There is compelling evidence from randomized clinical trials that therapeutic hypothermia for full term or near-term neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) improves survival without disability.¹ However, more than half of all infants with HIE have mild encephalopathy,² as shown by hyperalertness, agitation and hypertonia. These infants were not enrolled in the clinical trials because of their apparently lower risk for adverse outcomes, and so they do not meet current criteria for treatment. However, there is increasing evidence that infants who have mild encephalopathy in the first 6 hours of life may still have a high risk for brain injury. For example, in a level 3 cohort, 54% of 48 cases of mild HIE had cerebral abnormalities on magnetic resonance imaging.³ Consistent with this, in a prospective cohort study of infants who were not treated with therapeutic hypothermia, cases with mild HIE determined by both early electroencephalography and clinical examination had adverse cognitive and neuromotor outcomes at 5 years of age compared with healthy control infants.² Although intact survival was greater after mild than moderate or severe HIE, among survivors, there was no significant difference in the cognitive outcomes of infants who had mild or moderate HIE. This finding contrasts with historical observations that infants with mild encephalopathy had normal neurodevelopmental outcomes.⁴

来自随机临床试验的令人信服的证据表明，对于患有中度至重度缺氧缺血性脑病（HIE）的足月或近期新生儿进行治疗性体温过低可以提高生存率，而不会造成残疾。¹但是，所有HIE婴儿中有一半以上患有轻度脑病，²表现为机敏，躁动和高渗。这些婴儿由于不良后果的风险明显较低，因此未参加临床试验，因此不符合当前的治疗标准。但是，越来越多的证据表明，在生命的前6个小时内患有轻度脑病的婴儿仍可能有较高的脑损伤风险。例如，在3级队列中，48例轻度HIE病例中有54％的磁共振成像显示脑部异常。³与此一致，在一项针对未接受治疗性低温治疗的婴儿的前瞻性队列研究中，通过早期脑电图和临床检查确定的轻度HIE病例与健康对照婴儿相比，在5岁时认知和神经运动预后不良。²尽管轻度HIE的存活率高于中度或重度HIE，但幸存者中，轻度或中度HIE婴儿的认知结局没有显着差异。这一发现与历史上的观察结果相反，即轻度脑病婴儿的神经发育正常。⁴