Less Retinopathy of Prematurity Seen With Biphasic Oxygen Targets

By David Douglas

February 25, 2019

NEW YORK (Reuters Health) - In prematurely-born infants, compared to static oxygen standards, biphasic oxygen targets are associated with reduced rates of retinopathy of prematurity (ROP), without increased mortality, according to a new study.

"Although premature infants require oxygen supplementation to prevent mortality, excess oxygen can be simultaneously harmful to premature developing tissues such as the retina, leading to ROP," Dr. Jonathan E. Sears of the Cleveland Clinic Cole Eye Institute, in Ohio, explained in an email to Reuters Health.

"Early in premature life, in phase 1 of ROP, hyperoxia attenuates retinal growth, which provides the substrate for abnormal angiogenesis in phase 2 of ROP," he added.

"Using a biphasic approach," Dr. Sears continued, "phase 1 and phase 2 can be 'flipped' so that early physiologic hypoxia induces normal retinal growth to remove the substrate for ROP. Later in the course of prematurity, oxygen standards are increased to support increased metabolic demands and prevent tissue hypoxia."

To compare oxygenation approaches, Dr. Sears and colleagues examined retrospective data on 260 infants who underwent the biphasic approach and a further 302 who were treated with static standards in accordance with guidelines in the 2010 SUPPORT study.

All infants were treated at the same level III neonatal intensive care unit, were born at a corrected gestational age (CGA) of 31 weeks or less or had a birth weight of no more than 1,500 g. The pre-SUPPORT group underwent biphasic protocol target saturations of 85% to 92% at less than 34 weeks of CGA and greater than 95% at 34 weeks of CGA or more; the post-SUPPORT group underwent a constant 91% to 95% target.

There was a significant increase in any ROP overall from 20% pre-SUPPORT to 28% post-SUPPORT (P=0.03), the researchers report in JAMA Ophthalmology, online February 14.

Infants in the post-SUPPORT group also had significantly more treatment-requiring ROP (6% vs. 2%) and more-frequent vascularization delays (6% vs. 2%). However, there were no significant between-group differences in mortality (5% in the pre-SUPPORT group vs. 6%, P=0.81).

The researchers hypothesize "that biphasic oxygen saturation targets might be different than static oxygen targets."

Concluded Dr. Sears: "one approach to balancing the pros and cons of oxygen is to consider a biphasic approach."

In an accompanying editorial, Dr. Lois E. H. Smith of Harvard Medical School, in Boston, and colleagues note that the study "is an important first step in defining the use of oxygen while considering the timing of oxygen supplementation as well as the saturation targets. The use of lower SpO2 targets early and higher during a later period has the potential to become a preventive strategy for ROP."

Dr. Alex R. Kemper, division chief of Ambulatory Pediatrics at Nationwide Children's Hospital, in Columbus, Ohio, noted, "One of the important challenges in taking care of prematurely born infants is knowing how best to administer oxygen, which really should be considered a drug with both benefits and harms. If the levels of oxygen are too low, there is an increased risk of death but if too high, retinopathy of prematurity, potentially leading to blindness, can develop."

Dr. Kemper, who was not involved in the study, added that it "suggests that using a lower oxygen target for younger premature infants and a higher oxygen target for slightly older premature infants could reduce the risk of retinopathy of prematurity without increasing the risk of death."

"This is an important finding," he told Reuters Health by email, "but before it becomes a standard of care, much more research is needed, including evaluating the approach in more infants and following the infants for a longer period of time to make sure that problems do not develop later."

SOURCE: https://bit.ly/2XjFkpM and https://bit.ly/2tyrLVu

JAMA Ophthalmol 2019.