Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

EFFECT OF OROTIC ACID UPON SERUM BILIRUBIN IN NEWBORN INFANTS WITH ERYTHROCYTE G-6-PD DEFICIENCY

Fifty mature male newborns with erythrocyte G-6-PD deficiency were used for a study con cerning the effectiveness of orotic acid in preventing severe hyperbilirubinemia. Twentyfive randomly selected neonates were given orotic acid (100 mg/kg/day) orally in two daily doses from their 1st to their 5th day of life. Twenty-five newborns were not treated According to these results orotic acid does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn babies' with erythrocyte G-6-PD deficiency. and served as controls. Six exchange transfusions were performed in the test group and six in the controls.     

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］     

(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.     

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.     

Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns

OBJECTIVE: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. RESULTS: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.     

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。     

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。     

新生儿小时胆红素百分位曲线图的制备及早期预测高胆红素血症的初步探讨

目的绘制新生儿胆红素百分位曲线图预测新生儿高胆红素血症的发生风险。方法选择2009年1~9月南京医科大学附属南京妇幼保健院出生的母婴同室和普通婴儿室胎龄≥35周且出生体重≥2 000 g的正常新生儿为研究对象,监测生后7 d经皮胆红素值(TCB),对TCB≥250μmol.L-1者测定微量血胆红素,以所得到的胆红素值数据绘制小时胆红素百分位曲线图。以小时胆红素百分位曲线图将出院前末次胆红素值转换至危险区域(低危:≤P40;中低危:~P75;中高危:~P95;高危:P95)。选取72 h内对应最高危区域的胆红素测定值作为预测指标,采用ROC曲线分析胆红素百分位曲线图对新生儿高胆红素血症的预测价值。结果4 462例新生儿的27 271个对应不同小时龄的胆红素值纳入分析。出院前有5.2%(233/4 462例)的新生儿在生后72 h内的胆红素水平处于高危区,其中48.9%(114/233例)的新生儿在出院后胆红素水平仍处于高危区,预测新生儿发生高胆红素血症的似然比为9.5,敏感度为26.7%,特异度为97.1%,患病率为48.9%;出院前共有23.2%(1 034/4 462例)的新生儿胆红素水平处于高危区和中高危区,预测新生儿发生高胆红素血症的敏感度为78.9%,特异度为82.5%;出院前有41.3%(1 845/4 462例)的新生儿胆红素水平处于低危区,其中无一例在出院后发生高胆红素血症,似然比为0,敏感度为100%,特异度为45.5%,患病率为0。出院前胆红素水平预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.870。胎龄与出院前胆红素水平相结合预测高胆红素血症发生风险的ROCAUC为0.908。结论用出院前小时胆红素水平预测新生儿高胆红素血症的发生风险是一种有效的方法,结合胎龄可提高预测的准确性。     

A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia

OBJECTIVE: To evaluate the effectiveness of fluid supplementation in decreasing the rate of exchange transfusion and the duration of phototherapy in term neonates with severe nonhemolytic hyperbilirubinemia. STUDY DESIGN: This was a randomized controlled trial conducted in a tertiary care referral unit in northern India. Seventy-four term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin > 18 mg/dL [308 micromol/L] to < 25 mg/dL [427 micromol/L]). The subjects were randomized to an "extra fluids" group (intravenous fluid supplementation for 8 hours and oral supplementation for the duration of phototherapy; n = 37) or a control group (n = 37). RESULTS: At inclusion, 54 infants (73%) had high serum osmolality, including 28 (75%) in the extra fluids group and 26 (70%) in the control group. The proportion of infants who underwent exchange transfusion was lower in the extra fluids group than in the control group: 6 (16%) versus 20 (54%)(P = .001; relative risk = 0.30; 95% confidence interval = 0.14 to 0.66). The duration of phototherapy was also shorter in the extra fluids group: 52 +/- 18 hours versus 73 +/- 31 hours (P = .004). CONCLUSION: Fluid supplementation in term neonates presenting with severe hyperbilirubinemia decreased the rate of exchange transfusion and duration of phototherapy.     

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。     

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.     

不同G-6-PD活性新生儿光疗致溶血机制及其预防

目的探讨不同G6PD活性新生儿光疗溶血机制及预防。方法将G6PD正常与缺陷光疗患儿随机分为维生素E干预组和对照组,测定比较超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)、总胆红素(TB)、血红蛋白(Hb)及光疗指数。结果光疗前G6PD缺陷组比正常组SOD和Hb低,ROS高;光疗中G6PD缺陷干预组比正常干预组SOD高,MDA低,光疗指数小,G6PD缺陷对照组比正常对照组ROS、MDA高,光疗指数大(各组比较均P<0.01或P<0.05)。光疗后G6PD缺陷对照组Hb下降,并比干预组低,G6PD正常两组Hb均下降,干预组比对照组高(各组比较均P<0.01或P<0.05)。结论光疗可致抗氧化能力下降,脂质过氧化损伤致G6PD缺陷光疗者溶血更突出,维生素E干预更有效。     

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study

Background

Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia.

Aims

To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia.

Study design

prospective, observational, multicenter.

Subjects

2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy.

Methods

All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin > 17 mg/dL or need for phototherapy.

Results

Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.     

