Biomaterial Database

Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo. 2023

Hannah C Glass, and Courtney J Wusthoff, and Bryan A Comstock, and Adam L Numis, and Fernando F Gonzalez, and Nathalie Maitre, and Shavonne L Massey, and Dennis E Mayock, and Ulrike Mietzsch, and Niranjana Natarajan, and Gregory M Sokol, and Sonia L Bonifacio, and Krisa P Van Meurs, and Cameron Thomas, and Kaashif A Ahmad, and Patrick J Heagerty, and Sandra E Juul, and Yvonne W Wu

Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA. Hannah.Glass@ucsf.edu.

An ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo. Electroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose. Among neonates with seizures, differences across treatment groups in median maximal hourly seizure burden were assessed using adjusted quantile regression models. Forty-six of 150 (31%) neonates had EEG seizures (31% in Epo vs 30% in placebo, p = 0.96). Maximal hourly seizure burden after the study drug was not significantly different between groups (median 11.4 for Epo, IQR: 5.6, 18.1 vs median 9.7, IQR: 4.9, 21.0 min/h for placebo). In neonates with HIE treated with hypothermia who were randomized to Epo or placebo, we found no meaningful between-group difference in seizure risk or burden. These findings are consistent with overall trial results, which do not support Epo use for neonates with HIE undergoing therapeutic hypothermia. In the HEAL trial of erythropoietin (Epo) vs placebo for neonates with encephalopathy presumed due to hypoxic-ischemic encephalopathy (HIE) who were also treated with therapeutic hypothermia, electrographic seizures were detected in 31%, which is lower than most prior studies. Epo did not reduce the proportion of neonates with acute provoked seizures (31% in Epo vs 30% in placebo) or maximal hourly seizure burden after the study drug (median 11.4, IQR 5.6, 18.1 for Epo vs median 9.7, IQR 4.9, 21.0 min/h for placebo). There was no anti- or pro-convulsant effect of Epo when combined with therapeutic hypothermia for HIE.

