Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Public Health/Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Pediatr. 2019 Mar;206:49-55.e3. doi: 10.1016/j.jpeds.2018.10.036. Epub 2018 Dec 12.
To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE).
We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival.
sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value.
sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.
评估可溶性凝集素样氧化低密度脂蛋白受体-1（sLOX-1）作为新生儿缺氧缺血性脑病（HIE）严重程度分期和预后的生物标志物。
我们进行了一项观察性研究，纳入了 27 例 HIE 婴儿和 45 例胎龄≥36 周和出生体重≥1800g 的对照组婴儿。HIE 标准为出生后 60 分钟内 pH≤7.0 或碱缺失≥16mmol/L，10 分钟 Apgar 评分≤5 或复苏时间≥10 分钟。使用改良的 Sarnat 分期评估 HIE 严重程度。我们测量了血浆 sLOX-1 水平，并在出院时评估了一般和神经体征，并将无神经感觉障碍的婴儿分类为完整存活。
出生后 6 小时内 sLOX-1 水平与 HIE 的严重程度相关。sLOX-1 将中重度 HIE（中位数 1017pg/mL；IQR 553-1890pg/mL）与轻度 HIE（中位数 339pg/mL；IQR 288-595pg/mL；P=0.007）区分开来。分界值≥550pg/mL 的敏感性和特异性分别为 80.0%和 83.3%。在 19 例接受治疗性低温的婴儿中，sLOX-1 截断值<1000pg/mL 将完整存活（中位数 761pg/mL；IQR 533-1610pg/mL）与死亡或神经感觉障碍（中位数 1947pg/mL；IQR 1325-2506pg/mL；P=0.019）区分开来，特异性为 100%，阳性预测值为 100%。
sLOX-1 可能是新生儿 HIE 严重程度分期和预后预测的有用生物标志物。进一步的研究将促进其临床应用。
