The optimal oxygen saturation for extremely low birth weight infants: a meta-analysis

The optimal oxygen saturation in the first postnatal weeks for very low and extremely low birth weight infants has not yet been defined. This is in spite of the fact that hyperoxia is supposed to be an important pathogenetic factor for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) or chronic lung disease. Premature infants are more exposed to high oxidative stress not only because they are exposed to oxygen therapy but also because they are exposed to inflammation, have a poorly developed defense against oxidative stress, and often have free iron in tissues which triggers the production of hydroxyl radicals. Since therapies with different antioxidants so far have not been very useful in preventing oxygen radical-related conditions, at present the most rational approach to reduce oxidative stress is to control oxygen supplementation and prevent inflammation. Several studies have suggested the association between high SpO2 and high rates of ROP and BPD. To confirm these findings, two lead neonatologists have conducted a systematic review of the studies (both randomized and observational) published on high or low SaO2 targeting and outcomes such as ROP, BPD, and mortality.
In total, 10 studies were identified, of which 8 had severe ROP (n=3,811) and 8 had BPD/lung problems (n=4,612) as outcomes. Two studies also provided survival data. The relative risk (RR) in favor of low SpO2 was 0.42 (95% confidence interval, 95% CI 0.34–0.51) for severe ROP, 0.73 (95% CI 0.63–0.86) for BPD/lung problems, and 1.12 (95% CI 0.86–1.45) for mortality.
There was 1 randomized trial with ROP, 3 with BPD/lung problems, and 1 with mortality as outcome. When analyzing the randomized trials separately, the RR for severe ROP was 0.48 (95% CI 0.34–0.68), 0.79 (95% CI 0.64–0.97) for BPD/lung problems, and for 1.27 (95% CI 1.01–1.60) for mortality.
These data show that low oxygen saturation targeting results in a 50% reduction in severe ROP and in a 25% reduction of BDP in premature infants. However, only few randomized trials are available at present and the use of historical controls in observational studies makes it difficult to predict whether the changes in outcomes are related to changes in clinical practice. Results from ongoing randomized trials testing short- and long-term outcomes of high versus low oxygen saturation are awaited to draw firm conclusions and solve some open issues. For instance, we still do not know the optimal SpO2 for the smallest and most immature babies. Moreover, it is not known whether SpO2 should be increased at around 32 weeks of postconceptional age when children are prone to enter phase 2 of ROP, as some evidence indicates that this will increase lung complications. The authors conclude by suggesting that perhaps arterial oxygen saturation in the future should be monitored also in relation to changes in growth factors such as insulin-like growth factor, vascular endothelial growth factor, and others which indicate phase 2 ROP development.

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