On the efficacy of various irradiation regimens in phototherapy of neonatal hyperbilirubinaemia

The efficacy of various irradiation regimens in phototherapy of neonatal hyperbilirubinaemia was analysed. One hundred and one newborns were assigned to three groups at random. The best results were achieved when six special blue fluorescent lamps were used and the sides of the incubator were draped with white cloth to reflect the light diffusely. This simple measure increased the therapeutic effect by approx. 35%. Compared to standard phototherapy units equipped with fluorescent lights, a halide lamp was no more effective. The results of the clinical trial confirm the conclusions drawn from measurements, published previously. According to those findings, irradiating large areas of skin as homogeneously as possible should produce optinum results. Using a lamp with a large surface in combination with diffusely reflecting areas should best meet this requirement.     

Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia

The aim of this article is to investigate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonatal hyperbilirubinemia and to compare the clinical presentation and course of G6PD-deficient and normal patients. This study included a total of 624 term neonates with indirect hyperbilirubinemia from March 2001 to September 2004. Birth weight, sex, weight at admission, serum bilirubin at admission, maximum bilirubin, phototherapy duration, duration of hospitalization and the need for exchange transfusion were recorded. Laboratory evaluations included blood group typing of mother and newborn, complete blood count, peripheral blood smear, serum total and direct bilirubin, direct coombs test, reticulocyte count, serum-free T4 and TSH, urine analysis, urinary reducing substance and erythrocyte G6PD level. The analysis of the results indicated that 24 neonates with indirect hyperbilirubinemia were G6PD-deficient. No statistically significant difference was detected between G6PD-deficient and normal groups in relation to the time of onset of jaundice, reticulocyte count, hematocrit level, phototherapy duration and duration of hospitalization. Serum bilirubin at admission, maximum serum bilirubin level and the need for exchange transfusion were higher in G6PD-deficient group. From this study our conclusion is that the G6PD deficiency is a common enzyme defect causing severe indirect hyperbilirubinemia which may result in kernicterus. Early neonatal screening programmes should be instituted in countries where the deficiency is prevalent.     

浙江地区新生儿葡萄糖-6-磷酸脱氢酶缺乏症的遗传学分析

目的　分析浙江地区新生儿葡萄糖-6-磷酸脱氢酶（glucose-6-phosphate dehydrogenase，G6PD）缺乏症的基因突变特点，探讨其遗传多样性。方法　以2015年3月至2017年9月在浙江地区出生、经浙江省新生儿遗传代谢筛查中心G6PD缺乏症筛查发现的2242例患儿为对象，收集其新生儿筛查的G6PD活性值与剩余干滤纸血斑，并提取其血斑的基因组DNA。采用MassARRAY技术检测35个G6PD突变位点。采用SPSS 22.0软件统计分析基因型与G6PD活性的关系，P＜0.05为差异有统计学意义。结果　2163例检出突变，总检出率为96.47%，其中男性为96.51%（1995/2067），女性为96%（168/175）。共检出21种突变位点，44种变异基因型，其中男性半合子19型，女性杂合子14型，女性纯合子3型，女性复合杂合8型。95.93%的G6PD突变位于12、9、2、5外显子，其中c.1376G＞T、c.1388G＞A、c.1024C＞T、c.95A＞G、c.871G＞A、c.392G＞T占92.96%。c.1376G＞T、c.1388G＞A、c.1024C＞T、c.95A＞G四种基因型的G6PD活性差异有统计学意义（P＜0.0001）。结论　浙江地区G6PD缺乏症存在基因突变热点，c.1024 C＞T的突变频率具有明显地域特征，MassARRAY技术检测特定G6PD突变位点可推荐为G6PD缺乏症的二级筛查方法之一。     

Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis

We report a novel glucose-6-phosphate dehydrogenase (G6PD) mutation, which we propose to name G6PD Cincinnati (c.1037A > T, p.N346I), found in combination with G6PD Gastonia (c.637G > T, p.V213L) in an infant who presented with neonatal cholestasis. The G6PD Cincinnati mutation results in a non-conservative amino acid substitution at the tetramer interface disturbing its formation, as seen by native gel electrophoresis and immunoblotting. G6PD Gastonia disrupts dimerization of the enzyme and by itself causes chronic non-spherocytic hemolytic anemia. The G6PD Cincinnati mutation may have aggravated the clinical picture of G6PD Gastonia with the result of severe perinatal hemolysis causing cholestasis and associated liver injury.     

