Objective: The aim of this study was to compare the effect of targeting arterial oxygen saturation (SpO2) in the high (93–95%) versus the low portion (90–92%) of the recommended range of 90–95% on oxygenation stability in extremely premature infants. Methods: Premature infants of ≤28 weeks of gestational age who received a fraction of inspired oxygen (FiO2) > 0.21 after day 14 were eligible. FiO2 was adjusted by a dedicated investigator to keep SpO2 between 90–92% and 93–95% for 2 h each in random sequence. Episodes of intermittent hypoxemia (IH) were defined as SpO2 <90% for ≥10 s; severe IH episodes were defined as SpO2 <80% for ≥10 s. Hyperoxemia was defined as SpO2 >95% or >98%. Results: Eighteen premature infants were enrolled. Their (mean ± SD) GA was 26 ± 1.5 w. Seven infants were on mechanical ventilation, 4 infants on nasal ventilation, and 7 infants on nasal cannula. They were on a mean FiO2 0.38 ± 0.12 at study entry. Episodes of IH and severe IH were more frequent during the low compared to the high target (36.6 [27.0–41.3] vs. 16.0 [7.8–19.0], p < 0.001; 8.4 ± 9.3 vs. 3.2 ± 4.3, p = 0.002). The proportions of time with SpO2 >95% and >98% were greater with the high target (13.9 ± 11 vs. 34.1 ± 15.4%, p < 0.001; 0.9 [0–5.7] vs. 3.4 [0.5–16.1]%, p = 0.002). Conclusion: In this group of extremely premature infants, targeting SpO2 at the lower portion of the recommended range resulted in more frequent episodes of IH. However, targeting the higher SpO2 range led to more hyperoxemia. This trade-off warrants further investigation.

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