新生儿高胆红素血症的病因调查及相关基因研究
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摘要
第一部分新生儿高胆红素血症病因的多中心调查
目的：对我国不同地区三家医院的新生儿高胆红素血症病例进行多中心调查,了解新生儿高胆红素血症的病因,分析不同地区间的差异。方法：选取上海、广西、四川三个省/市/自治区进行多中心流行病学调查,每个地区选一家具备新生儿高胆救治技术和相关检查的三级甲等医院,分别为上海复旦大学附属儿科医院、广西自治区妇幼保健院、四川省妇幼保健院。登记在2010年8月～2011年7月间,所有因新生儿高胆红素血症或新生儿黄疸收治该院新生儿病房和新生儿重症监护室以及在新生儿科住院期间发生高胆的孕周大于等于34周晚期早产和足月患儿。统计分析所有病例高胆红素血症的病因及临床基本资料。
结果：三家医院共收集病例1103例,病例数分别为534例、238例、331例。所有1103例患儿按病因归类排序如下,因单纯溶血性疾病发生高胆患儿249例(22.57%)、不明原因220例(19.95%)、混合原因149例(13.51%)、其它原因128例(11.6%)、感染性病因110例(9.97%)、喂养不足或异常体重下降92例(8.34%)、母乳性91例(8.25%)、出血性病因37例(3.35%)、红细胞增多症9例(0.82%)、胎粪延迟排出9例(0.82%)、甲状腺功能异常9例(0.82%)。各单一病因分析排名前三位依次为溶血性、不明原因、感染性,病例数分别为溶血性299(27.11%)、不明原因220(19.95%)、感染性158(14.32%)。合并胆红素脑病的重症患儿在所有新生儿高胆患儿中占1.63%(18/1103),包括四川妇保2例,广西妇保8例,上海儿科医院8例,各地合并胆红素脑病患儿的高胆病因亦有所不同。三个地区病例临床资料比较,出生体重、入院年龄、入院体重、黄疸发生时间、血清总胆、血清直胆、血色素、网织红细胞百分比等均有差异(组间差异P<0.05-0.001),三个地区间两两比较显示差异主要表现为广西地区出生体重和入院体重小于另两个地区、广西地区入院年龄和黄疸发生时间早于另两个地区、广西患儿入院血色素低于而网织红细胞高于另两组(组间差异P<0.05-0.001)。
结论：三个地区新生儿高胆红素血症病因调查示溶血性疾病、不明原因、混合病因是所有高胆患儿最主要的三个病因,多种病因同时作用即混合病因情况临床多见,不容忽视。不明原因高胆患儿占所有高胆病例的20%,值得进一步探讨研究。各地区高胆临床特征有所不同,这种不同可能与各地区高胆病因构成不同有关。
第二部分新生儿不明原因高胆红素血症葡萄糖醛酰转移酶相关基因的多中心研究
目的：对我国四个地区新生儿不明原因高胆红素血症病例进行UGT1A1基因序列测定,了解该基因突变与不明原因新生儿高胆红素血症的关系,分析各地区间的差异。
方法：2009年7月-2011年6月间,选取4个不同区域,分别为华东地区上海、华南地区广西、东北地区吉林和西北地区新疆,每个地区选取一家具备新生儿救治技术的三级甲等医院,分别为上海复旦大学附属儿科医院、广西自治区妇幼保健院、吉林大学第一医院、新疆医科大学第一医院。收集新生儿期不明原因的高未结合胆红素血症病例,病例收集遵循纳入标准和剔除标准。另在上海选取50例日龄2周以上未发生过病理性高胆红素血症足月新生儿作为对照组。对于符合入选条件患儿进行临床资料记录并采集患儿静脉血标本,血标本按要求保存收集后统一进行DNA基因组提取,对UGT1A1基因所有5个外显子的全序列进行测序。
结果：共收集标本145例,根据纳入和剔除标准再次审核各地区收集病例的临床资料,排除27例存在临界值病因高胆患儿,符合要求病例共118例,按不同地区118例患儿分为华东、华南、北方(西北和东北地区病例较少合并入组为北方)三组。所有病例和对照组共发现8个位点的单核苷酸突变,通过组间卡方检验比较显示仅G71R位点突变在不明原因高胆组、病因明确高胆组和对照组间有显著差异P<0.001；三个不同地区的比较显示从南往北G71R等位基因频率逐渐增多,统计学分析华南地区和北方地区间G71R位点突变存在显著性差异P<0.01。不同地区不明原因高胆组之间在黄疸发生时间、生后开奶时间、入院时血清总胆值、血色素值等结果上存在显著组间差异,P<0.05-0.001：进而作G71R位点突变和不明原因高胆的发生时间及高胆程度的相关性分析,显示G71R位点突变与不明原因高胆发生时间存在相关性,G71R位点杂合子突变时P=0.0094, G71R位点纯合子突变时P=0.0499,但与高胆程度不存在相关性,P=0.526和0.399,均>0.05。母乳性黄疸和非母乳性黄疸患儿G71 R突变情况的分析中显示两组间无差异,P=0.725。
结论：UGT1A1基因中的G71R位点突变是我国部分地区新生儿期不明原因高胆红素血症的相关因素,各地区间该位点突变情况也有所不同。各地区不明原因高胆临床特征有所不同,这种不同可能与G71R位点突变情况在各地区的差异有关。G71R位点突变与不明原因高胆的发生时间存在相关性。
第三部分新生儿胆汁淤积的病因和临床特征分析
目的：总结新生儿胆汁淤积病例的病因和临床表现特征,分析早产儿和足月儿胆汁淤积的不同特点。方法：对2004年1月～2010年12月收住复旦大学儿科医院176例新生儿胆汁淤积病例进行回顾性分析。胆汁淤积诊断标准为总胆红素小于5mg/dL (85.5ummol/L)时,结合胆红素大于1mg/dL(17ummol/L),或总胆红素大于5mg/dL时,结合胆红素大于总胆红素20%。淤胆病因分为胃肠外营养相关胆汁淤积(PNAC)、感染、胆道疾病、先天畸形或染色体疾病、遗传代谢性疾病、其它和原因不明七大类。将所有患儿按出生孕周,分为足月儿组35例,早产儿组141例,观察两组在喂养、静脉营养使用、感染史、缺氧史等胆汁淤积相关因素,以及发病时间、总胆红素/结合胆红素水平、肝损情况、相关实验室指标等胆汁淤积临床特点的差异,并分析两组引起淤胆的病因和预后差异。
