Questions Remain on Best Oxygenation Targets in Preemies

May 06, 2013

By Megan Brooks

NEW YORK (Reuters Health) May 06 - The latest study on oxygenation therapy in extremely premature infants does little to help resolve uncertainty over whether targeting higher or lower oxygen saturations yields better outcomes.

The Canadian Oxygen Trial (COT) found similar rates of death or disability at 18 months with an oxygen saturation target of 85% to 89% compared with 91% to 95%, according to a report published online May 5 in the Journal of the American Medical Association to coincide with a presentation at the Pediatric Academic Societies annual meeting in Washington, D.C.

"Our findings should reassure clinicians and parents that it may be safe to include saturations in the high 80s in the oxygen saturation target range for extremely preterm infants," Dr. Barbara Schmidt, who worked on the study, told Reuters Health. However, "many questions remain," she added.

Dr. Schmidt, from Children's Hospital of Philadelphia, Pennsylvania, continued, "It will be crucial to study how the disparate results of the recent oxygen trials are translated into practice in different parts of the world and whether any changes in practice will be associated with changes in the mortality rate or the incidence of disabling retinopathy of prematurity (ROP)."

The randomized COT study involved 1,201 extremely preterm infants at 25 hospitals. The babies were monitored until a postmenstrual age of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced two treatment groups with true target saturations of 85% to 89% (n=602) or 91% to 95% (n=599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%.

The study team found no significant difference between groups in the primary outcome (a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness) at a corrected age of 18 months.

They say 298 of 578 infants (51.6%) with adequate data for this outcome assigned to the lower target range died or survived with disability, compared with 283 of 569 infants (49.7%) assigned to the higher target range.

Nor was there a significant difference with lower vs higher target ranges in mortality before 18 months (16.6% vs 15.3%; adjusted odds ratio 1.11; p=0.54) or in the secondary outcomes of severe retinopathy of prematurity (ROP) or bronchopulmonary dysplasia (BPD).

COT joins several randomized trials performed to resolve the long-standing uncertainty of how to titrate oxygen therapy in extremely preterm infants. All trials examined the efficacy and safety of decreasing the concentration of supplemental oxygen to target arterial oxygen saturations of 85% to 89% compared with 91% to 95%.

In the US SUPPORT trial, severe ROP was reduced but mortality increased in the lower saturation target group (see - but there was no difference between the two groups in the composite outcome of death or neurodevelopmental impairment at 18 months (see

The increased mortality with the lower oxygen saturation target was also observed in the BOOST II trials conducted in Australia and New Zealand. Recruitment in these trials was halted early after an interim subgroup analysis showed that infants who were monitored with oximeters that contained revised software had an increased survival with the higher saturation target range. Data from these trials on ROP, BDP and other outcomes have not been reported.

"The differences between the results of these trials may be partly due to important differences in their design and implementation," the COT investigators say.

In their view, "Clinicians who try to translate the disparate results of the recent oxygen saturation targeting trials into their practice may find it prudent to target saturations between 85% and 95% while strictly enforcing alarm limits of 85% at all times and of 95% during times of oxygen therapy. Our findings do not support recommendations that targeting saturations in the upper 80% range should be avoided."

In an editorial, Dr. Eduardo Bancalari and Dr. Nelson Claure from the Division of Neonatology, University of Miami Miller School of Medicine in Miami, Florida, comment on the latest oxygenation trial in relation to prior trials.

They say the fact that the long-term follow-up of infants in COT and SUPPORT did not reveal differences in neurodevelopmental outcome between the target ranges of saturation is "reassuring." However, the concerns raised by the higher mortality in the lower saturation target found in SUPPORT and BOOST II "should not be minimized until the planned meta-analysis including all three studies is completed."

"Unfortunately," Dr. Bancalari told Reuters Health, "the uncertainty on the best oxygen target for premature infants still persists. More detailed analysis of the data and future meta-analysis will hopefully help resolve the conundrum. However more studies are likely needed to answer the many remaining questions."

"Until the remaining questions raised by these studies are answered by the combined meta-analysis or new evidence becomes available, minimizing extreme oxygenation levels by targeting saturations between 90% and 95% appears to be a reasonable approach," Dr. Bancalari and Dr. Claure conclude in their editorial.

The study was funded exclusively by a grant from the Canadian Institutes of Health Research.


JAMA 2013.