Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy

An N. Massaro, Yvonne W. Wu, Theo K. Bammler, James W. MacDonald, Amit Mathur, Taeun Chang, Dennis Mayock, Sarah B. Mulkey, Krisa van Meurs, Zahra Afsharinejad, Sandra E. Juul

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)655-661
Number of pages7
JournalPediatric research
Volume85
Issue number5
DOIs
StatePublished - Apr 1 2019

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    Massaro, A. N., Wu, Y. W., Bammler, T. K., MacDonald, J. W., Mathur, A., Chang, T., Mayock, D., Mulkey, S. B., van Meurs, K., Afsharinejad, Z., & Juul, S. E. (2019). Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy. Pediatric research, 85(5), 655-661. https://doi.org/10.1038/s41390-019-0298-7