Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Oxygen targeting in preterm infants: a physiological interpretation

Subjects

Abstract

Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare ‘target SpO2 ranges’. In spite of this overlap, some of the studies did find signficant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 <85 or >95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (<85% SpO2) and hyperoxemia (>95% SpO2).

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4

References

  1. Vento M . Oxygen supplementation in the neonatal period: changing the paradigm. Neonatology 2014; 105 (4): 323–331.

    CAS  Article  Google Scholar 

  2. De Halleux V, Truttmann A, Gagnon C, Bard H . The effect of blood transfusion on the hemoglobin oxygen dissociation curve of very early preterm infants during the first week of life. Semin Perinatol 2002; 26 (6): 411–415.

    Article  Google Scholar 

  3. Weindling M, Paize F . Peripheral haemodynamics in newborns: best practice guidelines. Early Hum Dev 2011; 86 (3): 159–165.

    Article  Google Scholar 

  4. Sola A, Golombek S, Bueno MT, Lemus-Varela L, Zuluaga C, Dominguez F et al. Safe oxygen saturation targeting and monitoring in preterm infants. Can we avoid hypoxia and hyperoxia?. Acta Paediatr 2014; 103 (10): 1009–1018.

    Article  Google Scholar 

  5. Schmidt B, Whyte RK, Roberts RS . Trade-off between lower or higher oxygen saturations for extremely preterm infants: the first Benefits of Oxygen Saturation Targeting (BOOST) II Trial reports its primary outcome. J Pediatrics 2014; 165 (1): 6–8.

    Article  Google Scholar 

  6. Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 2010; 362 (21): 1959–1969.

    CAS  Article  Google Scholar 

  7. Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y et al. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA 2013; 309 (20): 2111–2120.

    CAS  Article  Google Scholar 

  8. Darlow BA, Marschner SL, Donoghoe M, Battin MR, Broadbent RS, Elder MJ et al. Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes. J Pediatrics 2014; 165 (1): 30–35.e2.

    Article  Google Scholar 

  9. Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simens J, Zuszczak E, Askie L et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med 2013; 368 (22): 2094–2104.

    Article  Google Scholar 

  10. Drazen JM, Solomon CG, Greene MF . Informed consent and SUPPORT. N Engl J Med 2013; 368 (20): 1929–1931.

    CAS  Article  Google Scholar 

  11. Fanaroff JM . Ethical support for surfactant, positive pressure, and oxygenation randomized trial (SUPPORT). J Pediatrics 2013; 163 (5): 1498–1499.

    Article  Google Scholar 

  12. Lantos JD . SUPPORTing premature infants. Pediatrics 2013; 132 (6): e1661–e1663.

    Article  Google Scholar 

  13. Wright CJ, Saugstad OD . OHRP and SUPPORT: lessons in balancing safety and improving the way we care for patients. J Pediatrics 2013; 163 (5): 1495–1497.

    Article  Google Scholar 

  14. Pharoah PD . The US Office for Human Research Protections' judgment of the SUPPORT trial seems entirely reasonable. BMJ 2013; 347: f4637.

    Article  Google Scholar 

  15. Thornton H . The US Office for Human Research Protections' intervention in the SUPPORT trial was indeed ill conceived. BMJ 2013; 347: f4639.

    Article  Google Scholar 

  16. Modi N . Ethical pitfalls in neonatal comparative effectiveness trials. Neonatology 2014; 105 (4): 350–351.

    Article  Google Scholar 

  17. US Department of Health & Human Services. Public meeting: Matters related to protection of human subjects and research considering standard of care interventions. Wednesday, 28 August 2013, Washington, DC, USA. Available from http://www.hhs.gov/ohrp/newsroom/rfc/Public%20Meeting%20August%2028,%202013/supportmeetingtranscriptfinal.html.

  18. Chan ED, Chan MM, Chan MM . Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med 2013; 107 (6): 789–799.

    Article  Google Scholar 

  19. Emond D, Lachance C, Gagnon J, Bard H . Arterial partial pressure of oxygen required to achieve 90% saturation of hemoglobin in very low birth weight newborns. Pediatrics 1993; 91 (3): 602–604.

    CAS  PubMed  Google Scholar 

  20. Harris AP, Sendak MJ, Donham RT, Thomas M, Duncan D . Absorption characteristics of human fetal hemoglobin at wavelengths used in pulse oximetry. J Clin Monit 1988; 4 (3): 175–177.

    CAS  Article  Google Scholar 

  21. Pologe JA, Raley DM . Effects of fetal hemoglobin on pulse oximetry. J Perinatol 1987; 7 (4): 324–326.

    CAS  PubMed  Google Scholar 

  22. Arikan GM, Haeusler MC, Haas J, Scholz H . Does the hemoglobin concentration in fetal blood interfere with the accuracy of fetal reflection pulse oximetry?. Fetal Diagn Ther 1998; 13 (4): 236–240.

    CAS  Article  Google Scholar 

  23. Rajadurai VS, Walker AM, Yu VY, Oates A . Effect of fetal haemoglobin on the accuracy of pulse oximetry in preterm infants. J Paediatrics Child Health 1992; 28 (1): 43–46.

    CAS  Article  Google Scholar 

  24. Masimo Radical 7 Signal Extraction Pulse CO-OXimeter with rainbow technology—Operator's manual 2010.

  25. Hay WW Jr., Rodden DJ, Collins SM, Melara DL, Hale KA, Fashaw LM . Reliability of conventional and new pulse oximetry in neonatal patients. J Perinatol 2002; 22 (5): 360–366.

