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

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. Author summaryWhy was this study done? Oxygen therapy is important for many acute medical conditions, particularly among unwell children and newborns, in whom hypoxaemia (low blood oxygen) is common. Oxygen access and use are suboptimal in many hospitals in low- and middle-income countries. Improved oxygen systems may reduce deaths from pneumonia. To scale up oxygen in resource-limited settings, we need better information about how to improve oxygen systems and stronger evidence on the benefits of improved oxygen systems for newborns and children. What did the researchers do and find? We introduced pulse oximetry and improved oxygen systems in 12 Nigerian hospitals, aiming to provide continuous oxygen therapy for every child and neonate who needed it. We evaluated the impact of pulse oximetry and the improved oxygen system on care practices and clinical outcomes for >24,000 unwell newborns and children. We found that the improved oxygen system had no effect on outcomes for children, when compared against the introduction of pulse oximetry. However, pulse oximetry may have reduced the risk of death from pneumonia by approximately 50% compared to baseline. We found that the improved oxygen system was associated with increased risk of neonatal death, when compared against the introduction of pulse oximetry. However, neither pulse oximetry nor the full oxygen system had any effect on neonatal death when compared against baseline. What do these findings mean? Pulse oximetry should be central to all activities aiming to improve access to oxygen therapy. Where some oxygen is already available, the introduction of pulse oximetry may improve how oxygen is used and may reduce deaths from pneumonia. The negative results for newborns are surprising but should be interpreted cautiously. Analysis of results from individual hospitals shows significant variability in outcomes for newborns and children. Our study was challenged by a major economic recession, resulting in unexpected changes in admission numbers, illness severity, and care practices and low power to detect change in clinical outcomes.