High-frequency oscillatory ventilation during physiological-based cord clamping attenuates inflammation in preterm lambs: high-frequency oscillatory ventilation during physiological-based cord clamping attenuates inflammation in preterm lambs

Benincasa, B.C.; Vandenberg, E.G.; Johnson, Z.; Zahra, V.; Kelly, S.B.; Lu, H.; Gill, A.W.; Thiel, A.; Blank, D.A.; Weeda, J.A.; Silveira, R.C.; Procianoy, R.S.; Roberts, C.T.; Polglase, G.R.

doi:doi:10.1136/archdischild-2025-329610

Background: Adequate lung aeration at birth is essential for a successful transition to extrauterine life. Premature infants are especially vulnerable to injury caused by mechanical ventilation, particularly when exposed to excessive tidal volumes during initial respiratory support. Objective: To evaluate whether high-frequency oscillatory ventilation (HFOV) initiated at birth facilitates lung aeration and reduces lung inflammation and injury, compared with conventional mechanical ventilation (CMV) in preterm lambs. Design: Preterm lambs (126±1 days' gestation, term ~148 days) were instrumented to assess blood flow, pressure, oxygenation and blood gases. Lambs were allocated to HFOV (n=6), CMV (n=7) or unventilated control (UVC, n=8) groups. In ventilated groups, respiratory support was initiated during physiological-based cord clamping (PBCC). Lung aeration was assessed by lung ultrasound (LUS) in HFOV...Show moreBackground: Adequate lung aeration at birth is essential for a successful transition to extrauterine life. Premature infants are especially vulnerable to injury caused by mechanical ventilation, particularly when exposed to excessive tidal volumes during initial respiratory support. Objective: To evaluate whether high-frequency oscillatory ventilation (HFOV) initiated at birth facilitates lung aeration and reduces lung inflammation and injury, compared with conventional mechanical ventilation (CMV) in preterm lambs. Design: Preterm lambs (126±1 days' gestation, term ~148 days) were instrumented to assess blood flow, pressure, oxygenation and blood gases. Lambs were allocated to HFOV (n=6), CMV (n=7) or unventilated control (UVC, n=8) groups. In ventilated groups, respiratory support was initiated during physiological-based cord clamping (PBCC). Lung aeration was assessed by lung ultrasound (LUS) in HFOV lambs. Postmortem lung tissues underwent histological and molecular analyses of inflammation and injury. Results: HFOV achieved effective respiratory stabilisation using significantly lower tidal volumes compared with CMV (1.7±0.4 vs 6.2±1.5 mL/kg, p<0.0001). LUS confirmed rapid lung aeration following HFOV. Histological analyses revealed significantly fewer CD45-positive and CD163-positive inflammatory cells in HFOV lungs compared with CMV (p<0.001 and p<0.05, respectively). Gene expression profiling demonstrated lower expression of key inflammatory and injury markers in HFOV versus CMV lambs, with some levels approaching those observed in UVC (p<0.05) Conclusions: HFOV initiated during PBCC supports efficient lung aeration while minimising lung inflammation and injury in preterm lambs. These findings suggest that HFOV may reduce lung inflammation during initial respiratory stabilisation in preterm neonates. Keywords: intensive care units, neonatal; neonatology; resuscitation.Show less

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High-frequency oscillatory ventilation during physiological-based cord clamping attenuates inflammation in preterm lambs: high-frequency oscillatory ventilation during physiological-based cord clamping attenuates inflammation in preterm lambs

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