PURPOSE: The incidence of neonatal hyperbilirubinemia is twice as high in Eastern Asians as in Caucasians. Although it has not been clearly defined, the UDP-glucuronosyltransferase gene (UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia. This study is to find an association of 1956G>C polymorphism of the UGT1A1 gene, which encodes for a key enzyme of bilirubin metabolism and neonatal hyperbilirubinemia in Korean infants. METHODS: The genomic DNA was isolated from 80 Korean full term neonates whose serum bilirubin greater than 12 mg/dL with no obvious cause. The genomic DNA was also isolated from 164 Korean neonates of the control population. We studied a single nucleotide polymorphism (SNP) of 1956G>C in the untranslated region of the UGT1A1 gene by direct sequencing. RESULTS: Three of the 80 neonates with a serum bilirubin level above 12 mg/dL had homozygous mutation and 10 of the neonates with a serum bilirubin level above 12 mg/dL had heterozygous mutation. Thirteen of the 164 neonates of the control group had homozygous mutation and 16 neonates of the control group had heterozygous mutation. The allele frequency of 1956G>C polymorphism of UGT1A1 in the hyperbilirubinemia group was 10.0 percent, which was not significantly different from the allelic frequency of 12.8 percent in the control group. CONCLUSIONS: In this study, the 1956G>C polymorphism of the UGT1A1 gene was detected in the Korean neonates with neonatal hyperbilirubinemia. Our results indicated that this SNP is not associated with the prevalence of hyperbilirubinemia in Korean.
Asian Continental Ancestry Group ; Bilirubin ; DNA ; Gene Frequency ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal* ; Incidence ; Infant ; Infant, Newborn ; Metabolism ; Polymorphism, Single Nucleotide ; Prevalence ; Risk Factors ; Untranslated Regions

PURPOSE: The incidence of neonatal hyperbilirubinemia is twice as high in East Asians as in Caucasians. However, its metabolic basis has not been clearly explained. The UDP-glucuronosyltransferase gene(UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia. We studied whether neonatal hyperbilirubinemia is associated with the 1828G>A(rs 10929303) polymorphism of the UGT1A1 gene, which encodes for a key enzyme of bilirubin metabolism. METHODS: The genomic DNA was isolated from 80 Korean full term neonates who had greater than a 12 mg/dL level of serum bilirubin with no obvious cause, and the genomic DNA was also isolated from 164 Korean neonates of the control population. We studied a single nucleotide polymorphism (SNP) of 1828G>A in the untranslated region of the UGT1A1 gene by direct sequencing. RESULTS: Three of the 80 neonates with a serum bilirubin level above 12 mg/dL had homozygous mutations and 10 of the 80 neonates with a serum bilirubin level above 12 mg/dL had heterozygous mutations. Thirteen of the 164 neonates of the control group had homozygous mutations and 16 neonates of the control group had heterozygous mutations. The allele frequency of 1828G>A polymorphism of UGT1A1 in the hyperbilirubinemia group was 10.0 percent, which was not significantly different from the allele frequency of 12.8 percent in the control group. CONCLUSION: In this study, the 1828G>A polymorphism of the UGT1A1 gene was detected in the Korean neonates with neonatal hyperbilirubinemia. Our results indicated that this SNP is not associated with the prevalence of hyperbilirubinemia in Koreans.
Asian Continental Ancestry Group ; Bilirubin ; DNA ; Gene Frequency ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal* ; Incidence ; Infant, Newborn ; Metabolism ; Polymorphism, Single Nucleotide ; Prevalence ; Risk Factors ; Untranslated Regions

PURPOSE: The incidence of neonatal hyperbilirubinemia is twice as high in East Asians as in whites and its metabolic basis has not been clearly explained. Recently, UDP-glucuronosyltransferase gene (UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia in Japanese and Taiwanese Chinese. We studied whether neonatal hyperbilirubinemia is associated with mutation of UGT1A1, which is a key enzyme of bilirubin catabolism, in Korean. METHODS: The genomic DNA was isolated from 45 Korean full term neonates who had hyperbilirubinemia(serum bilirubin >12 mg/dL) with no obvious causes, and the 64 Korean neonates of the control population. We detected a missense mutation of Gly71Arg of UGT1A1 gene by using allele-specific polymerase chain reaction. Polymorphism was confirmed by direct sequencing. RESULTS: Two of the 45 neonates with serum bilirubin above 12 mg/dL had homozygous mutation and 16 neonates had heterozygous mutation. Two of the 31 neonates with serum bilirubin above 15 mg/dL had homozygous mutation and 13 neonates had heterozygous mutation. Thirteen of the control group had heterozygous mutation and homozygous mutation was not found. Allele frequency of Gly71Arg mutation in hyperbilirubinemia group was 0.22, which was significantly higher than 0.11 in the control group(P<0.0144). CONCLUSION: The missense mutation causing Gly71Arg of UGT1A1 was detected in the Korean neonatal hyperbilirubinemia. The high frequency of this missense mutation may be attributed to the high prevalence of hyperbilirubinemia in the Korean.
Asian Continental Ancestry Group ; Bilirubin ; DNA ; Gene Frequency ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal* ; Incidence ; Infant, Newborn ; Korea* ; Metabolism ; Mutation, Missense ; Polymerase Chain Reaction ; Prevalence ; Risk Factors

OBJECTIVETo investigate the predictive value of umbilical cord serum (UCS) bilirubin for subsequent jaundice in healthy term newborns.

