遗传因素在广西新生儿高胆红素血症中的作用

目的探讨UGT1A1 G71R突变、OATP2A388G突变和G-6-PD缺乏对在广西新生儿高胆红素血症发病的作用。方法用四氮唑蓝定量法（NBT法）测定G-6-PD酶活性。聚合酶链反应-等位基因特异性寡核苷酸探针点杂交（PCR-ASO）法确定G71R基因型。限制性片段长度多态性分析（RFLP）检测A388G基因型。测定109例新生儿脐血的G-6-PD活性及G71R基因型,其中101例同时检测了A388G基因型。据G-6-PD活性及G71R或A388G基因型分组,分析UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏与足月新生儿高胆红素血症之间关系。结果G71R等位基因频率在G-6-PD缺乏组为22．03％,在G-6-PD正常组为28．00％。G-6-PD缺乏共存有G71R突变纯合子或杂合子的新生儿高胆红素血症发生率（95．50％）高于G-6-PD正常且G71R为野生型的新生儿（53．90％）,x^2=10．45,P=0．0012,前者发生高胆红素血症的机会比（95％可信区间）[OR（95％CI）]为18．00（2．12,152．9）。A388G等位基因频率在G-6-PD缺乏组为20．O％,在G-6-PD正常组为18．5％。G-6-PD缺乏共存有A388G突变新生儿的高胆红素血症发生率（90．0％）高于G-6-PD正常且A388G为野生型的新生）L（44．80％）,X2=10．39,P=0．0013,前者发生高胆红素血症的伽（95％CT）为11．08（2．15,56．48）。结论G71R突变与G-6-PD缺乏共存或A388G突变与G-6-PD缺乏共存对广西足月新生儿高胆红素血症的发生有协同作用。     

Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia

The variation rate within the coding region of UDP-glucuronosyl transferase 1A1 (UGT1A1) gene in Taiwan Chinese was found to be 29.3%. This study sought to determine whether that high variation rate of UGT1A1 gene is a risk factor for neonatal hyperbilirubinemia. The study subjects consisted of 123 newborn infants suffering from unconjugated hyperbilirubinemia who had no known risk factors for hyperbilirubinemia and 218 healthy control neonates. The promoter area, exons 1 to 4, coding region of exon 5, and the flanking intronic regions in UGT1A1 gene were determined by the PCR in all subjects. Wild UGT1A1 gene, variation in the promoter, variation at nucleotide 211, variation at nucleotide 1091, and compound heterozygous variation of UGT1A1 gene were found. The percentage of neonates with wild UGT1A1 gene and the percentage of neonates with variation at nucleotide 211 were significantly different between the study subjects and controls. The percentages with bilirubin >or=342 micro M (20.0 mg/dL) and with persistent hyperbilirubinemia in the subjects carrying homozygous variation at nucleotide 211 (Gly71Arg) were significantly higher than the neonates carrying wild type or other genotypes. In conclusion, this study has demonstrated that variation at nucleotide 211 of the UGT1A1 gene is a risk factor for the development of neonatal hyperbilirubinemia. Pediatricians should closely follow hyperbilirubinemic newborn infants who carry homozygous 211 G to A variation in UGT1A1 gene.     

Neonatal hyperbilirubinemia and Gly71Arg mutation of UGT1A1 gene: a Chinese case-control study followed by systematic review of existing evidence

Aim: To determine whether the UDP‐glucuronosyltransferase 1A1 gene (UGT1A1) Gly71Arg (211G>A) mutation is associated with neonatal hyperbilirubinemia. Methods: The study consisted of two parts. The case–control study included 112 hyperbilirubinemic infants and 105 control subjects from the Fifth People’s Hospital of Shenzhen. Polymerase chain reaction, restriction fragment length polymorphisms and agarose gel electrophoresis techniques were used to detect the UGT1A1 211G>A mutation. Meta‐analyses was performed to assess the association between neonatal hyperbilirubinemia and UGT1A1 211G>A. Results: Our case–control study revealed that the likelihood of developing neonatal hyperbilirubinemia was 2.65 times higher in the infants with the A allele in the UGT1A1 211G>A than in the infants with the G allele (95% CI, 1.60–4.39). Meta‐analyses (including data from our study) revealed that UGT1A1 211G>A is associated with an increased risk of neonatal hyperbilirubinemia [ odds ratio (OR), 2.37; 95% CI, 2.05–2.74]. In the subgroup analyses based on ethnicity, significantly elevated risks were found in Asian populations (OR, 2.45; 95% CI, 2.10–2.84), but no significant associations were present in Caucasian populations (OR, 1.54; 95% CI, 0.87–2.75). Conclusion: The UGT1A1 211G>A mutation is associated with neonatal hyperbilirubinemia in Asians, but not in Caucasians.     

