河北省多中心足月儿重度高胆红素血症病因、治疗方法以及预后调查

发布时间：2018-01-14 08:23

  本文关键词：河北省多中心足月儿重度高胆红素血症病因、治疗方法以及预后调查　出处：《河北医科大学》2016年硕士论文　论文类型：学位论文

  更多相关文章： 多中心 高胆红素血症 新生儿 病因 预后 随访

【摘要】：目的:黄疸是新生儿期常见的临床症状,生后2~3天出现,4~6天达到高峰。大部分黄疸可逐渐消退,但由于胆红素的毒性,少数患儿可出现严重高胆红素血症甚至引起胆红素脑病,遗留神经系统后遗症,对社会和家庭造成极大危害。从理论上讲,重度黄疸和胆红素脑病是完全可防、可控的,但经过我们近几十年的努力,二者尽管已很少见,但仍然发生[1]。对黄疸危害认识不足、重视不够、缺乏高效的随访措施,是造成重度黄疸及胆红素脑病的主要原因。由于人种、地区、环境的不同,新生儿黄疸的高峰期时间也有所不同。我国人口众多,医疗资源地区之间分布很不平衡,且亚洲人本身又是高胆红素血症的高危人群,更由于我国在新生儿黄疸领域研究的相对落后,特别是在黄疸流行病学资料方面的匮乏,缺乏大范围、多中心的流行病学资料[2],推测胆红素脑病和核黄疸的发生率高于西方国家[3]。总胆红素值TSB342μmol/L(20mg/d1)为重度高胆红素血症,TSB428μmol/L(25mg/d1)或513μmol/L(30mg/d1)为极重度高胆红素血症[4]。在某些情况下,血清总胆红素水平低于重度黄疸标准,却可能形成胆红素脑病,而极重度黄疸的健康足月儿却不一定会造成脑损伤,这与新生儿的日龄、健康状况等有关。新生儿生后血脑屏障的发育和胆红素水平是一个动态发育的过程,胎龄及日龄越小,出生体质量越低,血清总胆红素超过一定限度对新生儿造成脑损伤的可能性就越大,如同时伴有新生儿溶血病、窒息、酸中毒、败血症、高热、低体温、低蛋白血症、低血糖、G-6PD缺陷等高危因素,可使胆红素脑病发生几率增加,部分重度黄疸可有遗传基础[5],有学者发现在我国南部重度黄疸与胆红素尿苷二磷酸葡萄糖醛酸转移酶基因1A1(UGT1A1)突变有关[6]。为了尽快降低血清胆红素水平,我们可以采取多面冷光源强光疗、输注白蛋白、口服茵栀黄口服液及微生态制剂等保守治疗方法,而全血置换术亦是更加迅速减轻黄疸的方法,可快速置换出血液中的胆红素、抗体和致敏红细胞等有害物质,可最大程度减少和避免胆红素脑病的发生,但全血置换术系相对复杂的有创操作且存在潜在的输血风险,不少家长对此顾虑重重。许多血清总胆红素值达换血指征,但一般状况良好、且无明显合并症的重度黄疸患儿也只接受保守治疗,两种治疗方法的患儿预后究竟如何,还需要时间验证。本文即对河北省多中心足月儿重度黄疸的原因、治疗方法以及预后进行回顾性调查分析。方法:对2014年6月至2015年12月在河北省7家三级医院新生儿科住院治疗的474例重度黄疸患儿进行临床资料回顾性分析。入组标准:胎龄:37~41周,总胆红素342μmol/L,以未结合胆红素升高为主,出生体重2500g,除外应用耳毒性药物、颅内出血、颅内感染、窒息、中耳炎、家族性耳聋及颅脑先天发育异常者。应用表格的方式记录患儿的一般情况、父母职业、围产期高危因素、伴随疾病、胆红素峰值水平、治疗情况、临床转归等内容,以了解河北省地区重度高胆红素血症的病因、治疗方法,并利用标准化丹佛发育筛查试验(Denver Developmental Screening Test,DDST)于2015年12月份采用电话随访的方式,进行最长为期18个月随访,对患儿听力、智力、神经系统发育情况进行调查、评估。结果:1一般情况分析:2014年6月至2015年12月,7家医院共收集474例足月重度高胆红素血症病例,其中男275例,女199例,平均胎龄(38.41±1.71)周,平均出生体重(3306.9±450.4)g,平均入院日龄(6.08±1.49)d。474例患儿平均黄疸出现的时间(2.94±1.66)d;平均黄疸持续时间(4.52±3.77)d;剖宫产189例(39.8%),自然分娩285例(60.2%);平均TSB峰值(417.17±82.32)μmol/L,平均值B/A(0.78±0.15)(详见表一)。入院时有胆红素脑损伤表现者49例(10.3%),无胆红素脑损伤表现者425例(89.7%)。2黄疸病因分析:474例河北省地区重度黄疸患儿,病因以同族免疫性溶血为首(157例,33.1%),感染性因素占第2位(121例,29.5%),早发型母乳性黄疸占第3位(111例,占27.1%),晚发型母乳性黄疸占第4位(44例,9.2%)。3采用的治疗方法分析:本组474例重度黄疸患儿,65例接受了积极的全血置换术治疗(简称换血组),占13.7%,另409患儿接受了保守的内科治疗(简称常规组),占全部患儿的86.3%。对这两组患儿进一步分析显示:(1)换血组患儿入院平均日龄(3.95±3.09)d,小于常规组平均入院日龄(7.34±4.78)d,两组对比差异有统计学意义(P0.05)。(2)换血组患儿血清总胆红素峰值均值为(496.83±126.42)μmol/L,常规组为(404.00±64.22)μmol/L,换血组明显高于常规组,差异达到统计学意义(P0.05)。(3)换血组与常规治疗组在出生方式、出生体重、喂养方式、黄疸持续时间、黄疸出现时间、男女比例差异无统计学意义(P0.05)。(4)黄疸原因分析:474例河北省地区重度黄疸患儿,病因以同族免疫性溶血为首,其中换血组37例(56.9%),常规组120例(29.3%),换血组溶血病比例明显高于常规组,差异有统计学意义(P0.05);感染性因素占第2位,其中换血组22例(33.8%),常规组99例(24.2%),差异无统计学意义(P0.05);早发型母乳性黄疸占第3位,换血组仅有1例(1.5%),常规组共110例(46.8%)。(5)临床胆红素脑病患者百分比分析:换血组中入院时合并胆红素脑病48例(73.8%),常规组1例(0.24%),家属签字拒绝换血,要求常规治疗。4脑干听觉诱发电位(BAEP)检查结果:接受调查的7家医院中,仅有两家医院可行BAEP检查,共43例患儿行BAEP检查,其中换血组8例(18.60%),常规组35例(81.40%)。最后检出轻-中度听力异常29例,换血组有3例(37.50%),常规组有26例(74.29%),3~6个月复查上述29例患儿均恢复正常。重度听力异常3例,换血组2例(66.7%),常规组1例(33.3%),6个月复查听力时,听力均无改善。换血组2例(25%)确诊听力障碍,常规组1例(2.8%)确诊听力障碍,换血组明显高于常规组,差异有统计学意义(P0.05),目前听力障碍患儿均于专科医院接受听力训练。5头颅核磁检查结果:头颅核磁提示双侧苍白球T1WI或T2WI高信号改变视为异常。