足月及近足月新生儿胆红素脑病的临床分析

发布时间：2018-04-13 06:30

  本文选题：胆红素脑病 + 流行病学　； 参考：《浙江大学》2016年博士论文

【摘要】：背景大多数新生儿在生后都会出现暂时性的胆红素升高,虽然这个过程多数为良性的,但仍有部分高胆红素血症的患儿由于胆红素的神经毒性作用,发展成了胆红素脑病。胆红素脑病是新生儿高胆红素血症的严重并发症,在全球范围内都有报道。根据病程可分为急性胆红素脑病(Acute bilirubin encephalopathy, ABE)和慢性胆红素脑病。虽然随着经济和社会的发展,人们对疾病的重视程度和医疗手段均有了提高,但临床工作中仍不时发现胆红素脑病案例。目前在预测和早期识别急性胆红素脑病发生方面,主要依靠临床症状和体征、血清总胆红素(Total serum bilirubin, TSB)、血清总胆红素与白蛋白比值(Bilirubin to albumin ratio, B/A)、听性脑干反应(Auditory brainstem responses, ABR)以及头颅磁共振成像(Magnetic resonance imaging, MRI)等检查。对于临床症状和体征的评估,国内有人采用新生儿神经行为测定(Neonatal behavioral neurological assessment, NBNA)评分法,但此法繁琐且特异性低。国外多采用胆红素所致的神经功能紊乱(Bilirubin-induced neurological dysfunction, BIND)评分法。此法操作简便,但国内对其应用的研究不多。在实验室检查方面,国内外对TSB和B/A在预测胆红素脑病发生的有效性方面争议较多。总体来说目前尚无哪项指标在预测胆红素脑病发生的准确性方面得到公认,临床决策取决于多方面的综合评估。对胆红素脑病的流行病学分析也能为临床决策提供依据。距离我国上次多中心的胆红素脑病流行病学调查已有数年,近年来胆红素脑病的流行病学特点有无变化,仍需更多研究。本研究对近年来的胆红素脑病案例进行资料收集和分析,总结出其流行病学特点,并与既往的流行病学调查结果作比较；同时也评估不同监测指标在预测胆红素脑病发生及其预后方面的有效性,希望能为临床决策提供依据。第一部分足月和近足月新生儿胆红素脑病的流行病学分析目的：1.通过流行病学调查,总结出近年来胆红素脑病患儿的临床特点,为临床干预提供依据。2.比较近年来胆红素脑病的流行病学特点和既往我国多中心流行病学调查结果有无差异,并对出现差异的原因进行探讨。方法：1.回顾性收集2011.1.1至2015.12.31之间浙江大学附属儿童医院新生儿重症监护室和普通新生儿病房收治的,胎龄≥35周的胆红素脑病患儿资料。2.对一般资料、伴发疾病、检查结果、接受的治疗手段以及出院时的转归进行分析。3.将本研究结果与2012年国内的多中心流行病学资料进行比较。结果：1.一般资料：5年内研究病区共收治患病新生儿32063例,被诊断为胆红素脑病且胎龄≥35周的共112例(3.5%)。其中汉族107例(95.5%),浙江本省84例(75.0%),男性81例(72.3%),男女比2.61：1,母亲为初产妇的55例(49.1%),自然分娩的72例(64.3%),全部或部分母乳喂养的87例(78.4%),平均胎龄38.5±1.6周,胎龄芝37周的97例(86.6%),平均出生体重3174.8±493.3g,低出生体重儿6例(5.4%),小于胎龄儿8例(7.1%),黄疸出现日龄的中位数和四分位数为2.3(2.0-3.0)天,入院日龄的中位数和四分位数为6.0(4.0～8.4)天。2.伴发疾病：共94例(83.9%)存在伴发疾病,49例(43.8%)有多种伴发疾病,伴发疾病最常见的四种是,败血症或感染(42.9%)、ABO溶血(31.2%)、G6PD缺乏症(25.0%)、出生相关的创伤性疾病(24.1%)。3.检查结果：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,听力异常率(ABR和AABR检查)为74.4%,头颅MRI发现急性胆红素脑病典型改变的有48.3%。