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Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmH2O on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (∼7 mL/kg, control, n = 11) or cesarean section [∼37 mL/kg; elevated liquid (EL), n = 11] were mechanically ventilated (tidal volume = 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmH2O (control, n = 6; EL, n = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmH2O (control, n = 5; EL, n = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmH2O PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmH2O PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress.NEW & NOTEWORTHY Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory dist

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4-28) vs. 38 (29-46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2-50.1%) vs. 27.5% (18.6-36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are ma