住院期间行头颅核磁检查,换血组异常20例(30.7%),常规组54例(13.2%),均提示苍白球T1WI高信号改变。3月后复查常规组有1例(1.8%)提示T2WI高信号,换血组有2例(10%)提示T2WI高信号,换血组异常比例高于常规组,差异有统计学意义(P0.05)。6治疗转归及电话随访结果:474例重度黄疸患儿,有1例患儿因住院期间换血治疗7小时后出现心跳骤停,急查电解质提示高钾血症,抢救无效,死亡。86例好转,签字出院,387例治愈,正常出院。473例均行电话随访,愿意接受电话调查351例(74.2%),拒绝调查13例(2.7%),无应答59例(12.4%),无效21例(4.4%),更换电话号码29例(6.1%),失访率为25.8%。评估DDST结果:换血组:可疑5例(7.6%),2例精细运动落后、2例大运动发育迟缓、1例语言发育落后;异常3例(4.6%),包括运动障碍1例,运动合并语言发育障碍2例。常规组:可疑3例(0.73%),这3例患儿住院期间一般状况良好,均无明显急性胆红素脑病表现,但随访时出现大运动、认知及语言发育迟缓;异常1例(0.24%),存在大运动、精细运动障碍。换血组中可疑及异常患儿比例均高于常规组,差异具有统计学意义(P0.05)。结论:1河北省地区足月儿重度黄疸采取换血治疗组总胆红素(496.83±126.42)μmol/L,常规组总胆红素(404.00±64.22)μmol/L,换血组明显高于常规组。2河北省地区足月儿重度黄疸原因常见于溶血病、感染、早发型母乳性黄疸。3换血组以溶血病为主,且平均日龄7天;常规治疗组中以母乳性黄疸为主,平均日龄7天。4丹佛发育筛查试验(DDST)电话随访结果提示换血组中可疑及异常患儿比例均高于常规组。对有胆红素脑病表现、达换血指征的重度黄疸患儿积极换血可减少或避免核黄疸的发生;对重度黄疸但一般状况良好的患儿,采取常规治疗可能增加核黄疸的发生率。
[Abstract]:Objective: the clinical symptoms of neonatal jaundice is a common, after 2~3 days, 4~6 days to reach the peak. Most jaundice gradually subsided, but due to the toxicity of bilirubin, a small number of children have severe hyperbilirubinemia and even cause bilirubin encephalopathy, any neurological sequelae caused great harm to society and family. In theory severe jaundice and bilirubin encephalopathy, is completely preventable and controllable, but after our decades of efforts, although the two have been rare, but still [1]. on jaundice awareness of harm is not enough, lack of follow-up measures, and is a major cause of severe jaundice and bilirubin encephalopathy. Because of race, region and the environment is different, the peak time of neonatal jaundice is also different. China has a large population, the distribution of medical resources between regions is not balanced, and Asians itself is hyperbilirubinemia People at high risk of disease, but because our country in the research field of neonatal jaundice is relatively backward, especially in the lack of epidemiological data of the lack of jaundice, large scale, multi center epidemiological data [2], speculated that the bilirubin encephalopathy and kernicteras incidence was higher than that of the western countries [3]. total bilirubin TSB342 mol/L (20mg/d1) for severe hyperbilirubinemia TSB428, mol/L (25mg/d1) or 513 mol/L (30mg/d1) [4]. for extremely severe hyperbilirubinemia in some cases, the serum total bilirubin level is lower than the standard but may form severe jaundice, bilirubin encephalopathy, and severe jaundice of full-term healthy infants will not cause brain damage, and the neonatal age. Health status. The blood brain barrier after birth and development of bilirubin is a dynamic development process, gestational age and age is smaller, more low birth body weight, serum total bilirubin The possibility was beyond a certain limit on neonatal brain injury caused by the greater, as with hemolytic disease, neonatal