S100β、NSE、乳酸及IBI在早产儿脑损伤中的应用价值评估

发布时间：2018-02-27 18:33

本文关键词： 早产儿脑损伤神经元特异性烯醇化酶 S100β 乳酸爆发间期新生儿神经行为评分听力筛查　出处：《广州医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的早产儿脑损伤是早产儿常见疾病之一,可严重影响早产儿神经系统预后及生存质量。由于脑组织血管发育不成熟,脑血流自主调节能力差,极易出现脑血流动力学紊乱,并且早产儿神经元、少突胶质细胞及其前体对缺氧缺血异常敏感,耐受性低,易损性高,导致早产儿脑损伤及神经系统后遗症发生率较足月儿高,好发年龄多见于小于32周的早产儿,特别是小于28周的超未成熟儿。但临床上早产儿脑损伤早期往往缺乏明显的神经系统症状和体征,不易发现,容易漏诊而错过治疗时机,本研究通过将三个血清学指标(神经元特异性烯醇化酶(NSE)、S100β蛋白、乳酸)和脑电图中爆发间期(IBI)与头颅超声及头颅核磁共振进行比较,评价所选取的外周血清学指标和爆发间期在诊断早产儿脑损伤上的灵敏度和特异度,获取受试者工作曲线(ROC曲线)及曲线下面积,并得出其与新生儿神经行为评分(NBNA评分)及听力筛查之间的关系。方法本实验为前瞻性临床诊断试验。根据纳入及剔除标准,出生胎龄小于32周且出生体重小于1500克的早产儿在生后早期三个不同时间点(生后第1天、生后第3天及生后第7天)进行外周血血清学指标检测,在生后第1天、纠正胎龄32周及纠正胎龄36周时行脑电图监测,同时在生后第1周内及以后每隔2周或根据病情需要行头颅超声检查,纠正胎龄满37周或正常出院前完善头颅核磁共振、NBNA评分及听力筛查,并且记录早产儿及其母亲的一般住院信息及相关病情情况。根据头颅超声及核磁共振结果,将最终纳入实验的早产儿分为脑损伤组和无脑损伤组,并将NSE、S100β、乳酸和IBI结果与头颅超声和头颅核磁共振结果进行比较,得出四者在诊断早产儿脑损伤上的灵敏度、特异度和ROC曲线;同时将各指标与NBNA评分行相关性分析、与听力筛查行Logistic回归分析,得出S100β、NSE、乳酸及IBI在早产儿神经系统短期不良预后的预测价值评估。所有的数据均采用SPSS 13.0软件进行统计学分析。结果1.外周血清学检查结果生后第1天检测结果示,血清S100β、NSE、乳酸的ROC曲线下面积分别为0.699、0.755、0.763;生后第3天检测结果示,血清S100β、NSE、乳酸的ROC曲线下面积分别为0.745、0.731、0.593;生后第7天结果示,血清S100β、NSE、乳酸的ROC曲线下面积分别为0.662、0.501、0.470(P值均0.05)。2.脑电图监测结果生后第1天、纠正胎龄32周及纠正胎龄36周脑电图监测中,IBI的ROC曲线下面积分别为0.557、0.660、0.668(P值均0.05)。3.外周血清学和脑电图检查结果与NBNA评分及听力筛查结果之间的关系比较脑损伤组NBNA评分显著低于无脑损伤组(34.95±0.38,35.94±0.37,t=-3.716,P0.05),脑损伤组听力筛查不通过率高于无脑损伤组(X2=4.006,P0.05),经检验分析,差异均有统计学意义。根据四个实验指标在各时间点的ROC曲线下面积的比较结果,本研究选取生后第1天NSE及乳酸血清浓度,生后第3天S100β血清浓度,纠正胎龄36周脑电图中的IBI秒数作为分析因素,通过Spearman相关性分析发现,生后第1天血清NSE及乳酸浓度,生后第3天血清S100β浓度,纠正胎龄36周脑电图中的IBI秒数与NBNA评分均呈显著负相关(r NSE=-0.456,r Lac=-0.483,r S100β=-0.544,r IBI=-0.269,P0.01),并且通过Logistic回归分析结果发现,S100β和IBI与听力筛查不通过事件的发生有密切关系(ORS100β=4.758,ORIBI=2.126),对回归系数进行Wald检验,P0.05,均有统计学意义。结论1.生后第1天NSE的ROC曲线下面积比生后第3天和生后第7天的面积均大,NSE在生后第1天诊断早产儿脑损伤价值最高;乳酸与NSE相似,在生后第1天即有较高的诊断价值;S100β的ROC曲线下面积在生后第3天出现峰值,此时诊断价值最高;脑电图监测中,纠正胎龄36周IBI的ROC曲线下面积最大,此时诊断早产儿脑损伤价值显著高于生后第1天和纠正胎龄32周。2.对于发生早产儿脑损伤的患儿,在其生后早期,血清NSE、S100β及乳酸的ROC曲线下面积均较大,提示临床诊断价值较高,可作为早产儿脑损伤早期诊断的血生化指标,但由于半衰期的影响,三者的诊断价值随着出生日龄的渐增而下降;随着生后纠正胎龄的增加,以IBI为观察指标的脑电图ROC曲线下面积随之增加,诊断价值不断升高,可协同头颅超声及核磁共振作为早产儿脑损伤后期诊断,弥补血液学指标后期诊断的不足。3.血清NSE、S100β、乳酸浓度水平及脑电图中爆发间期时间与NBNA评分呈负相关;S100β和脑电图中爆发间期时间与听力筛查不通过事件的发生有关。4.血清NSE、S100β、乳酸及脑电图IBI可应用于临床,评估分析早产儿神经系统损伤短期预后,提示临床工作者尽早给予脑损伤患儿康复治疗,改善生存质量。
[Abstract]:The purpose of brain injury in preterm infants is one of the common diseases of premature infants, can seriously affect the prognosis and quality of life in preterm infants. The nervous system due to brain vascular maturation, cerebral blood flow autoregulation ability is poor, prone to cerebral hemodynamic disorder and premature neurons, oligodendrocytes and their precursors are very sensitive to hypoxia ischemia, tolerance to low the vulnerability is high, resulting in premature infants, brain injury and neurological sequelae rate than full-term infants, good hair age in less than 32 weeks premature, especially premature infants less than 28 weeks. But the clinical early brain injury in preterm infants often lack obvious neurological symptoms and signs, not easy to find, easy to leak diagnosis and missed treatment time, this study