The initial results of the SUPPORT trial examining the effects of different oxygen limits stopped a lot of us in our tracks. We started these trials because most of us thought that aiming for lower oxygen saturation targets would reduce eye disease, would reduce chronic lung disease and would be safe. We were uncertain enough however to put together randomized trials to scientifically compare the effects of choosing 2 different oxygen targets, to make sure that what we thought we were seeing from observational studies was in fact true.
We confirmed that less oxygen meant less retinal disease, including more retinal disease severe enough to need surgery, there wasn’t really any effect on chronic lung disease (a probably chance reduction from 39.7 to 37%) but there was an increase in mortality. More babies died in the lower oxygen group than the higher group.
The newly published results (Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, Laptook AR, Yoder BA, Faix RG, Das A et al: Neurodevelopmental outcomes in the early cpap and pulse oximetry trial. The New England journal of medicine 2012, 367(26):2495-2504) from the 20 month follow up confirm that the difference in survival persists, and now shows that all the actual outcomes on visual function were not different, neither blindness, severe visual impairments nor squint. Even though there were twice as many infants who had eye surgery in the high saturation group as the low sat group.
In addition the neurological and developmental outcomes (at least as measured by the Bayley score) were not different. Significant cerebral palsy was 5% in each group, and a Bayley score less than 70 was about 7.5% in each group.
With the interim analysis that stopped the BOOST2 trials in the UK and Australia also showing an increased mortality, it certainly looks like we should avoid the lower saturation range of 85 to 89% that was targeted in each of the low groups of the oxygen trials. This evidence is also enough I think to encourage us to do further trials examining other targets, as well as looking for other ways of avoiding hyperoxia. If we are to target 90 to 95% saturation, then the risk of episodic hyperoxia will be increased, maybe automated FiO2 controllers, adaptive alarms and other interventions can help us make the higher limits safer to the eyes.
Neonatal Research 
Good to meet you during your visit to Buenos Aires years ago and in Miami 2011 Neonatal conference.NR is an excellent source of information in neonatal-perinatal medicine. I will recommend to my staff (Bazterrica Clinic.in Buenos Aires Argentina. Maternity , Level iii NICU.and cardiovascular surgery). I’ll follow you with interest.Thank you for the hard work you always do for neonatologists (and for newborn babies too !!) Best wishes Enrique
Dr Enrique Gebara
Chief of Neonatology Service at Bazterrica Clinic
Buenos Aires
Argentina
Thanks so much for your kind comments, I loved Argentina, and especially meeting all the many dedicated people, like you, who were working for the good of babies.
Dr Barrington…
Toxicity due to hyperoxia seems to have become a widely accepted fact. But I am not sure why there have been no great advancements in Oxygen delivery systems. From your experience, what have been the barriers to creating acceptable automated closed loop oxygen delivery systems?
I don’t really know why this hasn’t taken off in the past. There have been reports of prototypes since the days of transcutaneous PO2 monitors, but nothing commercialized. I wonder if the risks of litigation have been an issue, if someone on your machine develops RoP anyway, are you liable? Maybe it is just a question of investment, to get people to use such a device you would have to show that it was safe and effective, and that is expensive. The recent work from the Miami group is promising, they did show that babies were more often in the target range with their system (Claure N, D’Ugard C, Bancalari E: Automated adjustment of inspired oxygen in preterm infants with frequent fluctuations in oxygenation: A pilot clinical trial. The Journal of pediatrics 2009, 155(5):640-645.e642.) but they also showed that the babies were more often hypoxic, which with these O2 studies making you think that hypoxia is more dangerous than we thought, would make me pause before buying such a system.
One thing that I think would really help would be an oximeter that was linked to an O2 analyzer. So whenever the baby was in O2 the high alarms would be automatically switched on, and when the baby went into room air the high alarm would be cancelled. That way the common occurrence of a baby needing O2 intermittently and ending up having the high alarms off could be avoided.
I had a question on oxygen saturation limits once a baby reaches 36 weeks corrected gestational age. Is it reasonable to keep sat limit parameters 92-97 as during the second phase of ROP, one needs to avoid hypoxia?
I don’t know of any good data to support a change in saturation limits at 36 weeks. The only direct study of that particular question, of babies with early RoP who were randomized to saturation limits in the high 90s vs the low 90s, found no effect on RoP, but the pulmonary outcomes were somewhat worse with higher saturations.
Our current practice, based on the best available data is to maintain the same limits throughout, aim for low 90’s and find an alarm setting protocol which is tolerable and which will eb followed by the bedside caregivers.