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

Abstract

CONTEXT: The optimal oxygen saturation target for extremely preterm infants remains unclear.OBJECTIVE: To systematically review evidence evaluating the effect of lower (85%-89%) versus higher (91%-95%) pulse oxygen saturation (SpO 2 ) target on mortality and neurodevelopmental impairment (NDI) at 18 to 24 months. DATA SOURCES:Electronic databases and all published randomized trials evaluating lower versus higher SpO 2 target in preterm infants. STUDY SELECTION:A total of 2896 relevant citations were identified; 5 trials were included in the final analysis.DATA EXTRACTION: Data from 5 trials were analyzed for quality of evidence and risk of bias. LIMITATIONS:Limitations include heterogeneity in age at enrollment and comorbidities between trials and change in oximeter algorithm midway through 3 trials. RESULTS:There was no difference in the incidence of primary outcome (death/NDI at 18-24 months) in the 2 groups; risk ratio, 1.05, 95% confidence interval 0.98-1.12, P = .18. Mortality before 18 to 24 months was higher in the lower-target group (risk ratio, 1.16, 95% confidence interval 1.03-1.31, P = .02). Rates of NDI and severe visual loss did not differ between the 2 groups. Proportion of time infants spent outside the target range while on supplemental oxygen ranged from 8.2% to 27.4% <85% and 8.1% to 22.4% >95% with significant overlap between the 2 groups.CONCLUSIONS: There was no difference in primary outcome between the 2 SpO 2 target groups. The collective data suggest that risks associated with restricting the upper SpO 2 target limit to 89% outweigh the benefits. The quality of evidence was moderate. We speculate that a wider target range (lower alarm limit, 89% and upper, 96%) may increase time spent within range, but the safety profile of this approach remains to be determined. Dr Manja conceptualized and designed the study, reviewed the literature, carried out the initial analyses, and reviewed and revised the manuscript; Dr Saugstad critically reviewed and extensively revised the manuscript; Dr Lakshminrusimha was the second reviewer of the literature and drafted the initial manuscript; and all authors approved the fi nal manuscript as submitted and agree to be accountable for all aspects of work.

Oxygen saturation targeting by pulse oximetry in the extremely low gestational age neonate: a quixotic quest

“…[13] However, this did not take into account the different BSID cutoffs between SUPPORT and the other trials in defining disability; in separate meta-analyses using a uniform BSID cutoff and with additional data provided by the SUPPORT investigators, no difference in the primary outcome was found (Figure 1). [14, 15]…”

“…[16] In a meta-analysis of outcomes before and after study oximeter software revision, differences in mortality were not seen among more than 3000 infants monitored with the original software. [14, 15] Some have attributed the differences seen following the revised algorithm to better separation between study groups; however, post hoc analyses show no improvement in study group separation following software revision, [17] and no enhancement of treatment effect (mortality differences) among NICUs that achieved better separation. [18] An additional confounder in interpreting the mortality results is that two of the BOOST-II trials were stopped early based on an interim analysis of mortality, [10] thus biasing the results towards this outcome; this may explain why these two trials show the largest differences in death between study groups in the NeOProM collaborative.…”

“…In all NeOProM trials, infants in the lower saturation group spent relatively more time with SpO 2 < 85%, as might be expected; however, a systematic review could not demonstrate a relationship between time spent <85% and mortality. [15] Also, when comparing the original to the revised oximeter data, a greater mortality difference was seen although the amount of time infants spent <85% did not change. [4] Considering that the revised algorithm only affected readings between 87–91%, there may be modifying factors that place a subset of ELGANs at increased risk of mortality, even when subjected to only mild hypoxemia (SpO 2 85–89%); for example, post hoc analyses of SUPPORT found that SGA but not AGA infants in the lower SpO 2 group were at increased risk of mortality.…”

Oxygenation of the Immature Infant: A Commentary and Recommendations for Oxygen Saturation Targets and Alarm Limits

“…In the present review, data are lumped together regardless of the algorithm used in the pulse oximeters. Four meta-analyses and systematic reviews of these data have been published [19, 21-23]; data from these are summarized in Table 2.…”

“…Mortality separately showed a significant increase in RR from 1.16 (95% CI 1.03–1.31) [19] to 1.18 (95% CI 1.03–1.36) [23] in the low saturation target group. For NDI alone, no differences were found between both groups (RR 1.01, 95% CI 0.93–1.09).…”