早期光疗对早产儿黄疸的影响

目的：探讨在经皮胆红素监测下早期蓝光干预对早产儿高胆红素血症的防治作用。方法：选择2009年10月-2011年10月我院新生儿科收治的86例出生体重≤2000g,无出生窒息史的早产儿,按住院号单双号分为观察组46例和对照组40例。对照组按照我国2000年制定的新生儿黄疸干预推荐方案的干预标准进行光疗。观察组于出现黄疸和／或经皮胆红素〉85．50μmol／L,但尚未达方案的干预标准就进行光疗,监测经皮胆红素至黄痘消失。经皮胆红素值达187．5μmol／L以上时同时查静脉血监测血清总胆红素。比较2组早产儿经皮胆红素峰值及恢复正常时间。结果：观察组与对照组比较经皮胆红素峰值较低,黄疸持续时间较短,两组比较P均〈0．05,有统计学差异。结论：早产儿在经皮胆红素监测下进行早期蓝光干预有利于降低早产儿胆红素峰值,缩短黄疸持续时间。有效预防早产儿胆红素脑病。     

Seasonal Pattern of Phototherapy: A Study in the Sardinian Population

The relationship between season of birth and human diseases is well known and it has been suggested that such a relationship could be mediated by seasonal and environmental effects on early events of extrauterine life. In this context the physiological increase of bilirubin occurring in all infants during the neonatal period may be of paramount importance. Indeed, recent studies suggest a beneficial action of bilirubin in the early stages of extrauterine life due to its protective action against secondary oxidants. The newborn infant is particularly sensible to oxidative damage, thus seasonal variation of bilirubin level in the first few days of life could influence further development and susceptibility to pathological manifestations. In the present paper we have analysed the seasonal effect on the level of the serum bilirubin during the neonatal period by an analysis of the incidence of phototherapy in a sample of 5540 infants born consecutively in the population of Sassari during the years 1993-96. The proportion of infants undergoing phototherapy for neonatal hyperbilirubinemia is lower in those without glucose-6-phosphate-dehydrogenaser (G-6-PD) deficiency than in those with G-6-PD deficiency and in both categories the proportion is lower in females than in males. A highly significant association between the date of birth and the proportion of infants undergoing phototherapy has been observed in males without G-6-PD deficiency. The maximum incidence of phototherapy has been observed in the period May-August. A Fourier analysis carried out on these infants has shown the presence of two main components (harmonics) contributing to the seasonal cycle and corresponding respectively to a one year and to a two years period.     

Seasonal Pattern of Phototherapy: A Study in the Sardinian Population

The relationship between season of birth and human diseases is well known and it has been suggested that such a relationship could be mediated by seasonal and environmental effects on early events of extrauterine life. In this context the physiological increase of bilirubin occurring in all infants during the neonatal period may be of paramount importance. Indeed, recent studies suggest a beneficial action of bilirubin in the early stages of extrauterine life due to its protective action against secondary oxidants. The newborn infant is particularly sensible to oxidative damage, thus seasonal variation of bilirubin level in the first few days of life could influence further development and susceptibility to pathological manifestations. In the present paper we have analysed the seasonal effect on the level of the serum bilirubin during the neonatal period by an analysis of the incidence of phototherapy in a sample of 5540 infants born consecutively in the population of Sassari during the years 1993-96. The proportion of infants undergoing phototherapy for neonatal hyperbilirubinemia is lower in those without glucose-6-phosphate-dehydrogenaser (G-6-PD) deficiency than in those with G-6-PD deficiency and in both categories the proportion is lower in females than in males. A highly significant association between the date of birth and the proportion of infants undergoing phototherapy has been observed in males without G-6-PD deficiency. The maximum incidence of phototherapy has been observed in the period May-August. A Fourier analysis carried out on these infants has shown the presence of two main components (harmonics) contributing to the seasonal cycle and corresponding respectively to a one year and to a two years period.     

酪酸梭菌活菌散辅助治疗新生儿黄疸的随机多中心临床疗效观察

目的观察酪酸梭菌活菌散(商品名:宝乐安)辅助治疗新生儿黄疸的临床疗效。方法将543例新生儿黄疸患儿随机分为观察组和对照组,观察组274例,对照组269例。观察组在蓝光治疗的同时给予酪酸梭菌活菌散口服,0.5g/次,3次/d,服至黄疸消退;对照组只给予蓝光治疗。于治疗后48h、72h、96h检测血清胆红素值。结果治疗72h、96h后观察组血清胆红素水平较对照组明显下降(P0.05)。结论在蓝光治疗新生儿黄疸的同时服用酪酸梭菌活菌散,可迅速降低胆红素水平,缩短治疗时间。     

Efficacy of phototherapy in non-haemolytic hyperbilirubinaemia.

Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe.     

Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer

Crigler-Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease is lethal due to bilirubin-induced neurological damage unless phototherapy is applied from birth. However, treatment becomes less effective during growth, and liver transplantation is required. To investigate the pathophysiology of the disease and therapeutic approaches in mice, we generated a mouse model by introducing a premature stop codon in the UGT1a1 gene, which results in an inactive enzyme. Homozygous mutant mice developed severe jaundice soon after birth and died within 11 d, showing significant cerebellar alterations. To rescue neonatal lethality, newborns were injected with a single dose of adeno-associated viral vector 9 (AAV9) expressing the human UGT1A1. Gene therapy treatment completely rescued all AAV-treated mutant mice, accompanied by lower plasma bilirubin levels and normal brain histology and motor coordination. Our mouse model of CNI reproduces genetic and phenotypic features of the human disease. We have shown, for the first time, the full recovery of the lethal effects of neonatal hyperbilirubinemia. We believe that, besides gene-addition-based therapies, our mice could represent a very useful model to develop and test novel technologies based on gene correction by homologous recombination.     

Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthus amarus root in phenylhydrazine-induced neonatal jaundice in mice

The ability of ethanol extract of Phyllanthus amarus root (EEPA) to decrease bilirubin level and oxidative stress in phenylhydrazine-induced neonatal jaundice in mice was investigated. Administration of phenylhydrazine (75 mg/kg b.w.) significantly elevated total and unconjugated serum bilirubin level compared to control mice. EEPA (5, 10, and 20 mg/kg b.w., oral) dose-dependently reduced the bilirubin level. EEPA treatment also upregulated hepatic CAR and CYP3A1, accounting for its ability to facilitate bilirubin clearance. A single dose of EEPA (20 mg/kg b.w.) induced higher level of bilirubin clearance than phototherapy, widely used for treating neonatal jaundice. Furthermore, phenylhydrazine administration significantly increased MDA, protein carbonyl, and total thiol content and lowered the GSH level along with superoxide dismutase and catalase activity in erythrocyte compared to the control group. Single administration of EEPA (20 mg/kg b.w.) significantly reversed the trend. Presence of gallic acid, gentisic acid, and ortho-coumaric acid in EEPA was identified by HPLC analysis. Amongst these, the major phenolic constituent, gallic acid, exhibited significant bilirubin-lowering effect. These results suggested that P. amarus may be beneficial in reducing bilirubin level as well as oxidative stress in neonatal jaundice.     

Red Cell Glucose-6-Phosphate Dehydrogenase Deficiency—A Newly Recognized Cause of Neonatal Jaundice and Kernicterus in Canada

Seven male newborns of Chinese, Greek and Italian origin presented with severe hemolytic jaundice due to red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. In five, the hemolysis was precipitated by inhalation of mothball vapours in the home. Kernicterus was evident upon admission in six infants and was fatal in four of these.G-6-PD deficiency should be suspected as a cause of jaundice in all full-term male infants of these ethnic groups. The diagnosis can be confirmed in any hospital by the methemoglobin reduction test. In areas similar to Toronto, Canada, where these high-risk ethnic groups prevail, the following measures are recommended: (1) detection of G-6-PD deficient newborns by screening cord bloods of all infants of these ethnic groups; (2) protection of affected infants from potentially hemolytic agents such as naphthalene, certain vitamin K preparations, and sulfonamides; and (3) observation of serum bilirubin levels to assess the need for exchange transfusion for hyperbilirubinemia.     

Nitric oxide levels and antioxidant enzyme activities in jaundices of premature infants

Free radicals are effective in the genesis of several diseases in the neonatal period. This study aimed to show the relationship between serum bilirubin levels and plasma nitric oxide and the activity of enzymes in the erythrocyte such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in premature infants. In the study, 20 premature infants with newborn jaundice were included and the control group was formed by 15 premature infants without jaundice. Venous blood samples were taken from all neonates in the study and control groups on the first day of hospitalization. Plasma nitric oxide levels and activities of SOD, GSH-Px and CAT enzymes in the erythrocytes were investigated in these samples. Plasma nitric oxide and serum bilirubin levels were found to be significantly higher in the study group (47.4 +/- 7.25 micromol l(-1), 18.41 +/- 3.28 mg dl(-1), respectively) than those in the control group (33.46 +/- 6.43 micromol l(-1), 4.35 +/- 0.60 mg dl(-1), respectively; p < 0.001). In addition, erythrocyte SOD, GSH-Px and CAT enzyme activities (724 +/- 78.61, 673 +/- 90.5, 63 +/- 12.8 U g(-1) Hb, respectively) were found to be significantly lower in the study group than those in the control group (1208 +/- 129.04, 1097.6 +/- 75.8, 99.06 +/- 12.4 U g(-1) Hb, respectively, p < 0.001). It was concluded that in the aetiology of hyperbilirubinemia, neonatal erythrocytes and nitric oxide reactions are affected differently and that erythrocyte haemolysis caused as a result of these effects may play a role in the aetiopathogenesis of unconjugated hyperbilirubinemia. Haemolysis may also be seen because of the inadequacy of the protection by erythrocytes against the cytotoxic effects of free radicals resulting from the lack of antioxidant enzymes in these cells.     