结果：35例足月儿淤胆病因中感染11例(31.4%)、胆道闭锁4例(11.4%)、先天畸形或染色体异常7例(20.0%)、遗传代谢性疾病3例(8.6%)、其它,包括缺氧和高胆后淤胆7例(20.0%)、不明原因3例(8.6%)。141例早产儿中达到PNAC诊断标准97例(68.8%),这97例PNAC早产儿平均出生孕周30+4(25“～36+2)周；另44例(31.2%)早产儿不符合PNAC诊断,平均孕周33+3(27-36+5)周。44例非PNAC早产儿中进一步病因分析,感染21例(14.9%)、胆道疾病3例(2.1%)、遗传代谢性疾病2例(1.4%)、其它包括高胆后淤胆、婴儿肝炎综合征、自身免疫性疾病(新生儿红斑狼疮)、乳糜胸共5例(3.6%)、原因不明13例(9.2%)。所有感染病例中除常见的细菌性、病毒性、真菌性感染外,新生儿梅毒最多共18例,占新生儿胆汁淤积总病人数的10.2%,其中足月儿4例,早产儿14例。早产儿组禁食、开奶、达到全量喂养时间均较足月儿组明显延长(组间差异P<0.001),使用静脉营养比例、时间及发生感染比例均高于足月儿组(组间差异P<0.05～0.001)：而足月儿发生淤胆、出现肝功能损害时间却较早产儿明显提前(组间差异P<0.05-0.001)。
结论：新生儿胆汁淤积病因繁多,其中早产儿PNAC病例逐年明显增多,但非PNAC胆汁淤积的病因更为复杂。有必要对住院新生儿进行常规筛查,早期发现淤胆,对明确淤胆患儿应尽早进行病因诊断,并长期随访。
Part One:A Multicenter Survey About The Etiology of Neonatal Hyperbilirubinemia
[Abstracts] Objectives:To understand the current situation of the etiology of neonatal hyperbilirubinemia in China, and compare the difference between different areas. Methods:Three tertiary neonatal wards with NICU from three provinces were selected. The data of all neonatal hyperbilirubinemia cases including new admission and inpatients with the gestational age from 34 weeks to term were collected by using a survey form during the period from Aug,2010 to July,2011. All data were analyzed after they had been rechecked by one medical staff to confirm the diagnosis of etiology for hyperbilirubinemia. Results:There were 1103 cases in total from all three areas, the separate number of the cases from different areas were 534,238 and 331. All the cases were classified as different etiologic categories, the percentage of each showed as 249/1103 (22.57%), unknown reasons 220/1103 (19.95%) combined reasons 149/1103 (13.51%), other reasons (such as prterm, LGA, infants of GDM, et al) 128/1103 (11.6%), infection diseases 110/1103 (9.97%), breast feeding related jaundice or excessive weight loss or insufficient intake 92 (8.34%), breast milk jaundice 91(8.25%), haemorrhage 37(3.35%)、polycythemia 9(0.82%), delay of meconium 9例(0.82%), thyroid function disorder 9 (0.82%)。The first three single etiological causes are hemolysis, unknown reason, and infection. The clinical features of three groups were different in BW, admission age, admission weight, onset time of jaundice, feeding pattern, feeding starting time, TB, DB, Hb, and Ret,.P<0.05～0.001. The most significant difference was between the south area and the other two areas. Conclusions:This multi-center survey showed the major causes of neonatal hyperbilirubinemia in China were hemolysis, unknown reason and infection. But some of the causes may work together as combined cause. There were about 20% of neonatal hyperbilirubinemia cases having unknown reason, which is interested to us for further investigation. The differences of clinical features between centers may also because of the etiologic difference.
