本文選題：膽紅素腦病 + 流行病學(xué)��； 參考：《浙江大學(xué)》2016年博士論文

【摘要】：背景大多數(shù)新生兒在生后都會(huì)出現(xiàn)暫時(shí)性的膽紅素升高,雖然這個(gè)過程多數(shù)為良性的,但仍有部分高膽紅素血癥的患兒由于膽紅素的神經(jīng)毒性作用,發(fā)展成了膽紅素腦病。膽紅素腦病是新生兒高膽紅素血癥的嚴(yán)重并發(fā)癥,在全球范圍內(nèi)都有報(bào)道。根據(jù)病程可分為急性膽紅素腦病(Acute bilirubin encephalopathy, ABE)和慢性膽紅素腦病。雖然隨著經(jīng)濟(jì)和社會(huì)的發(fā)展,人們對(duì)疾病的重視程度和醫(yī)療手段均有了提高,但臨床工作中仍不時(shí)發(fā)現(xiàn)膽紅素腦病案例。目前在預(yù)測(cè)和早期識(shí)別急性膽紅素腦病發(fā)生方面,主要依靠臨床癥狀和體征、血清總膽紅素(Total serum bilirubin, TSB)、血清總膽紅素與白蛋白比值(Bilirubin to albumin ratio, B/A)、聽性腦干反應(yīng)(Auditory brainstem responses, ABR)以及頭顱磁共振成像(Magnetic resonance imaging, MRI)等檢查。對(duì)于臨床癥狀和體征的評(píng)估,國(guó)內(nèi)有人采用新生兒神經(jīng)行為測(cè)定(Neonatal behavioral neurological assessment, NBNA)評(píng)分法,但此法繁瑣且特異性低。國(guó)外多采用膽紅素所致的神經(jīng)功能紊亂(Bilirubin-induced neurological dysfunction, BIND)評(píng)分法。此法操作簡(jiǎn)便,但國(guó)內(nèi)對(duì)其應(yīng)用的研究不多。在實(shí)驗(yàn)室檢查方面,國(guó)內(nèi)外對(duì)TSB和B/A在預(yù)測(cè)膽紅素腦病發(fā)生的有效性方面爭(zhēng)議較多�？傮w來(lái)說目前尚無(wú)哪項(xiàng)指標(biāo)在預(yù)測(cè)膽紅素腦病發(fā)生的準(zhǔn)確性方面得到公認(rèn),臨床決策取決于多方面的綜合評(píng)估。對(duì)膽紅素腦病的流行病學(xué)分析也能為臨床決策提供依據(jù)。距離我國(guó)上次多中心的膽紅素腦病流行病學(xué)調(diào)查已有數(shù)年,近年來(lái)膽紅素腦病的流行病學(xué)特點(diǎn)有無(wú)變化,仍需更多研究。本研究對(duì)近年來(lái)的膽紅素腦病案例進(jìn)行資料收集和分析,總結(jié)出其流行病學(xué)特點(diǎn),并與既往的流行病學(xué)調(diào)查結(jié)果作比較；同時(shí)也評(píng)估不同監(jiān)測(cè)指標(biāo)在預(yù)測(cè)膽紅素腦病發(fā)生及其預(yù)后方面的有效性,希望能為臨床決策提供依據(jù)。第一部分足月和近足月新生兒膽紅素腦病的流行病學(xué)分析目的：1.通過流行病學(xué)調(diào)查,總結(jié)出近年來(lái)膽紅素腦病患兒的臨床特點(diǎn),為臨床干預(yù)提供依據(jù)。2.比較近年來(lái)膽紅素腦病的流行病學(xué)特點(diǎn)和既往我國(guó)多中心流行病學(xué)調(diào)查結(jié)果有無(wú)差異,并對(duì)出現(xiàn)差異的原因進(jìn)行探討。方法：1.回顧性收集2011.1.1至2015.12.31之間浙江大學(xué)附屬兒童醫(yī)院新生兒重癥監(jiān)護(hù)室和普通新生兒病房收治的,胎齡≥35周的膽紅素腦病患兒資料。2.對(duì)一般資料、伴發(fā)疾病、檢查結(jié)果、接受的治療手段以及出院時(shí)的轉(zhuǎn)歸進(jìn)行分析。3.將本研究結(jié)果與2012年國(guó)內(nèi)的多中心流行病學(xué)資料進(jìn)行比較。結(jié)果：1.一般資料：5年內(nèi)研究病區(qū)共收治患病新生兒32063例,被診斷為膽紅素腦病且胎齡≥35周的共112例(3.5%)。其中漢族107例(95.5%),浙江本省84例(75.0%),男性81例(72.3%),男女比2.61：1,母親為初產(chǎn)婦的55例(49.1%),自然分娩的72例(64.3%),全部或部分母乳喂養(yǎng)的87例(78.4%),平均胎齡38.5±1.6周,胎齡芝37周的97例(86.6%),平均出生體重3174.8±493.3g,低出生體重兒6例(5.4%),小于胎齡兒8例(7.1%),黃疸出現(xiàn)日齡的中位數(shù)和四分位數(shù)為2.3(2.0-3.0)天,入院日齡的中位數(shù)和四分位數(shù)為6.0(4.0～8.4)天。2.伴發(fā)疾�。汗�94例(83.9%)存在伴發(fā)疾病,49例(43.8%)有多種伴發(fā)疾病,伴發(fā)疾病最常見的四種是,敗血癥或感染(42.9%)、ABO溶血(31.2%)、G6PD缺乏癥(25.0%)、出生相關(guān)的創(chuàng)傷性疾病(24.1%)。3.檢查結(jié)果：TSB峰值平均516.0±144.7μmol/L,小于342.0μmol/L的有11例,B/A平均7.9±2.5mg/g,白蛋白平均36.9±3.6g/L,聽力異常率(ABR和AABR檢查)為74.4%,頭顱MRI發(fā)現(xiàn)急性膽紅素腦病典型改變的有48.3%。4.治療和轉(zhuǎn)歸：接受各種治療手段的比例分別為光療100%,靜脈輸注白蛋白83.0%,換血49.1%,靜脈應(yīng)用丙種免疫球蛋白31.3%,酶誘導(dǎo)劑和口服退黃中成藥69.6%；抗生素使用較多(86.6%),52.6%為預(yù)防性使用,但有逐年下降趨勢(shì)。院內(nèi)死亡(7例)和自動(dòng)出院后確認(rèn)死亡(3例)的共有10例(8.9%),院內(nèi)死亡的其中3例為低出生體重兒；出院時(shí)存活的105例中存在肌張力障礙的有38.1%。5.與2012年國(guó)內(nèi)多中心流行病學(xué)資料比較：基本資料方面(包括胎齡、性別、出生體重、母乳喂養(yǎng)比例、入院日齡)總體相似。本研究中出現(xiàn)多種伴發(fā)疾病的比例更高,但最常見的兩種伴發(fā)疾病一致。本研究中TSB峰值水平、聽力異常率更高,B/A水平和MRI異常率相近。