    Article  Google Scholar 

  26. Johnston ED, Boyle B, Juszczak E, King A, Brocklehurst P, Stenson BJ . Oxygen targeting in preterm infants using the Masimo SET Radical pulse oximeter. Arch Dis Child Fetal Neonatal Edn 2011; 96 (6): F429–F433.

    Article  Google Scholar 

  27. Saugstad OD, Aune D . Optimal oxygenation of extremely low birth weight infants: a meta-analysis and systematic review of the oxygen saturation target studies. Neonatology 2014; 105 (1): 55–63.

    CAS  Article  Google Scholar 

  28. Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA et al. Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatrics 2012; 161 (6): 1047–1052.

    Article  Google Scholar 

  29. Bateman D, Polin RA . A lower oxygen-saturation target decreases retinopathy of prematurity but increases mortality in premature infants. J Pediatrics 2013; 163 (5): 1528–1529.

    Article  Google Scholar 

  30. Guyatt GH, Briel M, Glasziou P, Bassler D, Montori VM . Problems of stopping trials early. BMJ 2012; 344: e3863.

    Article  Google Scholar 

  31. Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q et al. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 2010; 303 (12): 1180–1187.

    CAS  Article  Google Scholar 

  32. Manja V, Mathew B, Carrion V, Lakshminrusimha S . Critical congenital heart disease screening by pulse oximetry in a neonatal intensive care unit. J Perinatol 2014 (e-pub ahead of print).

  33. Milner QJ, Mathews GR . An assessment of the accuracy of pulse oximeters. Anaesthesia 2012; 67 (4): 396–401.

    CAS  Article  Google Scholar 

  34. O'Reilly M . Masimo signal extraction technology pulse oximetry. Concerning the article by R.J. Rosychuk et al.: Discrepancies between arterial oxygen saturation and functional oxygen saturation measured with pulse oximetry in very preterm infants [Neonatology 2012;101:14-19]. Neonatology 2012; 101 (4): 239–240 author reply 240.

    Article  Google Scholar 

  35. Rosychuk RJ, Hudson-Mason A, Eklund D, Lacaze-Masmonteil T . Discrepancies between arterial oxygen saturation and functional oxygen saturation measured with pulse oximetry in very preterm infants. Neonatology 2012; 101 (1): 14–19.

    CAS  Article  Google Scholar 

  36. Quine D, Stenson BJ . Arterial oxygen tension (Pao2) values in infants &lt;29 weeks of gestation at currently targeted saturations. Arch Dis Child Fetal Neonatal Edn 2009; 94 (1): F51–F53.

    CAS  Article  Google Scholar 

  37. Quine D, Stenson BJ . Does the monitoring method influence stability of oxygenation in preterm infants? A randomised crossover study of saturation versus transcutaneous monitoring. Arch Dis Child Fetal Neonatal Edn 2008; 93 (5): F347–F350.

    CAS  Article  Google Scholar 

  38. De Halleux V, Gagnon C, Bard H . Decreasing oxygen saturation in very early preterm newborn infants after transfusion. Arch Dis Child Fetal Neonatal Edn 2003; 88 (2): F163.

    CAS  Article  Google Scholar 

  39. Furfaro S, Prosmanne J, Bard H . Hemoglobin oxygen dissociation (P50) in bronchopulmonary dysplasia. Biol Neonate 1990; 57 (2): 72–76.

    CAS  Article  Google Scholar 

  40. Shiao SY . Effects of fetal hemoglobin on accurate measurements of oxygen saturation in neonates. J Perinat Neonatal Nurs 2005; 19 (4): 348–361.

    Article  Google Scholar 

  41. Polin RA, Fox WW, Abman SH . Fetal and Neonatal Physiology: Expert Consult—Online and Print 4th ednvol. 2. Elsevier Limited: Oxford, UK, 2011.

    Google Scholar 

  42. Wimberley PD . Fetal hemoglobin, 2,3-diphosphoglycerate and oxygen transport in the newborn premature infant. Scand J Clin Lab Invest Suppl 1982; 160: 1–149.

    CAS  PubMed  Google Scholar 

  43. Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM . Oxygen-saturation targets and outcomes in extremely preterm infants. N Engl J Med 2003; 349 (10): 959–967.

    CAS  Article  Google Scholar 

  44. Schmidt B, Roberts RS, Whyte RK, Asztalos EV, Poets C, Rabi Y et al. Impact of study oximeter masking algorithm on titration of oxygen therapy in the Canadian Oxygen Trial. J Pediatrics 2014; 165 (4): 666–671.e2.

    CAS  Article  Google Scholar 

  45. Alderliesten T, Lemmers PM, Smarius JJ, van de Vosse RE, Baerts W, van Bel F . Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatrics 2013; 162 (4): 698–704 e692.

    Article  Google Scholar 

  46. Claure N, Bancalari E . Automated closed loop control of inspired oxygen concentration. Respir Care 2013; 58 (1): 151–161.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant 5 R01 HD072929 (Optimal oxygenation in neonatal lung injury) to SL.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Lakshminrusimha.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lakshminrusimha, S., Manja, V., Mathew, B. et al. Oxygen targeting in preterm infants: a physiological interpretation. J Perinatol 35, 8–15 (2015). https://doi.org/10.1038/jp.2014.199

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2014.199

Further reading

Search

Quick links