Outcomes of two trials of oxygen-saturation targets in preterm infants

William Tarnow-Mordi, Ben Stenson, Adrienne Kirby, Edmund Juszczak, Mark Donoghoe, Sanjeev Deshpande, Colin Morley, Andrew King, Lex W. Doyle, Brian W. Fleck, Peter G. Davis, Henry L. Halliday, Wendy Hague, Pamela Cairns, Brian A. Darlow, Alistair R. Fielder, Val Gebski, Neil Marlow, Karen Simmer, Win Tin & 20 others Alpana Ghadge, Cathy Williams, Anthony Keech, Stephen P. Wardle, Zsuzsoka Kecskes, Martin Kluckow, Glen Gole, Nicholas Evans, Girvan Malcolm, Melissa Luig, Ian Wright, Jacqueline Stack, Kenneth Tan, Margo Pritchard, Peter H. Gray, Scott Morris, Bevan Headley, Peter Dargaville, R. John Simes, Peter Brocklehurst

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. 

METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. 

RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P = 0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P = 0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P = 0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P = 0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P = 0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P = 0.001). 

CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Original languageEnglish
Pages (from-to)749-760
Number of pages12
JournalNew England Journal of Medicine
Volume374
Issue number8
DOIs
Publication statusPublished - 25 Feb 2016

Cite this

Tarnow-Mordi, W., Stenson, B., Kirby, A., Juszczak, E., Donoghoe, M., Deshpande, S., ... Brocklehurst, P. (2016). Outcomes of two trials of oxygen-saturation targets in preterm infants. New England Journal of Medicine, 374(8), 749-760. https://doi.org/10.1056/NEJMoa1514212
Tarnow-Mordi, William ; Stenson, Ben ; Kirby, Adrienne ; Juszczak, Edmund ; Donoghoe, Mark ; Deshpande, Sanjeev ; Morley, Colin ; King, Andrew ; Doyle, Lex W. ; Fleck, Brian W. ; Davis, Peter G. ; Halliday, Henry L. ; Hague, Wendy ; Cairns, Pamela ; Darlow, Brian A. ; Fielder, Alistair R. ; Gebski, Val ; Marlow, Neil ; Simmer, Karen ; Tin, Win ; Ghadge, Alpana ; Williams, Cathy ; Keech, Anthony ; Wardle, Stephen P. ; Kecskes, Zsuzsoka ; Kluckow, Martin ; Gole, Glen ; Evans, Nicholas ; Malcolm, Girvan ; Luig, Melissa ; Wright, Ian ; Stack, Jacqueline ; Tan, Kenneth ; Pritchard, Margo ; Gray, Peter H. ; Morris, Scott ; Headley, Bevan ; Dargaville, Peter ; Simes, R. John ; Brocklehurst, Peter. / Outcomes of two trials of oxygen-saturation targets in preterm infants. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 8. pp. 749-760.
@article{d9827e96dedb45309c99e99a56e5acd9,
title = "Outcomes of two trials of oxygen-saturation targets in preterm infants",
abstract = "BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89{\%}) or a higher (91 to 95{\%}) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0{\%}) in the lower-target group versus 217 of 545 infants (39.8{\%}) in the higher-target group (adjusted relative risk, 1.12; 95{\%} confidence interval [CI], 0.98 to 1.27; P = 0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5{\%}) in the lower-target group versus 164 of 357 infants (45.9{\%}) in the higher-target group (adjusted relative risk, 1.10; 95{\%} CI, 0.97 to 1.24; P = 0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1{\%}) in the lower-target group versus 437 of 1013 infants (43.1{\%}) in the higher-target group (relative risk, 1.11; 95{\%} CI, 1.01 to 1.23; P = 0.02), and death occurred in 222 of 1045 infants (21.2{\%}) in the lower-target group versus 185 of 1045 infants (17.7{\%}) in the higher-target group (relative risk, 1.20; 95{\%} CI, 1.01 to 1.43; P = 0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5{\%}) in the lower-target group versus 248 of 563 infants (44.0{\%}) in the higher-target group (relative risk, 1.12; 95{\%} CI, 0.99 to 1.27; P = 0.07), and death occurred in 144 of 587 infants (24.5{\%}) versus 99 of 586 infants (16.9{\%}) (relative risk, 1.45; 95{\%} CI, 1.16 to 1.82; P = 0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89{\%} versus 91 to 95{\%} resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).",
author = "William Tarnow-Mordi and Ben Stenson and Adrienne Kirby and Edmund Juszczak and Mark Donoghoe and Sanjeev Deshpande and Colin Morley and Andrew King and Doyle, {Lex W.} and Fleck, {Brian W.} and Davis, {Peter G.} and Halliday, {Henry L.} and Wendy Hague and Pamela Cairns and Darlow, {Brian A.} and Fielder, {Alistair R.} and Val Gebski and Neil Marlow and Karen Simmer and Win Tin and Alpana Ghadge and Cathy Williams and Anthony Keech and Wardle, {Stephen P.} and Zsuzsoka Kecskes and Martin Kluckow and Glen Gole and Nicholas Evans and Girvan Malcolm and Melissa Luig and Ian Wright and Jacqueline Stack and Kenneth Tan and Margo Pritchard and Gray, {Peter H.} and Scott Morris and Bevan Headley and Peter Dargaville and Simes, {R. John} and Peter Brocklehurst",
year = "2016",
month = "2",
day = "25",
doi = "10.1056/NEJMoa1514212",
language = "English",
volume = "374",
pages = "749--760",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "8",

