Efectos de los objetivos más bajos versus más altos de saturación de oxígeno en sangre arterial sobre la muerte o la discapacidad en lactantes prematuros
Información
- DOI:
- https://doi.org/10.1002/14651858.CD011190.pub2Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 11 abril 2017see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Neonatología
- Copyright:
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- Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Autores
Contributions of authors
All authors contributed to the conception and design of the study, and the interpretation of data, reviewed and commented on the intellectual content, and gave final approval of the document to be published. Additional tasks undertaken by specific authors included:
Lisa Askie: screened the search results, extracted and entered data into RevMan, checked the extracted data for accuracy, undertook the initial 'Risk of bias' assessments, contributed to the subsequent 'Risk of bias' assessments discussions, and drafted the manuscript.
Brian Darlow: screened the search results, checked the extracted data for accuracy, and contributed to the 'Risk of bias' assessments discussions.
Peter Davis: screened the search results, checked the extracted data for accuracy, and contributed to the 'Risk of bias' assessments discussions.
Neil Finer: checked the extracted data for accuracy and contributed to the 'Risk of bias' assessments discussions.
Ben Stenson: checked the extracted data for accuracy and contributed to the 'Risk of bias' assessments discussions.
Maximo Vento: checked the extracted data for accuracy and contributed to the 'Risk of bias' assessments discussions.
Robin Whyte: checked the extracted data for accuracy, undertook the initial 'Risk of bias' assessments, and contributed to the subsequent 'Risk of bias' assessments discussions.
Sources of support
Internal sources
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NHMRC Clinical Trials Centre, University of Sydney, Australia.
A/Prof Askie's time on this Cochrane Review was partly supported by a National Health and Medical Research Council Program Grant (1037786).
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Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA.
A/Prof Askie's time on this Cochrane Review was partly supported by a grant (R03HD 079867) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health.
External sources
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Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA.
Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN275201100016C.
Declarations of interest
Six members of the authorship team were investigators in the included studies and the NeOProM Collaboration. One member was included for his expertise in the field but had no affiliation with the included studies.
Lisa Askie is a member of the BOOST II Australia writing committee and the NeOProM Collaboration.
Brian Darlow is a member of the BOOST‐NZ trial management committee, the BOOST II Australia trial management committee, and the NeOProM Collaboration.
Peter Davis is a member of the BOOST‐II Australia trial management committee and the NeOProM Collaboration.
Neil Finer is a member of the SUPPORT trial management committee and the NeOProM Collaboration.
Ben Stenson is a member of the BOOST‐II UK steering committee and the NeOProM Collaboration.
Maximo Vento has no conflicts of interest to declare.
Robin Whyte is a member of the COT trial management committee and the NeOProM Collaboration.
Acknowledgements
We wish to acknowledge the following people who have contributed to the preparation of this review in many important ways over many years: Kylie Hunter, Lucy Davies, Cynthia Cole, Win Tin, the investigators/statisticians/data managers/research nurses of the included trials, and all the members of the NeOProM Collaboration. We also wish to pay tribute to several (sadly now deceased) colleagues who have challenged and inspired us to continue this work over several decades: David Henderson‐Smart, Jack Sinclair, Edmund Hey, and Bill Silverman.
