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Neonatology 2011;100:217–218 DOI: 10.1159/000329845

Oxygen Saturation in Immature Babies:Revisited with Updated Recommendations

Ola D. Saugstad   a Christian P. Speer   b Henry L. Halliday   c  

a   Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Oslo , Norway; b   University Children’s Hospital, University of Würzburg, Würzburg , Germany; c   Retired Professor of Child Health, Queen’s University of Belfast, Belfast , UK

The present data therefore clearly indicate that a low saturation is beneficial with respect to minimizing both eye and lung problems in ELBW infants. Clinical recom-mendations, such as the recent European guidelines for management of respiratory distress syndrome, therefore recommend SpO 2 targets between 85 and 93%. The level of evidence for these recommendations was, however, considered low, based on case series, case reports or ex-pert opinion [5] .

Mortality and Oxygen Saturation Targets

The SUPPORT trial was the only randomized trial re-porting mortality. It was therefore of concern when this study reported a significantly increased mortality in the low compared with the high saturation group (19.9 vs. 16.2%; RR 1.27; 95% CI 1.01–1.60) [4] . Despite these find-ings, many neonatologists did not change their clinical practice but waited for the ongoing randomized studies using similar high and low oxygen target limits as the SUPPORT trial reported. Very recently, the BOOST II trials in Australia, New Zealand and the UK were closed on recommendation of the data monitoring committees after detecting a significant increase in mortality. How-ever, this increase in mortality in the lower oxygen satu-ration target group was only discovered after the calibra-

Although 60 years ago hyperoxia was shown to be a risk factor for retinopathy of prematurity (ROP), for the last 10 years there has been a search for the optimal oxy-gen saturation targets for immature and extremely low birth weight (ELBW) infants [1] . Recent evidence indi-cates that these babies are more vulnerable to even slight hyperoxia than previously acknowledged [2] .

Retinopathy of Prematurity, Bronchopulmonary

Dysplasia and Oxygen Targets

A recent meta-analysis and systematic review of all published randomized studies concluded that a low com-pared with a high saturation reduced the relative risk (RR) of severe ROP (0.48; 95% CI 0.34–0.68) and bron-chopulmonary dysplasia (BPD)/lung problems (0.79; 95% CI 0.64–0.97). When both randomized and non-ran-domized studies were assessed together, severe ROP was reduced from 20.9 to 9.5% and BPD/lung problems from 40.8 to 29.7% [3] . This is in agreement with the random-ized SUPPORT trial which found similar reductions in a group of babies of 24–28 weeks’ gestation treated with low (85–89%) versus high (91–95%) oxygen saturation targets assessed by pulse oximetry (SpO 2 ). In this trial, reduc-tions of severe ROP from 17.9 to 8.6% and BPD from 41.7 to 38.0% were found [4] .

Received: June 6, 2011 Accepted: June 6, 2011 Published online: July 15, 2011

Ola Didrik Saugstad, MD, PhD, FRCPE Department of Pediatric Research Oslo University Hospital, Rikshospitalet PB 4950 Nydalen, NO–0424 Oslo (Norway) Tel. +47 2307 2790/94, E-Mail odsaugstad   @   rr-research.no

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Saugstad  /Speer /Halliday     Neonatology 2011;100:217–218218

tion algorithm in the Masimo oximeter, used in all these trials, was revised in 2009 [6] . The new algorithm was as-sociated with improved SpO 2 targeting and after it had been adopted in BOOST II for a period of time, survival at 36 weeks’ postmenstrual age was analyzed by pooling 2,315 infants in the BOOST II trials with 1,316 infantsin the SUPPORT trial [7] . The infants, randomized to a SpO 2 of 91–95% had a lower mortality than those as-signed to an SpO 2 of 85–89% (14.4 vs. 17.3%; RR 1.21; p = 0.015). When analyzing the 1,055 infants in the UK and Australia/New Zealand BOOST II trials studied after change of the algorithm, the difference in mortality was even greater (21.8 vs. 13.3%; RR 1.65; p ! 0.001). The BOOST II trials consequently were closed.

Clinical Consequences

Data from another randomized study from Canada, the COT study, are pending. Until these results and fol-low-up data of SUPPORT and BOOST II trials are avail-able, we agree with the BOOST II investigators who state that presently SpO 2 targets of 85–89% should be avoided

[7] . This recommendation may be controversial knowing that even if mortality is slightly reduced a higher target may lead to considerably higher rates of severe ROP and BPD in these infants [3] . The SpO 2 targets describing the optimal balance between mortality on the one hand and complications such as ROP and BPD on the other are therefore presently not known. In fact, it may take sev-eral years until more precise information is available to guide clinical practice. In the future, a more dynamic ap-proach may be adopted keeping the SpO 2 lower in the first weeks of life and increasing the target range after, for instance, 32 weeks’ postmenstrual age during the second phase of ROP [8] . There are experimental data indicating that hyperoxia increases oxygenation and oxidative stress in the brain [9, 10] , and that oxidative stress contributes to regulation of the circulation [11] . A more comprehen-sive understanding of pathogenetic mechanisms leading to oxidative damage in immature infants may also lead to improved outcomes in the future [12] .

In conclusion, until more data become available, SpO 2 in immature babies should not be targeted between 85–89%. The optimal SpO 2 is presently not known.

References

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