{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:04:57Z","timestamp":1791813897193,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCHU-CSMU-11009 and MOST 110-2314-B-040-011.","award":["NCHU-CSMU-11009 and MOST 110-2314-B-040-011."],"award-info":[{"award-number":["NCHU-CSMU-11009 and MOST 110-2314-B-040-011."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The antioxidant defense system is involved in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). To analyze the relationship between first serum blood glucose levels and outcomes in neonatal HIE, seventy-four patients were divided, based on the first glucose level, into group 1 (&gt;0 mg\/dL and &lt;60 mg\/dL, n =11), group 2 (\u226560 mg\/dL and &lt;150 mg\/dL, n = 49), and group 3 (\u2265150 mg\/dL, n = 14). Abnormal glucose levels had poor outcomes among three groups in terms of the clinical stage (p = 0.001), brain parenchymal lesion (p = 0.004), and neurodevelopmental outcomes (p = 0.029). Hearing impairment was more common in group 3 than in group 1 (p = 0.062) and group 2 (p = 0.010). The MRI findings of group 3 exhibited more thalamus and basal ganglion lesions than those of group 1 (p = 0.012). The glucose level was significantly correlated with clinical staging (p&lt; 0.001), parenchymal brain lesions (p = 0.044), hearing impairment (p = 0.003), and neurodevelopmental outcomes (p = 0.005) by Pearson\u2019s test. The first blood glucose level in neonatal HIE is an important biomarker for clinical staging, MRI findings, as well as hearing and neurodevelopment outcomes. Hyperglycemic patients had a higher odds ratio for thalamus, basal ganglia, and brain stem lesions than hypoglycemic patients with white matter and focal ischemic injury. Hyperglycemia can be due to prolonged or intermittent hypoxia and can be associated with poor outcomes.<\/jats:p>","DOI":"10.3390\/antiox11010039","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Early Blood Glucose Level Post-Admission Correlates with the Outcomes and Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy"],"prefix":"10.3390","volume":"11","author":[{"given":"Inn-Chi","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9019-2178","authenticated-orcid":false,"given":"Jiann-Jou","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-7629","authenticated-orcid":false,"given":"Ying-Ming","family":"Liou","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, National Chung-Hsing University, Taichung 40227, Taiwan"},{"name":"The iEGG and Animal Biotechnology Center and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Badurdeen, S., Roberts, C., Blank, D., Miller, S., Stojanovska, V., Davis, P., Hooper, S., and Polglase, G. (2019). Haemodynamic Instability and Brain Injury in Neonates Exposed to Hypoxia(-)Ischaemia. Brain Sci., 9.","DOI":"10.3390\/brainsci9030049"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1136\/adc.2011.214205","article-title":"Cardiovascular dysfunction in infants with neonatal encephalopathy","volume":"97","author":"Armstrong","year":"2012","journal-title":"Arch. Dis. Child."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1542\/peds.102.1.e1","article-title":"Resuscitation of asphyxiated newborn infants with room air or oxygen: An international controlled trial: The Resair 2 study","volume":"102","author":"Saugstad","year":"1998","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/tropej\/46.3.155","article-title":"Incidence, clinical spectrum, and outcome of intrauterine infections in neonates","volume":"46","author":"Deorari","year":"2000","journal-title":"J. Trop. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"c363","DOI":"10.1136\/bmj.c363","article-title":"Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: Synthesis and meta-analysis of trial data","volume":"340","author":"Edwards","year":"2010","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/ped.13377","article-title":"Multicenter study for brain\/body hypothermia for hypoxic-ischemic encephalopathy: Changes in HMGB-1","volume":"59","author":"Nakamura","year":"2017","journal-title":"Pediatr. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1542\/peds.2007-1673","article-title":"Elevated temperature after hypoxic-ischemic encephalopathy: Risk factor for adverse outcomes","volume":"122","author":"Laptook","year":"2008","journal-title":"Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/B978-0-444-64029-1.00013-8","article-title":"Biomarkers in neonatal hypoxic-ischemic encephalopathy-Review of the literature to date and future directions for research","volume":"162","author":"Murray","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41390-019-0400-1","article-title":"Encephalopathy in neonates with subgaleal hemorrhage is a key predictor of outcome","volume":"86","author":"Parziale","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F458","DOI":"10.1136\/archdischild-2013-305763","article-title":"Therapeutic hypothermia delays the C-reactive protein response and suppresses white blood cell and platelet count in infants with neonatal encephalopathy","volume":"99","author":"Chakkarapani","year":"2014","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41372-019-0551-2","article-title":"Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia","volume":"40","author":"Goswami","year":"2020","journal-title":"J. Perinatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1177\/0883073819828625","article-title":"Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy","volume":"34","author":"Saw","year":"2019","journal-title":"J. Child Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jpeds.2012.06.042","article-title":"Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy","volume":"162","author":"DuPont","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.neuroscience.2015.08.034","article-title":"Genomic approach to selective vulnerability of the hippocampus in brain ischemia-hypoxia","volume":"309","year":"2015","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/0166-2236(90)90107-L","article-title":"Functional architecture of basal ganglia circuits: Neural substrates of parallel processing","volume":"13","author":"Alexander","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1523\/JNEUROSCI.23-08-03308.2003","article-title":"Selective vulnerability of subplate neurons after early neonatal hypoxia-ischemia","volume":"23","author":"McQuillen","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1203\/00006450-200106000-00003","article-title":"Neurobiology of hypoxic-ischemic injury in the developing brain","volume":"49","author":"Johnston","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7994","DOI":"10.1523\/JNEUROSCI.20-21-07994.2000","article-title":"Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat","volume":"20","author":"Nakajima","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0022-510X(98)00036-7","article-title":"Intact, Injured, Necrotic and apoptotic cells after focal cerebral ischemia in the rat","volume":"156","author":"Li","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Arteaga, O., \u00c1lvarez, A., Revuelta, M., Santaolalla, F., Urtasun, A., and Hilario, E. (2017). Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020265"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.drudis.2015.09.001","article-title":"Neuroprotective agents for neonatal hypoxic-ischemic brain injury","volume":"20","author":"Wu","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fneur.2015.00198","article-title":"Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy\u2014Where to from Here?","volume":"6","author":"Davidson","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1203\/00006450-199004000-00001","article-title":"Experimental biology of cerebral hypoxia-ischemia: Relation to perinatal brain damage","volume":"27","author":"Vannucci","year":"1990","journal-title":"Pediatr. Res."},{"key":"ref_25","first-page":"181","article-title":"Fetal circulatory responses to oxygen lack","volume":"16","author":"Jensen","year":"1991","journal-title":"J. Dev. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Esih, K., Gori\u010dar, K., Soltirovska-\u0160alamon, A., Dol\u017ean, V., and Rener-Primec, Z. (2021). Genetic Polymorphisms, Gene-Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia. Antioxidants, 10.","DOI":"10.3390\/antiox10091495"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.ejpn.2016.05.018","article-title":"The association between antioxidant enzyme polymorphisms and cerebral palsy after perinatal hypoxic-ischaemic encephalopathy","volume":"20","author":"Esih","year":"2016","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fnmol.2019.00088","article-title":"Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy","volume":"12","author":"Qin","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/jcb.23088","article-title":"High glucose concentration affects the oxidant-antioxidant balance in cultured mouse podocytes","volume":"112","author":"Piwkowska","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1089\/ars.2021.0168","article-title":"Do Levels of Lipid Peroxidation Biomarkers Reflect the Degree of Brain Injury in Newborns?","volume":"35","author":"Oger","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1017\/S2040174413000561","article-title":"Acute and chronic immunomodulatory changes in rat liver after fetal and perinatal asphyxia","volume":"5","author":"Vlassaks","year":"2014","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/adc.88.3.238","article-title":"What is the normal range of blood glucose concentrations in healthy term newborns?","volume":"88","author":"Nicholl","year":"2003","journal-title":"Arch. Dis. Child."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1152\/jappl.1991.70.2.919","article-title":"Increased dependence on blood glucose after acclimatization to 4300 m","volume":"70","author":"Brooks","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1164\/rccm.200308-1200OC","article-title":"Hypoxia causes glucose intolerance in humans","volume":"169","author":"Oltmanns","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1113\/jphysiol.2003.048173","article-title":"Intermittent hypoxia increases insulin resistance in genetically obese mice","volume":"552","author":"Polotsky","year":"2003","journal-title":"J. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1203\/00006450-199706000-00009","article-title":"Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves","volume":"41","author":"Cheng","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1210\/en.2006-1224","article-title":"Effects of hypoxia on glucose, insulin, glucagon, and modulation by corticotropin-releasing factor receptor type 1 in the rat","volume":"148","author":"Chen","year":"2007","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1385\/ENDO:11:1:37","article-title":"The effect of hypoxia on plasma leptin and insulin in newborn and juvenile rats","volume":"11","author":"Raff","year":"1999","journal-title":"Endocrine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/BF00571554","article-title":"Glucoregulatory hormones in man at high altitude","volume":"62","author":"Sawhney","year":"1991","journal-title":"Eur. J. Appl. Physiol. Occup. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1152\/jappl.1992.73.6.2574","article-title":"Operation Everest II: Metabolic and hormonal responses to incremental exercise to exhaustion","volume":"73","author":"Young","year":"1992","journal-title":"J. Appl. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.3174\/ajnr.A3423","article-title":"Brain injury patterns in hypoglycemia in neonatal encephalopathy","volume":"34","author":"Wong","year":"2013","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jpeds.2018.07.041","article-title":"Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy","volume":"203","author":"Basu","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jpeds.2011.12.047","article-title":"Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy","volume":"161","author":"Tam","year":"2012","journal-title":"J. Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"F149","DOI":"10.1136\/archdischild-2015-308733","article-title":"Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: A post hoc analysis of the CoolCap Study","volume":"101","author":"Basu","year":"2016","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/NPM-15814107","article-title":"High glucose variability is associated with poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy","volume":"8","author":"Narvey","year":"2015","journal-title":"J. Neonatal-Perinat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ejpn.2018.10.002","article-title":"Hearing impairment and hypoxia ischaemic encephalopathy: Incidence and associated factors","volume":"23","author":"Fitzgerald","year":"2019","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/pr.2016.250","article-title":"Universal newborn hearing screening: Methods and results, obstacles, and benefits","volume":"81","author":"Dabrowski","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s13023-021-01817-1","article-title":"Hearing characteristics of infantile-onset Pompe disease after early enzyme-replacement therapy","volume":"16","author":"Hsueh","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1597\/06-078.1","article-title":"Hearing thresholds in newborns with a cleft palate assessed by auditory brain stem response","volume":"45","author":"Viswanathan","year":"2008","journal-title":"Cleft Palate-Craniofac. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1542\/neo.21-1-e14","article-title":"Glucose Homeostasis in Newborns: An Endocrinology Perspective","volume":"21","author":"Tas","year":"2020","journal-title":"NeoReviews"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17787","DOI":"10.1073\/pnas.0902380106","article-title":"Insulin resistance is a cellular antioxidant defense mechanism","volume":"106","author":"Hoehn","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:53:10Z","timestamp":1760169190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["antiox11010039"],"URL":"https:\/\/doi.org\/10.3390\/antiox11010039","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]}}}