Abstract
Background
Data correlating dried blood spots (DBS) and plasma concentrations for neonatal biomarkers of brain injury are lacking. We hypothesized that candidate biomarker levels determined from DBS can serve as a reliable surrogate for plasma levels.
Methods
In the context of a phase II multi-center trial evaluating erythropoietin for neuroprotection in neonatal encephalopathy (NE), DBS were collected at enrollment ( < 24 h), day 2, 4, and 5. Plasma was collected with the first and last DBS. The relationship between paired DBS-plasma determinations of brain-specific proteins and cytokines was assessed by correlation and Bland–Altman analyses. For analytes with consistent DBS-plasma associations, DBS-derived biomarker levels were related to brain injury by MRI and 1-year outcomes.
Results
We enrolled 50 newborns with NE. While S100B protein, tumor necrosis factor α, interleukin (IL)1 β, IL-6, IL-8 demonstrated significant DBS-plasma correlations, Bland–Altman plots demonstrated that the methods are not interchangeable, with a 2 to 4-fold error between measurements. No significant relationships were found between DBS levels of TNFα, IL-6, and IL-8 and outcomes.
Conclusion
Further work is needed to optimize elution and assay methods before using DBS specimens as a reliable surrogate for plasma levels of candidate brain injury biomarkers in NE.
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Acknowledgements
We thank Jessica Kan Vedder for her devoted organizational support of the study, and Ron McPherson for his assistance with biorepository maintenance. We thank Michael Msall for his expertize, guidance and training in the use of the AIMS and WIDEA neurodevelopmental evaluations. The authors greatly appreciate the work of the Data Safety Monitoring Board: Robin Ohls (Chair), Janet Soul and John Barks.
Funding
This study was funded by the Cerebral Palsy Alliance Research Foundation and the Thrasher Research Fund.
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A.N.M. made substantial contributions to conception and design of the study and interpretation of data; prepared the first draft of the article and revised it critically for important intellectual content; and approved of the version to be published. Y.W.W., T.K.B., and S.J. made substantial contributions to conception and design of the study, and interpretation of data; revised the article critically for important intellectual content; and approved of the version to be published. J.W.M made substantial contributions to the analysis and interpretation of data; revised the article critically for important intellectual content; and approved of the version to be published. A.M., T.C., D.M., S.B.M., K.v.M., and Z.A. made substantial contributions to the acquisition of data, revised the article critically for important intellectual content; and approved of the version to be published.
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Massaro, A.N., Wu, Y.W., Bammler, T.K. et al. Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy. Pediatr Res 85, 655–661 (2019). https://doi.org/10.1038/s41390-019-0298-7
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DOI: https://doi.org/10.1038/s41390-019-0298-7
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