{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:03:45Z","timestamp":1789495425055,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022099","name":"Cerebral Palsy Alliance","doi-asserted-by":"publisher","award":["ERG02123"],"award-info":[{"award-number":["ERG02123"]}],"id":[{"id":"10.13039\/501100022099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1090890"],"award-info":[{"award-number":["1090890"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1105526"],"award-info":[{"award-number":["1105526"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1124493"],"award-info":[{"award-number":["1124493"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1125539"],"award-info":[{"award-number":["1125539"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1164954"],"award-info":[{"award-number":["1164954"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hypoxic\u2013ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia\u2010induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fetal sheep (118\u2009\u00b1\u20091\u2009days\u2019 gestational age [dGA]; 0.8 gestation) were implanted with electrodes to continuously record EEG and nuchal electromyogram activity. At 121 dGA, fetuses were randomly assigned to sham control (i.v. saline infusion without umbilical cord occlusion [UCO]; SalCon), continuous i.v. creatine infusion (6\u2009mg\/kg\/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128\u2009\u00b1\u20092 dGA that lasted until the mean arterial blood pressure reached 19\u2009mmHg. Brain tissue was collected for histopathology after 72\u2009hours of recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Creatine supplementation had no effects on basal systemic or neurological physiology. UCO duration did not differ between CrUCO and SalUCO. After reperfusion, CrUCO fetuses had improved EEG power and frequency recovery and reduced electrographic seizure incidence (SalUCO, 86% vs CrUCO, 29%) and burden. At 72\u2009hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Creatine supplementation reduced post\u2010asphyxial seizures and improved EEG recovery. Improvements in functional recovery with creatine were associated with regional reductions in cell death and astrogliosis. Prophylactic creatine treatment has the potential to mitigate functional indices of HIE in the late gestation fetal brain. ANN NEUROL 2025;97:673\u2013687<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.27150","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T11:50:16Z","timestamp":1733572216000},"page":"673-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prophylactic Fetal Creatine Supplementation Improves Post\u2010Asphyxial <scp>EEG<\/scp> Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic\u2013Ischemic Encephalopathy"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-9760","authenticated-orcid":false,"given":"Nhi T.","family":"Tran","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Chatton","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lu","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme R.","family":"Polglase","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Pediatrics Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod J.","family":"Snow","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition Deakin University  Melbourne Victoria 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