Optimal Oxygen Use Differs for Preterm, Term Newborn Resuscitation

By Will Boggs MD

December 31, 2018

NEW YORK (Reuters Health) - Room-air resuscitation reduces short-term mortality in term newborns compared with pure oxygen, while the optimal oxygen concentration for preterm newborn resuscitation remains unclear, according to two systematic reviews.

"Oxygen can cause harm, and it should be used judiciously," Dr. Michelle Welsford from McMaster University, in Hamilton, Canada, told Reuters Health by email. "Do not start resuscitation in term neonates with oxygen. Almost all preterm newborns <=32 weeks' gestation will require oxygen supplementation within the first five minutes after delivery. Start low and titrate using oxygen saturation targets, avoiding hyperoxia."

Dr. Welsford and colleagues on the International Liaison Committee on Resuscitation Neonatal Life Support Task Force undertook two systematic reviews with meta-analyses in an effort to ascertain the optimal initial fraction of inspired oxygen (FIO2) for preterm- and term-newborn resuscitation.

For preterm neonates (<35 weeks' gestation), short-term mortality and long-term mortality did not differ between starting respiratory support with lower FIO2 (0.5 or lower) or with higher FIO2 (above 0.5), the team reports in Pediatrics, online December 21.

Similarly, there was no difference in long-term neurodevelopmental impairment (NDI) rates between preterm newborns receiving respiratory support starting with lower compared with higher FIO2.

Moreover, there were no significant differences in any of the additional secondary outcomes that were deemed important markers of morbidity, and subgroup analyses by gestational age (32 weeks and earlier and 28 weeks and earlier) revealed no significant differences when comparing lower with higher FIO2.

For term neonates, however, the use of room air for resuscitation led to a 27% reduction in short-term mortality compared with 100% oxygen (an absolute survival benefit of 4.6 percentage points). The number needed to treat with room air to have one additional survivor was 22.

Long-term moderate-to-severe neurodevelopmental impairment did not differ by initial FIO2, and there were no differences between low and high FIO2 in the rates of hypoxic-ischemic encephalopathy (HIE).

All studies of term neonates compared room-air oxygen levels with 100% oxygen levels, making it impossible to undertake subgroup analysis according to different oxygen concentrations.

The GRADE certainty of evidence for preterm outcomes was very low because of issues with risk of bias, inconsistency and imprecision, while the GRADE certainty of evidence for term outcomes was low for short-term mortality and HIE and very low for NDI.

"Although term newborns who require respiratory support at birth have proven reduction in mortality with room air, the same benefit is not confirmed in preterm newborns and should not be automatically assumed," Dr. Welsford said. "The majority of newborns <=32 weeks' gestation will require oxygen supplementation in the first 5 minutes, therefore, starting with low oxygen and titrating using saturation targeting will allow life-sustaining oxygenation but limit injury from hyperoxia."

"There is a knowledge gap on the ideal initial FIO2 for preterm neonates <=32 weeks' gestation and this should be further explored," she said. "The International Liaison Committee on Resuscitation (ILCOR) will release a new consensus on science with treatment recommendation (CoSTR) on this topic on-line at www.ilcor.org in the next month and in print in the fall of 2019."

"Guideline developers must not only grapple with the quality or certainty of the evidence but also account for individual and societal values and preferences, resource implications, and feasibility," writes Dr. Roger F. Soll of the University of Vermont, in Burlington, in an accompanying editorial.

"As these reviews move toward recommendations, the fact is that we will begin our resuscitation with some oxygen (as low as 21% or as high as 100%)," he said. "Ultimately, a decision will have to be made regarding how much oxygen with which we start. Yet, given the paucity of evidence, the single greatest point we can take from these analyses is that we are uncertain."

"Although we must act, our obligation is not simply to conduct the well-thought-out recommendations that will evolve from this process but to acknowledge the huge gaps in knowledge that exist and commit to further research on the subject," Dr. Soll concluded.

Dr. Maximo Vento Torres of the University of Valencia, Spain, and Dr. Ju-Lee Oei from Royal Hospital for Women, in Randwick, Australia, told Reuters Health in a joint email, "Clinicians embrace change with alarming rapidity even without robust evidence of benefit or harm. Even after more than a decade from when guidelines were first changed in 2005, we still do not know whether lower or higher oxygenation is best for preterm infants at birth. Physicians should be encouraged to support studies designed to answer this question as soon as possible in order to avoid death and harm to thousands of newborn infants around the world every year."

"Reliable advances in knowledge of interventions to improve disability-free survival in preterm infants at delivery have been unacceptably slow," said Dr. Vento and Dr. Oei, both members of the Advanced Neonatal Resuscitation study group. "We need support for new generations of internationally coordinated trials, designed to be at least ten times larger and faster, at fractions of current costs."

SOURCE: https://bit.ly/2T2ddZ9 and https://bit.ly/2PUpnkB

Pediatrics 2018.