asphyxia, acidosis, sepsis, high fever, hypothermia, hypoproteinemia, hypoglycemia, G-6PD defects and other risk factors, the incidence of increased bilirubin encephalopathy, severe jaundice can have a genetic basis for [5] scholars found in Southern China with severe jaundice and bilirubin enzyme gene 1A1 two phosphate uridine glucuronyl transferase (UGT1A1) mutations in [6]. in order to reduce the serum bilirubin level as soon as possible, we can take a cold light source intensity phototherapy, albumin infusion, oral Yinzhihuang oral liquid and probiotics treatment method, and blood replacement operation is also more rapid relief of jaundice, rapid replacement of bilirubin in the blood, antibody and Zhi Minhong cells and other harmful substances, can reduce and avoid the maximum degree of bilirubin The occurrence of encephalopathy, but blood replacement system is relatively complex invasive operation and the potential risk of blood transfusion, many parents are full of worries. Many of the serum total bilirubin value of blood transfusion indications, but generally in good condition, and no obvious complications of severe jaundice only received conservative treatment, the prognosis of two treatment methods how, also need time to verify. This paper is on Hebei province center full-term infants with severe jaundice, treatment and prognosis were retrospectively analyzed. Methods: from June 2014 to December 2015 in Hebei Province 7 grade three hospital neonatal hospital treatment of 474 cases of severe jaundice were retrospectively analyzed in clinical data. Standard group: gestational age 37~41 weeks, total bilirubin of 342 mol/L, with unconjugated bilirubin increased, birth weight 2500g, except ototoxic drugs, intracranial hemorrhage, intracranial infection. Interest, otitis media, familial deafness and head congenital dysplasia. In general, recorded in the application form of parental occupation, perinatal risk factors, comorbidities, the peak level of bilirubin, treatment, content of clinical outcomes, to understand the etiology of severe hyperbilirubinemia in Hebei province area of treatment, and the use of standard Denver developmental screening test (Denver Developmental Screening Test, DDST) in 2015 December by telephone follow-up, for a maximum period of 18 months of follow-up, the intelligence of children with hearing, investigation, development, neurological evaluation. Results: analysis of 1 general situation: from June 2014 to December 2015, 7 hospitals were collected in 474 cases in case of severe hyperbilirubinemia, male 275 cases, female 199 cases, mean gestational age (38.41 + 1.71) weeks, the average birth weight (3306.9 + 450.4) g, the average hospitalization days of age (6.08 + 1.4 9)d.474渚嬫偅鍎垮钩鍧囬粍鐤稿嚭鐜扮殑鏃堕棿(2.94卤1.66)d;骞冲潎榛勭柛鎸佺画鏃堕棿(4.52卤3.77)d;鍓栧��浜，

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