An audit of phototherapy units

Audit of phototherapy aims to examine their efficacy and functioning. Twenty-four centres providing neonatal care were visited by a team of two persons. Data form were completed with information regarding age of phototherapy units, its buildup in relation to number of tubelights, type of light and irradiance provided. Total of 58 units examined had a wide variety in relation to their build. There were only 21 units (36.2%) in which all the lights were in working order. Only five of the units (8.6%) had the recommended special blue lights. Only 18 of the units (31 %) provided an acceptable level of irradiance. Phototherapy demonstrates a dose response relationship. By not providing optimum irradiance, the efficacy is compromised. This prolongs hospital stay and treatment costs. Acceptable standards should be insisted upon in purchase and maintenance of medical equipments.     

Apoptosis in the small intestine of neonatal rat using blue light-emitting diode devices and conventional halogen-quartz devices in phototherapy

Phototherapy is the most frequently used treatment for the neonatal jaundice. However, recent papers report that phototherapy increased apoptosis in peripheral mononuclear leukocytes in vivo and in mouse lymphoma cell line in vitro. We have investigated the cytotoxicity of phototherapy on the small intestine of neonatal rat using conventional halogen-quartz device (conventional device) and blue light-emitting device (LED device) by measuring apoptotic cells. Four-day-old male Wistar rats were divided into three groups as follows: group 1, exposure to conventional device for 72 h; group 2, exposure to LED device for 72 h; and group 3, control (without phototherapy). After light exposure, the small intestine was examined for apoptosis. Apoptotic cells were detected by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, by immunohistochemistry for caspase-3 and by transmission electron microscopy. The proportion of positive cells by the TUNEL method in the epithelium of the small intestine was 6.2, 3.1 and 1.7% in the conventional device group, the LED device group and the control group, respectively. The apoptotic cells of the conventional device group is significantly higher than the LED device group (P < 0.01) and that of the LED device group was higher than that of the control group (P < 0.05). We suspected that phototherapy induced apoptosis in neonatal small intestine and the conventional device introduces more apoptosis than the LED device.     

Transient liver injury and severe neonatal cholestasis in infant with glucose-6-phosphate dehydrogenase deficiency due to a new mutation

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys» was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.     

Hemolysis in a glucose-6-phosphate dehydrogenase-deficient boy with rheumatic fever

Summary A 12-year-old black boy with the A type of glucose-6-phosphate dehydrogenase (G6PD) deficiency had a hemolytic episode concurrent with acute rheumatic fever. Aspirin nevertheless remains the drug of choice for acute rheumatic fever even in the A type of G6PD deficiency.     

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目的探讨葡萄糖醛酸转移酶1A1(UGT1A1)基因G71R突变、葡萄糖-6-磷酸脱氢酶(G6PD)缺陷对新生儿生后前3d胆红素浓度的影响.方法测定81例新生儿脐血的G6PD活性及G71R基因型,分组比较生后前3d光疗前胆红素值的组间差异.用等位基因特异性寡核苷酸探针点杂交法(ASO)确定G71R基因型.结果在G71R野生型新生儿中,G6PD缺乏组与G6PD正常组相比,生后前3d胆红素值间无统计学差异.G6PD正常新生儿中,G71R突变纯合子或杂合子的新生儿生后前3d胆红素浓度与G71R正常野生型新生儿相比无统计学差异.G6PD缺陷新生儿中,同时合并有G71R突变纯合子或杂合子的新生儿组生后第2天、第3天胆红素浓度高于G71R正常野生型新生儿组.结论G6PD缺乏与G71R基因突变并存加重新生儿黄疸程度.     

