Supplemental oxygen for the treatment of prethreshold retinopathy of prematurity

Oxygen has long been implicated in the pathogenesis of retinopathy of prematurity (ROP) and is rigorously monitored in today's neonatal intensive care units. Recent research using a feline model has shown an improvement in ROP outcome of kittens treated with supplemental oxygen. Current treatment for ROP by retinal ablation is not without complications so a non-invasive method of treatment is preferred. The possible effects of long term oxygen supplementation on chronic lung disease, length of hospital stay and growth and development are, however, unknown.

To determine whether, in preterm or low birth weight infants with prethreshold ROP, targeting higher as compared to normal transcutaneous oxygen levels or pulse oximetry levels when using supplemental oxygen reduces the progression of ROP to threshold disease and improves visual outcome without any adverse effects.

The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching. An additional literature search of the MEDLINE (1966-June 2002), EMBASE (1980-April 2002), and CINAHL (1982-April 2002) databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR, The Cochrane Library Issue 2, 2002).

All randomised or quasi randomised studies comparing higher versus normal target oxygen levels in preterm or low birthweight infants with prethreshold ROP were eligible for inclusion.

The methodological quality of the one eligible trial was assessed independently by two authors for the degree of selection, performance, attrition and detection bias. Data regarding clinical outcomes including progression to threshold ROP, blindness or severe visual impairment, mortality, respiratory morbidities and long term growth were extracted and reviewed independently by two authors. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.

The one trial included in this review enrolled 649 infants. There was a trend for supplemental oxygen to reduce the progression to threshold ROP, however this did not reach statistical significance (RR 0.84, 95% CI 0.70, 1.02). A subgroup analysis of those infants without plus disease showed significantly fewer infants progressing to threshold ROP in infants treated with supplemental oxygen. However this analysis was not pre-specified so these results should be interpreted with caution. No significant effects were detected on blindness or severe visual function at three months corrected age, mortality, pneumonia, chronic lung disease or weight gain. Adverse pulmonary events were more common in the higher oxygen saturation group and these infants were in hospital and on supplemental oxygen for longer. Longer term visual outcomes were not reported.

The results of this systematic review do not show a statistically significant reduction in the rate of progression to threshold ROP with supplemental oxygen treatment, but reveal increased adverse pulmonary sequelae with higher oxygen targeting in this group of preterm infants. Future research needs to be directed towards the question of whether infants without plus disease are more likely to respond to supplemental oxygen therapy than those with plus disease.