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Chronic foetal hypoxaemia does not cause elevation of serum markers of brain injury

Published online by Cambridge University Press:  09 August 2021

Camilla Omann*
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Kendall M. Lawrence
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Mallory L. Hunt
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
James K. Moon
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jamuna Buchanan
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Daniel J. Licht
Affiliation:
Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Richard F. Ittenbach
Affiliation:
Division of Biostatistics and Epidemiology and Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Patrick McGovern
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jonathan M. Chen
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Marcus Davey
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Vibeke E. Hjortdal
Affiliation:
Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
Alan W. Flake
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
J. William Gaynor
Affiliation:
Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
*
Address for correspondence: Camilla Omann, MD, Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200Aarhus N, Denmark. Tel: +45 29401223. E-mail: camillaomann@clin.au.dk

Abstract

Objectives:

The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.

Methods:

Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.

Results:

Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.

Conclusion:

Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

Presented at the 34th EACTS Annual Meeting, Barcelona, Spain; October 9, 2020.

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