Version history
| Published | Title | Stage | Authors | Version |
| 2017 Apr 11 | Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants | Review | Lisa M Askie, Brian A Darlow, Peter G Davis, Neil Finer, Ben Stenson, Maximo Vento, Robin Whyte | |
| 2014 Jul 23 | Effects of targeting higher versus lower arterial oxygen saturations on death or disability in preterm infants | Protocol | Lisa M Askie, Brian A Darlow, Peter G Davis, Neil Finer, Ben Stenson, Maximo Vento, Robin Whyte | |
Differences between protocol and review
The title of the review was changed to the "Effects of targeting lower versus higher arterial oxygen saturations..." from the original "...higher versus lower ..." to better reflect that, for the purposes of this review, lower oxygen targeting was considered the experimental treatment.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- *Infant Mortality;
- *Infant, Extremely Premature;
- Age Factors;
- Arteries;
- Blindness [epidemiology, etiology];
- Cerebral Palsy [epidemiology];
- Enterocolitis, Necrotizing [epidemiology, etiology];
- Incidence;
- Oximetry;
- Oxygen [*administration & dosage, adverse effects, *blood];
- Publication Bias;
- Randomized Controlled Trials as Topic;
- Retinopathy of Prematurity [epidemiology, etiology, prevention & control];
- Selection Bias;
- Software;
Medical Subject Headings Check Words
Humans; Infant; Infant, Newborn;
PICO
Study flow diagram
Participant flow chart for the combined five NeOProM trials
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Oximeter offset to achieve masking as used in the five NeOProM trials
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 1 Death or major disability by 18 to 24 months corrected age (aligned definition).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 2 Death or major disability by 18 to 24 months corrected age (trialist defined).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 3 Death to 18 to 24 months corrected age.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 4 Major disability by 18 to 24 months corrected age (aligned definition).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 5 Major disability by 18 to 24 months corrected age (trialist defined).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 6 Death to discharge.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 7 Severe retinopathy of prematurity or retinal therapy (trialist defined).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 8 Patent ductus arteriosus requiring medical or surgical treatment.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 9 Necrotising enterocolitis.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 10 Cerebral palsy with GMFCS level 2 or higher at 18 to 24 months corrected age.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 11 Blindness.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 12 Severe hearing loss.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 13 Proportion of infants re‐admitted to hospital up to 18 to 24 months corrected age.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 14 Weight (grams) at discharge home.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 15 Weight (kilograms) at 18 or 24 months corrected age.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 16 Days of endotracheal intubation.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 17 Days of CPAP.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 18 Days of supplemental oxygen.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 19 Supplemental oxygen requirement at 36 weeks postmenstrual age.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 20 Days on home oxygen.
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 21 Quantitative Bayley III scores (Composite Cognitive Score (CCS)).
Comparison 1 Lower versus higher targeted oxygen saturations (no subgroups), Outcome 22 Quantitative Bayley III scores (Composite Language Score (CLS)).
Comparison 2 Lower versus higher targeted oxygen saturations (primary outcome, subgrouped by gestational age), Outcome 1 Death or major disability by 18 to 24 months corrected age (trialist defined).
Comparison 3 Lower versus higher targeted oxygen saturations (primary outcome, subgrouped by sex), Outcome 1 Death or major disability by 18 to 24 months corrected age (trialist defined).
Comparison 4 Lower versus higher targeted oxygen saturations (primary outcome, subgrouped by multiples), Outcome 1 Death or major disability by 18 to 24 months corrected age (trialist defined).
Comparison 5 Lower versus higher targeted oxygen saturations (primary outcome, subgrouped by oximeter calibration software), Outcome 1 Death or major disability by 18 to 24 months corrected age (aligned definition).
Comparison 5 Lower versus higher targeted oxygen saturations (primary outcome, subgrouped by oximeter calibration software), Outcome 2 Death or major disability by 18 to 24 months corrected age (trialist defined).
Comparison 6 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by oximeter calibration software), Outcome 1 Death by 18 to 24 months corrected age.
Comparison 6 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by oximeter calibration software), Outcome 2 Major disability by 18 to 24 months corrected age (aligned definition).
Comparison 6 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by oximeter calibration software), Outcome 3 Major disability by 18 to 24 months corrected age (trialist defined).
Comparison 6 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by oximeter calibration software), Outcome 4 Death to discharge.
Comparison 6 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by oximeter calibration software), Outcome 5 Severe retinopathy of prematurity or retinal therapy.
Comparison 7 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by gestational age), Outcome 1 Death by 18 to 24 months corrected age.