G-6-PD缺乏症和新生儿高胆红素血症

葡萄糖-6-磷酸脱氢酶缺乏症是一种常见的单基因遗传性疾病,在全球范围内分布非常广泛,而且人群中携带者频率很高。患者突然出现的急性溶血会导致血清总胆红素升高,引起高胆红素血症,甚至胆红素脑病。新生儿高胆红素血症是儿科医生经常遇到的问题,需要及时发现和处理。     

A prolonged neonatal jaundice associated with a rare G6PD mutation

Glucose‐6‐phosphate dehydrogenase (G6PD), a X‐linked hereditary deficiency, is one of most common clinically significant enzyme defects. Despite its largely known role in acute and life‐threatening haemolytic crises, G6PD deficiency may be also associated with neonatal jaundice that, when severe and untreated, may lead to the potential of bilirubin encephalopathy. A prolonged neonatal jaundice was found to be associated with a rare G6PD mutation (c.383T>G; p.L128R), the latter simply annotated in literature database. In this article, we clinically and phenotipically describe a case of an Italian neonate carrying the c.383T>G G6PD mutation. Finally, we named this variant “G6PD Salerno.” Pediatr Blood Cancer 2009;53:475–478. © 2009 Wiley‐Liss, Inc.     

Effects of phototherapy using different light sources on oxidant and antioxidant status of neonates with jaundice

Background/aim

Neonates have limited antioxidant protective capacity. It has recently been demonstrated that phototherapy used for treatment of neonatal jaundice produces oxidative stress. Various phototherapy devices using different light sources are available for phototherapy. We aimed to investigate the effects of phototherapy applied with different light sources on the global oxidant/antioxidant status in neonates.

Methods

Term and late-preterm (≥ 35 weeks) newborn infants hospitalized to receive phototherapy for non-hemolytic jaundice in the 2–9 days of life were enrolled. Infants who received conventional phototherapy with fluorescent lamps were defined as group 1, intensive light emitting diode (LED) phototherapy as group 2, and fiberoptic phototherapy as group 3. The serum total antioxidant capacity (TAC) and total oxidant status (TOS) were measured before and 24 h after phototherapy. Oxidative stress index (OSI) was calculated.

Results

Twenty nine patients were included in each group. At the beginning of phototherapy serum TAC, TOS and OSI levels were similar in all groups. After phototherapy serum TAC decreased significantly in all three groups (p < 0.001). Total oxidant status increased significantly in group 1 (p < 0.001) and group 2 (p = 0.001) whereas a statistically insignificant increase was observed in group 3 (p = 0.057). After phototherapy OSI increased significantly in group 1 (p < 0.001), group 2 (p = 0.001), and group 3 (p = 0.038).

Conclusion

As indicated by increased OSI, oxidant/antioxidant balance is disturbed in favor of oxidants after blue fluorescent light, LED and fiberoptic phototherapy.     

The distribution of radiant power in a phototherapy unit equipped with a metal halide lamp

The effective radiant power of a metal halide lamp for phototherapy of neonatal jaundice was measured in an incubator. This new lamp is characterised by an extremely heterogenous field of irradiance with a high intensity in the centre and a marked decrease towards the sides. The mean radiant intensity in a central area (20×40 cm) of the incubator can be compared with the values achieved with standard fluorescent lamps in an incubator lined with white cloth. As the field of irradiance is more homogeneous in the latter case, advances in therapy are not to be expected from the use of metal halide lamps in their present form.     

Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia

We report two children with hemolytic anemia during the course of hepatitis A infection. On admission, the patients had high blood urea nitrogen, creatinine, and uric acid levels, as well as anemia, leucocytosis, and direct and indirect hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on admission. Inadvertent administration of vitamin K could have been related to an acute reduction in hemoglobin concentration. To prevent renal damage, plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute tubular necrosis complicated the clinical course in one patient, and several sessions of hemodialysis were required. In conclusion, intravascular hemolysis should be considered in patients with hepatitis A infection, marked hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet recommended for routine administration, high-risk patients, including those with a G6PD deficiency, should be vaccinated against hepatitis A.     

Uniform national guidelines do not prevent wide variations in the clinical application of phototherapy for neonatal jaundice

Aim

This study compared the use of phototherapy for neonatal jaundice in all 21 Norwegian neonatal intensive care units (NICUs) from 2013‐2014 to improve practice.

Methods

Information on all types of phototherapy devices was collected, and irradiance was measured from random units at 20 cm and 50 cm from the light source. We gathered information on local practice rules, including the use of single, double or triple phototherapy, how infants were positioned, the frequency of blood sampling, rules for using reflective surfaces and interrupting phototherapy. In every NICU, we asked one nurse with more than five years of experience and one with less than one year to set up phototherapy equipment, then measured the irradiance and distance.