(TA)n UGT 1A1 promoter polymorphism: a crucial factor in the pathophysiology of jaundice in G-6-PD deficient neonates

Increased heme catabolism has been reported in glucose-6-phosphate dehydrogenase (G-6-PD)-normal neonates who were also homozygous for (TA)7/(TA)7 (UGT1A1*28) uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT) promoter polymorphism (Gilbert syndrome). As G-6-PD deficiency is associated with increased hemolysis, we hypothesized that in G-6-PD-deficient neonates who also have the (TA)7/(TA)7 UGT promoter genotype, steady-state hemolysis would be even further increased. Male G-6-PD-deficient neonates were sampled for plasma total bilirubin (PTB), blood carboxyhemoglobin corrected for inhaled carbon monoxide in ambient air (COHbc) (an index of heme catabolism), and UGT (TA)n promoter genotype determination and compared with previously published G-6-PD-normal neonates. Although COHbc values were higher in the G-6-PD-deficient than in the G-6-PD-normal cohorts (0.97 +/- 0.32% of total Hb (tHb) versus 0.76 +/- 0.19% of tHb, p < 0.001), PTB values were similar (9.2 +/- 3.4 mg/dL versus 8.9 +/- 3.0 mg/dL, respectively, p = 0.3). Within the G-6-PD-deficient group, although COHbc values were alike between the three UGT promoter genotypes, PTB was higher in the (TA)7/(TA)7 homozygotes (11.1 +/- 4.0 mg/dL) compared with (TA)6/(TA)7 heterozygotes (9.1 +/- 3.2 mg/dL, p = 0.03) and wild-type (TA)6/(TA)6 homozygotes (8.8 +/- 3.4 mg/dL, p = 0.02). In the steady state, similar rates of hemolysis, but increased PTB in the G-6-PD- deficient, (TA)7/(TA)7 homozygotes, imply that (TA)7/(TA)7, homozygosity is central to increased PTB.     

Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates

The objective was to compare the contribution to perinatal bilirubinemia of hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD-deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of delivery (first sample) and on d 3 (second sample), were analyzed in relation to blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G-6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/- 0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p = 0.002. First sample COHbc and STB values did not correlate in either the G-6-PD-deficient or control groups, whereas second sample COHbc values correlated significantly with corresponding STB values in the control population only (r = 0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the variant UGT promoter among those with STB values > or =75th percentile than those <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p = 0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those infants with at least one variant UGT promoter allele, STB values were higher in the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56 microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between the G-6-PD-deficient and control groups, our data demonstrate changing and differing contributions of hemolysis and UGT promoter polymorphism to bilirubinemia during the first 3 d of life.     

新生儿高胆红素血症的风险预测

目的探讨一种无创性、按每小时计的经皮胆红素(TcB)百分位列线图,以预测新生儿高胆红素血症的发生风险。方法选择2010年1月至2010年3月出生、胎龄≥35周且出生体质量≥2 000 g的健康新生儿679例,测定其出生后152 h内的TcB值。将出生后68 h内对应最高危区域的胆红素测定值作为预测指标,利用以小时为单位的胆红素曲线图评估其高胆红素血症的危险度,利用诊断试验特征曲线(ROC曲线)分析胆红素百分位列线图预测高胆红素血症的发生风险。结果将679例新生儿7 482个对应不同小时龄的TcB值纳入分析。42例新生儿出生后68 h内的胆红素水平处于高危区,预测高胆红素血症的灵敏度为34.52%,特异度为97.82%;212例新生儿胆红素水平处于高危区和中高危区,预测高胆红素血症的灵敏度为80.95%,特异度为75.80%;213例新生儿胆红素水平处于低危区,预测高胆红素血症的灵敏度为98.81%,特异度为35.63%。以TcB百分位列线图危险区域表示的出院前胆红素水平预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.846;胎龄与出生68 h内的胆红素水平结合预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.857;出生后前3 d的生理性体质量下降与出院前胆红素水平结合预测高胆红素血症发生风险的AUC为0.859。结论根据新生儿出院前胆红素水平结合胎龄、出生后前3天的生理性体质量下降能简单而准确地预测新生儿高胆红素血症的发生风险。     

Normal serum bilirubin levels in the newborn and the effect of breast-feeding

We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well-baby nursery. The maximum serum bilirubin concentration exceeded 12.9 mg/dL (221 mumol/L) in 147 infants (6.1%), and these infants were compared with 147 randomly selected control infants with maximum serum bilirubin levels less than or equal to 12.9 mg/dL. In 66 infants (44.9%), we identified an apparent cause for the jaundice, but in 81 (55%), no cause was found. Of infants for whom no cause for hyperbilirubinemia was found, 82.7% were breast-fed v 46.9% in the control group (P less than .0001). Breast-feeding was significantly associated with hyperbilirubinemia, even in the first three days of life. The 95th percentile for bottle-fed infants is a serum bilirubin level of 11.4 mg/dL v 14.5 mg/dL for the breast-fed population, and the 97th percentiles are 12.4 and 14.8 mg/dL, respectively. Of the formula-fed infants, 2.24% had serum bilirubin levels greater than 12.9 mg/dL v 8.97% of breast-fed infants (P less than .000001). When compared with previous large studies, the incidence of "readily visible" jaundice (serum bilirubin level greater than 8 mg/dL) appears to be increasing. The dramatic increase in breast-feeding in the United States in the last 25 years may explain this observation. There is a strong association between breast-feeding and jaundice in the healthy newborn infant. Investigations for the cause of hyperbilirubinemia in healthy breast-fed infants may not be indicated unless the serum bilirubin level exceeds approximately 15 mg/dL, whereas in the bottle-fed infant, such investigations may be indicated if the serum bilirubin exceeds approximately 12 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)