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Higher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: a meta-analysis
  1. Ju Lee Oei1,2,3,
  2. Maximo Vento4,
  3. Yacov Rabi5,6,
  4. Ian Wright7,
  5. Neil Finer8,9,
  6. Wade Rich9,
  7. Vishal Kapadia10,
  8. Dagfinn Aune11,
  9. Denise Rook12,
  10. William Tarnow-Mordi3,
  11. Ola D Saugstad13
  1. 1Department of Newborn Care, The Royal Hospital for Women, Randwick, New South Wales, Australia
  2. 2School of Women's and Children's Health, University of New South Wales, Randwick, New South Wales, Australia
  3. 3NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia
  4. 4Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain
  5. 5Department of Paediatrics, University of Calgary, Calgary, Alberta, Canada
  6. 6Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada
  7. 7Illawarra Health and Medical Research Institute and Graduate School of Medicine, The University of Wollongong, Wollongong, New South Wales, Australia
  8. 8Department of Pediatrics, Neonatology, University of California, San Diego, California, USA
  9. 9Sharp Mary Birch Hospital for Women and Newborns, San Diego, California, USA
  10. 10Division of Neonatal-Perinatal Medicine, UT Southwestern Medical Center at Dallas, Dallas, Texas, USA
  11. 11Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  12. 12Division of Neonatology, Department of Pediatrics, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands
  13. 13Department of Pediatric Research, University of Oslo, Oslo University Hospital, Oslo, Norway
  1. Correspondence to Dr Ju Lee Oei, Department of Newborn Care, The Royal Hospital for Women, Randwick, NSW 2031, Australia; j.oei{at}


Objective To systematically review outcomes of infants ≤28+6 weeks gestation randomised to resuscitation with low (≤0.3) vs high (≥0.6) fraction of inspired oxygen (FiO2) at delivery.

Design Systematic review of randomised controlled trials of low (≤0.3) vs high (≥0.6) FiO2 resuscitation. Information was obtained from databases (Medline/Pub Med, EMBASE,, Cochrane) and meeting abstracts between 1990 to 2015. Search index terms: preterm/ resuscitation/oxygen. Data for infants ≤28+6 weeks gestation were independently extracted and pooled using a random effects model. Analyses were performed with Revman V.5.

Main outcome measures Death in hospital, bronchopulmonary dysplasia (BPD), retinopathy of prematurity >grade 2 (ROP), intraventricular haemorrhage >grade 2 (IVH), patent ductus arteriosus (PDA) and necrotising enterocolitis (NEC).

Results A total of 251 and 253 infants were enrolled in 8 studies (6 masked, 2 unmasked) in the lower and higher oxygen groups, respectively, (mean gestation 26 weeks) between 2005 and 2014. There were no differences in BPD (relative risk, 95% CIs 0.88 (0.68 to 1.14)), IVH (0.81 (0.52 to 1.27)), ROP (0.82 (0.46 to 1.46)), PDA (0.95 (0.80 to 1.14)) and NEC (1.61 (0.67 to 3.36)) and overall mortality (0.99 (0.52 to 1.91)). Mortality was lower in low oxygen arms of masked studies (0.46 (0.23 to 0.92), p=0.03) and higher in low oxygen arms of unmasked studies (1.94 (1.02 to 3.68), p=0.04).

Conclusions There is no difference in the overall risk of death or other common preterm morbidities after resuscitation is initiated at delivery with lower (≤0.30) or higher (≥0.6) FiO2 in infants ≤28+6 weeks gestation. The opposing results for masked and unmasked trials may represent a Type I error, emphasising the need for larger, well designed studies.

  • oxygen
  • preterm
  • Resuscitation
  • metaanalysis

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  • Contributors JLO: Developed the project idea, performed statistical analysis, drafted the initial manuscript, and prepared and approved final manuscript to be submitted. MV, IW, NF, WR, VK, DR and WT-M: Reviewed and approved the final manuscript to be submitted. YR: Assisted with statistical interpretation, reviewed and approved the final manuscript to be submitted. DA: Oversaw statistical analysis and reviewed and approved the final manuscript to be submitted. ODS: Supervised the overall project and reviewed and approved the final manuscript to be submitted.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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