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Cerebral blood flow in neonatal encephalopathy: biomarker or potential target?

Pediatric Research volume 97, pages 1416–1417 (2025)Cite this article

Hypoxia-ischemia is the most common cause of neonatal encephalopathy (NE). In most cases, an intrapartum event is presumed to lead to perinatal hypoxia ischemia, but the exact pathogenesis, and therefore timing, are often not known.1 In well-resourced settings, therapeutic hypothermia (TH) reduces death and major neurodevelopmental disability in infants with NE.2 However, there is heterogeneity in outcomes, and major neurodevelopmental disability is still seen in about one third of survivors who are treated with therapeutic hypothermia.3 The heterogeneity in response of NE to TH means alternative treatments are desperately sought. As such, many biomarkers have been studied as surrogate measures of long-term outcome, in order to expedite assessment of potential treatments. Moreover, an important goal is to personalize treatment for NE such that individuals who might benefit from a different approach to TH, might be detected early. It is also important to study biomarkers that can discriminate between which babies benefit from TH versus those who may be at higher risk of an adverse outcome.4

In the study by O’Gorman Tuura et al., the authors have explored the link between perfusion and neurodevelopmental outcomes using arterial spine labeling (ASL) as a neuroimaging marker for outcome prediction.5 ASL is a noninvasive magnetic resonance imaging (MRI) technique in which protons in blood and water are magnetically labeled and the signal generated by the endogenous labels are detected by subtracting MRI signals during alternating labeled and unlabeled acquisitions. The images demonstrate signal intensity proportional to the amount of perfusion in each voxel and a quantitative measurement of cerebral blood flow (CBF) can be calculated.6 Previous authors have described patterns of CBF using ASL in NE. Wintermark et al. demonstrated initial hypoperfusion on day 1 followed by hyperperfusion at days 2–3.7 A study by Tang et al. reported lower CBF values in neonates with NE at 0–24 h and 3–7 days with higher values in the 1–3 day-old group.8 The mean age at MRI in O’Gorman Tuura’s paper was 5 days (range 3–9 days), which means that any hyperperfusion identified may not represent the ‘peak’ perfusion phase, but rather the tail end of the more severe cases. The problem with that theory is that the cohort studied included infants with mild to moderate NE and the authors found a relationship between altered perfusion and outcome even in those children with mild to moderate impairment following NE.

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Acknowledgements

The authors received no current funding support beyond clinical salaried positions.

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  1. Department of Pediatrics, University of British Columbia, Vancouver, Canada

    Julia K. Charlton & Khushboo Kanwal

  2. Neonatal Program, British Columbia Women’s Hospital, Vancouver, Canada

    Julia K. Charlton & Khushboo Kanwal

  3. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    Julia K. Charlton

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Charlton, J.K., Kanwal, K. Cerebral blood flow in neonatal encephalopathy: biomarker or potential target?. Pediatr Res 97, 1416–1417 (2025). https://doi.org/10.1038/s41390-024-03684-5

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