Prophylactic Fetal Creatine Supplementation Improves Post‐Asphyxial <scp>EEG</scp> Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic–Ischemic Encephalopathy
Bibliographic record
Abstract
OBJECTIVE: Hypoxic-ischemic 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-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology. METHODS: Fetal sheep (118 ± 1 days' 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 mg/kg/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128 ± 2 dGA that lasted until the mean arterial blood pressure reached 19 mmHg. Brain tissue was collected for histopathology after 72 hours of recovery. RESULTS: 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 hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO. INTERPRETATION: Creatine supplementation reduced post-asphyxial 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;97:673-687.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".