Part Two:A Multicenter Study About UGT1A1 Gene In The Neonates With Unknown Reason Hyperbilirubinemia
[Abstracts] Objectives:To investigate the mutation of UGT1A1 in the neonates with unknown-reason hyperbilirubinemia. The DNA sequences of UGT1A1 were tested and analyzed. Methods:There were four different places in China involved in the study. The neonatal hyperbilirubinemia cases who have unknown causes were selected following the criteria of including and excluding.50 term babies without pathological jaundice during newborn period were enrolled as control group. The clinical history and venous blood sample were collected. The whole five exons sequences of UGT1A1 were tested and analyzed for all the individuals. Results: There were total of 145 cases enrolled, but only 118 cases were confirmed as unknown reason group, the rest 27 cases were separated as the group of hyperbilirubnemia with clear reason after history review by one single medical staff after all the data collected. The patients from two places were combined as one group because of the cases numbers, so three groups from east, south and north of China were defined. There were totally eight different site of mutations found, and the only one spot showing the statistical difference between all groups was G71R, P<0.001. The frequencies of allele G71R showed increasing from south to north area in China, the difference between north and south area was significant, P<0.01. The clinical features of the onset time, feeding starting time, the TB and DB level showed the differences between three groups, P<0.05～0.001. The statistical analysis between G71R mutation and time of jaundice presence and severity of hyperbilirubinemia showed the correlation between G71R mutation and the jaundice present time, P=0.0094 and P=0.0499. Conclusions:The mutation of UGT1A1 on G71R probably is the potential etiology of unknown-reason hyperbilirubinemia in part areas of China. The differences of G71R mutation between three areas may be related to the clinical features of cases from different areas. The time of jaundice presenting is related to the status of with or without G71R mutation in these patients.
Part Three:The Etiology and Clinical Features of Cholestasis in Neonates
[Abstracts] Objectives:To explore the etiology and clinical features of cholestasis in neonates, and find the difference between preterm and term infants.
