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 (Spo₂) 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 Spo₂ 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 Spo₂ target groups. The collective data suggest that risks associated with restricting the upper Spo₂ 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.

FIGURE 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. (From Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med. 2009;6(6):e1000097. For more information, visit www.prisma-statement.org.)

FIGURE 2

Forest plot demonstrating the incidence of death and/or NDI (BSID-III <85) at follow-up. Data for the SUPPORT trial include information provided by the steering committee of the neonatal research network (National Institute of Child Health and Human Development). A, Pooled data from both original and revised algorithms. B, Data from original algorithm only. C, Data from revised algorithm only. The pooled data with both algorithms has 70 additional babies from the COT trial who were exposed to both the original and revised software.

FIGURE 3

Forest plot demonstrating the incidence of death at follow-up. A, Pooled data from both original and revised algorithms. B, Data from original algorithm only. C, Data from revised algorithm only. The pooled data with both algorithms has 70 additional babies from the COT trial who were exposed to both the original and revised software.

FIGURE 4

Forest plots demonstrating the incidence of NDI (BSID-III <85) at follow-up. Data for the SUPPORT trial include information provided by the steering committee of the neonatal research network (National Institute of Child Health and Human Development). A, Pooled data from both original and revised algorithms. B, Data from original algorithm only. C, Data from revised algorithm only. The pooled data with both algorithms has additional babies from the COT trial who were exposed to both the original and revised software.

FIGURE 5

Forest plots demonstrating the incidence of severe visual impairment and hearing loss at follow-up.

FIGURE 6

Combination chart showing mortality (shown as shaded gray area) and bar diagrams showing proportion of time spent <85% while on supplemental oxygen. Lower-oxygen target groups spent more time <85% Spo₂ compared with higher-oxygen target groups.