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Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs
  1. Graeme R Polglase1,2,
  2. Douglas A Blank1,
  3. Samantha K Barton1,3,
  4. Suzanne L Miller1,3,
  5. Vanesa Stojanovska1,
  6. Martin Kluckow4,
  7. Andrew W Gill5,
  8. Domenic LaRosa1,
  9. Arjan B te Pas6,
  10. Stuart B Hooper1,2
  1. 1 The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia
  2. 2 Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
  3. 3 Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
  4. 4 Department of Neonatology, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia
  5. 5 Centre for Neonatal Research and Education, The University of Western Australia, Subiaco, Western Australia, Australia
  6. 6 Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Graeme R Polglase, The Ritchie Centre, HudsonInstitute of Medical Research,Clayton, Victoria 3168, Australia; graeme.polglase{at}


Background Physiologically based cord clamping (PBCC) has advantages over immediate cord clamping (ICC) during preterm delivery, but its efficacy in asphyxiated infants is not known. We investigated the physiology of PBCC following perinatal asphyxia in near-term lambs.

Methods Near-term sheep fetuses (139±2 (SD) days’ gestation) were instrumented to measure umbilical, carotid, pulmonary and femoral arterial flows and pressures. Systemic and cerebral oxygenation was recorded using pulse oximetry and near-infrared spectroscopy, respectively. Fetal asphyxia was induced until mean blood pressure reached ~20 mm Hg, where lambs underwent ICC and initiation of ventilation (n=7), or ventilation for 15 min prior to umbilical cord clamping (PBCC; n=8). Cardiovascular parameters were measured and white and grey matter microvascular integrity assessed using qRT-PCR and immunohistochemistry.

Results PBCC restored oxygenation and cardiac output at the same rate and in a similar fashion to lambs resuscitated following ICC. However, ICC lambs had a rapid and marked overshoot in mean systemic arterial blood pressure from 1 to 10 min after ventilation onset, which was largely absent in PBCC lambs. ICC lambs had increased cerebrovascular injury, as indicated by reduced expression of blood–brain barrier proteins and increased cerebrovascular protein leakage in the subcortical white matter (by 86%) and grey matter (by 47%).

Conclusion PBCC restored cardiac output and oxygenation in an identical time frame as ICC, but greatly mitigated the postasphyxia rebound hypertension measured in ICC lambs. This likely protected the asphyxiated brain from cerebrovascular injury. PBCC may be a more suitable option for the resuscitation of the asphyxiated newborn compared with the current standard of ICC.

  • delayed cord clamping
  • asphyxia
  • depressed
  • resuscitation
  • immediate cord clamping

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  • Contributors Substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data: GRP, DAB, SKB, SLM, MK, AWG, ABP, SBH. Drafting the work or revising it critically for important intellectual content: GRP, DAB, SKB, SLM, VS, MK, AWG, DL, ABP, SBH. Final approval of the version published: GRP, DAB, SKB, SLM, VS, MK, AWG, DL, ABP, SBH. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: GRP, DAB, SKB, SLM, VS, MK, AWG, DL, ABP, SBH.

  • Funding This research was supported by the National Institute of Health (R01HD072848-01A1), the Research Foundation of the Cerebral Palsy Alliance, a joint National Heart Foundation of Australia and National Health and Medical Research Council (NH&MRC) Research Fellowship (GRP: 1105526), an NH&MRC Research Fellowship (SKB: 545921), an NHMRC-Australian Research Council Dementia Research Development Fellowship (SKB: 1110040), Australian Research Council Future Fellowship (SLM) and the Victorian Government’s Operational Infrastructure Support Program.

  • Competing interests None declared.

  • Ethics approval Experimental procedures were approved by the Monash Medical Centre Animal Ethics Committee A, Monash University.

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

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