TY - JOUR
T1 - Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy
AU - Toorell, Hanna
AU - Carlsson, Ylva
AU - Hallberg, BouBou
AU - O'Riordian, Mairead N
AU - Walsh, Brian Henry
AU - O'Sullivan, Marc Paul
AU - Boylan, Geraldine B
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Murray, Deirdre
AU - Hagberg, Henrik
N1 - Funding Sources
This work was supported by Rune and Ulla Almlövs stiftelse SEB (Y.C., 2019), Mary Von Sydow (Y.C., 2019-2219), Frimurarfonden Barnhusdirektionen Foundation (Y.C., GLS 7000991), Wilhelm and Martina Lundgren Foundation (Y.C., 2019-2941), Linnea and Josef Carlsson Foundation (Y.C., 2019), and VR 2019-01320 (H.H.). The study was also financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (Y.C.: ALFGBG-77860, ALFGBG-75710, H.H.: ALFGBG-965174, H.Z.: ALFGBG-71320). The BiHIVE study was funded by the Molecular Medicine Ireland Clinical Translational Scholars Award. The BiHIVE2 study was funded by the Irish Health Research Board (ref CSA 2012/40). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), and the European Research Council (#681712 and #101053962). K.B. is supported by the Swedish Research Council (#2017-00915), Hjärnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240).
PY - 2023/9/29
Y1 - 2023/9/29
N2 - OBJECTIVES: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE.STUDY DESIGN: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers.RESULTS: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases.CONCLUSIONS: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.
AB - OBJECTIVES: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE.STUDY DESIGN: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers.RESULTS: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases.CONCLUSIONS: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.
UR - https://pubmed.ncbi.nlm.nih.gov/37778335
U2 - 10.1159/000533473
DO - 10.1159/000533473
M3 - Article
C2 - 37778335
SN - 1661-7800
SP - 1
EP - 9
JO - Neonatology
JF - Neonatology
ER -