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.     

Multiple dose IVIG treatment in neonatal immune hemolytic jaundice

Isoimmune hemolytic jaundice due to ABO and Rh blood group incompatibility is an important problem in the neonatal period. Intravenous immune globulin (IVIG) treatment in isoimmune jaundice has been shown to be effective, but the response to treatment is variable. In this study, the effect of multiple doses IVIG therapy versus single dose MG therapy was investigated in 61 babies who had ABO and Rh hemolytic disease. Patients were divided into three groups. Group I received multiple dose IVIG treatment, group II received single dose MG treatment, and group III was not given any IVIG. All three groups received phototherapy. No exchange transfusion was needed in group I. The rate of exchange transfusion was 12 per cent in group II and 33 per cent in group III. Duration of phototherapy was shorter in group I than in groups II and III. It was concluded that IVIG treatment reduces the need of exchange transfusion in neonatal isoimmune hemolytic jaundice by lowering hemolysis. Multiple doses IVIG treatment appears to be better at blocking ongoing hemolysis.     

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。     

Exchange transfusion in neonatal hyperbilirubinemia

Four hundred and thirty three exchange transfusions (ET) for neonatal hyperbilirubinemia in 225 full term (Group I) and 110 premature/low birth weight (Group II) babies were analyzed. A total of 78.5% cases required one, 15.22% two, 4.8% three and 1.5% four ET. In Group I ABO HDN (35.94%), Rh HDN (10.7%), septicemia (8.9%), and G-6-PD deficiency (6.2%) were the major causes. Nearly 20% had multiple factors and in 9.3% no cause was identified. In multifactorial cases 13.3% had septicemia, 17.3% ABO HDN and 6.2% Rh HDN in various combinations. Common causes in Group II babies were septicemia (20.9%), ABO HDN (19.07%), Rh HDN (6.4%) and G-6-PD deficiency (5.4%). Nearly 8% had multifactorial etiology while 30.9% were idiopathic. Complications occurred in 20.4% Group I and 41.8% in Group II babies during ET. Procedure related mortality was 3.2/100 ET which declined to 0.9/100 ET when high risk babies were excluded. Overall mortality in babies subjected to ET was 10.6/100 ET. Cardiorespiratory arrest during procedure (30.4%), septicemia (26.1%) and kernicterus (19.6%) were the leading causes of death. Anemia (23.5% Group I and 50.9% Group II babies) and clinical septicemia (14.2% Group I and 16.4% Group II babies) were major delayed complications.     

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)     

Carboxyhemoglobin Measurements in the Diagnosis of ABO Hemolytic Disease

To assess hemolysis in hyperbilirubinemic infants with ABO isoimmunization, we measured the carboxyhemoglobin (HbCO) concentrations in full-term infants with ABO isoimmunization during the first week of life. Two groups of infants, ABO compatible (n=34) and ABO incompatible (n=30), were further divided into two groups with and without hyperbilirubi-nemia. All the infants from ABO incompatible pregnancies showed a positive indirect Coombs' test. The groups with hyperbilirubinemia included infants with maximum serum total bilirubin levels about 15 mg/dL and infants treated by phototherapy or exchange transfusion. In the ABO incompatible infants, the HbCO levels in those with hyperbilirubinemia were significantly higher than in infants without hyperbilirubinemia during the first week after birth (p < 0.01 at 24, 72, 120 hours after birth, respectively). The levels of HbCO in the ABO incompatible infants with hyperbilirubinemia were significantly higher compared with the levels in the ABO compatible infants with hyperbilirubinemia (p < 0.05 at 24 hours, p < 0.01 at 72 and 120 hours after birth, respectively). HbCO measurement may facilitate the early diagnosis of hemolytic disease and the prediction of jaundice caused by ABO isoimmunization.     

