Optimal Oxygenation of Extremely Low Birth Weight Infants: A Meta-Analysis and Systematic Review of the Oxygen Saturation Target Studies

Background: The optimal oxygen saturation for extremely low birth weight infants in the postnatal period beyond the delivery room is not known. Objectives: To summarize and discuss the results of the randomized trials, constituting the NEOPROM (Neonatal Oxygenation Prospective Meta-analysis) collaborative study, examining the effect of low versus high functional oxygen saturation targets in the postnatal period in premature infants with gestational age <28 weeks. Methods: A meta-analysis of SUPPORT (Surfactant, Positive Pressure and Pulse Oximetry Randomized Trial), the three BOOST II (Benefits of Oxygen Saturation Targeting) studies and the COT (Canadian Oxygen Trial) was performed including a total of 4,911 infants randomized to either a low (85-89%) or high (91-95%) functional oxygen saturation (SpO2) within the first 24 h after birth. Results: Relative risks (RR; 95% CIs) comparing a low versus a high oxygen saturation target were 1.41 (1.14-1.74) for mortality at discharge or at follow-up, 0.74 (0.59-0.92) for severe retinopathy of prematurity, 0.95 (0.86-1.04) for physiologic bronchopulmonary dysplasia, 1.25 (1.05-1.49) for necrotizing enterocolitis, 1.02 (0.88-1.19) for brain injury, and 1.01 (0.95-1.08) for patent ductus arteriosus. RR >1.0 favors a high oxygen saturation. Conclusions: RRs for mortality and necrotizing enterocolitis are significantly increased and severe retinopathy of prematurity significantly reduced in low compared to high oxygen saturation target infants. There are no differences regarding physiologic bronchopulmonary dysplasia, brain injury or patent ductus arteriosus between the groups. Based on these results, it is suggested that functional SpO2 should be targeted at 90-95% in infants with gestational age <28 weeks until 36 weeks' postmenstrual age. However, there are still several unanswered questions in this field.

[1]  G. Greisen,et al.  [European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants--2013 update]. , 2014, Zhonghua er ke za zhi = Chinese journal of pediatrics.

[2]  B. Schmidt,et al.  NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol , 2011, BMC pediatrics.

[3]  W. Silverman,et al.  A cautionary tale about supplemental oxygen: the albatross of neonatal medicine. , 2004, Pediatrics.

[4]  K. Dickersin,et al.  Meta-analysis: state-of-the-science. , 1992, Epidemiologic reviews.

[5]  W. Tarnow-Mordi,et al.  Increased 36 week survival with high oxygen saturation target in extremely preterm infants , 2011, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[6]  B. Poindexter,et al.  Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial. , 2012, The New England journal of medicine.

[7]  M. Meyer,et al.  Oxygen saturation and outcomes in preterm infants. , 2013, The New England journal of medicine.

[8]  J. Flynn,et al.  Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. , 2000, Pediatrics.

[9]  W. Tasman,et al.  Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. , 2004, Archives of ophthalmology.

[10]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[11]  D. Henderson-smart,et al.  Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants. , 2001, The Cochrane database of systematic reviews.

[12]  J. McCord,et al.  Oxygen-derived free radicals in postischemic tissue injury. , 1985, The New England journal of medicine.

[13]  H. Lagercrantz,et al.  Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS) , 2010, Acta paediatrica.

[14]  N. Paneth,et al.  Hypocapnia and Other Ventilation-Related Risk Factors for Cerebral Palsy in Low Birth Weight Infants , 2001, Pediatric Research.

[15]  K. Wright,et al.  A physiologic reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity. , 2006, Transactions of the American Ophthalmological Society.

[16]  D. Wallace,et al.  Incidence of severe retinopathy of prematurity before and after a modest reduction in target oxygen saturation levels. , 2007, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[17]  Andy King,et al.  Oxygen targeting in preterm infants using the Masimo SET Radical pulse oximeter , 2011, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[18]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[19]  K. Campbell INTENSIVE OXYGEN THERAPY AS A POSSIBLE CAUSE OF RETROLENTAL FIBROPLASIA: A CLINICAL APPROACH , 1951, The Medical journal of Australia.

[20]  O. Saugstad Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production , 1988, Pediatric Research.

[21]  B. Schmidt,et al.  Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. , 2013, JAMA.

[22]  G. Buonocore,et al.  Oxidative Stress in Preterm Neonates at Birth and on the Seventh Day of Life , 2002, Pediatric Research.

[23]  I. Adams-Chapman,et al.  Avoiding hyperoxia in infants ⩽1250 g is associated with improved short- and long-term outcomes , 2006, Journal of Perinatology.

[24]  Michele Walsh,et al.  Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. , 2012, The Journal of pediatrics.

[25]  A. Patz Clinical and experimental studies on role of oxygen in retrolental fibroplasia. , 1954, Transactions - American Academy of Ophthalmology and Otolaryngology. American Academy of Ophthalmology and Otolaryngology.

[26]  A. Fielder,et al.  Preliminary results of treatment of eyes with high-risk prethreshold retinopathy of prematurity in the early treatment for retinopathy of prematurity randomized trial. , 2003, Archives of ophthalmology.

[27]  Problems of stopping trials early , 2012, BMJ : British Medical Journal.

[28]  J. Flynn,et al.  A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity. , 1992, The New England journal of medicine.

[29]  D. Aune,et al.  In Search of the Optimal Oxygen Saturation for Extremely Low Birth Weight Infants: A Systematic Review and Meta-Analysis , 2010, Neonatology.

[30]  L. Irwig,et al.  Oxygen-saturation targets and outcomes in extremely preterm infants. , 2003, The New England journal of medicine.

[31]  G. Buonocore,et al.  Free Radicals and Brain Damage in the Newborn , 2001, Neonatology.

[32]  J. Flynn,et al.  A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity. , 1992, Transactions of the American Ophthalmological Society.

[33]  Lois E. H. Smith,et al.  High or Low Oxygen Saturation and Severe Retinopathy of Prematurity: A Meta-analysis , 2010, Pediatrics.

[34]  Gorm Greisen,et al.  European Consensus Guidelines on the Management of Neonatal Respiratory Distress Syndrome in Preterm Infants - 2013 Update , 2013, Neonatology.

[35]  O. Saugstad,et al.  Plasma hypoxanthine concentrations in pigs. A prognostic aid in hypoxia. , 1980, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[36]  M. Richards Retrolental Fibroplasia: A Modern Parable. By W. A. Silverman. (Grune & Stratton, New York 1980) Price £13.20 (US $23.50). , 1981, Journal of Biosocial Science.

[37]  A. Madan,et al.  Retinopathy of Prematurity and Pulse Oximetry: A National Survey of Recent Practices , 2004, Journal of Perinatology.

[38]  B. Poindexter,et al.  Target ranges of oxygen saturation in extremely preterm infants. , 2010, The New England journal of medicine.

[39]  D. Vanderveen,et al.  Lower oxygen saturation alarm limits decrease the severity of retinopathy of prematurity. , 2006, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[40]  W Tin,et al.  Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation , 2001, Archives of disease in childhood. Fetal and neonatal edition.

[41]  O. Saugstad,et al.  Plasma Hypoxanthine Concentrations in Pigs , 1980 .

[42]  B. Siassi,et al.  Effects of low oxygen saturation limits on the ductus arteriosus in extremely low birth weight infants , 2009, Journal of Perinatology.