METHODSFive hundred and twenty-three healthy term newborns (275 boys, 248 girls) were selected. The cord blood total serum bilirubin concentration and the serum albumin concentration were determined. All the infants were assessed for jaundice daily by measurement of transcutaneous bilirubin (TCB). When the infant's TCB was >or= 18 within the first 24 h after birth, >or= 21 at 48 h, >or= 25 at or after 72 h, the venous total serum bilirubin (TSB) was determined and treatment against jaundice was applied as needed. The infants were aligned into four groups according to their UCS bilirubin levels, starting from < 30 micromol/L(group 1); >or= 30 micromol/L(group 2); >or= 36 micromol/L(group 3); >or= 42 micromol/L(group 4). The frequency of hyperbilirubinemia and phototherapy (PT) were compared among the four groups. An analysis of UCS bilirubin as a predictor of later development of jaundice was performed. The characteristics of the infants who became jaundiced (jaundiced group) were compared with the normal infants (non-jaundiced group).

RESULTSA clear correlation between UCS bilirubin level and the development of hyperbilirubinemia was found in all populations of the four groups. Only eight of the 194 infants in group 1 showed a TCB index >or= 25. TSB values > 205 micromol/L but < 257 micromol/L were observed in 2 newborns. None of the infants in this group showed TSB > 257 micromol/L or needed PT. Thirty-two infants in group 2 showed TCB >or= 25, 12 infants had TSB > 205 micromol/L but < 257 micromol/L, 2 infants had TSB > 205 micromol/L and received PT. In group 3, one infant developed hyperbilirubinemia at 48 h after birth and received PT. Thirty-nine infants showed TCB >or= 25, 16 infants TSB > 205 micromol/L but < 257 micromol/L, 2 infants had TSB > 205 micromol/L and also received PT. In group 4, 4 infants showed a range of TSB from 200 to 215 micromol/L at 48 h and received PT. Twenty-two infants showed TCB >or= 25, 17 of them showed TSB > 205 micromol/L but < 257 micromol/L, and 5 of them had TSB > 205 micromol/L and received PT. The frequency of TSB > 205 micromol/L increased from 1.03% in group 1, 5.77% in group 2, 19.75% in group 3 and to 42.5% in group 4. None of the 194 newborns in group 1 needed phototherapy, whereas 0.96%, 3.70% and 22.5% of the newborns in groups 2 - 4, needed PT. The frequency of patients with hyperbilirubinemia or phototherapy increased with increasing UCS bilirubin levels. For the prediction of TCB >or= 25 using a UCS bilirubin cut-off level, such as >or= 35 micromol/L, we found a positive predictive value of 45.68% and sensitivity of 68.27%. It is significant to predict neonatal jaundice by UCS bilirubin levels (P < 0.001). In the jaundiced group (TCB >or= 25) UCS bilirubin levels were significantly higher than those in the non-jaundiced group (t = 10.96, P < 0.001). No significant differences were found in the cord blood serum albumin concentration (t = 2.38, P > 0.05), the gestational age (t = -0.90, P > 0.05), and birthweight (t = 0.10, P > 0.05) between the jaundiced and non-jaundiced groups.

CONCLUSIONSUCS bilirubin level is useful in predicting the subsequent jaundice in healthy term infants. The use of UCS bilirubin values may help detect infants at low or high risk for hyperbilirubinemia and minimize an unnecessary prolongation of hospitalization.

Bilirubin ; blood ; Birth Weight ; physiology ; Fetal Blood ; chemistry ; Gestational Age ; Humans ; Hyperbilirubinemia ; diagnosis ; Hyperbilirubinemia, Neonatal ; diagnosis ; Infant ; Infant, Newborn ; Jaundice ; blood ; Jaundice, Neonatal ; metabolism ; prevention & control ; Male ; Predictive Value of Tests ; Umbilical Cord ; blood supply

OBJECTIVETo analyze potential mutations of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene in patients with unconjugated hyperbilirubinemia, and to explore the correlation between the mutations and total serum bilirubin levels.

METHODSGenomic DNA was extracted from peripheral blood samples of patients. Coding sequence and promoter region of the UGT1A1 gene were amplified. Mutations were identified through DNA sequencing.

RESULTSMutations of the UGT1A1 gene were found in 46 out of 61 patients with unconjugated hyperbilirubinemia. Five types of mutations were detected, with a decreasing order of 211G>A, TA insertion in the TATAA promoter element, 686C>A, 1091C>T and 1352C>T. Compared with those carrying a single homozygous mutation or compound heterozygous mutations, total serum bilirubin was higher in those carrying a homozygous mutation in combination with other heterozygous mutations (P< 0.05). Based on the UGT1A1 gene mutations and level of total serum bilirubin, 44 patients were diagnosed with Gilbert syndrome, and 2 were diagnosed with Crigler-Najjar syndrome type 2.