Comparison 7 Lower versus higher targeted oxygen saturations (secondary outcomes, subgrouped by gestational age), Outcome 2 Major disability by 18 to 24 months corrected age (trialist defined).
| Lower compared to higher targeted oxygen saturations (no subgroups) in preterm infants | ||||||
| Patient or population: extremely preterm infants | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
| Risk with higher targeted oxygen saturations (no subgroups) | Risk with lower targeted oxygen saturations | |||||
| Death or major disability by 18 to 24 months corrected age (aligned definition) | Study population | RR 1.04 | 4754 | ⊕⊕⊕⊕ | — | |
| 493 per 1000 | 513 per 1000 | |||||
| Death to 18 to 24 months corrected age | Study population | RR 1.16 | 4873 | ⊕⊕⊕⊕ | — | |
| 171 per 1000 | 199 per 1000 | |||||
| Major disability by 18 to 24 months corrected age (aligned definition) | Study population | RR 1.01 | 3867 | ⊕⊕⊕⊕ | — | |
| 383 per 1000 | 387 per 1000 | |||||
| Retinopathy of prematurity requiring treatment | Study population | RR 0.72 | 4089 | ⊕⊕⊕⊝ | — | |
| 148 per 1000 | 106 per 1000 | |||||
| Necrotising enterocolitis | Study population | RR 1.24 | 4929 | ⊕⊕⊕⊕ | — | |
| 90 per 1000 | 112 per 1000 | |||||
| Blindness | Study population | RR 1.13 | 3875 | ⊕⊕⊕⊝ | — | |
| 12 per 1000 | 13 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded to moderate for inconsistency due to moderate heterogeneity (I² = 72%). 2Downgraded to moderate for imprecision due to low event rates. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death or major disability by 18 to 24 months corrected age (aligned definition) Show forest plot | 5 | 4754 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.98, 1.10] |
| 2 Death or major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 5 | 4751 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [1.00, 1.14] |
| 3 Death to 18 to 24 months corrected age Show forest plot | 5 | 4873 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.16 [1.03, 1.31] |
| 4 Major disability by 18 to 24 months corrected age (aligned definition) Show forest plot | 5 | 3867 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.93, 1.09] |
| 5 Major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 5 | 3864 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.94, 1.14] |
| 6 Death to discharge Show forest plot | 5 | 4958 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.16 [1.03, 1.31] |
| 7 Severe retinopathy of prematurity or retinal therapy (trialist defined) Show forest plot | 5 | 4089 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.61, 0.85] |
| 8 Patent ductus arteriosus requiring medical or surgical treatment Show forest plot | 5 | 4928 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.95, 1.06] |
| 9 Necrotising enterocolitis Show forest plot | 5 | 4929 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.24 [1.05, 1.47] |
| 10 Cerebral palsy with GMFCS level 2 or higher at 18 to 24 months corrected age Show forest plot | 5 | 3877 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.79, 1.32] |
| 11 Blindness Show forest plot | 5 | 3875 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.65, 1.97] |
| 12 Severe hearing loss Show forest plot | 5 | 3869 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.73, 1.43] |
| 13 Proportion of infants re‐admitted to hospital up to 18 to 24 months corrected age Show forest plot | 1 | 295 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.93, 1.26] |
| 14 Weight (grams) at discharge home Show forest plot | 1 | 295 | Mean Difference (IV, Fixed, 95% CI) | ‐52.0 [‐214.25, 110.25] |
| 15 Weight (kilograms) at 18 or 24 months corrected age Show forest plot | 1 | 280 | Mean Difference (IV, Fixed, 95% CI) | 0.80 [‐0.24, 1.84] |
| 16 Days of endotracheal intubation Show forest plot | 2 | 1386 | Mean Difference (IV, Fixed, 95% CI) | 0.28 [‐1.16, 1.72] |
| 17 Days of CPAP Show forest plot | 3 | 2526 | Mean Difference (IV, Fixed, 95% CI) | ‐0.04 [‐1.38, 1.30] |
| 18 Days of supplemental oxygen Show forest plot | 3 | 2507 | Mean Difference (IV, Fixed, 95% CI) | ‐8.78 [‐12.02, ‐5.54] |
| 19 Supplemental oxygen requirement at 36 weeks postmenstrual age Show forest plot | 5 | 4175 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.81, 0.94] |
| 20 Days on home oxygen Show forest plot | 2 | 237 | Mean Difference (IV, Fixed, 95% CI) | ‐24.17 [‐57.99, 9.66] |
