Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Department of Bioengineering, University of Texas at Arlington, Arlington, TX, United States of America.
Early Hum Dev. 2023 Aug;183:105815. doi: 10.1016/j.earlhumdev.2023.105815. Epub 2023 Jul 3.
There is a critical need for development of physiological biomarkers in infants with birth asphyxia to identify the physiologic response to therapies in real time. This is an ancillary single site study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (Wu et al., 2022 [1]) to measure neurovascular coupling (NVC) non-invasively during an ongoing blinded randomized trial.
Neonates who randomized in the HEAL enrolled at a single-center Level III Neonatal Intensive Care Unit were recruited between 2017 and 2019. Neurodevelopmental impairment was blinded and defined as any of the following: cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition (BSID-III), Gross Motor Function Classification Score (GMFCS) ≥1.
All twenty-seven neonates enrolled in HEAL were recruited and 3 died before complete recording. The rank-based analysis of covariance models demonstrated lack of difference in NVC between the two groups (Epo versus Placebo) that was consistent with the observed lack of effect on neurodevelopmental outcomes.
We demonstrate no difference in neurovascular coupling after Epo administration. These findings are consistent with overall negative trial results. Physiological biomarkers can help elucidate mechanisms of neuroprotective therapies in real time in future trials.
对于出生窒息的婴儿，迫切需要开发生理生物标志物，以便实时识别治疗的生理反应。这是对高剂量促红细胞生成素治疗窒息和脑病（Wu 等人，2022 [1]）的单一站点辅助研究，以在正在进行的盲法随机试验中无创测量神经血管耦合（NVC）。
在单一中心 III 级新生儿重症监护病房随机分组的 HEAL 新生儿在 2017 年至 2019 年间招募。神经发育障碍是盲法的，并定义为以下任何一种：Bayley 婴儿-幼儿发育量表第三版（BSID-III）的认知评分<90，总运动功能分类评分（GMFCS）≥1。
HEAL 纳入的所有 27 名新生儿均被招募，3 名新生儿在完成记录前死亡。基于秩的协方差模型分析表明，两组（Epo 与安慰剂）之间的 NVC 无差异，这与神经发育结局的观察到的无效应一致。
我们证明 Epo 给药后神经血管耦合无差异。这些发现与总体负面试验结果一致。生理生物标志物可以帮助在未来的试验中实时阐明神经保护治疗的机制。
