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

• Published in: Cardiology in the young Vol. 32; no. 5; pp. 732 - 737
• Main Authors: Omann, Camilla, Lawrence, Kendall M., Hunt, Mallory L., Moon, James K., Buchanan, Jamuna, Licht, Daniel J., Ittenbach, Richard F., McGovern, Patrick, Chen, Jonathan M., Davey, Marcus, Hjortdal, Vibeke E., Flake, Alan W., Gaynor, J. William
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.05.2022
• Subjects: Animals; Biomarkers; Brain; Brain Injuries - complications; Brain injury; Circuits; Confidence intervals; Female; Fetal Cardiology; Fetus; Fetuses; Gestation; Gestational age; Glial Fibrillary Acidic Protein; Head injuries; Humans; Hypoxia; Intrauterine exposure; Ischemia; Myelin; Myelin basic protein; Myelin Basic Protein - analysis; Myelin Basic Protein - metabolism; Myelination; Original Article; Oxygen; Oxygen - metabolism; Oxygen saturation; Pregnancy; Proteins; Serum levels; Sheep; Statistical analysis; Statistical significance; Substantia alba; Surgical apparatus & instruments; Traumatic brain injury; United States > US; Congenital heart defect; Serum biomarkers; Chronic foetal hypoxaemia; Brain development
• ISSN: 1047-9511; 1467-1107
• DOI: 10.1017/S1047951121002894

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. 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. 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. 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.