Johns Hopkins University School of Medicine, Baltimore, MD.
Paediatrics, Trinity College, The University of Dublin & Coombe Women and Infants University Hospital, Dublin, Ireland.
J Pediatr. 2020 Nov;226:71-79.e5. doi: 10.1016/j.jpeds.2020.06.078. Epub 2020 Jun 28.
To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months.
A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, ≥36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months.
Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities.
Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.
确定与新生儿脑病严重程度相关的候选生物标志物，这些标志物可通过脑病分级、癫痫发作、磁共振成像（MRI）显示的脑损伤以及 15-30 个月时的神经发育结果进行评估。
对患有新生儿脑病和足月出生的健康新生儿（胎龄≥36 周，n=30，生后 0-1 天）的血浆（n=155）和脑脊液（n=30，生后 0-7 天）进行了回顾性队列研究。我们测量了中枢神经系统坏死（胶质纤维酸性蛋白 [GFAP]、神经颗粒素 [NRGN]、tau）、炎症（白细胞介素 [IL]-6、IL-8、IL-10）和营养（脑源性神经营养因子 [BDNF]、血管内皮生长因子）蛋白。临床结局为 15-30 个月时的 Sarnat 脑病评分、癫痫发作、MRI 评分和贝利婴幼儿发育量表第三版。
与对照组相比，新生儿脑病患者的血浆 NRGN、tau、IL-6、IL-8 和 IL-10 水平更高，而 BDNF 和血管内皮生长因子水平更低。在血浆中，tau、GFAP 和 NRGN 与脑病分级呈直接相关，BDNF 呈负相关。IL-6 与癫痫发作呈负相关。tau 与 MRI 异常呈直接相关。tau 与贝利婴幼儿发育量表第三版认知和运动结果呈负相关。在脑脊液中，NRGN 与认知、运动和语言测量值呈负相关。GFAP、IL-6 和 IL-10 与认知和运动结果呈负相关。IL-8 与运动结果呈负相关。脑脊液候选生物标志物与脑病分级、癫痫发作或 MRI 异常无显著关系。
血浆候选生物标志物可预测 15-30 个月时的脑病严重程度、癫痫发作、MRI 异常和神经发育结果。
