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Cited by 52Pneumonia and Respiratory InfectionsRespiratory Support and MechanismsGlobal Maternal and Child Health

Oxygen systems to improve clinical care and outcomes for children and neonates: a stepped-wedge cluster-randomised trial in Nigeria

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Graham, Hamish R., Bakare, Ayobami A., Ayede, Adejumoke I., Gray, Amy Z., McPake, Barbara, Peel, David, Olatinwo, Olatayo, Oyewole, Oladapo B. +7 more·2019·PLOS Medicine
DOI 10.1371/journal.pmed.1002951PMC PMC6844455
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Abstract

BACKGROUND: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. METHODS AND FINDINGS: We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. CONCLUSIONS: We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

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  • Graham et al. (2019) chose the stepped wedge design to ensure all clusters eventually receive potentially beneficial intervention while allowing rigorous evaluation, balancing ethical considerations with the need for a control period.

    “The stepped wedge design was chosen to ensure that all clusters eventually receive potentially beneficial intervention while allowing for a rigorous evaluation of its effectiveness. This design helps to balance the ethical consideration of providing the intervention to all participants with the need for a control period for comparison”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [57]

    Methods > Study design says the stepped-wedge design allowed every hospital to receive the intervention and was chosen as an efficient, pragmatic fit for implementation logistics. Discussion > Limitations says it preserved the benefits of randomisation, and Methods > Statistical analysis describes comparisons across intervention periods. The paper does not state that balancing ethical considerations against a control period was a reason for choosing the design. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Graham et al. (2019) used 12 steps in the intervention rollout, with the full oxygen system introduced in steps 7-12.

    “The study involves 12 steps in the intervention rollout, with the full oxygen system being introduced in steps 7–12”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [57]

    The Methods (Study design, Fig. 1 caption) describe trial steps and identify step 7 as November 2015, when all hospitals received pulse oximeters. The full oxygen system was introduced later, beginning in March 2016, according to the Study design and Procedures sections. Thus, the claim includes step 7 incorrectly; no page numbers are available in our copy. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Graham et al. (2019) used a stepped wedge design involving sequentially rolling out the intervention to different clusters (hospitals) at regular intervals until all clusters receive the intervention.

    “Randomization in the stepped wedge design involves sequentially rolling out the intervention to different clusters (hospitals) at regular intervals until all clusters receive the intervention”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [57]

  • Graham et al. (2019) had a time between steps of 4 months.

    “The time between steps is 4 months”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [57]

  • Some studies aimed to assess the impact of interventions on patients' quality of life and satisfaction with healthcare services.

    “Some studies aimed to assess the impact of interventions on patients' quality of life and satisfaction with healthcare services (57, 58).”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [57]

    The Methods > Outcomes section lists death and oxygen-related care practices as the outcomes assessed. It does not mention patients’ quality of life or satisfaction with healthcare services; searches for those terms found no supporting passage in our copy. No page number was available for the indexed passage. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 40

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Authors
Graham, H. R., Bakare, A. A., Ayede, A. I., Gray, A. Z., McPake, B., Peel, D., Olatinwo, O., Oyewole, O. B., Neal, E. F. G., Nguyen, C. D., Qazi, S. A., Izadnegahdar, R., Carlin, J. B., Falade, A. G., & Duke, T.
Affiliations
  • Royal Children's Hospital (AU)
  • University College Hospital, Ibadan (NG)
  • University of Ibadan (NG)
  • The University of Melbourne (AU)
  • World Health Organization (CH)
  • Gates Foundation (US)
Corresponding author
Graham, Hamish R.
ORCID
Venue
PLOS Medicine
Publisher
Public Library of Science (PLoS)
Published
2019-11-11
Volume
16
Issue
11
Pages
e1002951
ISSN
  • 1549-1277 (ISSN-L)
  • 1549-1676
DOI
10.1371/journal.pmed.1002951
PMC
PMC6844455
OpenAlex
W2987742324
Cited by
52
References
6
Citations by year
2026: 6 · 2025: 8 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 6
FWCI
4.19
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
Bill and Melinda Gates Foundation (OPP1123577)
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Global Maternal and Child Health
Keywords
pulse oximetry, acute lower respiratory tract infection, neonatal mortality, preterm infants, low birth weight infants, child mortality, clinical practice change, Nigeria, oxygen saturation monitoring, neonatal intensive care, health system strengthening
MeSH terms
Adolescent, Child, Child, Preschool, Female, Hospitalization, Humans, Infant, Infant, Newborn, Male, Nigeria, Oximetry, Oxygen, Oxygen Inhalation Therapy, Respiratory Distress Syndrome, Respiratory Tract Infections, Cluster Analysis, Odds Ratio, Treatment Outcome, Cross-Over Studies

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