An N Massaro1, Yvonne W Wu2, Theo K Bammler3, James W MacDonald3, Amit Mathur4, Taeun Chang5, Dennis Mayock6, Sarah B Mulkey5, Krisa van Meurs7, Zahra Afsharinejad3, Sandra E Juul6. 1. Pediatrics - Division of Neonatology, Children's National Health Systems and The George Washington University School of Medicine, Washington, DC, USA. anguyenm@cnmc.org. 2. Neurology and Pediatrics, UCSF, San Francisco, CA, USA. 3. Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA, USA. 4. Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. 5. Neurology and Pediatrics, Children's National Health Systems and The George Washington University School of Medicine, Washington, DC, USA. 6. Pediatrics-Division of Neonatology, University of Washington, Seattle, WA, USA. 7. Pediatrics, Stanford, Palo Alto, CA, USA.
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.
RCT Entities:
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.
Authors: Jenalee R Doom; Brie M Reid; Emily Nagel; Sheila Gahagan; Ellen W Demerath; Julie C Lumeng Journal: Dev Psychobiol Date: 2020-09-09 Impact factor: 3.038
Authors: Magdalena Fandiño-Del-Rio; Josiah L Kephart; Kendra N Williams; Gary Malpartida; Dana Boyd Barr; Kyle Steenland; Kirsten Koehler; William Checkley Journal: Indoor Air Date: 2021-03-22 Impact factor: 6.554