Supplementary Material for: Magnetic Resonance Biomarkers and Neurological Outcome of Infants with Mild Hypoxic-Ischaemic Encephalopathy Who Progress to Moderate Hypoxic-Ischaemic Encephalopathy

<b><i>Background:</i></b> There is increasing concern that infants with mild hypoxic-ischaemic encephalopathy (HIE) may develop seizures and progress to moderate HIE beyond the therapeutic window for cooling. <b><i>Objective:</i></b> The aim of this study was to examine the effect of therapeutic hypothermia on magnetic resonance imaging (MRI) biomarkers and neurological outcomes in infants with mild HIE and seizures within 24 h after birth. <b><i>Methods:</i></b> This study shows an observational cohort study on 366 (near)-term infants with mild HIE and normal amplitude-integrated electroencephalography background. <b><i>Results:</i></b> Forty-one infants showed progression (11.2%); 29/41 (70.7%) were cooled. Infants with progression showed cerebral metabolite perturbations and higher white matter injury scores compared to those without in both cooled and non-cooled groups (<i>p</i> = 0.001, <i>p</i> = 0.02). Abnormal outcomes were seen in 5/12 (42%) non-cooled and 7/29 (24%) cooled infants with progression (<i>p</i> = 0.26). <b><i>Conclusions:</i></b> Early biomarkers are needed to identify infants with mild HIE at risk of progression. Mild HIE infants with progression showed a higher incidence of brain injury and abnormal outcomes.

**背景**：目前学界愈发关注，轻度缺氧缺血性脑病（hypoxic-ischaemic encephalopathy, HIE）患儿可能出现癫痫发作，并在低温治疗的时间窗之外进展为中度HIE。
**目的**：本研究旨在探究出生后24小时内伴癫痫发作的轻度HIE患儿中，治疗性低温（therapeutic hypothermia）对其磁共振成像（magnetic resonance imaging, MRI）生物标志物及神经预后的影响。
**方法**：本研究为一项观察性队列研究，共纳入366例伴正常振幅整合脑电图背景的轻度HIE（近）足月儿。
**结果**：共计41例患儿出现病情进展（占比11.2%），其中29例（70.7%）接受了低温治疗。无论是否接受低温治疗，出现病情进展的患儿相较于未进展者，均表现出脑代谢紊乱及更高的白质损伤评分（p=0.001，p=0.02）。在出现病情进展的患儿中，未接受低温治疗者的预后异常比例为5/12（42%），接受低温治疗者为7/29（24%），组间差异无统计学意义（p=0.26）。
**结论**：亟需早期生物标志物以识别存在病情进展风险的轻度HIE患儿。出现病情进展的轻度HIE患儿，其脑损伤发生率及预后异常比例均显著更高。