of the three indicators (serum neuron specific enolase (NSE), S100 protein, lactic acid) outbreak interval and electroencephalogram (IBI) and Cranial ultrasound and cranial MRI were compared, peripheral serological evaluation index selected and outbreak interval in diagnosis of brain injury in preterm infants on the sensitivity and specificity of obtaining the receiver operating characteristic curve (ROC curve) and area under the curve, and draw with the neonatal behavioral neurological assessment (NBNA score) and the relationship between listening screening. Methods the study was a prospective clinical diagnostic test. According to the inclusion and exclusion criteria, gestational age less than 32 weeks and birth weight less than 1500 grams of premature infants early in three different time points (first days after birth third days after birth and seventh days after birth) were detected in peripheral blood serum the index, in first days after birth, the corrected gestational age of 32 weeks and 36 weeks after correcting gestational age EEG monitoring, at the same time within first week after birth and after every 2 weeks or according to the condition of cranial ultrasound, corrected gestational age over 37 weeks or normal Hospital improvement before the cranial MRI, NBNA score and hearing screening, and records of general hospital information and related disease in preterm infants and their mothers. According to cranial ultrasound and MRI results, will eventually be included in the experiment of premature infants were divided into brain injury group and brain injury group, and NSE, S100 beta, lactic acid and IBI results compared with cranial ultrasound and cranial MRI results, obtained four sensitivity in the diagnosis of brain injury in preterm infants on the specificity and ROC curve; at the same time the analysis of indexes and the correlation with the NBNA score, hearing screening for Logistic regression analysis, the S100 beta, NSE, lactic acid and IBI value in the prediction of nervous system in premature infants in short term poor prognosis. All data were analyzed with SPSS 13. Results 1. peripheral serologic results first days after birth detection showed that the serum beta S100, NSE, ROC, lactic acid The line area were 0.699,0.755,0.763; third days after birth detection showed that the serum beta S100, NSE, ROC area under the curve of lactic acid were 0.745,0.731,0.593; seventh days after birth showed that the serum beta S100, NSE, ROC area under the curve of lactic acid were 0.662,0.501,0.470 (P 0.05).2. EEG monitoring results of students after first days, the corrected gestational age of 32 weeks and 36 weeks of gestational age corrected EEG monitoring, ROC area under the IBI curve was 0.557,0.660,0.668 (P 0.05).3. in peripheral serum and EEG results with NBNA score and hearing screening results of the relationship between brain injury group NBNA scores were significantly lower than those without brain injury group (34.95 + 0.38,35.94 + 0.37, t=-3.716, P0.05), brain injury group was higher than that of non hearing screening by brain