Glucose-6-phosphate dehydrogenase deficiency and kernicterus of South-East anatolia

OBJECTIVE: We aimed to investigate the rate of kernicterus, and physical and laboratory examination findings in hyperbilirubinemic infants with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. MATERIALS AND METHODS: This study was carried out in the Dicle University Hospital Neonatal Intensive Care Unit between June 2005 and June 2006. Out of 56 male neonates who needed an exchange transfusion due to hyperbilirubinemia, 10 with G-6-PD deficiency were included in the study. Maternal age, gestational age, route of delivery, birth weight, age at the time of admission, and treatment and outcome were recorded. Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct Coomb test, complete blood count, blood smear, thyroid-stimulating hormone, T4, C-reactive protein, urine analysis, and G-6-PD level. RESULTS: Out of 56 male neonates requiring exchange transfusion, 10 had G-6-PD deficiency (18%). In G-6-PD deficient neonates, other factors known to cause hyperbilirubinemia were excluded. The mean gestational age and the mean maternal age was 38.2+/-1.0 weeks and 31.3+/-5.9 years, respectively. The mean bilirubin level was 42.1+/-13.7 mg/dL. Four patients required a second exchange transfusions, and only 1 transfusion was sufficient for the remaining patients. Five patients (55%) developed kernicterus. CONCLUSIONS: Early detection of G-6-PD deficiency in the affected newborns may be important for reducing the risk of severe hyperbilirubinemia, kernicterus, and the need for exchange transfusion.     

(TA)n UDP-glucuronosyltransferase 1A1 promoter polymorphism in Nigerian neonates

Nigerian neonates have a high incidence of bilirubin encephalopathy. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is prevalent in this population. (TA)7 promoter polymorphism in the gene encoding the bilirubin conjugating enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) potentiates hyperbilirubinemia in G-6-PD deficient neonates. We studied (TA)n allele frequency to determine, at least in part, its contribution to the frequency and severity of hyperbilirubinemia. DNA was extracted from umbilical cord blood of sequentially born Nigerian neonates and the (TA)n UGT1A1 promoter sequence determined. The (TA)n allele distribution was compared with reported adults of varying African ancestry and Sephardic Jewish neonates. Among 88 Nigerian neonates, (TA)6 and (TA)7 alleles were almost equally distributed (0.46 and 0.43, respectively). Some individuals with (TA)5 and (TA)8 sequences were encountered. Allele distribution was similar to that of the African ancestry population but differed from the Sephardic Jewish newborns, in whom the (TA)6/(TA)7 distribution was 0.65/0.35. Whereas 45% of Nigerian alleles and 50% of African ancestry alleles, respectively, included a (TA)7 or (TA)8 sequence, only 35% of Jewish alleles were (TA)7 (p < 0.001), and no (TA)8 alleles were encountered. The high frequency of (TA)n promoter polymorphism, coupled with G-6-PD deficiency, may contribute to the pathogenesis of extreme neonatal hyperbilirubinemia in Nigeria.     

G-6-PD缺陷与新生儿高胆、婴幼儿贫血及婴儿肝炎综合征关系的调查

广西是我国Ｇ－６－ＰＤ缺陷高发区。Ｇ－６－ＰＤ缺陷发病的主要表现为急慢性溶血性贫血和由此而产生的高间胆红素血症及胆汁郁积。近十年我院门诊及病房４４０例患儿：２３７例新生儿高间胆包括核黄症后遗症患儿。Ｇ－６－ＰＤ缺陷检出率达６９．６％，其中显著缺陷４３．９％（１０４／２３７），中间值２５．７％（６１／２３７）；１０３例３个月以下的婴儿贫血原因待查患儿，Ｇ－６－ＰＤ缺陷检出率达５９．２２％（３６／１０３）；１００例婴儿肝炎综合征患儿，Ｇ－６－ＰＤ缺陷检出率达１８％（１８／１００）。Ｇ－６－ＰＤ缺陷男女经例为２．３７：１。６７例进行家系调查，２８例Ｇ－６－ＰＤ缺陷男婴，母亲检出率为６７．８％（１８／２８）；１４例Ｇ－６－ＰＤ缺陷女婴，父亲检出率４３％（６／１４），母亲检出率５０％（７／１４）。说明了在我区Ｇ－６－ＰＤ缺陷是引起新生儿高间胆以及核黄痊后遗症、婴幼儿贫血较常见而且重要原因之一。     

Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia

Background: The aim of the present study was to compare, in a case–control study, the prevalence of nucleotide 211 guanine to adenine (G→A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 µmol/L during first 48 h of life or ≥300 µmol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia. Methods: Seventy‐four term infants of Chinese descent admitted with severe hyperbilirubinemia were recruited. Infants without severe hyperbilirubinemia (n = 125) were randomly selected from among healthy Chinese term infants. UGT1A1 nucleotide 211 polymorphism was assayed using the Taqman single nucleotide polymorphism genotyping method. Using gestational age, types of feeds, G6PD mutation, G6PD enzyme levels, and UGT1A1 gene mutation status as independent variables, logistic regression analysis was carried out to determine the significant risk factors associated with severe hyperbilirubinemia. Results: UGT1A1 gene mutation was significantly more common among hyperbilirubinemic infants (39.2%) than controls (25.6%; P = 0.04). Gestational age (adjusted odds ratio [OR], 0.7; 95% confidence intervals [CI]: 0.5–0.9; P = 0.01), G6PD mutation (adjusted OR, 7.2; 95%CI: 2.7–19.0; P < 0.0001), exclusive breast‐feeding (adjusted OR, 11.7; 95%CI: 2.7–49.9; P = 0.001), and homozygous variant of UGT1A1 gene mutation (adjusted OR, 32.2; 95%CI: 3.8–273.2; P = 0.001) were significant risk factors. Heterozygous variant of UGT1A1 gene mutation, actual levels of G6PD enzyme, and mixed feeding were not. Conclusion: Homozygous variant of nucleotide 211 G→A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns.     

211 G to a variation of UDP-glucuronosyl transferase 1A1 gene and neonatal breastfeeding jaundice

Breastfeeding jaundice is a common problem in neonates who were exclusively breastfed, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. We prospectively enrolled 688 near-term and term infants who were exclusively breastfed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than WTs (GG). This phenomenon was only seen in BF group but not in SF group when subset analysis was performed. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.     

UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关

目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因G71R突变与新生儿严重高胆红素血症的相关性。方法采用病例对照研究的方法,病例组为复旦大学附属儿科医院(我院)收治的不明原因严重高胆红素血症(血清总胆红素水平≥342μmol·L-1)新生儿,采用PCR对外周血UGT1A1基因进行检测。对照组为我院新生儿出生缺陷生物样本数据库中血清总胆红素水平221μmol·L-1病例。病例组及对照组新生儿均要求胎龄≥35周,出生体重≥2 500 g。结果病例组和对照组各65例。UGT1A1 G71R是病例组中最常见的突变类型(73.8%,48/65)。对照组UGT1A1 G71R突变位点与既往Meta分析中提取的中国健康新生儿对比,在基因型分布及等位基因频率上差异均无统计学意义(P0.05)。病例组和对照组UGT1A1基因G71R突变中A等位基因频率分别为0.5和0.15,差异有统计学意义(P0.001),把握度为0.993。与携带G/G基因型新生儿相比,UGT1A1 G71R突变(A/A+G/A基因)可增加新生儿严重高胆红素血症的发病风险(OR=7.373,95%CI:3.395~16.008),把握度为1.0。结论 UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关。     

Neonatal screening for Glucose-6-Phosphate dehydrogenase deficiency

Objective : This study was carried out to detect the incidence of erythrocytic Glucose-6-Phosphate dehydrogenase (G-6-PD) deficiency, to compare the incidence of hyperbilirubinernia in G-6-PD deficient neonates as compared to G-6-PD normal neonates and to asses the usefulness of neonatal screening for G-6-PD deficiency.Method : In a retrospective hospital based study 2,479 male and female neonates consecutively born at Indraprastha Apollo hospital between July 1998 to June 2003 who were screened for G-6-PD levels were evaluated for the incidence of G-6-PD deficiency.Results : Incidence of G-6-PD deficiency was found to be 2.0%. Incidence in males was 283% and femle was 1.05%. The incidence of hyperbilirubinemia was found to be 32% in G-6-PD deficient neonates which was significantly higher than the incidence of hyperbilirubinemia in neonates with normal G-6-PD, which was 12.3% (P<0.001).Conclusion : Our data suggests that neonatal screening for G-6-PD deficiency is a useful test for preventing and early treatment of complications associated with it.     

