Among moderate- to late-preterm newborns who required respiratory support shortly following birth, initiating support with 30% oxygen rather than room air did not reduce ongoing respiratory support when leaving the delivery room. Current international guidelines cite insufficient evidence to recommend an initial oxygen concentration for newborns at 32 to 35 weeks’ gestation.
The AIROPLANE trial was an unblinded, cluster-randomized crossover trial conducted at 26 maternity hospitals in Victoria and New South Wales, Australia, from December 2022 to September 2025. Researchers included 1,818 newborns born at 32 weeks 0 days to 35 weeks 6 days’ gestation who began respiratory support within 3 minutes of birth and had no known major cardiorespiratory or craniofacial anomalies. Hospitals were randomly assigned to initiate respiratory support with a fraction of inspired oxygen (FIO₂) of 0.30 or 0.21 before crossing over to the alternative strategy midway through recruitment. Of the newborns included, 964 were assigned to FIO₂ 0.30 and 854 to FIO₂ 0.21.
The primary outcome was ongoing respiratory support when newborns left the delivery room. Secondary outcomes included the level of respiratory support provided in the delivery room, oxygen exposure, respiratory interventions during hospitalization, surfactant administration, hospital length of stay, transfer for escalating care, and death before discharge. Prespecified subgroup analyses assessed outcomes according to gestational age and hospital capability.
Ongoing respiratory support at delivery-room exit occurred in approximately 73% of newborns assigned to both FIO₂ 0.30 and FIO₂ 0.21 groups, with a risk difference of less than one percentage point. An analysis adjusting for antenatal corticosteroid exposure, gestational age, and delivery mode yielded a similar result. Most newborns who remained on respiratory support were receiving noninvasive support.
The primary finding was also consistent across prespecified subgroups. Among newborns born at 32 to 33 weeks’ gestation, 84% in each group required ongoing respiratory support. Among those born at 34 to 35 weeks’ gestation, the corresponding rates were 62% with FIO₂ 0.30 and 66% with FIO₂ 0.21. Researchers found no evidence that the treatment effect differed by gestational age or hospital capability.
Exploratory findings suggested differences in the intensity of respiratory care. Newborns assigned to FIO₂ 0.30 were less likely to receive progressively higher levels of respiratory support in the delivery room. Endotracheal ventilation after leaving the delivery room was also less common with FIO₂ 0.30, occurring in 6% of newborns compared with 9% receiving to FIO₂ 0.21. However, only 2 of 12 secondary outcomes showed clinically important differences between groups, and the analyses were not adjusted for multiple comparisons. The researchers therefore characterized these findings as exploratory.
Treatment separation was also limited during stabilization. Most newborns in both groups received increases in oxygen concentration beyond their assigned starting concentration. An FIO₂ above the initially assigned concentration was administered to 64% of newborns in the FIO₂ 0.30 group and 83% in the FIO₂ 0.21 group.
The difference between the two starting oxygen concentrations was relatively small, and the intervention period was brief, potentially limiting the ability to detect a difference. The trial was unblinded; physiological data and the timing of oxygen changes were not collected, and follow-up did not extend beyond hospital discharge. The primary outcome was also relatively subjective and may have been influenced by factors including how long newborns remained in the delivery room.
Overall, initiating respiratory support with FIO₂ 0.30 rather than FIO₂ 0.21 did not reduce ongoing respiratory support at delivery-room exit among moderate- to late-preterm newborns, while the exploratory secondary findings raised questions about whether starting oxygen concentration could affect the intensity of subsequent respiratory care. “These findings will inform international practice recommendations and provide a foundation for further trials,” wrote lead study author Stacey R. Peart, MBBS, of The Royal Women’s Hospital, and colleagues.
Several authors reported receiving grants from the National Health and Medical Research Council and other organizations; 1 reported grants from Chiesi Farmaceutici outside the submitted work. The study was supported by the National Health and Medical Research Council, University of Melbourne, and Rowden White Trust. No other disclosures were reported.
Source: JAMA