Hemolytic Disease of the Newborn- Anti c Antibody Induced Hemolysis

Hemolytic disease in the newborn, as a cause of early jaundice, is not uncommon. This is mostly due to Rh (D), ABO incompatibility and rarely due to other minor blood group incompatibility. The authors report two cases of Rh anti c isoimmunization presenting as significant early neonatal jaundice within the 20 h of life. Both the babies were treated with intensive phototherapy. One baby underwent exchange transfusion and the other required packed cell transfusion for anemia.     

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。     

Hemolytic disease of the newborn due to isoimmunization with anti-E antibodies: a case report

Minor blood group hemolytic disease is extremely rare, since the overall potency of minor blood groups in inducing antibodies is significantly lower when compared with that of Rh (D) antigen. We hereby report a very rare case of severe neonatal anti-E hemolytic disease due to E minor blood group incompatibility. A term newborn born to a 27-year-old, gravida 3, para 3 mother was referred due to a high and increasing serum bilirubin level despite phototherapy on the 4th day of life. On admission physical examination was normal except for the jaundice, and results of the laboratory investigation demonstrated a moderate-to-severe anemia (hemoglobin 7.8 g/dl) and a severe hemolytic hyperbilirubinemia (serum total and indirect bilirubin levels 36 mg/ dl and 32.8 mg/dl, respectively; reticulocyte count 15%; and a positive direct antiglobulin test). As there was no apparent cause of the hemolytic disease such as Rh or ABO incompatibilities, further investigation (a positive indirect antiglobulin test and a positive irregular anti-E antibody in both the patient and mother, and minor blood group antigen profiles in family members compatible with E minor blood group isoimmunization) revealed the presence of anti-E hemolytic disease due to E minor blood group incompatibility. Two exchange transfusions with a 12-hour-interval were performed with minor blood group compatible fresh whole blood, and the patient was discharged in a healthy condition on the 10th postnatal day. If the most common causes of severe neonatal hemolytic disease such as Rh and ABO incompatibilities cannot be demonstrated in a newborn with significant hemolytic hyperbilirubinemia, anti-E hemolytic disease should strongly be considered in differential diagnosis. It should be kept in mind that a very severe from of minor group antibody hemolytic disease characterized by anemia and severe hyperbilirubinemia many exchange transfusions may be encountered during the course of the disease.     

同型血外周动静脉同步换血对不同病因高胆红素血症的疗效对比研究

目的探讨同型血外周动静脉同步换血对不同病因所致高胆红素血症的疗效。方法对不同病因高胆红素血症患儿均采用同型血外周动静脉同步换血,换血前后行血常规、生化、胆红素、血培养等检查。结果不同病因的高胆红素血症患儿换血前后胆红素对比均有显著降低（Ｐ＜００１）,总胆红素换出率分别是３７８２％、４５５２％和４８４１％,平均换出率是４２６２％。在体重、输入量和换出量无显著差异（Ｐ＞００５）的情况下,各组间总胆红素和间接胆红素换出率无显著差异（Ｐ＞００５）。结论采用同型血对不同病因所致的高胆红素血症换血效果相近;外周动静脉同步换血是简单、实用的方法,值得推广。     

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。     

Neonatal hyperbilirubinemia

Five hundred Monates referred with unconjugated hyperbilirubinemia were studied. ABO incompatibility was responsible for 22.6% G-6PD deficiency for 18.2%, septicemia for 11.6% and Rh incompatibility for 9.8% of the cases. No cause could be established in 35% of the cases. 74.8% of the babies were treated outside before being referred and in 5% of these the level of bilirubin was more than 40 mg/dl. The type of treatment given included antibiotics, steroids, livertonics, phenobarbitone besides phototherapy. 10.4% of the cases had evidence of kemicterus at admission. 54% needed exchange transfusion with 27% requiring more than one. It is recommended that a better understanding and awareness about neonatal hyperbilirubinemia be created among all doctors coming in contact with neonates to ensure a timely referral.     

