<p>Objective: To evaluate the performance of a rapidly responsive adaptive algorithm (VDL1.1) for automated oxygen control in preterm infants with respiratory insufficiency.</p>
<p>Design: Interventional cross-over study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking periods of manual control (12 hours each).</p>
<p>Setting: Neonatal intensive care unit.</p>
<p>Participants: Preterm infants receiving non-invasive respiratory support and supplemental oxygen; median birth gestation 27 weeks (IQR 26-28) and postnatal age 17 (12-23) days.</p>
<p>Intervention: Automated oxygen titration with the VDL1.1 algorithm, with the incoming SpO<sub>2</sub> signal derived from a standard oximetry probe, and the computed inspired oxygen concentration (FiO<sub>2</sub>) adjustments actuated by a motorised blender. The desired SpO<sub>2</sub> range was 90%-94%, with bedside clinicians able to make corrective manual FiO<sub>2</sub> adjustments at all times.</p>
<p>Main outcome measures: Target range (TR) time (SpO<sub>2</sub> 90%-94% or 90%-100% if in air), periods of SpO<sub>2</sub> deviation, number of manual FiO<sub>2</sub> adjustments and oxygen requirement were compared between automated and manual control periods.</p>
<p>Results: In 60 cross-over studies in 35 infants, automated oxygen titration resulted in greater TR time (manual 58 (51-64)% vs automated 81 (72-85)%, p<0.001), less time at both extremes of oxygenation and considerably fewer prolonged hypoxaemic and hyperoxaemic episodes. The algorithm functioned effectively in every infant. Manual FiO<sub>2</sub> adjustments were infrequent during automated control (0.11 adjustments/hour), and oxygen requirements were similar (manual 28 (25-32)% and automated 26 (24-32)%, p=0.13).</p>
<p>Conclusion: The VDL1.1 algorithm was safe and effective in SpO<sub>2</sub> targeting in preterm infants on non-invasive respiratory support. Trial registration number: ACTRN12616000300471.</p>