UI	MeSH Term	Description	Entries
D007035	Hypothermia	Lower than normal body temperature, especially in warm-blooded animals.	Hypothermia, Accidental,Accidental Hypothermia,Accidental Hypothermias,Hypothermias,Hypothermias, Accidental
D007036	Hypothermia, Induced	Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries.	Induced Hypothermia,Mild Hypothermia, Induced,Moderate Hypothermia, Induced,Targeted Temperature Management,Therapeutic Hypothermia,Hypothermia, Therapeutic,Induced Mild Hypothermia,Induced Mild Hypothermias,Induced Moderate Hypothermia,Induced Moderate Hypothermias,Mild Hypothermias, Induced,Moderate Hypothermias, Induced,Targeted Temperature Managements
D007231	Infant, Newborn	An infant during the first 28 days after birth.	Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D004921	Erythropoietin	Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001237	Asphyxia	A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life.	Suffocation,Asphyxias,Suffocations
D012640	Seizures	Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."	Absence Seizure,Absence Seizures,Atonic Absence Seizure,Atonic Seizure,Clonic Seizure,Complex Partial Seizure,Convulsion,Convulsions,Convulsive Seizure,Convulsive Seizures,Epileptic Seizure,Epileptic Seizures,Generalized Absence Seizure,Generalized Tonic-Clonic Seizures,Jacksonian Seizure,Myoclonic Seizure,Non-Epileptic Seizure,Nonepileptic Seizure,Partial Seizure,Seizure,Seizures, Convulsive,Seizures, Focal,Seizures, Generalized,Seizures, Motor,Seizures, Sensory,Tonic Clonic Seizure,Tonic Seizure,Tonic-Clonic Seizure,Atonic Absence Seizures,Atonic Seizures,Clonic Seizures,Complex Partial Seizures,Convulsion, Non-Epileptic,Generalized Absence Seizures,Myoclonic Seizures,Non-Epileptic Seizures,Nonepileptic Seizures,Partial Seizures,Petit Mal Convulsion,Seizures, Auditory,Seizures, Clonic,Seizures, Epileptic,Seizures, Gustatory,Seizures, Olfactory,Seizures, Somatosensory,Seizures, Tonic,Seizures, Tonic-Clonic,Seizures, Vertiginous,Seizures, Vestibular,Seizures, Visual,Single Seizure,Tonic Seizures,Tonic-Clonic Seizures,Absence Seizure, Atonic,Absence Seizure, Generalized,Absence Seizures, Atonic,Absence Seizures, Generalized,Auditory Seizure,Auditory Seizures,Clonic Seizure, Tonic,Clonic Seizures, Tonic,Convulsion, Non Epileptic,Convulsion, Petit Mal,Convulsions, Non-Epileptic,Focal Seizure,Focal Seizures,Generalized Seizure,Generalized Seizures,Generalized Tonic Clonic Seizures,Generalized Tonic-Clonic Seizure,Gustatory Seizure,Gustatory Seizures,Motor Seizure,Motor Seizures,Non Epileptic Seizure,Non Epileptic Seizures,Non-Epileptic Convulsion,Non-Epileptic Convulsions,Olfactory Seizure,Olfactory Seizures,Partial Seizure, Complex,Partial Seizures, Complex,Seizure, Absence,Seizure, Atonic,Seizure, Atonic Absence,Seizure, Auditory,Seizure, Clonic,Seizure, Complex Partial,Seizure, Convulsive,Seizure, Epileptic,Seizure, Focal,Seizure, Generalized,Seizure, Generalized Absence,Seizure, Generalized Tonic-Clonic,Seizure, Gustatory,Seizure, Jacksonian,Seizure, Motor,Seizure, Myoclonic,Seizure, Non-Epileptic,Seizure, Nonepileptic,Seizure, Olfactory,Seizure, Partial,Seizure, Sensory,Seizure, Single,Seizure, Somatosensory,Seizure, Tonic,Seizure, Tonic Clonic,Seizure, Tonic-Clonic,Seizure, Vertiginous,Seizure, Vestibular,Seizure, Visual,Seizures, Generalized Tonic-Clonic,Seizures, Nonepileptic,Sensory Seizure,Sensory Seizures,Single Seizures,Somatosensory Seizure,Somatosensory Seizures,Tonic Clonic Seizures,Tonic-Clonic Seizure, Generalized,Tonic-Clonic Seizures, Generalized,Vertiginous Seizure,Vertiginous Seizures,Vestibular Seizure,Vestibular Seizures,Visual Seizure,Visual Seizures
D020925	Hypoxia-Ischemia, Brain	A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.	Anoxia-Ischemia, Brain,Anoxia-Ischemia, Cerebral,Anoxic-Ischemic Encephalopathy,Brain Anoxia-Ischemia,Brain Hypoxia-Ischemia,Brain Ischemia-Anoxia,Brain Ischemia-Hypoxia,Cerebral Anoxia-Ischemia,Cerebral Hypoxia-Ischemia,Cerebral Ischemia-Anoxia,Cerebral Ischemia-Hypoxia,Hypoxia-Ischemia, Cerebral,Hypoxic-Ischemic Encephalopathy,Ischemia-Anoxia, Brain,Ischemia-Anoxia, Cerebral,Ischemia-Hypoxia, Brain,Ischemia-Hypoxia, Cerebral,Ischemic-Hypoxic Encephalopathy,Encephalopathy, Anoxic-Ischemic,Encephalopathy, Hypoxic-Ischemic,Anoxia Ischemia, Brain,Anoxia Ischemia, Cerebral,Anoxia-Ischemias, Brain,Anoxia-Ischemias, Cerebral,Anoxic Ischemic Encephalopathy,Anoxic-Ischemic Encephalopathies,Brain Anoxia Ischemia,Brain Anoxia-Ischemias,Brain Hypoxia Ischemia,Brain Hypoxia-Ischemias,Brain Ischemia Anoxia,Brain Ischemia Hypoxia,Brain Ischemia-Anoxias,Brain Ischemia-Hypoxias,Cerebral Anoxia Ischemia,Cerebral Anoxia-Ischemias,Cerebral Hypoxia Ischemia,Cerebral Hypoxia-Ischemias,Cerebral Ischemia Anoxia,Cerebral Ischemia Hypoxia,Cerebral Ischemia-Anoxias,Cerebral Ischemia-Hypoxias,Encephalopathies, Anoxic-Ischemic,Encephalopathies, Hypoxic-Ischemic,Encephalopathies, Ischemic-Hypoxic,Encephalopathy, Anoxic Ischemic,Encephalopathy, Hypoxic Ischemic,Encephalopathy, Ischemic-Hypoxic,Hypoxia Ischemia, Brain,Hypoxia Ischemia, Cerebral,Hypoxia-Ischemias, Brain,Hypoxia-Ischemias, Cerebral,Hypoxic Ischemic Encephalopathy,Hypoxic-Ischemic Encephalopathies,Ischemia Anoxia, Brain,Ischemia Anoxia, Cerebral,Ischemia Hypoxia, Brain,Ischemia Hypoxia, Cerebral,Ischemia-Anoxias, Brain,Ischemia-Anoxias, Cerebral,Ischemia-Hypoxias, Brain,Ischemia-Hypoxias, Cerebral,Ischemic Hypoxic Encephalopathy,Ischemic-Hypoxic Encephalopathies