Kelen Dorottya, Andorka Csilla, Szabó Miklós, Alafuzoff Aleksander, Kaila Kai, Summanen Milla
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Department of Biosciences, University of Helsinki, Helsinki, Finland.
PLoS One. 2017 Sep 20;12(9):e0184593. doi: 10.1371/journal.pone.0184593. eCollection 2017.
The objective of this study was to evaluate the early changes in serial serum levels of copeptin and neuron-specific enolase (NSE) in neonates diagnosed with birth asphyxia, and to determine whether these biomarkers measured in the first 168 hours after birth are predictive of long-term neurodevelopmental outcome. Copeptin and NSE levels were measured from serum samples collected 6, 12, 24, 48, 72, and 168 hours after birth from 75 term neonates diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia for 72 hours. In addition, serum copeptin levels after birth were measured from 10 HIE diagnosed neonates, who were randomized to the normothermic arm of the TOBY cohort. All neonates underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development-II at two years of age. Copeptin levels were highest at 6 hours after birth and steadily decreased, whereas the highest NSE levels were measured at 24 hours after birth. The biomarker levels correlated with blood-gas parameters (base excess, pH and lactate) at 6 and 12 hours after birth. Copeptin and NSE levels in the early postnatal period were significantly higher in neonates with poor outcome compared to those with favorable outcome at two years of age. Furthermore, in the TOBY cohort, copeptin levels were significantly lower in hypothermic compared to normothermic neonates. To conclude, copeptin and NSE measured in the early postnatal period are potential prognostic biomarkers of long-term neurodevelopmental outcome in term neonates diagnosed with HIE and treated with therapeutic hypothermia.
本研究的目的是评估诊断为出生窒息的新生儿血清中copeptin和神经元特异性烯醇化酶（NSE）的系列水平的早期变化，并确定出生后168小时内测量的这些生物标志物是否可预测长期神经发育结局。从75例诊断为缺氧缺血性脑病（HIE）并接受72小时治疗性低温治疗的足月儿出生后6、12、24、48、72和168小时采集的血清样本中测量copeptin和NSE水平。此外，从10例诊断为HIE的新生儿中测量出生后血清copeptin水平，这些新生儿被随机分配到TOBY队列的常温组。所有新生儿在两岁时使用贝利婴幼儿发展量表-II进行神经发育评估。Copeptin水平在出生后6小时最高，并稳步下降，而NSE最高水平在出生后24小时测量。生物标志物水平与出生后6和12小时的血气参数（碱剩余、pH值和乳酸）相关。与两岁时预后良好的新生儿相比，预后不良的新生儿出生后早期的copeptin和NSE水平显著更高。此外，在TOBY队列中，低温治疗的新生儿的copeptin水平显著低于常温治疗的新生儿。总之，出生后早期测量的copeptin和NSE是诊断为HIE并接受治疗性低温治疗的足月儿长期神经发育结局的潜在预后生物标志物。
