects of Targeting Lower versus Higher Arterial Oxygen Saturations on Death or Disability in Preterm Infants.” Cochrane Database of Systematic Reviews, edited by Brian A Darlow et al., no. 2. EBSCOhost, widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912. Accessed 27 Sept. 2020.
      • Chicago/Turabian: Humanities:
        Askie, Lisa M. “Effects of Targeting Lower versus Higher Arterial Oxygen Saturations on Death or Disability in Preterm Infants.” Edited by Brian A Darlow, Peter G Davis, Neil Finer, Ben Stenson, Maximo Vento, and Robin Whyte. Cochrane Database of Systematic Reviews, no. 2. Accessed September 27, 2020. http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912.
      • Vancouver/ICMJE:
        Askie LM. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Darlow BA, Davis PG, Finer N, Stenson B, Vento M, Whyte R, editors. Cochrane Database of Systematic Reviews [Internet]. [cited 2020 Sep 27];(2). Available from: http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edschh&AN=edschh.CD011190&authtype=sso&custid=s5834912