Methods:A retrospective study was conducted for the cases of cholestasis during neonatal periods. A total of 176 cases from January 2004 to December 2010 were identified by the etiology as PNAC, infection, biliary tract disorders, congenital abnormalities and chromosomal disorders, metabolic diseases, others (prenatal hypoxia, post unconjugated hyperbilirubinemia, neonatal lupus, and congenital chylothorax) and unknown reason. They were also classified to term and preterm groups according to gestational age, the relative factors, such as feeding patterns, using of PN, infection and hypoxia history, and the clinical features, such as cholestasis onset age, bilirubin level, liver function, and outcome were compared between these two groups. Results:The etiology of 35 term infants was summarized as infection 11/35(31.4%), biliary tract disorders 4/35(11.4%), congenital abnormalities and chromosomal disorders 7/35(20.0%), metabolic diseases 3/35(8.6%), others 7/35(20.0%), unknown reason 3/35(8.6%). There were 97/141(68.8%) of PNAC in preterm infants, the average gestational age was 30+4 (25+3～36+2) weeks. And etiology of the rest 44 preterm cases without PNAC was infection 21/141(14.9%), biliary tract disorders 3/141(2.1%), metabolic diseases 2/141(1.4%), others 5/141(3.6%)、unknown reason 13/141(9.2%).The time of fasting, the age of starting feeding, the age of reaching to full feeding was longer than in preterm than term group (P<0.001). The preterm group had more PN and infection cases, and overall PN time was longer in this group (P<0.05～0.001). The term group presented cholestasis and liver function damage was earlier than preterm (P<0.05～0.001). Conclusions:The etiology of neonatal cholestasis is various, it may more complicated in term and non PNAC preterm infants. It is important to screen cholestasis in neonatal inpatients. Investigation of the basic etiology and long term follow up is necessary for the positive cases.
目的：对我国不同地区三家医院的新生儿高胆红素血症病例进行多中心调查,了解新生儿高胆红素血症的病因,分析不同地区间的差异。方法：选取上海、广西、四川三个省/市/自治区进行多中心流行病学调查,每个地区选一家具备新生儿高胆救治技术和相关检查的三级甲等医院,分别为上海复旦大学附属儿科医院、广西自治区妇幼保健院、四川省妇幼保健院。登记在2010年8月～2011年7月间,所有因新生儿高胆红素血症或新生儿黄疸收治该院新生儿病房和新生儿重症监护室以及在新生儿科住院期间发生高胆的孕周大于等于34周晚期早产和足月患儿。统计分析所有病例高胆红素血症的病因及临床基本资料。
