Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis

Abstract

Importance: The optimal oxygen saturation (SpO2) target for extremely preterm infants is unknown.

Objective: To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants.

Data sources: MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014.

Study selection: All published randomized trials evaluating the effect of restricted (SpO2, 85%-89%) vs liberal (SpO2, 91%-95%) oxygen exposure in preterm infants (<28 weeks' gestation at birth).

Data extraction and synthesis: All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model.

Main outcomes and measures: Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity.

Results: Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio [RR], 1.02 [95% CI, 0.92-1.14]). Mortality before 24 months was not different (RR, 1.13 [95% CI, 0.97-1.33]); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 [95% CI, 1.03-1.36]). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 [95% CI, 1.05-1.47]). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low.

Conclusions and relevance: Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.

Figure 1. Distribution of Actual Median Oxygen Saturation

Distribution in the low oxygen saturation (SpO₂) (85%–89%) and high SpO₂ (91%–95%) arms in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), the Canadian Oxygen Trial (COT), and the Benefits of Oxygen Saturation Targeting II (BOOST II) trials. The mortality numbers currently available are shown as percentages (note that the 18- to 22-month mortality numbers are currently not available for the BOOST II UK and Australia trials). Because the SUPPORT and the original algorithm BOOST II data are reported using the original algorithm, corresponding SpO₂ numbers on the revised algorithm are shown as well. A saturation of 90% in the original algorithm corresponds to a saturation of 88% on the revised algorithm. This figure was adapted from Figure 4 in Lakshminrusimha et al.

Figure 2. Mortality Associated With Restrictive or Liberal Use of Oxygen

The phrase “favors liberal oxygen” means that the negative outcome is less common in that arm and vice versa. The numbers shown in this plot are raw, unadjusted values and differ from the adjusted risk ratios provided in the references. BOOST indicates Benefits of Oxygen Saturation Targeting; COT, Canadian Oxygen Trial; and SUPPORT, Surfactant, Positive Pressure, and Oxygenation Randomized Trial.

Figure 3. Morbidity Associated With Restrictive or Liberal Use of Oxygen: Bronchopulmonary Dysplasia, Necrotizing Enterocolitis, and Neurodevelopmental Outcomes

The phrase “favors liberal oxygen” means that the negative outcome is less common in that arm and vice versa. BOOST indicates Benefits of Oxygen Saturation Targeting; COT, Canadian Oxygen Trial; GMFCS, Gross Motor Function Classification System; and SUPPORT, Surfactant, Positive Pressure, and Oxygenation Randomized Trial.

Figure 4. Morbidity Associated With Restrictive or Liberal Use of Oxygen: Hearing Loss/Impairment and Retinopathy of Prematurity

The phrase “favors liberal oxygen” means that the negative outcome is less common in that arm and vice versa. BOOST indicates Benefits of Oxygen Saturation Targeting; COT, Canadian Oxygen Trial; and SUPPORT, Surfactant, Positive Pressure, and Oxygenation Randomized Trial.