目的 探究血清tau蛋白水平与新生儿缺血缺氧性脑病(hypoxic-ischemic encephalopathy,HIE)的严重程度及预后之间的关系。方法 测定比较本院收治的68例HIE新生儿(轻度29例、中度21例、重度18例)和16例对照组新生儿0、3、5、7 d及14 d时的血清tau蛋白水平的差异以及分析与神经系神经系统功能预后之间的关系。结果 出生后血清tau蛋白水平呈先升高后降低趋势,并于第5天达峰值,但第14天时仍处于较高水平。对照组各时间点tau蛋白水平均显著低于HIE组(P<0.05)。同时间点tau蛋白水平:重度组高于中度组和轻度组,中度组高于轻度组,且差异均有统计学意义(P<0.05)。1年随访期内,神经预后不良患者15例,其中轻度HIE组1例(3.4%)、中度组4例(19.0%)、重度组10例(55.6%),重度组预后不良率与其他组相比差均有统计学意义(P<0.05),其他组组间相比差异无统计学意义(P>0.05);预后不良的患者各时间点血tau蛋白水平均显著高于预后良好的患者(P<0.05);ROC曲线表明第14天时血清tau蛋白水平>667.1 pg/ml可较准确的预测HIE新生儿的神经发育不良预后,AUC=0.96,敏感度93.33%,特异度90.57%,此时的阳性预测值也最大(73.68%)。结论 血清tau蛋白可以作为反映新生儿HIE的严重程度的标志物,持续较高水平的血清tau蛋白可能预示不良的神经系统发育预后。
Abstract
Objective To explore the relationship of serum tau protien levels with the severity and neurodevelopmental prognosis in neonatal hypoxic-ischemic encephalopathy (HIE ). Methods A total of 68 full-term neonates with HIE were enrolled,including 29 cases mild,21 moderate and 18 severe,and 16 cases without HIE(control group) were enrolled too.Serum samples were collected at day 0,3,5,7 and 14 after birth.Tau protein levels in each group were studied to reveal the relation between serum tau protiens levels and severity and prognosis in neonates with HIE. Results Tau protein in serum was changed with the trend of increasing and then decreasing.The peak concentration of serum tau protein was reached at 5 day and still remained high level at 14th day.The serum tau protein level in control group was significantly lower than HIE groups at any time points(P<0.05).Serum tau protien level in severe group was significantly higher than other three group at all time points (P<0.05).After one year's follow-up,15 cases got a poor neurodevelopmental outcome:1 case in the mild group,4 cases in moderate group and 10 cases in severe group.Compared with other groups,the rate of poor neurodevelopmental outcome in severe group was significantly higher.Among those with a poor neurodevelopmental outcome,serum tau protein level was higher than the rest neonates with a good prognosis at different time points.No correlation was found between Apgar score and serum tau protien level at any time points (P>0.05).ROC analysis showed that serum tau protein level at the 14th day(>667.1 pg/ml) predict accurately of neurodevelopmental prognosis of HIE neonates:AUC=0.96,sensitivity 93.3%,specificity 90.57% and with the maximum positive predictive value(73.68%). Conclusion Serum tau protein can serve as a biomarker reflecting the severity and predicting the neurodevelopmental prognosis of neonates with HIE.
关键词
tau蛋白 /
新生儿 /
缺血缺氧性脑病 /
神经发育预后
Key words
tau protein /
neonates /
hypoxic-ischemic encephalopathy /
neurodevelopmental prognosis
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Hill A,Volpe JJ.Seizures,hypoxic-ischemic brain injury,and intraventricular hemorrhage in the newborn[J].Ann Neurol,1981,10(2):109-121.
[2] Simunek VZ.Birth asphyxia in term newborns:Diagnosis,prognosis,neuroprotection [J].Arch Pediatr,2010,17(5):578-582.
[3] Yeh P,Emary K,Impey L.The relationship between umbilical cord arterial pH and serious adverse neonatal outcome:Analysis of 51,519 consecutive validated samples [J].BJOG,2012,119(7):824-831.
[4] Morris M,Maeda S,Vossel K,et al.The many faces of tau [J].Neuron,2011,70(3):410-426.
[5] Liliang PC,Liang CL,Lu K,et al.Relationship between injury severity and serum tau protein levels in traumatic brain injured rats [J].Resuscitation,2010,81(9):1205-1208.
[6] Randall J,Mortberg E,Provuncher GK,et al.Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest:Results of a pilot study [J].Resuscitation,2013,84(3):351-356.
[7] Takahashi K,Hasegawa S,Maeba S,et al.Serum tau protein level serves as a predictive factor for neurological prognosis in neonatal asphyxia [J].Brain Dev,2014,36(8):670-675.
[8] Tunc T,Karaoglu A,Cayci T,et al.The relation between delivery type and tau protein levels in cord blood [J].Pediatr Int,2010,52(6):872-875.
[9] Liu F,Yang S,Du Z,et al.Dynamic changes of cerebral-specific proteins in full-term newborns with hypoxic-ischemic encephalopathy [J].Cell Biochem Biophys,2013,66(2):389-396.
[10] 中华医学会儿科学分会新生儿学组.新生儿缺氧缺血性脑病诊断标准 [J].中华儿科杂志,2005,43(8):584-584.
[11] 鲍秀兰.0~3岁儿童最佳的人生开端 中国宝宝早期教育和潜能开发指南 高危儿卷 [M].北京:中国妇女出版社,2013.
[12] 吴卫红,鲍秀兰,席冰玉,等.0~1 岁 52 项神经运动检查和简化 20 项相关性研究 [J].中国儿童保健杂志,2014,22(3):310-311.
[13] 马秀伟,封志纯.脑瘫诊断面面观 [J].中国儿童保健杂志,2014,22(1):41-44.
[14] Shah P,Riphagen S,Beyene J,et al.Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy[J].Archives of Disease in Childhood-Fetal and Neonatal Edition,2004,89(2):F152-F155.
[15] Murray DM,Ryan CA,Boylan GB,et al.Prediction of seizures in asphyxiated neonates:Correlation with continuous video-electroencephalographic monitoring [J].Pediatrics,2006,118(1):41-46.
[16] Aridas JD,Yawno T,Sutherland AE,et al.Detecting brain injury in neonatal hypoxic ischemic encephalopathy:Closing the gap between experimental and clinical research [J].Exp Neurol,2014,261(12):281-290.
[17] Chalak LF,Sanchez PJ,Adams-Huet B,et al.Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy [J].J Pediatr,2014,164(3):468-474,e461.
[18] Inoue H,Matsushige T,Hasegawa S,et al.Elevation of tau protein levels in the cerebrospinal fluid of children with west syndrome[J].Epilepsy Res,2012,102(1-2):8-12.
[19] Perlman JM.Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy[J].Pediatrics,2006,117(Suppl3 Pt 2):28-33.
[20] Aito H,Aalto KT,Raivio KO.Biphasic ATP depletion caused by transient oxidative exposure is associated with apoptotic cell death in rat embryonal cortical neurons [J].Pediatr Res,2002,52(1):40-45.