{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:18:07Z","timestamp":1782937087632,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neonatal encephalopathy (NE) that purportedly arises from hypoxia\u2010ischemia is labeled hypoxic\u2010ischemic encephalopathy (HIE). Perinatal asphyxia is a clinical syndrome involving acidosis, a low Apgar score and the need for resuscitation in the delivery room; asphyxia alerts one to the possibility of NE. In the present systematic review, we focused on the noninflammatory biomarkers in cerebrospinal fluid (CSF) that are involved in the development of possible brain injury in asphyxia or HIE. A literature search in PubMed and EMBASE for case\u2013control studies was conducted and 17 studies were found suitable by\n                    <jats:italic>a priori<\/jats:italic>\n                    criteria. Statistical analysis used the Mantel\u2013Haenszel model for dichotomous data. The pooled mean difference and 95% confidence intervals (CIs) were determined. We identified the best biomarkers, based on the estimation approach in evaluating the biological significance, out of hundreds in three categories: cell adhesion and proliferation, oxidants and antioxidants, and cell damage. The following subtotal\u2010population comparisons were made: perinatal asphyxia versus no asphyxia, asphyxia with HIE versus asphyxia without HIE, asphyxia with HIE versus no asphyxia, and term versus preterm HIE newborn with asphyxia. Biological significance of the biomarkers was determined by using a modification of the estimation approach, by ranking the biomarkers according to the difference in the bounds of the CIs. The most promising CSF biomarkers for prognostication especially for the severest HIE include creatine kinase, xanthine oxidase, vascular endothelial growth factor, neuron\u2010specific enolase, superoxide dismutase, and malondialdehyde. Future studies are recommended using such a combined test to prognosticate the most severely affected patients.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24801","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T21:18:35Z","timestamp":1612732715000},"page":"2154-2173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A systematic review of noninflammatory cerebrospinal fluid biomarkers for clinical outcome in neonates with perinatal hypoxic brain injury that could be biologically significant"],"prefix":"10.1002","volume":"100","author":[{"given":"Zhongjie","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Wayne State University  Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wayne State University  Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saihaj","family":"Deol","sequence":"additional","affiliation":[{"name":"Department of Psychology College of Liberal Arts &amp; Sciences Wayne State University  Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidhartha","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wayne State University  Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010198905000\u201000004"},{"key":"e_1_2_9_3_1","first-page":"323","article-title":"Free radical production during perinatal birth asphyxia","volume":"26","author":"Batra S.","year":"1998","journal-title":"Medical Science Research"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000244193"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164105x25216"},{"issue":"10","key":"e_1_2_9_6_1","first-page":"783","article-title":"Endogenous opioid\u2010like substances in perinatal asphyxia and cerebral injury due to anoxia","volume":"106","author":"Cao L.","year":"1993","journal-title":"Chinese Medical Journal"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/eog.10.7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.1981.tb04390.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651\u20102227.1981.tb05779.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.65"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000105470"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000374107"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e318180ebe6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.1986.tb04621.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70058\u20103"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.06.094"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0303\u20108467(99)00035\u20109"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0320139"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000084905"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119153"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.8.4985"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715760903548245"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891\u20105849(90)90131\u20102"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527315666160915120758"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199911000\u201000009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103835(90)90262\u2010v"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304\u20103940(97)00937\u20103"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.10.008"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102288\u201014\u201045"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884\u2010020\u201002876\u20101"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.84"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.01.004"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622970802123695"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.1999.0720734.x"},{"key":"e_1_2_9_35_1","first-page":"87","article-title":"Xanthine oxidase: Biochemistry, distribution and physiology","volume":"548","author":"Parks D. 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