TY - JOUR
T1 - Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy
AU - Massaro, An N.
AU - Wu, Yvonne W.
AU - Bammler, Theo K.
AU - MacDonald, James W.
AU - Mathur, Amit
AU - Chang, Taeun
AU - Mayock, Dennis
AU - Mulkey, Sarah B.
AU - van Meurs, Krisa
AU - Afsharinejad, Zahra
AU - Juul, Sandra E.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061246840&partnerID=8YFLogxK
U2 - 10.1038/s41390-019-0298-7
DO - 10.1038/s41390-019-0298-7
M3 - Article
C2 - 30661082
AN - SCOPUS:85061246840
VL - 85
SP - 655
EP - 661
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 5
ER -