TY - JOUR
T1 - Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes
AU - Dietrick, Barbara
AU - Molloy, Eleanor
AU - Massaro, An N.
AU - Strickland, Tammy
AU - Zhu, Jie
AU - Slevin, Marie
AU - Donoghue, Veronica
AU - Sweetman, Deirdre
AU - Kelly, Lynne
AU - O'Dea, Mary
AU - McGowan, Meaghan
AU - Vezina, Gilbert
AU - Glass, Penny
AU - Vaidya, Dhananjay
AU - Brooks, Sandra
AU - Northington, Frances
AU - Everett, Allen D.
N1 - Funding Information:
We thank the patients and their families for their participation and contributions to this study. We thank the Everett research group at Johns Hopkins University School of Medicine for their support and contributions. We thank the Johns Hopkins University School of Medicine Scholarly Concentration mentor Dr Meredith Atkinson and the Johns Hopkins University School of Medicine Dean's Funding for their support and contributions.
Funding Information:
Supported by National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD086058 [to A.E. and F.N.]); Health Research Board, Ireland; Trinity College Dublin; National Children's Research Centre; Clinical and Translational Science Institute at Children's National (UL1TR000075, 1KL2RR031987-01 [to A.M.]); and the Intellectual and Developmental Disabilities Research Consortium (NIH P30HD040677 [to A.M.]). Under a license agreement between ImmunArray Ltd and the Johns Hopkins University, the University and A.E. are entitled to royalties on an invention described in this study and discussed in this publication. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The other authors declare no conflicts of interest.We thank the patients and their families for their participation and contributions to this study. We thank the Everett research group at Johns Hopkins University School of Medicine for their support and contributions. We thank the Johns Hopkins University School of Medicine Scholarly Concentration mentor Dr Meredith Atkinson and the Johns Hopkins University School of Medicine Dean's Funding for their support and contributions.
Funding Information:
Supported by National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD086058 [to A.E. and F.N.]); Health Research Board , Ireland; Trinity College Dublin; National Children's Research Centre; Clinical and Translational Science Institute at Children's National (UL1TR000075, 1KL2RR031987-01 [to A.M.]); and the Intellectual and Developmental Disabilities Research Consortium ( NIH P30HD040677 [to A.M.]). Under a license agreement between ImmunArray Ltd and the Johns Hopkins University, the University and A.E. are entitled to royalties on an invention described in this study and discussed in this publication. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The other authors declare no conflicts of interest.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/11
Y1 - 2020/11
N2 - Objectives: To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months. Study design: A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, ≥36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months. Results: Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities. Conclusions: Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.
AB - Objectives: To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months. Study design: A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, ≥36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months. Results: Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities. Conclusions: Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.
KW - brain injury
KW - development
KW - marker
KW - neonate
KW - neurology
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UR - http://www.scopus.com/inward/citedby.url?scp=85090147640&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2020.06.078
DO - 10.1016/j.jpeds.2020.06.078
M3 - Article
C2 - 32610169
AN - SCOPUS:85090147640
SN - 0022-3476
VL - 226
SP - 71-79.e5
JO - Journal of Pediatrics
JF - Journal of Pediatrics
ER -