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Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia
  1. Aidan J Kashyap1,2,
  2. Kelly J Crossley1,2,
  3. Philip L J DeKoninck1,3,
  4. Karyn A Rodgers1,2,
  5. Marta Thio4,5,
  6. Sasha M Skinner1,2,
  7. Jan A Deprest6,7,
  8. Stuart B Hooper1,2,
  9. Ryan J Hodges1,8
  1. 1 The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  2. 2 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia
  3. 3 Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
  4. 4 Newborn Research, Neonatal Services, The Royal Women’s Hospital, Melbourne, Victoria, Australia
  5. 5 The Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  6. 6 Fetal Medicine Unit, Division Woman and Child, Department of Obstetrics and Gynecology, Katholieke Univ Leuven, Leuven, Belgium
  7. 7 Institute of Women’s Health, University College London Hospitals, University College London Medical School, London, UK
  8. 8 Monash Women’s Service, Monash Health, Melbourne, Victoria, Australia
  1. Correspondence to Dr Ryan J Hodges, Department Obstetrics and Gynaecology, Monash University, Clayton VIC 3800, Australia; ryan.hodges{at}


Objective Infants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to characterise the changes in cardiopulmonary physiology during the neonatal transition in an ovine model of CDH.

Methods A diaphragmatic hernia (DH) was surgically created at 80 days of gestational age (dGA) in 10 fetuses, whereas controls underwent sham surgery (n=6). At 138 dGA, lambs 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 DH lambs had lower wet lung-to-body-weight ratio (0.016±0.002vs0.033±0.004), reduced dynamic lung compliance (0.4±0.1mL/cmH2O vs1.2±0.1 mL/cmH2O) and reduced arterial pH (7.11±0.05vs7.26±0.05), compared with controls. While measured pulmonary blood flow (PBF) was lower in DH lambs, after correction for lung weight, PBF was not different between groups (4.05±0.60mL/min/gvs4.29±0.57 mL/min/g). Cerebral tissue oxygen saturation was lower in DH compared with control lambs (55.7±3.5vs67.7%±3.9%).

Conclusions Immediately after birth, DH lambs have small, non-compliant lungs, respiratory acidosis and poor cerebral oxygenation that reflects the clinical phenotype of human CDH. PBF (indexed to lung weight) was similar in DH and control lambs, suggesting that the reduction in PBF associated with CDH is proportional to the degree of lung hypoplasia during the neonatal cardiopulmonary transition.

  • congenital abnorm
  • fetal medicine
  • neonatology
  • animal research
  • physiology

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  • 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. AJK, PLJD, KJC and SH were responsible for data analysis. AJK, KJC and PLJD 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 Foundation, Cabrini Foundation, CDH Australia, and the Victorian Government’s Operational Infrastructure Support Program.

  • 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. This study was approved by the relevant animal ethics committee at Monash University.

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

  • Patient consent for publication Not required.