Resuscitation of very preterm infants with 30% vs. 65% oxygen at birth: study protocol for a randomized controlled trial

Background: Resuscitation at birth with 100% oxygen is known to increase the oxidative burden with concomitant deleterious effects. Although fractions of inspired oxygen (FiO(2)) < 100% are widely used in preterm infants, starting resuscitation at a (too) low FiO(2) may result in hypoxia. The objective of this study is to compare the safety and efficacy of resuscitating very preterm infants with an initial FiO(2) of 30% versus 65%. Methods/design: In this double-blind, randomized controlled trial, 200 very preterm infants with a gestational age < 32 weeks will be randomized to start resuscitation after birth with either 30% or 65% oxygen. The FiO(2) will be adjusted based on oxygen saturation measured by pulse oximetry (SpO(2)) and pulse rate (which should be over 100 beats per minute) in order to achieve a target SpO(2) of 88-94% at 10 min of life. The FiO(2) and pulse oximetry data will be continuously recorded. The primary outcome is survival without bronchopulmonary dysplasia, as assessed by a physiological test at 36 weeks postmenstrual age. The secondary outcomes include the time to achieve SpO(2) > 88%, Apgar score at 5 min, cumulative O-2 exposure, oxidative stress (as determined by glutathione synthesis and oxidative stress markers), retinopathy of prematurity, brain injury and neurodevelopmental outcome at 2 years of age. This study will provide insight into determining the appropriate initial FiO(2) to start resuscitation of very preterm infants.