结果：三家医院共收集病例1103例,病例数分别为534例、238例、331例。所有1103例患儿按病因归类排序如下,因单纯溶血性疾病发生高胆患儿249例(22.57%)、不明原因220例(19.95%)、混合原因149例(13.51%)、其它原因128例(11.6%)、感染性病因110例(9.97%)、喂养不足或异常体重下降92例(8.34%)、母乳性91例(8.25%)、出血性病因37例(3.35%)、红细胞增多症9例(0.82%)、胎粪延迟排出9例(0.82%)、甲状腺功能异常9例(0.82%)。各单一病因分析排名前三位依次为溶血性、不明原因、感染性,病例数分别为溶血性299(27.11%)、不明原因220(19.95%)、感染性158(14.32%)。合并胆红素脑病的重症患儿在所有新生儿高胆患儿中占1.63%(18/1103),包括四川妇保2例,广西妇保8例,上海儿科医院8例,各地合并胆红素脑病患儿的高胆病因亦有所不同。三个地区病例临床资料比较,出生体重、入院年龄、入院体重、黄疸发生时间、血清总胆、血清直胆、血色素、网织红细胞百分比等均有差异(组间差异P<0.05-0.001),三个地区间两两比较显示差异主要表现为广西地区出生体重和入院体重小于另两个地区、广西地区入院年龄和黄疸发生时间早于另两个地区、广西患儿入院血色素低于而网织红细胞高于另两组(组间差异P<0.05-0.001)。
结论：三个地区新生儿高胆红素血症病因调查示溶血性疾病、不明原因、混合病因是所有高胆患儿最主要的三个病因,多种病因同时作用即混合病因情况临床多见,不容忽视。不明原因高胆患儿占所有高胆病例的20%,值得进一步探讨研究。各地区高胆临床特征有所不同,这种不同可能与各地区高胆病因构成不同有关。
第二部分新生儿不明原因高胆红素血症葡萄糖醛酰转移酶相关基因的多中心研究
目的：对我国四个地区新生儿不明原因高胆红素血症病例进行UGT1A1基因序列测定,了解该基因突变与不明原因新生儿高胆红素血症的关系,分析各地区间的差异。
方法：2009年7月-2011年6月间,选取4个不同区域,分别为华东地区上海、华南地区广西、东北地区吉林和西北地区新疆,每个地区选取一家具备新生儿救治技术的三级甲等医院,分别为上海复旦大学附属儿科医院、广西自治区妇幼保健院、吉林大学第一医院、新疆医科大学第一医院。收集新生儿期不明原因的高未结合胆红素血症病例,病例收集遵循纳入标准和剔除标准。另在上海选取50例日龄2周以上未发生过病理性高胆红素血症足月新生儿作为对照组。对于符合入选条件患儿进行临床资料记录并采集患儿静脉血标本,血标本按要求保存收集后统一进行DNA基因组提取,对UGT1A1基因所有5个外显子的全序列进行测序。
结果：共收集标本145例,根据纳入和剔除标准再次审核各地区收集病例的临床资料,排除27例存在临界值病因高胆患儿,符合要求病例共118例,按不同地区118例患儿分为华东、华南、北方(西北和东北地区病例较少合并入组为北方)三组。所有病例和对照组共发现8个位点的单核苷酸突变,通过组间卡方检验比较显示仅G71R位点突变在不明原因高胆组、病因明确高胆组和对照组间有显著差异P<0.001；三个不同地区的比较显示从南往北G71R等位基因频率逐渐增多,统计学分析华南地区和北方地区间G71R位点突变存在显著性差异P<0.01。不同地区不明原因高胆组之间在黄疸发生时间、生后开奶时间、入院时血清总胆值、血色素值等结果上存在显著组间差异,P<0.05-0.001：进而作G71R位点突变和不明原因高胆的发生时间及高胆程度的相关性分析,显示G71R位点突变与不明原因高胆发生时间存在相关性,G71R位点杂合子突变时P=0.0094, G71R位点纯合子突变时P=0.0499,但与高胆程度不存在相关性,P=0.526和0.399,均>0.05。母乳性黄疸和非母乳性黄疸患儿G71 R突变情况的分析中显示两组间无差异,P=0.725。
结论：UGT1A1基因中的G71R位点突变是我国部分地区新生儿期不明原因高胆红素血症的相关因素,各地区间该位点突变情况也有所不同。各地区不明原因高胆临床特征有所不同,这种不同可能与G71R位点突变情况在各地区的差异有关。G71R位点突变与不明原因高胆的发生时间存在相关性。
第三部分新生儿胆汁淤积的病因和临床特征分析
目的：总结新生儿胆汁淤积病例的病因和临床表现特征,分析早产儿和足月儿胆汁淤积的不同特点。方法：对2004年1月～2010年12月收住复旦大学儿科医院176例新生儿胆汁淤积病例进行回顾性分析。胆汁淤积诊断标准为总胆红素小于5mg/dL (85.5ummol/L)时,结合胆红素大于1mg/dL(17ummol/L),或总胆红素大于5mg/dL时,结合胆红素大于总胆红素20%。淤胆病因分为胃肠外营养相关胆汁淤积(PNAC)、感染、胆道疾病、先天畸形或染色体疾病、遗传代谢性疾病、其它和原因不明七大类。将所有患儿按出生孕周,分为足月儿组35例,早产儿组141例,观察两组在喂养、静脉营养使用、感染史、缺氧史等胆汁淤积相关因素,以及发病时间、总胆红素/结合胆红素水平、肝损情况、相关实验室指标等胆汁淤积临床特点的差异,并分析两组引起淤胆的病因和预后差异。
结果：35例足月儿淤胆病因中感染11例(31.4%)、胆道闭锁4例(11.4%)、先天畸形或染色体异常7例(20.0%)、遗传代谢性疾病3例(8.6%)、其它,包括缺氧和高胆后淤胆7例(20.0%)、不明原因3例(8.6%)。141例早产儿中达到PNAC诊断标准97例(68.8%),这97例PNAC早产儿平均出生孕周30+4(25“～36+2)周；另44例(31.2%)早产儿不符合PNAC诊断,平均孕周33+3(27-36+5)周。44例非PNAC早产儿中进一步病因分析,感染21例(14.9%)、胆道疾病3例(2.1%)、遗传代谢性疾病2例(1.4%)、其它包括高胆后淤胆、婴儿肝炎综合征、自身免疫性疾病(新生儿红斑狼疮)、乳糜胸共5例(3.6%)、原因不明13例(9.2%)。所有感染病例中除常见的细菌性、病毒性、真菌性感染外,新生儿梅毒最多共18例,占新生儿胆汁淤积总病人数的10.2%,其中足月儿4例,早产儿14例。早产儿组禁食、开奶、达到全量喂养时间均较足月儿组明显延长(组间差异P<0.001),使用静脉营养比例、时间及发生感染比例均高于足月儿组(组间差异P<0.05～0.001)：而足月儿发生淤胆、出现肝功能损害时间却较早产儿明显提前(组间差异P<0.05-0.001)。