}

Tarnow-Mordi, W, Stenson, B, Kirby, A, Juszczak, E, Donoghoe, M, Deshpande, S, Morley, C, King, A, Doyle, LW, Fleck, BW, Davis, PG, Halliday, HL, Hague, W, Cairns, P, Darlow, BA, Fielder, AR, Gebski, V, Marlow, N, Simmer, K, Tin, W, Ghadge, A, Williams, C, Keech, A, Wardle, SP, Kecskes, Z, Kluckow, M, Gole, G, Evans, N, Malcolm, G, Luig, M, Wright, I, Stack, J, Tan, K, Pritchard, M, Gray, PH, Morris, S, Headley, B, Dargaville, P, Simes, RJ & Brocklehurst, P 2016, 'Outcomes of two trials of oxygen-saturation targets in preterm infants' New England Journal of Medicine, vol. 374, no. 8, pp. 749-760. https://doi.org/10.1056/NEJMoa1514212

Outcomes of two trials of oxygen-saturation targets in preterm infants. / Tarnow-Mordi, William; Stenson, Ben; Kirby, Adrienne; Juszczak, Edmund; Donoghoe, Mark; Deshpande, Sanjeev; Morley, Colin; King, Andrew; Doyle, Lex W.; Fleck, Brian W.; Davis, Peter G.; Halliday, Henry L.; Hague, Wendy; Cairns, Pamela; Darlow, Brian A.; Fielder, Alistair R.; Gebski, Val; Marlow, Neil; Simmer, Karen; Tin, Win; Ghadge, Alpana; Williams, Cathy; Keech, Anthony; Wardle, Stephen P.; Kecskes, Zsuzsoka; Kluckow, Martin; Gole, Glen; Evans, Nicholas; Malcolm, Girvan; Luig, Melissa; Wright, Ian; Stack, Jacqueline; Tan, Kenneth; Pritchard, Margo; Gray, Peter H.; Morris, Scott; Headley, Bevan; Dargaville, Peter; Simes, R. John; Brocklehurst, Peter.

In: New England Journal of Medicine, Vol. 374, No. 8, 25.02.2016, p. 749-760.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Outcomes of two trials of oxygen-saturation targets in preterm infants

AU - Tarnow-Mordi, William

AU - Stenson, Ben

AU - Kirby, Adrienne

AU - Juszczak, Edmund

AU - Donoghoe, Mark

AU - Deshpande, Sanjeev

AU - Morley, Colin

AU - King, Andrew

AU - Doyle, Lex W.

AU - Fleck, Brian W.

AU - Davis, Peter G.

AU - Halliday, Henry L.

AU - Hague, Wendy

AU - Cairns, Pamela

AU - Darlow, Brian A.

AU - Fielder, Alistair R.

AU - Gebski, Val

AU - Marlow, Neil

AU - Simmer, Karen

AU - Tin, Win

AU - Ghadge, Alpana

AU - Williams, Cathy

AU - Keech, Anthony

AU - Wardle, Stephen P.

AU - Kecskes, Zsuzsoka

AU - Kluckow, Martin

AU - Gole, Glen

AU - Evans, Nicholas

AU - Malcolm, Girvan

AU - Luig, Melissa

AU - Wright, Ian

AU - Stack, Jacqueline

AU - Tan, Kenneth

AU - Pritchard, Margo

AU - Gray, Peter H.

AU - Morris, Scott

AU - Headley, Bevan

AU - Dargaville, Peter

AU - Simes, R. John

AU - Brocklehurst, Peter

PY - 2016/2/25

Y1 - 2016/2/25

N2 - BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P = 0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P = 0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P = 0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P = 0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P = 0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P = 0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

AB - BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P = 0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P = 0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P = 0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P = 0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P = 0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P = 0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

UR - http://www.scopus.com/inward/record.url?scp=84959441253&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1514212

DO - 10.1056/NEJMoa1514212

M3 - Article

VL - 374

SP - 749

EP - 760

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 8

ER -

Tarnow-Mordi W, Stenson B, Kirby A, Juszczak E, Donoghoe M, Deshpande S et al. Outcomes of two trials of oxygen-saturation targets in preterm infants. New England Journal of Medicine. 2016 Feb 25;374(8):749-760. https://doi.org/10.1056/NEJMoa1514212