Target ranges of oxygen saturation in extremely preterm infants

Abstract

Background: Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes.

Methods: We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant.

Results: The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events.

Conclusions: A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)

Figure 1

The numbers shown exclude infants of women who were screened during pregnancy but whose babies were not subsequently born at a study center between 24 weeks 0 days and 27 weeks 6 days of gestation. The outcome of severe retinopathy of prematurity (ROP) could not be determined in some infants because of loss to follow-up. CPAP denotes continuous positive airway pressure.

Figure 2. Kaplan–Meier Estimate of Survival to Hospital Discharge, Transfer, or 1 Year of Life

Cox proportional-hazards analysis indicated that there was an increased hazard of death in the lower-oxygen-saturation group as compared with the higher-oxygen-saturation group (hazard ratio, 1.28; 95% CI, 0.98 to 1.68; P = 0.07). The analysis assumed that infants who were discharged or transferred from the hospital survived to 1 year of age.

Figure 3. Actual Median Oxygen Saturation with Oxygen Supplementation in the Two Treatment Groups

The medians of the distributions were significantly different on the basis of a rank-sum test (P<0.001). The 80% level of oxygen saturation shown includes all values at or below 80%.