治療上都是光療為主,白蛋白輸注和換血次之。結(jié)論：1.近年來(lái)新生兒膽紅素腦病的收治率總體未見下降趨勢(shì)。2.近年來(lái)膽紅素腦病的流行病學(xué)特點(diǎn)與國(guó)內(nèi)既往的一項(xiàng)多中心流行病學(xué)調(diào)查結(jié)果相似。3.發(fā)生膽紅素腦病的TSB范圍較廣,低膽紅素水平的膽紅素腦病發(fā)生比例不低。4.光療在治療方面占絕對(duì)主導(dǎo)地位。預(yù)防性使用抗生素的比例較高,但近年來(lái)有逐年下降趨勢(shì)。第二部分不同指標(biāo)在預(yù)測(cè)急性膽紅素腦病發(fā)生和預(yù)后評(píng)估中的作用目的：評(píng)價(jià)TSB、B/A、BIND評(píng)分在預(yù)測(cè)急性膽紅素腦病發(fā)生以及預(yù)后評(píng)估方面的作用。方法：研究數(shù)據(jù)來(lái)自第一部分的患兒病例資料。1.根據(jù)存在的危險(xiǎn)因素,分組比較TSB和B/A水平。2.以聽力檢查為金標(biāo)準(zhǔn),通過ROC曲線評(píng)價(jià)TSB和B/A對(duì)聽力損傷預(yù)測(cè)的準(zhǔn)確性,并尋找預(yù)測(cè)聽力損傷的最佳截?cái)帱c(diǎn)。3.比較不同BIND評(píng)分組的各項(xiàng)檢查結(jié)果和短期預(yù)后情況。4.比較BIND評(píng)分最高組中死亡和存活患兒的基本資料、伴發(fā)疾病,以及TSB和B/A水平。結(jié)果：1.發(fā)生膽紅素腦病的患兒中,胎齡35～37周的近足月兒和足月兒之間、低出生體重兒和正常體重兒之間,TSB.B/A的范圍和總體水平均沒有差異。沒有G6PD缺乏癥、同族免疫性溶血、敗血癥(或感染)這三種危險(xiǎn)因素時(shí),TSB的范圍在248.0～695.0μmol/L,平均501.1±142.2μmol/L; B/A的范圍在3.6-11.9mg/g,平均7.7±2.7mg/g。在胎齡、出生體重、性別、喂養(yǎng)方式等基本資料沒有差異的情況下,存在G6PD缺乏癥時(shí)TSB (654.8±36.3μmol/L, P=0.001)和B/A (9.9±1.0 mg/g, P=0.014)的總體水平比無(wú)三種危險(xiǎn)因素組更高；存在同族免疫性溶血時(shí)TSB(384.1±100μmol/L, P=0.024)和B/A (5.7±1.5 mg/g, P=0.025)的總體水平則更低；存在敗血癥時(shí)總體TSB, B/A水平無(wú)差異,但TSB的下限更低(219.0μmol/L).2.對(duì)聽力損傷的預(yù)測(cè)：TSB的ROC曲線下面積為0.698,最佳截?cái)帱c(diǎn)為524.5μmol/L; B/A的ROC曲線下面積為0.676,最佳截?cái)帱c(diǎn)為6.6mg/g。3.隨著BIND評(píng)分上升,伴發(fā)G6PD缺乏癥(P=0.003)、敗血癥或感染(P=0.002)的比例、TSB(P=0.000)和B/A(P=0.000)水平、出院時(shí)死亡率(P=0.000)和存活者肌張力障礙(P=0.000)發(fā)生比例均顯著升高。4.在BIND評(píng)分最高組,死亡亞組和存活亞組之間的基本資料、各危險(xiǎn)因素發(fā)生比例,以及TSB和B/A水平均沒有顯著差異。結(jié)論：1.單獨(dú)運(yùn)用TSB或B/A對(duì)急性膽紅素腦病的發(fā)生及其預(yù)后的預(yù)測(cè)作用有限。2.TSB和B/A對(duì)聽力損傷的預(yù)測(cè)均接近中度準(zhǔn)確性。3.B/A在預(yù)測(cè)膽紅素腦病的發(fā)生、聽力損傷和短期預(yù)后方面均未優(yōu)于TSB。4. BIND評(píng)分與各項(xiàng)輔助檢查的相關(guān)性好,在反映急性膽紅素腦病嚴(yán)重程度的同時(shí),也對(duì)短期預(yù)后有一定預(yù)測(cè)作用。
[Abstract]:Background most newborn there will be a temporary increase in bilirubin after birth, although this process is mostly benign, but there are still some children because of hyperbilirubinemia bilirubin neurotoxicity, developed into bilirubin encephalopathy. Bilirubin encephalopathy is a serious complication in neonatal hyperbilirubinemia, have been reported worldwide. According to the duration of divided into acute bilirubin encephalopathy (Acute bilirubin, encephalopathy, ABE) and chronic bilirubin encephalopathy. Although with the development of economy and society, people of the disease and the importance of medical treatments have improved, but still found in clinical work. In the case of bilirubin encephalopathy prediction and early identification of acute bilirubin encephalopathy occurred, mainly depends on the clinical the symptoms and signs, serum total bilirubin (Total serum, bilirubin, TSB), serum total bilirubin and albumin ratio Value (Bilirubin to albumin ratio, B/A), auditory brainstem response (Auditory brainstem, responses, ABR) and magnetic resonance