Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
20
07
2022
accepted:
03
11
2022
revised:
27
10
2022
medline:
21
7
2023
pubmed:
6
12
2022
entrez:
5
12
2022
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
IMPACT
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.
Identifiants
pubmed: 36470964
doi: 10.1038/s41390-022-02398-w
pii: 10.1038/s41390-022-02398-w
pmc: PMC10239788
mid: NIHMS1849528
doi:
Substances chimiques
Erythropoietin
11096-26-7
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
252-259Subventions
Organisme : NINDS NIH HHS
ID : K23 NS105918
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104322
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS092553
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS092764
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
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