结论：新生儿胆汁淤积病因繁多,其中早产儿PNAC病例逐年明显增多,但非PNAC胆汁淤积的病因更为复杂。有必要对住院新生儿进行常规筛查,早期发现淤胆,对明确淤胆患儿应尽早进行病因诊断,并长期随访。
Part One:A Multicenter Survey About The Etiology of Neonatal Hyperbilirubinemia
[Abstracts] Objectives:To understand the current situation of the etiology of neonatal hyperbilirubinemia in China, and compare the difference between different areas. Methods:Three tertiary neonatal wards with NICU from three provinces were selected. The data of all neonatal hyperbilirubinemia cases including new admission and inpatients with the gestational age from 34 weeks to term were collected by using a survey form during the period from Aug,2010 to July,2011. All data were analyzed after they had been rechecked by one medical staff to confirm the diagnosis of etiology for hyperbilirubinemia. Results:There were 1103 cases in total from all three areas, the separate number of the cases from different areas were 534,238 and 331. All the cases were classified as different etiologic categories, the percentage of each showed as 249/1103 (22.57%), unknown reasons 220/1103 (19.95%) combined reasons 149/1103 (13.51%), other reasons (such as prterm, LGA, infants of GDM, et al) 128/1103 (11.6%), infection diseases 110/1103 (9.97%), breast feeding related jaundice or excessive weight loss or insufficient intake 92 (8.34%), breast milk jaundice 91(8.25%), haemorrhage 37(3.35%)、polycythemia 9(0.82%), delay of meconium 9例(0.82%), thyroid function disorder 9 (0.82%)。The first three single etiological causes are hemolysis, unknown reason, and infection. The clinical features of three groups were different in BW, admission age, admission weight, onset time of jaundice, feeding pattern, feeding starting time, TB, DB, Hb, and Ret,.P<0.05～0.001. The most significant difference was between the south area and the other two areas. Conclusions:This multi-center survey showed the major causes of neonatal hyperbilirubinemia in China were hemolysis, unknown reason and infection. But some of the causes may work together as combined cause. There were about 20% of neonatal hyperbilirubinemia cases having unknown reason, which is interested to us for further investigation. The differences of clinical features between centers may also because of the etiologic difference.
