Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs

Graeme R. Polglase, Douglas A. Blank, Samantha K. Barton, Suzanne L. Miller, Vanesa Stojanovska, Martin Kluckow, Andrew W. Gill, Domenic Larosa, Arjan B. Te Pas, Stuart B. Hooper

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)F530-F538
Number of pages9
JournalArchives of Disease in Childhood: Fetal and Neonatal Edition
Volume103
Issue number6
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

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

Cite this

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title = "Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs",
abstract = "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.",
keywords = "asphyxia, delayed cord clamping, depressed, immediate cord clamping, resuscitation",
author = "Polglase, {Graeme R.} and Blank, {Douglas A.} and Barton, {Samantha K.} and Miller, {Suzanne L.} and Vanesa Stojanovska and Martin Kluckow and Gill, {Andrew W.} and Domenic Larosa and {Te Pas}, {Arjan B.} and Hooper, {Stuart B.}",
year = "2018",
month = "11",
day = "1",
doi = "10.1136/archdischild-2017-313657",
language = "English",
volume = "103",
pages = "F530--F538",
journal = "Archives of Disease in Childhood: Fetal and Neonatal Edition",
issn = "1359-2998",
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Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs. / Polglase, Graeme R.; Blank, Douglas A.; Barton, Samantha K.; Miller, Suzanne L.; Stojanovska, Vanesa; Kluckow, Martin; Gill, Andrew W.; Larosa, Domenic; Te Pas, Arjan B.; Hooper, Stuart B.

In: Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol. 103, No. 6, 01.11.2018, p. F530-F538.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs

AU - Polglase, Graeme R.

AU - Blank, Douglas A.

AU - Barton, Samantha K.

AU - Miller, Suzanne L.

AU - Stojanovska, Vanesa

AU - Kluckow, Martin

AU - Gill, Andrew W.

AU - Larosa, Domenic

AU - Te Pas, Arjan B.

AU - Hooper, Stuart B.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

KW - asphyxia

KW - delayed cord clamping

KW - depressed

KW - immediate cord clamping

KW - resuscitation

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U2 - 10.1136/archdischild-2017-313657

DO - 10.1136/archdischild-2017-313657

M3 - Article

VL - 103

SP - F530-F538

JO - Archives of Disease in Childhood: Fetal and Neonatal Edition

JF - Archives of Disease in Childhood: Fetal and Neonatal Edition

SN - 1359-2998

IS - 6

ER -