β-Thalassemia trait and hyperbilirubinemia in G-6-PD deficient newborn infants

Hb A₂ was determined in 50 subjects with erythrocyte G-6-PD deficiency who presented with hyperbilirubinemia in the neonatal period and in 100 non-hyperbilirubinemic G-6-PD deficient newborn infants, at the age of 12 months or more. Six subjects in the first group and 13 in the second were found to be carriers of the -thalassemia trait. Statistical analysis of the data did not show any significant difference between the two groups. It seems that the -thalassemia trait does not provide any protection against neonatal hyperbilirubinemia associated with G-6-PD deficiency.     

Risk factors for severe hyperbilirubinemia in neonates

The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels > or =342 microM and <256.5 microM, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios (ORs) of 4.64 [95% confidence interval (CI): 2.25-9.57; p < 0.001], 3.36 (95% CI: 1.54-7.35; p=0.002), and 3.02 (95% CI: 1.30-6.99; p=0.010) for neonates who were fed with breast milk, and carry the variant UGT1A1 gene at nucleotide 211 and the variant OATP 2 gene at nucleotide 388, respectively. The ORs, adjusted for covariates, for the other six risk factors were not statistically significant. The ORs in neonates who had one, two, and three significant risk factors were 8.46 (95% CI: 2.75-34.48; p < 0.001), 22.0 (95% CI: 5.50-88.0; p < 0.001), and 88.0 (95% CI: 12.50-642.50; p < 0.001), respectively. In conclusion, neonates who carry the 211 and 388 variants in the UGT1A1 and OATP 2 genes, respectively, as well as feed with breast milk are at high risk to develop severe hyperbilirubinemia.     

The impact of SLCO1B1 genetic polymorphisms on neonatal hyperbilirubinemia: a systematic review with meta-analysis

ObjectiveTo determine whether three variants (388 G>A, 521 T>C, and 463 C>A) of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) are associated with neonatal hyperbilirubinemia.Data sourceThe China National Knowledge Infrastructure and MEDLINE databases were searched. The systematic review with meta-analysis included genetic studies which assessed the association between neonatal hyperbilirubinemia and 388 G>A, 521 T>C, and 463 C>A variants of SLCO1B1 between January of 1980 and December of 2012. Data selection and extraction were performed independently by two reviewers.Summary of the findingsTen articles were included in the study. The results revealed that SLCO1B1 388 G>A is associated with an increased risk of neonatal hyperbilirubinemia (OR, 1.39; 95% CI, 1.07–1.82) in Chinese neonates, but not in white, Thai, Latin American, or Malaysian neonates. The SLCO1B1 521 T>C mutation showed a low risk of neonatal hyperbilirubinemia in Chinese neonates, while no significant associations were found in Brazilian, white, Asian, Thai, and Malaysian neonates. There were no significant differences in SLCO1B1 463 C>A between the hyperbilirubinemia and the control group.ConclusionThis study demonstrated that the 388 G>A mutation of the SLCO1B1 gene is a risk factor for developing neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations; the SLCO1B1 521 T>C mutation provides protection for neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations.     

Cord plasma alpha-fetoprotein values and neonatal jaundice

Umbilical cord plasma alpha-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean alpha-fetoprotein value of 173 +/- 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 +/- 21.7 mg/L) for the control infants (P less than .001). G-6-PD status and sex did not significantly affect the alpha-fetoprotein values. Using an alpha-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.     

广西南宁地区G6PD基因突变与新生儿黄疸的关系

目的：分析本地区最常见的三种基因突变型G1388A、G1376T和A95G与葡萄糖-6-磷酸脱氢酶（G-6-PD）活性之间的相关性,并探讨G-6-PD基因突变对新生儿黄疸的影响。方法：124例广西南宁的高胆红素血症新生儿为研究对象。应用突变特异性扩增系统法检测G-6-PD基因突变,应用硝基四氮唑蓝（NBT）定量法检测G-6-PD活性。比较G-6-PD不同基因突变型之间以及与正常组之间胆红素脑病发生率、出生72 h后血清胆红素峰值组间的差异。采用非条件logistic回归分析血清胆红素值>340 μmol/L的危险度。结果：124例中有37例G-6-PD 基因突变（G1388A 20例,G1376T 14例,A95G 4例,1例同时存在G1388A与A95G突变）。20例G1388A突变者中5例（25%）G-6-PD酶活性正常,14例G1376T突变者中4例（29%）G-6-PD酶活性正常,4例A95G突变者G-6-PD 酶活性均缺乏。G1388A与G1376T组胆红素脑病发生率及出生72 h后血清胆红素峰值差异无显著性。G-6-PD 突变组出生72 h后血清胆红素峰值、胆红素脑病发生率及血清胆红素>340 μmol/L的危险度与G-6-PD正常组相比,差异无显著性。结论：广西南宁地区G-6-PD突变仍常见G1388A、G1376T和A95G基因型。NBT法诊断G-6-PD缺乏存在假阴性。不同基因型对出生72 h后血清胆红素峰值、胆红素脑病发生率的影响无差异。单独的G-6-PD基因突变对生后72 h血清胆红素峰值、急性胆红素脑病发生率及血清胆红素大于340 μmol/L危险性均无影响。［中国当代儿科杂志,2009,11（12）：970-972］     