Part Two:A Multicenter Study About UGT1A1 Gene In The Neonates With Unknown Reason Hyperbilirubinemia
[Abstracts] Objectives:To investigate the mutation of UGT1A1 in the neonates with unknown-reason hyperbilirubinemia. The DNA sequences of UGT1A1 were tested and analyzed. Methods:There were four different places in China involved in the study. The neonatal hyperbilirubinemia cases who have unknown causes were selected following the criteria of including and excluding.50 term babies without pathological jaundice during newborn period were enrolled as control group. The clinical history and venous blood sample were collected. The whole five exons sequences of UGT1A1 were tested and analyzed for all the individuals. Results: There were total of 145 cases enrolled, but only 118 cases were confirmed as unknown reason group, the rest 27 cases were separated as the group of hyperbilirubnemia with clear reason after history review by one single medical staff after all the data collected. The patients from two places were combined as one group because of the cases numbers, so three groups from east, south and north of China were defined. There were totally eight different site of mutations found, and the only one spot showing the statistical difference between all groups was G71R, P<0.001. The frequencies of allele G71R showed increasing from south to north area in China, the difference between north and south area was significant, P<0.01. The clinical features of the onset time, feeding starting time, the TB and DB level showed the differences between three groups, P<0.05～0.001. The statistical analysis between G71R mutation and time of jaundice presence and severity of hyperbilirubinemia showed the correlation between G71R mutation and the jaundice present time, P=0.0094 and P=0.0499. Conclusions:The mutation of UGT1A1 on G71R probably is the potential etiology of unknown-reason hyperbilirubinemia in part areas of China. The differences of G71R mutation between three areas may be related to the clinical features of cases from different areas. The time of jaundice presenting is related to the status of with or without G71R mutation in these patients.
Part Three:The Etiology and Clinical Features of Cholestasis in Neonates
[Abstracts] Objectives:To explore the etiology and clinical features of cholestasis in neonates, and find the difference between preterm and term infants.
Methods:A retrospective study was conducted for the cases of cholestasis during neonatal periods. A total of 176 cases from January 2004 to December 2010 were identified by the etiology as PNAC, infection, biliary tract disorders, congenital abnormalities and chromosomal disorders, metabolic diseases, others (prenatal hypoxia, post unconjugated hyperbilirubinemia, neonatal lupus, and congenital chylothorax) and unknown reason. They were also classified to term and preterm groups according to gestational age, the relative factors, such as feeding patterns, using of PN, infection and hypoxia history, and the clinical features, such as cholestasis onset age, bilirubin level, liver function, and outcome were compared between these two groups. Results:The etiology of 35 term infants was summarized as infection 11/35(31.4%), biliary tract disorders 4/35(11.4%), congenital abnormalities and chromosomal disorders 7/35(20.0%), metabolic diseases 3/35(8.6%), others 7/35(20.0%), unknown reason 3/35(8.6%). There were 97/141(68.8%) of PNAC in preterm infants, the average gestational age was 30+4 (25+3～36+2) weeks. And etiology of the rest 44 preterm cases without PNAC was infection 21/141(14.9%), biliary tract disorders 3/141(2.1%), metabolic diseases 2/141(1.4%), others 5/141(3.6%)、unknown reason 13/141(9.2%).The time of fasting, the age of starting feeding, the age of reaching to full feeding was longer than in preterm than term group (P<0.001). The preterm group had more PN and infection cases, and overall PN time was longer in this group (P<0.05～0.001). The term group presented cholestasis and liver function damage was earlier than preterm (P<0.05～0.001). Conclusions:The etiology of neonatal cholestasis is various, it may more complicated in term and non PNAC preterm infants. It is important to screen cholestasis in neonatal inpatients. Investigation of the basic etiology and long term follow up is necessary for the positive cases.
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[9]. Ritter JK, Crawford JM, Owens IS. Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem 1991;266:1043-7.
[10]. Iyanagi T, Emi Y, Ikushiro S. Biochemical and molecular aspects of genetic disorders of bilirubin metabolism. Biochim Biophys Acta 1998; 1407:173-84.
[11]. Robertson KJ, Clarke D, Sutherland L, Wooster R, Coughtrie MW, Burchell B. Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome. J Inherit Metab Dis 1991;14:563-79.
[12]. Passon RG, Howard TA, Zimmerman SA, Schultz WH, Ware RE. Influence of bilirubin uridine diphosphate-glucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia. J Pediatr Hematol Oncol 2001;23:448-51.
[13]. Bock KW. Vertebrate UDP-glucuronosyltransferases:functional and evolutionary aspects. Biochem Pharmacol 2003;66:691-6.
[14]. van Es HH, Bout A, Liu J, et al. Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37. Cytogenet Cell Genet 1993;63:114-6.
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