Abstract
Background
Inflammation plays a crucial role in the pathogenesis of hypoxic–ischemic encephalopathy (HIE). The aim of this study was to measure inflammation in HIE through an analysis of CSF neopterin and β2-microglobulin and to study the association with brain injury as shown by MRI findings and neurodevelopmental outcomes.
Methods
CSF biomarkers were measured in study patients at 12 and 72 h. Brain injury was evaluated by MRI, and neurodevelopmental outcomes were assessed at 2–3 years of life. An adverse outcome was defined as the presence of motor or cognitive impairment.
Results
Sixty-nine HIE infants were included. Median values of neopterin and β2-microglobulin paralleled the severity of HIE. Adverse outcomes were associated with early neopterin and β2-microglobulin values, late neopterin values, and the neopterin percentage change between the two samples. A cutoff value of 75% neopterin change predicted adverse outcomes with a specificity of 0.9 and a sensitivity of 0.75.
Conclusions
CSF neopterin and β2-microglobulin are elevated in HIE, indicating the activation of inflammation processes. Infants with adverse neurodevelopmental outcomes show higher levels of CSF neopterin and β2-microglobulin. The evolution of neopterin levels provides a better predictive capacity than a single determination.
Impact
-
Brain inflammation in newborns with HIE could be measurable through the analysis of CSF neopterin and β2-microglobulin, both of which are associated with neurodevelopmental outcomes.
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Our study introduces two inflammatory biomarkers for infants with HIE that seem to show a more stable profile and are easier to interpret than cytokines.
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CSF neopterin and β2-m may become clinical tools to monitor inflammation in HIE and might eventually be helpful in measuring the response to emerging therapies.
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Funding
The authors declare financial support from the “Gerencia Regional de Salud de Castilla y León” (GRS 679/B/11).
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N.C. participated in the interpretation of data and the literature search and wrote the manuscript. A.G.-A. designed the study, participated in the acquisition and interpretation of data, and contributed to the drafting of the manuscript. J.A. participated in the acquisition and interpretation of data, reviewed the manuscript, and contributed to the drafting of the article. T.A., A.V., and C.S. participated in the acquisition of data and reviewed the manuscript. All authors approved the final manuscript.
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Carreras, N., Arnaez, J., Valls, A. et al. CSF neopterin and beta-2-microglobulin as inflammation biomarkers in newborns with hypoxic–ischemic encephalopathy. Pediatr Res 93, 1328–1335 (2023). https://doi.org/10.1038/s41390-022-02011-0
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DOI: https://doi.org/10.1038/s41390-022-02011-0