Results

Photodiodes were the most common of the eight types of phototherapy devices used. Rules for the distance from the device to the infant varied from 10 to 40 cm and in practice they varied from 15 to 48 cm, with irradiance ranging from 11.1–56.1 W/m². There were significant variations between NICUs with regard to the overall treatment duration and duration in most birthweight categories.

Conclusion

There were considerable variations in phototherapy practices among Norwegian NICUs. In particular, the significant variations in duration need to be addressed.     

Screening for glucose-6-phosphate dehydrogenase deficiency using a modified formazan method: A pilot study on Filipino male newborns

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has increased prevalence rates in tropical Africa, tropical and subtropical Asia and some parts of the Mediterranean. Earlier studies on G6PD deficiency in the Philippines have shown prevalence rates of 4.5% to 25.7%. METHODS: In the present study, 3278 male newborns were screened for G6PD deficiency using the modified formazan method, a simple screening procedure affordable in the setting of a developing country. Subjects with positive screening results were recalled for confirmatory testing using a commercial assay kit for quantitative enzyme determination. RESULTS: Of the 3278 boys studied, 186 revealed positive screening results. Of the 186, 65 boys had confirmatory testing. Of these 65 boys, 45 were confirmed to have G6PD deficiency and 20 had normal results. This study reveals an incidence of G6PD deficiency of 3.9% among male Filipinos. CONCLUSIONS: This study recommends the inclusion of G6PD deficiency in the panel of disorders for newborn screening among Filipino newborns.     

Leucocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity in G-6-PD deficient subjects

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied in the following groups of Greek people.Group 1: 43 male children and 16 male students with mean values of enzyme activity of 27.7±16.6 units and 24.6±5.6 units, respectively.Group 2: 15 G-6-PD deficient male children who had never experienced an acute haemolytic episode with a mean value of 10.8±4.6 units.Group 3: 19 G-6-PD deficient male children during favism and 3 months after the haemolytic crisis with mean values of 8±4 units and 9.2±1.9 units, respectively.Group 4: 19 mothers of children from group 3 who by definition were carriers of G-6-PD deficiency had a mean value of 18.2±8.2 units.The difference between means for group 1 and groups 2, 3 and 4 is highly significant (P<0.001).Therefore the enzymatic defect in Greek people is not limited to the erythrocytes but can be also demonstrated in leucocytes.     

Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal erythrocytes in vitro

AIM: To determine whether vitamin K1, which is routinely administered to neonates, could act as an exogenous oxidising agent and be partly responsible for haemolysis in glucose-6-phosphat-dehydrogenase (G-6-PD). METHODS: G-6-PD deficient (n = 7) and control (n = 10) umbilical cord blood red blood cells were incubated in vitro with a vitamin K1 preparation (Konakion). Two concentrations of Vitamin K1 were used, both higher than that of expected serum concentrations, following routine injection of 1 mg vitamin K1. Concentrations of reduced glutathione (GSH) and methaemoglobin, indicators of oxidative red blood cell damage, were determined before and after incubation, and the mean percentage change from baseline calculated. RESULTS: Values (mean (SD)) for GSH, at baseline, and after incubation with vitamin K1 at concentrations of 44 and 444 microM, respectively, and percentage change from baseline (mean (SD)) were 1.97 + 0.31 mumol/g haemoglobin, 1.89 +/- 0.44 mumol/g (-4.3 +/- 13.1%), and 1.69 +/- 0.41 mumol/g (-14.5 +/- 9.3%) for the G-6-PD deficient red blood cells, and 2.27 +/- 0.31 mumol/g haemoglobin, 2.09 +/- 0.56 mumol/g (-7.2 +/- 23.2%), and 2.12 +/- 0.38 mumol/g (-6.0 + 14.1%) for the control cells. For methaemoglobin (percentage of total haemoglobin), the corresponding values were 2.01 +/- 0.53%, 1.93 +/- 0.37% (-0.6 +/- 17.4%) and 2.06 +/- 0.43% (5.7 +/- 14.2%) for the G-6-PD deficient red blood cells, and 1.56 +/- 0.74%, 1.70 +/- 0.78% (12.7 +/- 21.9%), and 1.78 +/- 0.71% (20.6 +/- 26.8%) for the control red blood cells. None of the corresponding percentage changes from baseline was significantly different when G-6-PD deficient and control red blood cells were compared. CONCLUSIONS: These findings suggest that G-6-PD deficient red blood cells are not at increased risk of oxidative damage from vitamin K1.