The Effect of Initial High vs. Low FiO₂ on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled...

Background: Infants are currently stabilized at birth with initial low FiO₂ 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 O₂ concentration, followed by titration, would improve breathing effort when compared to a low O₂ concentration, followed by titration. Methods: In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O₂ 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 SpO₂ values in the first 10 min. Hypoxemia was defined as SpO₂ < 25th percentile and hyperoxemia as SpO₂ >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% O₂-group: n = 20, 30% O₂-group: n = 24). Minute volumes were significantly higher in the 100% O₂-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O₂-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O₂-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% O₂-group [85 (64-93)%] compared to the 30% O₂-group [58 (46-67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O₂-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% O₂ led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O₂, without increasing the risk for hyperoxia or oxidative stress. Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.