4.治疗和转归：接受各种治疗手段的比例分别为光疗100%,静脉输注白蛋白83.0%,换血49.1%,静脉应用丙种免疫球蛋白31.3%,酶诱导剂和口服退黄中成药69.6%；抗生素使用较多(86.6%),52.6%为预防性使用,但有逐年下降趋势。院内死亡(7例)和自动出院后确认死亡(3例)的共有10例(8.9%),院内死亡的其中3例为低出生体重儿；出院时存活的105例中存在肌张力障碍的有38.1%。5.与2012年国内多中心流行病学资料比较：基本资料方面(包括胎龄、性别、出生体重、母乳喂养比例、入院日龄)总体相似。本研究中出现多种伴发疾病的比例更高,但最常见的两种伴发疾病一致。本研究中TSB峰值水平、听力异常率更高,B/A水平和MRI异常率相近。治疗上都是光疗为主,白蛋白输注和换血次之。结论：1.近年来新生儿胆红素脑病的收治率总体未见下降趋势。2.近年来胆红素脑病的流行病学特点与国内既往的一项多中心流行病学调查结果相似。3.发生胆红素脑病的TSB范围较广,低胆红素水平的胆红素脑病发生比例不低。4.光疗在治疗方面占绝对主导地位。预防性使用抗生素的比例较高,但近年来有逐年下降趋势。第二部分不同指标在预测急性胆红素脑病发生和预后评估中的作用目的：评价TSB、B/A、BIND评分在预测急性胆红素脑病发生以及预后评估方面的作用。方法：研究数据来自第一部分的患儿病例资料。1.根据存在的危险因素,分组比较TSB和B/A水平。2.以听力检查为金标准,通过ROC曲线评价TSB和B/A对听力损伤预测的准确性,并寻找预测听力损伤的最佳截断点。3.比较不同BIND评分组的各项检查结果和短期预后情况。4.比较BIND评分最高组中死亡和存活患儿的基本资料、伴发疾病,以及TSB和B/A水平。结果：1.发生胆红素脑病的患儿中,胎龄35～37周的近足月儿和足月儿之间、低出生体重儿和正常体重儿之间,TSB.B/A的范围和总体水平均没有差异。没有G6PD缺乏症、同族免疫性溶血、败血症(或感染)这三种危险因素时,TSB的范围在248.0～695.0μmol/L,平均501.1±142.2μmol/L; B/A的范围在3.6-11.9mg/g,平均7.7±2.7mg/g。在胎龄、出生体重、性别、喂养方式等基本资料没有差异的情况下,存在G6PD缺乏症时TSB (654.8±36.3μmol/L, P=0.001)和B/A (9.9±1.0 mg/g, P=0.014)的总体水平比无三种危险因素组更高；存在同族免疫性溶血时TSB(384.1±100μmol/L, P=0.024)和B/A (5.7±1.5 mg/g, P=0.025)的总体水平则更低；存在败血症时总体TSB, B/A水平无差异,但TSB的下限更低(219.0μmol/L).2.对听力损伤的预测：TSB的ROC曲线下面积为0.698,最佳截断点为524.5μmol/L; B/A的ROC曲线下面积为0.676,最佳截断点为6.6mg/g。3.随着BIND评分上升,伴发G6PD缺乏症(P=0.003)、败血症或感染(P=0.002)的比例、TSB(P=0.000)和B/A(P=0.000)水平、出院时死亡率(P=0.000)和存活者肌张力障碍(P=0.000)发生比例均显著升高。4.在BIND评分最高组,死亡亚组和存活亚组之间的基本资料、各危险因素发生比例,以及TSB和B/A水平均没有显著差异。结论：1.单独运用TSB或B/A对急性胆红素脑病的发生及其预后的预测作用有限。2.TSB和B/A对听力损伤的预测均接近中度准确性。3.B/A在预测胆红素脑病的发生、听力损伤和短期预后方面均未优于TSB。4. BIND评分与各项辅助检查的相关性好,在反映急性胆红素脑病严重程度的同时,也对短期预后有一定预测作用。
[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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