imaging (Magnetic resonance, imaging, MRI) examination. For the assessment of clinical symptoms and signs, some people with neonatal behavioral neurological determination (Neonatal behavioral neurological assessment, NBNA) score. But this method is tedious and low specificity. The foreign nerve dysfunction caused by bilirubin (Bilirubin-induced neurological, dysfunction, BIND) score method. This method is simple, but the research on its application is not enough. In laboratory tests, both at home and abroad of TSB and B/A in predicting the effectiveness of controversial bilirubin encephalopathy general. At present no indicators of the predictive accuracy of bilirubin encephalopathy have been recognized, comprehensive evaluation of clinical decision depends on many aspects Estimated. Epidemiological analysis on bilirubin encephalopathy can also provide the basis for clinical decision. Bilirubin encephalopathy epidemiological survey from China has multi center last several years, in recent years the epidemiological characteristics of bilirubin encephalopathy have no change, still need more research. The research data were collected and analyzed in recent years the bilirubin encephalopathy cases, summed up the epidemiological characteristics, and compared with previous epidemiological survey results; at the same time, different monitoring indicators in predicting the effectiveness of bilirubin encephalopathy and prognosis of the evaluation, hoping to provide the basis for clinical decision. The first part of term and near term epidemiological analysis of neonatal bilirubin encephalopathy Objective: 1. through epidemiological investigation, summarized the clinical characteristics bilirubin encephalopathy in recent years, provide the basis for clinical intervention of.2. flow of bilirubin encephalopathy in recent years Epidemiological survey of China's multi center epidemiological characteristics and had no difference, and the reasons for the difference are discussed. Methods: retrospectively collected 1. NICU between 2011.1.1 and 2015.12.31 children's Hospital Affiliated to Zhejiang University and ordinary neonatal ward, bilirubin encephalopathy.2. gestational age over 35 weeks in general the data, associated diseases, examination results, treatment and prognosis of means at discharge was analyzed by.3. the results of this study and the 2012 domestic multi center epidemiological data were compared. Results: 1. general information: 5 years of ward were treated sick newborns 32063 cases, diagnosed with bilirubin encephalopathy and gestational age of more than 35 the week a total of 112 cases (3.5%). 107 cases of Han nationality in Zhejiang province (95.5%), 84 cases (75%), 81 cases were male (72.3%), and the ratio of 2.61:1, the mother of primipara 55 cases (49.1%), since 鐒跺垎濞╃殑72渚，

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