The Effect of Initial High vs. Low FiO(2) on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled Trial

Background: Infants are currently stabilized at birth with initial low FiO(2) which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O(2) concentration, followed by titration, would improve breathing effort when compared to a low O(2) concentration, followed by titration. Methods: In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O(2) concentration of 30 or 100%, followed by oxygen titration. Primary outcome was minute volume of spontaneous breathing. We also assessed tidal volumes, mean inspiratory flow rate (MIFR) and respiratory rate with a respiratory function monitor in the first 5 min after birth, and evaluated the duration of mask ventilation in the first 10 min after birth. Pulse oximetry was used to measure heart rate and SpO(2) values in the first 10 min. Hypoxemia was defined as SpO(2) < 25th percentile and hyperoxemia as SpO(2) >95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth. Results: Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O(2)-group: n = 20, 30% O(2)-group: n = 24). Minute volumes were significantly higher in the 100% O(2)-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O(2)-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O(2)-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O(2)-group [85 (64–93)%] compared to the 30% O(2)-group [58 (46–67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O(2)-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups. Conclusion: Initiating stabilization of preterm infants at birth with 100% O(2) led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O(2), without increasing the risk for hyperoxia or oxidative stress. Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.