本文關(guān)鍵詞：河北省多中心足月兒重度高膽紅素血癥病因、治療方法以及預(yù)后調(diào)查　出處：《河北醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 多中心 高膽紅素血癥 新生兒 病因 預(yù)后 隨訪

【摘要】：目的:黃疸是新生兒期常見的臨床癥狀,生后2~3天出現(xiàn),4~6天達(dá)到高峰。大部分黃疸可逐漸消退,但由于膽紅素的毒性,少數(shù)患兒可出現(xiàn)嚴(yán)重高膽紅素血癥甚至引起膽紅素腦病,遺留神經(jīng)系統(tǒng)后遺癥,對社會和家庭造成極大危害。從理論上講,重度黃疸和膽紅素腦病是完全可防、可控的,但經(jīng)過我們近幾十年的努力,二者盡管已很少見,但仍然發(fā)生[1]。對黃疸危害認(rèn)識不足、重視不夠、缺乏高效的隨訪措施,是造成重度黃疸及膽紅素腦病的主要原因。由于人種、地區(qū)、環(huán)境的不同,新生兒黃疸的高峰期時間也有所不同。我國人口眾多,醫(yī)療資源地區(qū)之間分布很不平衡,且亞洲人本身又是高膽紅素血癥的高危人群,更由于我國在新生兒黃疸領(lǐng)域研究的相對落后,特別是在黃疸流行病學(xué)資料方面的匱乏,缺乏大范圍、多中心的流行病學(xué)資料[2],推測膽紅素腦病和核黃疸的發(fā)生率高于西方國家[3]�？偰懠t素值TSB342μmol/L(20mg/d1)為重度高膽紅素血癥,TSB428μmol/L(25mg/d1)或513μmol/L(30mg/d1)為極重度高膽紅素血癥[4]。在某些情況下,血清總膽紅素水平低于重度黃疸標(biāo)準(zhǔn),卻可能形成膽紅素腦病,而極重度黃疸的健康足月兒卻不一定會造成腦損傷,這與新生兒的日齡、健康狀況等有關(guān)。新生兒生后血腦屏障的發(fā)育和膽紅素水平是一個動態(tài)發(fā)育的過程,胎齡及日齡越小,出生體質(zhì)量越低,血清總膽紅素超過一定限度對新生兒造成腦損傷的可能性就越大,如同時伴有新生兒溶血病、窒息、酸中毒、敗血癥、高熱、低體溫、低蛋白血癥、低血糖、G-6PD缺陷等高危因素,可使膽紅素腦病發(fā)生幾率增加,部分重度黃疸可有遺傳基礎(chǔ)[5],有學(xué)者發(fā)現(xiàn)在我國南部重度黃疸與膽紅素尿苷二磷酸葡萄糖醛酸轉(zhuǎn)移酶基因1A1(UGT1A1)突變有關(guān)[6]。為了盡快降低血清膽紅素水平,我們可以采取多面冷光源強(qiáng)光療、輸注白蛋白、口服茵梔黃口服液及微生態(tài)制劑等保守治療方法,而全血置換術(shù)亦是更加迅速減輕黃疸的方法,可快速置換出血液中的膽紅素、抗體和致敏紅細(xì)胞等有害物質(zhì),可最大程度減少和避免膽紅素腦病的發(fā)生,但全血置換術(shù)系相對復(fù)雜的有創(chuàng)操作且存在潛在的輸血風(fēng)險,不少家長對此顧慮重重。許多血清總膽紅素值達(dá)換血指征,但一般狀況良好、且無明顯合并癥的重度黃疸患兒也只接受保守治療,兩種治療方法的患兒預(yù)后究竟如何,還需要時間驗證。本文即對河北省多中心足月兒重度黃疸的原因、治療方法以及預(yù)后進(jìn)行回顧性調(diào)查分析。方法:對2014年6月至2015年12月在河北省7家三級醫(yī)院新生兒科住院治療的474例重度黃疸患兒進(jìn)行臨床資料回顧性分析。入組標(biāo)準(zhǔn):胎齡:37~41周,總膽紅素342μmol/L,以未結(jié)合膽紅素升高為主,出生體重2500g,除外應(yīng)用耳毒性藥物、顱內(nèi)出血、顱內(nèi)感染、窒息、中耳炎、家族性耳聾及顱腦先天發(fā)育異常者。