TY - JOUR
T1 - Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia
AU - McGowan, Meaghan M.
AU - O’Kane, Alexandra C.
AU - Vezina, Gilbert
AU - Chang, Taeun
AU - Bendush, Nicole
AU - Glass, Penny
AU - Gai, Jiaxiang
AU - Bost, James
AU - Everett, Allen D.
AU - Massaro, An N.
N1 - Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/12
Y1 - 2021/12
N2 - Background: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. Methods: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers’ individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. Results: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). Conclusions: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. Impact: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use.This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE.In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone.Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.
AB - Background: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. Methods: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers’ individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. Results: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). Conclusions: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. Impact: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use.This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE.In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone.Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.
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U2 - 10.1038/s41390-021-01405-w
DO - 10.1038/s41390-021-01405-w
M3 - Article
C2 - 33654280
AN - SCOPUS:85102083119
SN - 0031-3998
VL - 90
SP - 1228
EP - 1234
JO - Pediatric research
JF - Pediatric research
IS - 6
ER -