酪酸梭菌活菌散联合光疗治疗新生儿母乳性黄疸临床观察

目的探讨酪酸梭菌活菌散（商品名：宝乐安）联合光疗治疗母乳性黄疸的临床疗效。方法将母乳性黄疸患儿116例随机分为观察组和对照组,观察组59例在光疗、补液等常规治疗的同时给予口服酪酸梭菌活菌散;对照组57例应用光疗、补液等常规治疗。治疗中观察患儿黄疸消退时间并定期检测血清胆红素含量,比较胆红素日均下降速度及治愈时间。结果观察组治愈时间短于对照组（P〈0．05）,观察组日均胆红素下降值高于对照组（P〈0．01）,差异具有非常显著性。结论酪酸梭菌活菌散联合光疗治疗母乳性黄疸能够缩短光疗时间和快速降低血清胆红素,值得临床推广应用。     

Metabolism of bilirubin and its photoisomers in newborn infants during phototherapy

Bilirubin and its photoisomers in the biological fluids of a hyperbilirubinaemic newborn infant before and during phototherapy were analyzed by a recently improved HPLC method. In the serum, the percentages of (EZ)- and (ZE)-bilirubin in the total bilirubin concentration before phototherapy were approximately 10% and on average increased over 1.5-fold at 2 h after initiation of phototherapy. The percentage of the (EZ)-cyclobilirubin in the serum bilirubin was under 1%. In the bile, the mean concentration of (ZZ)-bilirubin, derived mainly from (ZE)-bilirubin, nearly tripled during phototherapy. The (EZ)-cyclobilirubin concentration in the bile was very low before phototherapy, increased nearly ten-fold at 3 h after initiation of phototherapy, and was 5- to 6-fold as high as that of (ZZ)-bilirubin. In the urine, upon exposure to light, the urinary concentration of (EZ)-cyclobilirubin is apparently equivalent to half of the biliary concentration of (ZZ)-bilirubin and one-fifth of that of (EZ)-cyclobilirubin. It was concluded that during phototherapy of neonatal hyperbilirubinaemia the structural photoisomer [(EZ)-cyclobilirubin] predominates considerably over the geometric photoisomer [(ZE)-bilirubin].     

Heliotherapy for Neonatal Hyperbilirubinemia in Southwest,Nigeria: A Baseline Pre-Intervention Study

Background

A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital.

Methods

We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children’s Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression.

Results

Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%–19.3%) and 31.5% (95% CI: 28.8%–34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%–6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy.

Conclusions

Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings.     

High-pressure liquid chromatographic analysis of anaerobic photoproducts of bilirubin-IX alpha in vitro and its comparison with photoproducts in vivo.

To carry out photochemical experiments under conditions similar to those prevailing for neonatal bilirubin metabolism in jaundice phototherapy, we have studied photoproducts produced by the action of light on a bilirubin--albumin solution and further clarified the relationship between the photoproducts obtained from experiments in vitro and in vivo. (1) An accurate and sensitive separation method by high-pressure liquid chromatography for photoproducts of bilirubin under anaerobic irradiation of visible light is described. (2) There were two main photoproducts obtained from experiments both in vivo and in vitro. (3) Exact correspondence of retention time on high-pressure liquid chromatography, diazo-reactivity, thermal reversion and absorption-spectrum maxima was observed between unknown pigment and photobilirubin-IX alpha from biological fluids, and the comparable peaks 2 and 3 from experiments in vitro. (4) The behaviour of photoproducts in various solutions in the absence of light and O2 is described. (5) A lower affinity of photoproducts, especially unknown pigment, for human serum albumin than with bilirubin-IX alpha for the albumin was demonstrated by the gel-filtration method.     