injury group (X2=4.006, P0.05), by analysis, the differences were statistically significant. According to the four experimental index at different time points. Results area under the ROC curve, this study selected first days after birth NSE and serum lactic acid concentration, third days after birth S100 beta serum concentration, the corrected gestational age of 36 weeks in electroencephalogram IBI seconds as factor analysis, correlation analysis by Spearman first days after birth, the serum NSE and lactic acid concentration after birth the third day serum beta S100 concentration, the corrected gestational age of 36 weeks in electroencephalogram IBI seconds and NBNA scores were negatively correlated (R NSE=-0.456, R Lac=-0.483, R S100 R IBI=-0.269, beta =-0.544, P0.01), and through the Logistic regression analysis showed that S100 beta and IBI and not pass the hearing screening are closely related events (ORS100 beta =4.758, ORIBI=2.126), Wald test, the regression coefficient P0.05, were statistically significant. Conclusion ROC curve area 1. NSE under first days after birth than after third days and seventh days after the area was bigger, NSE in first days after the diagnosis of premature birth The highest value of infant with brain damage; lactic acid is similar to NSE, in the diagnostic value of first days after birth is higher; ROC curve area of S100 beta under the peak in third days after birth, the highest diagnostic value; EEG monitoring in the area of ROC curve, the corrected gestational age of 36 weeks IBI maximum, the diagnosis of brain the value of injury in preterm infants was significantly higher than that in first days after birth and the corrected gestational age of 32 weeks.2. for the occurrence of premature infant brain injury in children, in the early period after birth, serum NSE, ROC curve S100 beta and lactic acid under the area were larger, suggesting higher clinical value in the diagnosis of blood biochemical indexes for early diagnosis of brain injury in preterm infants, but because the half-life of influence, the diagnostic value of three decreased with increasing age after birth; with the increase of students after correcting gestational age, with IBI as the area of ROC curve under the observation of EEG index increased, diagnostic value increased continuously, can cooperate with head Ultrasound and MRI as a late diagnosis of premature infant brain injury, make up the haematological indexes late diagnosis of less than.3. of serum NSE, S100 beta, lactic acid concentration and electroencephalogram in outbreak interval was negatively correlated with NBNA score; S100 beta and EEG burst interval and hearing screening was related to serum.4. NSE, through the S100 event beta, lactic acid and IBI can be applied in clinical EEG analysis, premature nervous system damage short-term prognosis evaluation, prompt clinical workers given early rehabilitation of children with brain injury treatment, improve the quality of life.

【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742

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