接受低温治疗联合促红细胞生成素或安慰剂治疗的患有缺氧缺血性脑病的新生儿发生癫痫的风险。
Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo.
机构信息
Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
出版信息
Pediatr Res. 2023 Jul;94(1):252-259. doi: 10.1038/s41390-022-02398-w. Epub 2022 Dec 5.
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.
背景
一项对接受治疗性低温治疗的缺氧缺血性脑病（HIE）新生儿进行的高剂量促红细胞生成素治疗窒息和脑病（HEAL）试验的辅助研究检验了这样一个假设，即与接受安慰剂的新生儿相比，接受促红细胞生成素（Epo）治疗的新生儿的癫痫发作风险和负担较低。
方法
对来自 7/17 个 HEAL 试验中心的脑电图（EEG）进行了回顾。使用逻辑回归模型比较了治疗组之间的癫痫发作存在情况，该模型调整了治疗、HIE 严重程度、中心和首次剂量前的癫痫发作负担。在有癫痫发作的新生儿中，使用调整后的分位数回归模型评估了治疗组之间中位最大每小时癫痫发作负担的差异。
结果
150 名新生儿中有 46 名（31%）出现 EEG 癫痫发作（Epo 组为 31%，安慰剂组为 30%，p=0.96）。两组研究药物后最大每小时癫痫发作负担无显著差异（Epo 组中位数为 11.4，IQR：5.6，18.1 vs 安慰剂组中位数为 9.7，IQR：4.9，21.0min/h）。
结论
在接受低温治疗的 HIE 新生儿中，随机接受 Epo 或安慰剂治疗的两组之间，癫痫发作风险或负担无显著差异。这些发现与总体试验结果一致，不支持对接受治疗性低温治疗的 HIE 新生儿使用 Epo。
影响
在缺氧缺血性脑病（HIE）假设导致脑病的新生儿中进行的 Epo 与安慰剂治疗的 HEAL 试验中，接受治疗性低温治疗的新生儿中检测到脑电图癫痫发作的比例为 31%，低于大多数既往研究。Epo 并未降低急性诱发癫痫发作的新生儿比例（Epo 组为 31%，安慰剂组为 30%）或研究药物后最大每小时癫痫发作负担（Epo 组中位数为 11.4，IQR 为 5.6，18.1，安慰剂组中位数为 9.7，IQR 为 4.9，21.0min/h）。在 HIE 中，Epo 与治疗性低温联合使用时没有抗惊厥或促惊厥作用。
Zotero 插件