應(yīng)用表格的方式記錄患兒的一般情況、父母職業(yè)、圍產(chǎn)期高危因素、伴隨疾病、膽紅素峰值水平、治療情況、臨床轉(zhuǎn)歸等內(nèi)容,以了解河北省地區(qū)重度高膽紅素血癥的病因、治療方法,并利用標(biāo)準(zhǔn)化丹佛發(fā)育篩查試驗(Denver Developmental Screening Test,DDST)于2015年12月份采用電話隨訪的方式,進(jìn)行最長為期18個月隨訪,對患兒聽力、智力、神經(jīng)系統(tǒng)發(fā)育情況進(jìn)行調(diào)查、評估。結(jié)果:1一般情況分析:2014年6月至2015年12月,7家醫(yī)院共收集474例足月重度高膽紅素血癥病例,其中男275例,女199例,平均胎齡(38.41±1.71)周,平均出生體重(3306.9±450.4)g,平均入院日齡(6.08±1.49)d。474例患兒平均黃疸出現(xiàn)的時間(2.94±1.66)d;平均黃疸持續(xù)時間(4.52±3.77)d;剖宮產(chǎn)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)(詳見表一)。入院時有膽紅素腦損傷表現(xiàn)者49例(10.3%),無膽紅素腦損傷表現(xiàn)者425例(89.7%)。2黃疸病因分析:474例河北省地區(qū)重度黃疸患兒,病因以同族免疫性溶血為首(157例,33.1%),感染性因素占第2位(121例,29.5%),早發(fā)型母乳性黃疸占第3位(111例,占27.1%),晚發(fā)型母乳性黃疸占第4位(44例,9.2%)。3采用的治療方法分析:本組474例重度黃疸患兒,65例接受了積極的全血置換術(shù)治療(簡稱換血組),占13.7%,另409患兒接受了保守的內(nèi)科治療(簡稱常規(guī)組),占全部患兒的86.3%。對這兩組患兒進(jìn)一步分析顯示:(1)換血組患兒入院平均日齡(3.95±3.09)d,小于常規(guī)組平均入院日齡(7.34±4.78)d,兩組對比差異有統(tǒng)計學(xué)意義(P0.05)。(2)換血組患兒血清總膽紅素峰值均值為(496.83±126.42)μmol/L,常規(guī)組為(404.00±64.22)μmol/L,換血組明顯高于常規(guī)組,差異達(dá)到統(tǒng)計學(xué)意義(P0.05)。(3)換血組與常規(guī)治療組在出生方式、出生體重、喂養(yǎng)方式、黃疸持續(xù)時間、黃疸出現(xiàn)時間、男女比例差異無統(tǒng)計學(xué)意義(P0.05)。(4)黃疸原因分析:474例河北省地區(qū)重度黃疸患兒,病因以同族免疫性溶血為首,其中換血組37例(56.9%),常規(guī)組120例(29.3%),換血組溶血病比例明顯高于常規(guī)組,差異有統(tǒng)計學(xué)意義(P0.05);感染性因素占第2位,其中換血組22例(33.8%),常規(guī)組99例(24.2%),差異無統(tǒng)計學(xué)意義(P0.05);早發(fā)型母乳性黃疸占第3位,換血組僅有1例(1.5%),常規(guī)組共110例(46.8%)。(5)臨床膽紅素腦病患者百分比分析:換血組中入院時合并膽紅素腦病48例(73.8%),常規(guī)組1例(0.24%),家屬簽字拒絕換血,要求常規(guī)治療。4腦干聽覺誘發(fā)電位(BAEP)檢查結(jié)果:接受調(diào)查的7家醫(yī)院中,僅有兩家醫(yī)院可行BAEP檢查,共43例患兒行BAEP檢查,其中換血組8例(18.60%),常規(guī)組35例(81.40%)。