本文關鍵詞： 早產(chǎn)兒腦損傷 神經(jīng)元特異性烯醇化酶 S100β 乳酸 爆發(fā)間期 新生兒神經(jīng)行為評分 聽力篩查　出處：《廣州醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的早產(chǎn)兒腦損傷是早產(chǎn)兒常見疾病之一,可嚴重影響早產(chǎn)兒神經(jīng)系統(tǒng)預后及生存質(zhì)量。由于腦組織血管發(fā)育不成熟,腦血流自主調(diào)節(jié)能力差,極易出現(xiàn)腦血流動力學紊亂,并且早產(chǎn)兒神經(jīng)元、少突膠質(zhì)細胞及其前體對缺氧缺血異常敏感,耐受性低,易損性高,導致早產(chǎn)兒腦損傷及神經(jīng)系統(tǒng)后遺癥發(fā)生率較足月兒高,好發(fā)年齡多見于小于32周的早產(chǎn)兒,特別是小于28周的超未成熟兒。但臨床上早產(chǎn)兒腦損傷早期往往缺乏明顯的神經(jīng)系統(tǒng)癥狀和體征,不易發(fā)現(xiàn),容易漏診而錯過治療時機,本研究通過將三個血清學指標(神經(jīng)元特異性烯醇化酶(NSE)、S100β蛋白、乳酸)和腦電圖中爆發(fā)間期(IBI)與頭顱超聲及頭顱核磁共振進行比較,評價所選取的外周血清學指標和爆發(fā)間期在診斷早產(chǎn)兒腦損傷上的靈敏度和特異度,獲取受試者工作曲線(ROC曲線)及曲線下面積,并得出其與新生兒神經(jīng)行為評分(NBNA評分)及聽力篩查之間的關系。方法本實驗為前瞻性臨床診斷試驗。根據(jù)納入及剔除標準,出生胎齡小于32周且出生體重小于1500克的早產(chǎn)兒在生后早期三個不同時間點(生后第1天、生后第3天及生后第7天)進行外周血血清學指標檢測,在生后第1天、糾正胎齡32周及糾正胎齡36周時行腦電圖監(jiān)測,同時在生后第1周內(nèi)及以后每隔2周或根據(jù)病情需要行頭顱超聲檢查,糾正胎齡滿37周或正常出院前完善頭顱核磁共振、NBNA評分及聽力篩查,并且記錄早產(chǎn)兒及其母親的一般住院信息及相關病情情況。根據(jù)頭顱超聲及核磁共振結果,將最終納入實驗的早產(chǎn)兒分為腦損傷組和無腦損傷組,并將NSE、S100β、乳酸和IBI結果與頭顱超聲和頭顱核磁共振結果進行比較,得出四者在診斷早產(chǎn)兒腦損傷上的靈敏度、特異度和ROC曲線;同時將各指標與NBNA評分行相關性分析、與聽力篩查行Logistic回歸分析,得出S100β、NSE、乳酸及IBI在早產(chǎn)兒神經(jīng)系統(tǒng)短期不良預后的預測價值評估。所有的數(shù)據(jù)均采用SPSS 13.0軟件進行統(tǒng)計學分析。結果1.外周血清學檢查結果生后第1天檢測結果示,血清S100β、NSE、乳酸的ROC曲線下面積分別為0.699、0.755、0.763;生后第3天檢測結果示,血清S100β、NSE、乳酸的ROC曲線下面積分別為0.745、0.731、0.593;生后第7天結果示,血清S100β、NSE、乳酸的ROC曲線下面積分別為0.662、0.501、0.470(P值均0.05)。2.腦電圖監(jiān)測結果生后第1天、糾正胎齡32周及糾正胎齡36周腦電圖監(jiān)測中,IBI的ROC曲線下面積分別為0.557、0.660、0.668(P值均0.05)。3.外周血清學和腦電圖檢查結果與NBNA評分及聽力篩查結果之間的關系比較腦損傷組NBNA評分顯著低于無腦損傷組(34.95±0.38,35.94±0.37,t=-3.716,P0.05),腦損傷組聽力篩查不通過率高于無腦損傷組(X2=4.006,P0.05),經(jīng)檢驗分析,差異均有統(tǒng)計學意義。根據(jù)四個實驗指標在各時間點的ROC曲線下面積的比較結果,本研究選取生后第1天NSE及乳酸血清濃度,生后第3天S100β血清濃度,糾正胎齡36周腦電圖中的IBI秒數(shù)作為分析因素,通過Spearman相關性分析發(fā)現(xiàn),生后第1天血清NSE及乳酸濃度,生后第3天血清S100β濃度,糾正胎齡36周腦電圖中的IBI秒數(shù)與NBNA評分均呈顯著負相關(r NSE=-0.456,r Lac=-0.483,r S100β=-0.544,r IBI=-0.269,P0.01),并且通過Logistic回歸分析結果發(fā)現(xiàn),S100β和IBI與聽力篩查不通過事件的發(fā)生有密切關系(ORS100β=4.758,ORIBI=2.126),對回歸系數(shù)進行Wald檢驗,P0.05,均有統(tǒng)計學意義。結論1.生后第1天NSE的ROC曲線下面積比生后第3天和生后第7天的面積均大,NSE在生后第1天診斷早產(chǎn)兒腦損傷價值最高;乳酸與NSE相似,在生后第1天即有較高的診斷價值;S100β的ROC曲線下面積在生后第3天出現(xiàn)峰值,此時診斷價值最高;腦電圖監(jiān)測中,糾正胎齡36周IBI的ROC曲線下面積最大,此時診斷早產(chǎn)兒腦損傷價值顯著高于生后第1天和糾正胎齡32周。2.對于發(fā)生早產(chǎn)兒腦損傷的患兒,在其生后早期,血清NSE、S100β及乳酸的ROC曲線下面積均較大,提示臨床診斷價值較高,可作為早產(chǎn)兒腦損傷早期診斷的血生化指標,但由于半衰期的影響,三者的診斷價值隨著出生日齡的漸增而下降;隨著生后糾正胎齡的增加,以IBI為觀察指標的腦電圖ROC曲線下面積隨之增加,診斷價值不斷升高,可協(xié)同頭顱超聲及核磁共振作為早產(chǎn)兒腦損傷后期診斷,彌補血液學指標后期診斷的不足。3.血清NSE、S100β、乳酸濃度水平及腦電圖中爆發(fā)間期時間與NBNA評分呈負相關;S100β和腦電圖中爆發(fā)間期時間與聽力篩查不通過事件的發(fā)生有關。4.血清NSE、S100β、乳酸及腦電圖IBI可應用于臨床,評估分析早產(chǎn)兒神經(jīng)系統(tǒng)損傷短期預后,提示臨床工作者盡早給予腦損傷患兒康復治療,改善生存質(zhì)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.

【學位授予單位】：廣州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R742

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