Agar in control of hyperbilirubinemia of full-term newborn infants with erythrocyte G-6-PD deficiency.

40 full-term newborn infants with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were used for a study concerning the effectiveness of agar per os in preventing severe hyperbilirubinemia. 20 randomly selected neonates were given agar (1 g/kg/day) orally in 4 daily doses from their 1st to their 5th day of life. 20 infants were not treated and served as controls. Three exchange transfusions were performed in the experimental as well as in the control group. According to these results, agar does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn infants with erythrocyte G-6-PD deficiency.     

新生儿高胆红素血症再入院的现状和危险因素分析

目的 探讨新生儿高胆红素血症再入院情况及相关危险因素。方法 选择2017年1月至2019年12月新生儿高胆红素血症再入院患儿85例作为研究组,按1：2比例在同期新生儿高胆红素血症未再入院病例中配对随机选取170例作为对照组,分析比较两组患儿的临床资料及再入院的危险因素。结果 研究期间新生儿高胆红素血症再入院率为2.30%,中位再入院间隔天数为5 d。研究组首次出院时总胆红素和间接胆红素水平明显高于对照组（P < 0.05）;首次住院期间蓝光治疗时间长于对照组（P < 0.05）。研究组出生体重、胎龄、首次入院时年龄均低于对照组（P < 0.05）,研究组合并葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏症比例和合并溶血病比例高于对照组（P < 0.05）。多因素logsitic分析显示,胎龄小、首次入院时年龄小、合并G-6-PD缺乏症是新生儿高胆红素血症再入院的危险因素（分别OR=1.792、1.415、2.829,P < 0.05）。结论 对存在胎龄小、首次入院时年龄小、合并G-6-PD缺乏症等高危因素的高胆红素血症新生儿,应加强住院及出院后管理,防止该病再入院的发生。     

Cord blood bilirubin level in relation to bilirubin UDP-glucuronosyltransferase gene missense allele in Chinese neonates

AIM: To investigate bilirubin UDP-glucuronosyltransferase (UGT1A1) gene allele in healthy Chinese neonates, their cord bilirubin level and the subsequent hyperbilirubinemia to determine relationships among them. METHODS: Cord blood of 48 neonates was obtained to determine the exon 1 of UGT1A1 gene, total serum bilirubin, albumin, glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT) and haemoglobin (Hb) concentration. Neonatal jaundice was assessed by measurement of transcutaneous bilirubin (TCB) and serum bilirubin. Neonates were divided into two groups according to mutant or normal allele to compare the variables. RESULTS: Nineteen infants had the nucleotide 211 G-->A allele, 3 had the heterozygous variation (686C-->A, 845 A-->T, 231G-->A). In the 211 A allele group, cord bilirubin was significantly higher than in the 211 G allele group (p = 0.034), but there were no differences in albumin (p = 0.678), GPT (p = 0.460), GOT (p = 0.440) and Hb (p = 0.886). The TCB (at 48, 96 h), the frequency of the hyperbilirubinemia and prolonged jaundice were also significantly higher in the 211 A allele group. CONCLUSIONS: The UGT1A1 gene codon G71R allele is a risk factor for neonatal hyperbilirubinemia in the Chinese population. Its effect on bilirubin metabolism may present early on, as well as late in foetal life.     

Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5'-diphosphate-glucuronosyltransferase gene

Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbilirubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) from two leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic response. We isolated genomic DNA from peripheral blood samples and amplified UGT1A1 by polymerase chain reaction. The amplified DNA fragments were analyzed by direct sequencing. The genes of the two patients revealed an identical heterozygous missense mutation in exon 1 (211G-->A: G71R). This UGT1A1 mutation may be the basis of chemotherapy-induced unconjugated hyperbilirubinemia.     

Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency

OBJECTIVE: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. STUDY DESIGN: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age /=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram. RESULTS: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). CONCLUSIONS: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.