最后檢出輕-中度聽力異常29例,換血組有3例(37.50%),常規(guī)組有26例(74.29%),3~6個月復(fù)查上述29例患兒均恢復(fù)正常。重度聽力異常3例,換血組2例(66.7%),常規(guī)組1例(33.3%),6個月復(fù)查聽力時,聽力均無改善。換血組2例(25%)確診聽力障礙,常規(guī)組1例(2.8%)確診聽力障礙,換血組明顯高于常規(guī)組,差異有統(tǒng)計學(xué)意義(P0.05),目前聽力障礙患兒均于�？漆t(yī)院接受聽力訓(xùn)練。5頭顱核磁檢查結(jié)果:頭顱核磁提示雙側(cè)蒼白球T1WI或T2WI高信號改變視為異常。住院期間行頭顱核磁檢查,換血組異常20例(30.7%),常規(guī)組54例(13.2%),均提示蒼白球T1WI高信號改變。3月后復(fù)查常規(guī)組有1例(1.8%)提示T2WI高信號,換血組有2例(10%)提示T2WI高信號,換血組異常比例高于常規(guī)組,差異有統(tǒng)計學(xué)意義(P0.05)。6治療轉(zhuǎn)歸及電話隨訪結(jié)果:474例重度黃疸患兒,有1例患兒因住院期間換血治療7小時后出現(xiàn)心跳驟停,急查電解質(zhì)提示高鉀血癥,搶救無效,死亡。86例好轉(zhuǎn),簽字出院,387例治愈,正常出院。473例均行電話隨訪,愿意接受電話調(diào)查351例(74.2%),拒絕調(diào)查13例(2.7%),無應(yīng)答59例(12.4%),無效21例(4.4%),更換電話號碼29例(6.1%),失訪率為25.8%。評估DDST結(jié)果:換血組:可疑5例(7.6%),2例精細(xì)運(yùn)動落后、2例大運(yùn)動發(fā)育遲緩、1例語言發(fā)育落后;異常3例(4.6%),包括運(yùn)動障礙1例,運(yùn)動合并語言發(fā)育障礙2例。常規(guī)組:可疑3例(0.73%),這3例患兒住院期間一般狀況良好,均無明顯急性膽紅素腦病表現(xiàn),但隨訪時出現(xiàn)大運(yùn)動、認(rèn)知及語言發(fā)育遲緩;異常1例(0.24%),存在大運(yùn)動、精細(xì)運(yùn)動障礙。換血組中可疑及異�；純罕壤哂诔Ｒ�(guī)組,差異具有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:1河北省地區(qū)足月兒重度黃疸采取換血治療組總膽紅素(496.83±126.42)μmol/L,常規(guī)組總膽紅素(404.00±64.22)μmol/L,換血組明顯高于常規(guī)組。2河北省地區(qū)足月兒重度黃疸原因常見于溶血病、感染、早發(fā)型母乳性黃疸。3換血組以溶血病為主,且平均日齡7天;常規(guī)治療組中以母乳性黃疸為主,平均日齡7天。4丹佛發(fā)育篩查試驗(DDST)電話隨訪結(jié)果提示換血組中可疑及異�；純罕壤哂诔Ｒ�(guī)組。對有膽紅素腦病表現(xiàn)、達(dá)換血指征的重度黃疸患兒積極換血可減少或避免核黃疸的發(fā)生;對重度黃疸但一般狀況良好的患兒,采取常規(guī)治療可能增加核黃疸的發(fā)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?zhèn)ｅ効邈^鍧囬粍鐤稿嚭鐜扮殑鏃墮棿(2.94鹵1.66)d;騫沖潎榛勭柛鎸佺畫鏃墮棿(4.52鹵3.77)d;鍓栧浜，

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