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Effects of tracheal occlusion on the neonatal cardiopulmonary transition in an ovine model of diaphragmatic hernia
  1. Philip L J DeKoninck1,2,3,
  2. Kelly J Crossley1,2,
  3. Aidan J Kashyap1,2,
  4. Sasha M Skinner1,2,
  5. Marta Thio4,5,6,
  6. Karyn A Rodgers1,2,
  7. Jan A Deprest7,8,9,
  8. Stuart B Hooper1,2,
  9. Ryan J Hodges1,2,10
  1. 1The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  2. 2Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia
  3. 3Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands
  4. 4Newborn Research, The Royal Women’s Hospital, Melbourne, Victoria, Australia
  5. 5The Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  6. 6Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Victoria, Australia
  7. 7Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals Leuven, Leuven, Belgium
  8. 8Department of Development and Regeneration, Cluster Woman and Child, Faculty of Medicine, KU Leuven, Leuven, Belgium
  9. 9Institute for Women’s Health, University College London Hospital, London, UK
  10. 10Monash Women’s Service, Monash Health, Melbourne, Victoria, Australia
  1. Correspondence to Dr Ryan J Hodges, Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia; ryan.hodges{at}monash.edu

Abstract

Objective Fetoscopic endoluminal tracheal occlusion (FETO) aims to reverse pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) and mitigate the associated respiratory insufficiency and pulmonary hypertension after birth. We aimed to determine whether FETO improves the cardiopulmonary transition at birth in an ovine model of CDH.

Methods In 12 ovine fetuses with surgically induced diaphragmatic hernia (DH; 80 dGA), an endotracheal balloon was placed tracheoscopically at ≈110 dGA and removed at ≈131 dGA (DH+FETO), while 10 were left untreated (DH). At ≈138 dGA, all lambs (survival at delivery: 67% [DH+FETO], 70% [DH]) were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood-gas values were measured.

Results Compared with DH, DH+FETO lambs had increased wet lung-to-body-weight ratio (0.031±0.004 vs 0.016±0.002) and dynamic lung compliance (0.7±0.1 vs 0.4±0.1 mL/cmH2O). Pulmonary vascular resistance was lower in DH+FETO lambs (0.44±0.11 vs 1.06±0.17 mm Hg/[mL/min]). However, after correction for lung weight, pulmonary blood flow was not significantly different between the groups (4.19±0.57 vs 4.05±0.60 mL/min/g). Alveolar–arterial difference in oxygen tension was not significantly different between DH+FETO and DH (402±41mm Hg vs 401±45 mm Hg).

Conclusions FETO accelerated lung growth in fetuses with CDH and improved neonatal respiratory function during the cardiopulmonary transition at birth. However, despite improved lung compliance and reduced pulmonary vascular resistance, there were less pronounced benefits for gas exchange during the first 2 hours of life.

  • congenital diaphragmatic hernia
  • tracheal occlusion
  • FETO
  • neonatal transition
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Footnotes

  • Patient consent for publication Not required.

  • Contributors All authors included on this paper fulfil the criteria of authorship, specifically: PLJD, KJC, JAD, SBH, MT and RJH designed the experiments. PLJD, KJC, AJK, SMS, MT, SBH, JAD and RJH were essential for establishing the model. PLJD, KJC, AJK and SBH were responsible for data analysis. PLJD, KJC and AJK wrote the first draft of the manuscript. All authors contributed by modifying and editing the manuscript and all approved final version.

  • Funding This research project was funded by grants from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Foundation, Cabrini Foundation, CDH Australia and the Victorian Government’s Operational Infrastructure Support Program. JDP is supported by a grant of the Great Ormond Street Hospital Charity Fund.

  • Disclaimer These funders were not involved in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.

  • Competing interests None declared.

  • Ethics approval The experiment was performed in accordance with guidelines established by the National Health and Medical Research Council of Australia and was approved by the relevant animal ethics committee at Monash University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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