| 21 Quantitative Bayley III scores (Composite Cognitive Score (CCS)) Show forest plot | 2 | 1892 | Mean Difference (IV, Fixed, 95% CI) | 0.55 [‐0.91, 2.00] |
| 22 Quantitative Bayley III scores (Composite Language Score (CLS)) Show forest plot | 1 | 903 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [‐2.03, 2.43] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death or major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 < 26 weeks | 1 | 537 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.09 [0.89, 1.32] |
| 1.2 ≥ 26 weeks | 1 | 697 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.17 [0.86, 1.60] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death or major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 1 | 941 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.10 [0.97, 1.26] |
| 1.1 Male | 1 | 503 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.96, 1.33] |
| 1.2 Female | 1 | 438 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.87, 1.31] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death or major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Singleton | 1 | 670 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.10 [0.94, 1.29] |
| 1.2 Multiple | 1 | 271 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.88, 1.39] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death or major disability by 18 to 24 months corrected age (aligned definition) Show forest plot | 5 | 4684 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.98, 1.10] |
| 1.1 Original algorithm | 5 | 3003 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.94, 1.07] |
| 1.2 Revised algorithm | 3 | 1681 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [1.02, 1.24] |
| 2 Death or major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 5 | 4681 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [1.00, 1.15] |
| 2.1 Original algorithm | 5 | 3000 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.95, 1.13] |
| 2.2 Revised algorithm | 3 | 1681 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [1.02, 1.24] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death by 18 to 24 months corrected age Show forest plot | 5 | 4803 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.16 [1.03, 1.30] |
| 1.1 Original | 5 | 3087 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.91, 1.22] |
| 1.2 Revised | 3 | 1716 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.38 [1.13, 1.68] |
| 2 Major disability by 18 to 24 months corrected age (aligned definition) Show forest plot | 5 | 3967 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.93, 1.09] |
| 2.1 Original | 5 | 2529 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.99 [0.90, 1.09] |
| 2.2 Revised | 3 | 1438 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.91, 1.22] |
| 3 Major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 5 | 3964 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.94, 1.14] |
| 3.1 Original | 5 | 2526 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.89, 1.17] |
| 3.2 Revised | 3 | 1438 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.91, 1.22] |
| 4 Death to discharge Show forest plot | 4 | 3757 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.18 [1.03, 1.36] |
| 4.1 Original | 4 | 2575 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.06 [0.90, 1.26] |
| 4.2 Revised | 2 | 1182 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.45 [1.15, 1.84] |
| 5 Severe retinopathy of prematurity or retinal therapy Show forest plot | 4 | 3073 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.70 [0.58, 0.84] |
| 5.1 Original | 4 | 2085 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.53, 0.84] |
| 5.2 Revised | 2 | 988 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.56, 1.05] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Death by 18 to 24 months corrected age Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 < 26 weeks | 1 | 550 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.22 [0.95, 1.57] |
| 1.2 ≥ 26 weeks | 1 | 731 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.25 [0.84, 1.86] |
| 2 Major disability by 18 to 24 months corrected age (trialist defined) Show forest plot | 1 | 976 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.64, 1.35] |
| 2.1 < 26 weeks | 1 | 367 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.52, 1.37] |
| 2.2 ≥ 26 weeks | 1 | 609 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.59, 1.93] |
