Lower and higher oxygen saturation targets result in equal but contrasting outcomes for extremely preterm infants

1. In this meta-analysis, there was no significant difference between lower and higher oxygen saturation targets on a primary composite of mortality or major disability at a corrected age of 18-24 months for infants born extremely preterm.

2. Lower oxygen targets were associated with increased mortality and necrotizing enterocolitis while higher oxygen targets resulted in increased retinopathy of prematurity treatment.

Evidence Rating: 1 (Excellent)

Study Rundown: There is a delicate balance between too little and too much supplemental oxygen exposure in premature infants. An increased risk of reactive oxygen species resulting in retinopathy of prematurity and bronchopulmonary dysplasia with higher oxygen saturation targets must be weighed against impaired neurodevelopment and increased risk of death with lower saturation targets. This prospective meta-analysis showed that there was no significant difference in the primary composite outcome of death or major disability between higher versus lower oxygen saturations. However, when analyzed individually, lower oxygen targets were associated with increased mortality and necrotizing enterocolitis while higher oxygen targets resulted in increased retinopathy of prematurity treatment.

While these results are noteworthy, there were a few limitations to this study. First, all 5 trials reported less separation in oxygen exposure between treatment groups than anticipated because lower SpO2 target groups had higher than intended saturation levels. Second, 2 trials (BOOST II in UK and Australia) were stopped early which may have resulted in some overestimation of the effect on mortality in these trials. Third, the lack of association of SpO2 target range on blindness but with a clear difference on retinopathy of prematurity by treatment group may change with longer follow-up, when less severe visual impairments may become apparent. Ultimately, this study re-emphasizes the contrasting risks between high and low oxygen saturation targets for extremely preterm infants.

Click to read the study in JAMA

Relevant Reading: Oxygen Saturation Targets in Preterm Infants and Outcomes at 18–24 Months: A Systematic Review

In-Depth [meta-analysis]: This study collected data from 5 randomized, double-blind, multicenter trials with infants eligible if they were born before 28 weeks gestation and enrolled within 24 hours of birth: the SUPPORT trial, Canadian Oxygen Trial, BOOST in New Zealand trial, BOOST II in the United Kingdom, and BOOST II in Australia. 4965 infants were randomized to lower (85%-89%, n = 2480) or higher (91%-95%, n = 2485) SpO2 ranges. There was no significant difference between a lower compared with a higher SpO2 target range on the primary composite outcome of death or major disability at a corrected age of 18-24 months (relative risk 1.04; CI₉₅ 0.98 to 1.09). The lower SpO2 target range was associated with a significantly increased incidence of death at a corrected age of 18-24 months (RR 1.17; CI₉₅ 1.04 to 1.31) and necrotizing enterocolitis (RR 1.33; CI₉₅ 1.10 to 1.61) while the rate of retinopathy of prematurity treatment was lower than the higher SpO2 target range (RR 0.74; CI₉₅ 0.63 to 0.86).

Image: PD

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