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

Archives of Disease in Childhood Fetal & Neonatal, vol. 111, pp. F376–F383

Abstract

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 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.

Authors 14

1. Bianca Chassot Benincasa

   Universidade Federal do Rio Grande do Sul

   Affiliation as printed

   Programa de Pós-graduação em Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

2. Emma G Vandenberg

   Hudson Institute of Medical Research · Monash University

   Affiliation as printed

   Department of Paediatrics, Monash University, Melbourne, Victoria, Australia

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

3. Zoe Johnson

   Hudson Institute of Medical Research · Monash University

   Affiliation as printed

   Department of Paediatrics, Monash University, Melbourne, Victoria, Australia

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

4. Valerie A. Zahra

   Hudson Institute of Medical Research

   Affiliation as printed

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

5. Sharmony B. Kelly

   Hudson Institute of Medical Research

   Affiliation as printed

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

6. Hui Lü

   Hudson Institute of Medical Research

   Affiliation as printed

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

7. Andrew William Gill

   The University of Western Australia

   Affiliation as printed

   Centre for Neonatal Research and Education, University of Western Australia, Perth, Western Australia, Australia

8. Alison M. Thiel

   Hudson Institute of Medical Research

   Affiliation as printed

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

9. Douglas A. Blank

   Monash Medical Centre · Hudson Institute of Medical Research · Monash Health

   Affiliation as printed

   Monash Newborn, Monash Health, Clayton, Victoria, Australia

   The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

10. Jesse A. Weeda Aachen Division of Neonatology and Pediatric Cardiology

    Willem-Alexander Kinderziekenhuis

    Affiliation as printed

    Division of Neonatology and Pediatric Cardiology, Willem-Alexander Children’s Hospital, Leiden, The Netherlands

11. Rita C. Silveira

    Universidade Federal do Rio Grande do Sul · Hospital de Clínicas de Porto Alegre

    Affiliation as printed

    Pediatrics-Newborn Section, Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre Porto Alegre, Porto Alegre, Brazil

12. Renato S. Procianoy

    Universidade Federal do Rio Grande do Sul · Hospital de Clínicas de Porto Alegre

    Affiliation as printed

    Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

13. Calum T. Roberts

    Monash University

    Affiliation as printed

    Department of Paediatrics, Monash University, Melbourne, Victoria, Australia

14. Graeme R. Polglase corresponding

    Hudson Institute of Medical Research · Monash University

    Affiliation as printed

    Department of Paediatrics, Monash University, Melbourne, Victoria, Australia

    The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia