Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration | Gastroenterology | JAMA Network
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Original Investigation
June 5, 2018

Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration

Author Affiliations
  • 1National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia
  • 2Department of Paediatrics, University of Otago, Christchurch, New Zealand
  • 3Department of Pediatrics, University of California, San Diego
  • 4Division of Neonatology, University of Pennsylvania, Philadelphia
  • 5Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  • 6Department of Neonatology, Royal Infirmary of Edinburgh, Edinburgh, Scotland
  • 7Newborn Research, Royal Women’s Hospital, Departments of Obstetrics and Gynaecology, and Paediatrics, University of Melbourne, Melbourne, Australia
  • 8Clinical Sciences, Murdoch Children’s Research Institute, Melbourne, Australia
  • 9Department of Pediatrics, University of Alabama, Birmingham
  • 10Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, England
  • 11National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England
  • 12Statistics and Epidemiology Unit, RTI International, Rockville, Maryland
  • 13Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina
  • 14Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
  • 15Department of Neonatology, Tuebingen University Hospital, Tuebingen, Germany
  • 16Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
  • 17Newborn Services, Auckland City Hospital, Auckland, New Zealand
  • 18Royal Maternity Hospital, Belfast, Ireland
  • 19Department of Child Health, Queen’s University, Belfast, Ireland
  • 20EGA Institute for Women’s Health, University College London, London, England
  • 21Department of Neonatal Medicine, James Cook University, Middlesbrough, England
  • 22University of Cambridge, Department of Obstetrics and Gynaecology, Cambridge, England
JAMA. 2018;319(21):2190-2201. doi:10.1001/jama.2018.5725
Key Points

Question  For extremely preterm infants, is targeting a lower oxygen saturation (85%-89%) compared with a higher saturation (91%-95%) associated with a difference in death or major disability by a corrected age of 24 months?

Findings  In a prospectively designed meta-analysis of individual participant data from 4965 infants in 5 randomized clinical trials, there was no significant difference in the primary composite outcome of death or major disability between those treated with lower vs higher oxygen saturations (53.5% vs 51.6%, respectively). Lower oxygen targets were associated with increased death and necrotizing enterocolitis but reduced retinopathy of prematurity treatment.

Meaning  Among extremely preterm infants, there was no significant difference between lower and higher oxygen saturation targets on a composite of death or major disability; secondary end points may need to be considered in decision making.

Abstract

Importance  There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen.

Objective  To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity.

Design, Setting, and Participants  Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks’ gestation.

Exposures  Spo2 target range that was lower (85%-89%) vs higher (91%-95%).

Main Outcomes and Measures  The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities.

Results  A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, −1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, −4.0% [95% CI, −6.1% to −2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003).

Conclusions and Relevance  In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

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