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.     

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.     

Intravenous immunoglobulin in the management of hemolytic disease of the newborn

Jaundice caused by hemolysis continues to challenge practitioners caring for infants in the NICU. Bilirubin levels can rise quickly in the first days of life, and interventions must be prompt to prevent side effects related to hyperbilirubinemia. Conventional treatments such as hydration and phototherapy are common, but new studies suggest that use of intravenous immunoglobin (IVIG) as an additional treatment may prevent the need for exchange transfusion in some babies. This article presents a case study of an infant with blood-type incompatibility treated successfully with multiple doses of IVIG, discusses the pathophysiology and clinical presentation of hemolytic jaundice, and reviews current management strategies for this disease.     

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.     

Genetic polymorphisms in Thai neonates with hyperbilirubinemia

Aim:  Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been associated with significant hyperbilirubinemia. We would like to determine whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants.
Methods:  Ninety-one study subjects (hyperbilirubinemic group) and 86 control subjects were studied.
Results:  The cause of neonatal hyperbilirubinemia could not be identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1 at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p = 0.001). There were no significant differences between groups in the variants UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the control group) with an odds ratio (OR) of 5.37 (p =0.02). The relationship between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined.
Conclusion:  Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD deficiency are at higher risk for developing neonatal hyperbilirubinemia.     

Current validity of the exchange transfusion intervention by the classic indication. Our 15 years' experience

In this paper the Authors report their personal experience of the use of exchange transfusion, secondary to classic indication, in the treatment of neonatal hyperbilirubinemia, in order to: 1) determine the trend over the past wears in the number of exchange transfused neonates, both from a global point of view and in relation to indications; 2) critically assess the risks, in terms of complications and mortality, correlated to exchange transfusion. Four hundred and eighty-eight neonates, who were subjected to 693 exchange transfusions in the Pediatric Clinic and Neonatal Division of the Policlinico Gemelli in Roma, were studied over a period of 15 years (1972-1986), according to the following indications: 214 cases of neonatal hyperbilirubinemia with MEN-Rh, 106 cases of neonatal hyperbilirubinemia with MEN-ABO and 168 cases of idiopathic hyperbilirubinemia. The total number of exchange transfused neonates decreased drastically from 304 in the period 1972-76 to 65 in the period 1982-86. The frequency of exchange transfused neonates because of idiopathic hyperbilirubinemia decreased significantly (p greater than 0.001), booth in comparison to the number of live births and in comparison to the number of exchange transfused neonates, probably due to the gradual introduction of phototherapy. The frequency of exchange transfused neonates with iso-Rh and iso-ABO decreased or remained stationary on account of the confirmed relative lesser efficacy of phototherapy on hemolytic jaundice. With regard to mortality and morbidity, 27 out of 488 neonates died during the neonatal period, but only 4 within six hours of exchange transfusion; the majority of those who died had a reduced gestational age and low birthweight, and were affected by a severe associated pathology.     

A trial with high-dose gamma globulin therapy in 3 children with hyperbilirubinemia in rhesus incompatibility

The influence of high-dose intravenous gammaglobulin (HDivGG) on the course of hyperbilirubinemia was investigated in three newborn infants with rhesus hemolytic disease. In addition to phototherapy and appropriate hydration all children received gammaglobulin (Polyglobulin N, Tropon-Cutter, Cologne, FRG) at a dose of 500 mg/kg body weight intravenously. All three infants showed a marked decrease in bilirubin levels after HDivGG. In two cases exchange transfusion could be avoided. In the third an elevated bilirubin level after blood exchange dropped following HDivGG, and a further exchange transfusion became unnecessary. The suspected effect of HDivGG in Rhesus incompatibility may be due to a blockade of Fc-receptors of the reticuloendothelial system, which prevents further hemolysis and bilirubin production. We propose, that the efficacy of this new mode of treatment should be evaluated in a controlled study.