Placental Barrier to Coagulation Factors: Its Relevance to the Coagulation Defect at Birth and to Haemorrhage in the Newborn

The placental barrier to coagulation factors was assessed by measuring their levels in maternal venous and neonatal umbilical arterial and venous blood and was found to be largely complete. Detailed coagulation assessments in a large number of term and premature neonates showed that term neonates had a mild coagulation deficiency at birth. Premature neonates had a more definite deficiency, which became more severe with increasing prematurity. Mortality in low birth weight premature infants was associated with a severe coagulation deficiency, and was frequently due to cerebral haemorrhage. It is suggested that the coagulation system of low birth weight infants should be assessed to enable prophylactic treatment of those with a severe deficiency.     

Influence of Previous Oral Contraception and Maternal Oxytocin Infusion on Neonatal Jaundice

A prospective study of serum bilirubin levels on the first and sixth days of life in a series of 181 infants has failed to provide evidence to suggest that previous maternal oral contraception, maternal oxytocin infusion, epidural anaesthesia, or breast-feeding are factors influencing neonatal jaundice.     

Phototherapy increases DNA damage in lymphocytes of hyperbilirubinemic neonates

Phototherapy is commonly used in the treatment of hyperbilirubinemia in newborns. No serious side effects related to phototherapy have been observed, but concerns regarding its potential to damage DNA have been expressed, based on animal or cell-culture studies. The aim of this study was to investigate, in neonates with hyperbilirubinemia, the possible relation between phototherapy and DNA damage. The study included 33 full-term newborns with non-physiological jaundice and 14 healthy newborns with physiological jaundice as controls. Phototherapy was performed with an array of six fluorescent lamps producing radiation with wavelengths of 480-520 nm at 12 microW/cm(2)/nm. DNA damage in lymphocytes was determined by use of the alkaline comet assay. The DNA damage increased significantly with the duration of phototherapy, as shown by measurements at 24, 48, and 72 h (P<0.001). These findings indicate that phototherapy, widely used in neonatology units, increases DNA damage in newborns. It remains to be seen whether the genotoxic effect observed in the present study can cause any long-term health effect in phototherapy-treated infants in later life.     

Effects of phototherapy with blue light on chromosomes from human lymphocytes

The dangerous effects of phototherapy have been matter of discussion in recent years. In order to evaluate its in vitro action on the human DNA, the authors have performed the karyotypic analysis on 20 cultures of lymphocytes. In different times 16 cultures have been exposed to the action of a "blue light" fluorescent lamp, commonly used for the treatment of neonatal jaundice. The authors have not evidenced any morphological or numerical change of the karyotype in any of the cultures.     

Effect of phototherapy on the frequency of the use of exchange transfusion in the treatment of neonatal jaundice

The authors analysed an incidence of performed exchange blood transfusions at the newborn babies ward prior to and after introduction of phototherapy into practice. This analysis included the causes of jaundice in newborn. The study included the causes of jaundice in newborn. The study involved 8,937 newborn babies delivered between 1981 and 1985. Prior to phototherapy (period between January, 1981 and July, 1980), 45 blood transfusions and 9 retransfusions were performed. During the period II (between July, 1983 and December, 1985), i.e. phototherapy, 30 blood transfusions and 1 retransfusion were effected despite of the higher number of delivered babies. The obtained results have shown favourable effect of the phototherapy in jaundice of perinatal period, especially in jaundice unconnected with blood Rh factor conflict and in premature babies. Phototherapy decreased the number of performed transfusions and retransfusions.     

Idiopathic Neonatal Hepatitis: Discordance in Monozygotic Twins

Idiopathic neonatal hepatitis is the uncommon syndrome of prolonged obstructive jaundice associated with giant cell transformation in the liver and patent bile ducts. Either hepatitis virus or an inherited abnormality has been suggested as a likely pathogenic agent for the syndrome.Recent observation of discordance for idiopathic neonatal hepatitis in monozygotic twins is felt to be inconsistent with either an infectious or a simple genetic etiology. Immaturity of the hepatic parenchymal cell bilirubin excretory pathway is postulated as a cause of jaundice in some of these babies.     

Ward design and neonatal jaundice in the tropics: report of an epidemic.

Architectural modifications to an existing tropical obstetric ward involved extension of the roof overhangs to a width of several metres. These extensions excluded most of the daylight from the ward. An alarming increase in the incidence of jaundice (bilirubin concentration greater than or equal to 240 mumol/l (greater than or equal to 14 mg/100 ml] from 0.5% to 17% in newborn infants occurred after the modifications. Tropical obstetric wards and nurseries should continue to be built with windows facing north-south for coolness. They should, however, have as many windows as possible and the roof overhangs should be limited to about 1 m to allow adequate indirect sunlight to enter, giving a high intensity of illumination, and help prevent neonatal jaundice.