CONCLUSIONThe level of total serum bilirubin is correlated with the number of UGT1A1 gene mutations as well as their heterozygous or homozygous status.

Adolescent ; Adult ; Aged ; Base Sequence ; Bilirubin ; blood ; Case-Control Studies ; DNA Mutational Analysis ; Female ; Glucuronosyltransferase ; genetics ; metabolism ; Heterozygote ; Homozygote ; Humans ; Hyperbilirubinemia ; enzymology ; genetics ; metabolism ; Male ; Middle Aged ; Molecular Sequence Data ; Young Adult

OBJECTIVETo study the role of N-methyl-D-aspartate-receptor (NMDAR) expression in the development of hearing damage in neonatal rats with hyperbilirubinemia.

METHODSSixty seven-day-old Sprague-Dawley rats were randomly injected with bilirubin of 100 microg/g (low-dose treatment group) or 200 microg/g (high-dose treatment group) or normal saline (control group). Auditory brainstem response (ABR) was examined. The concentrations of bilirubin in blood and brain were measured. NMDAR expression in the cochlear nucleus slices was examined by immunohistochemistry assay.

RESULTSABR reflecting threshold obviously increased, and I, II and III wave latency as well as I-II, II-III and I-III interval were more prolonged in the two bilirubin treatment groups when compared with the control group. The NMDAR expression in the cochlear nucleuse in the two bilirubin treatment groups was obviously lower than that in the control group. The NMDAR expression in the cochlear nucleuse was negatively correlated with the brain bilirubin content and the ABR reflecting threshold in the two bilirubin treatment groups.

CONCLUSIONSAn increased NMDAR activity may play an important role in hearing damage following hyperbilirubinemia.

Animals ; Animals, Newborn ; Bilirubin ; analysis ; Cochlear Nucleus ; chemistry ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Disorders ; etiology ; Hyperbilirubinemia ; complications ; metabolism ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis

Clinical and statistical analysis were performed on 573 cases of neonates who were admitted in the special care baby unit, St. Benedict Hospital, from January 1978 to June 1979. The results were as following: 1) Sex ratio of male to female was 1.04:1. 2) According to the route of admission, The ratio of "non-referred patients" to "referred patients was 1.86:1. 3) About the parity incidence, the first baby was 57.1%, the second was 29.7%, and the third was 9.6%. 4) About the age on admission, the babies of the one day I\of age was 45.5% and 86.9% was within 1 week of age. 5) According to the duration of admission, 1-7 days group was the most common(59.6%) and the next were 8-14 days group(24.6%), 15-21 days group(6.1%) 6) According to the duration of admission, 1-7 days group was the most common(59.6%) and the next were 8-14 days group(24.6%), 15-21 days group(6.1%). 7) About the maternal education of non-referred patients, group of high school educated was the most common(45.6%), followed by college(22.3%), middle school(15.3%), and primary school(9.7%). 8) On distribution of the maternal age of non-referred patients, the group of 20-30 years of age was the most common(51.7%), followed by 20-25 years of age (23.3%). Admission rate according to maternal age, higher incidence was seen over 31 years of age. 9) The most common placentas weight of non-refered patients was 600-800 gm. Group(39.9%) and the highest incidence of pre-term was the group of 200-400gm. 10) The most frequent problem was hyperbilirubinemia, followed by prematurity, infectious diseases, respiratory tract diseases, congenital anomalies, diseases associated with metabolism and birth injury. 11) According to the age of initiation of treatment in hyperbilirubinemic patients, the most common age was 4 day(30.5%) and the next was 3 days(25.1%), Suspected causes ware idiopathic(51.2%), blood group incompatibility(17.1%), prematurity(15.3%) and so on. 12) The main diseases associated with prematurity were hyperbilirub-inemia(47.9%), pneumonia(15.1%), RDS(8.4%). 13) Mortality rate were 26.6% in pre-term, 7.4% in post-term, 2.6% in full-term and mortality rate of all admission was 8.0%. Generally, the shorter gestational age and lower birth weight, the higher the mortality rate of premature infants was observed. 14) The leading causes of death were immaturity(48.5%), RDS(24.2%), pneumonia(21.2%) in pre-term, pneumonia(27.3%), kernicterus(18.2%) in full-term and anencephaly & placental dysfunction syndrome in postern 2 cases.
Anencephaly ; Birth Injuries ; Birth Weight ; Cause of Death ; Communicable Diseases ; Education ; Female ; Gestational Age ; Humans ; Hyperbilirubinemia ; Incidence ; Infant, Newborn ; Infant, Premature ; Male ; Maternal Age ; Metabolism ; Mortality ; Parity ; Placenta ; Respiratory Tract Diseases ; Sex Ratio

OBJECTIVE: Gestational diabetes mellitus is defined as carbohydrate intolerance of variable severity first diagnosed during pregnancy. It is associated with adverse outcomes of pregnancy including obstetrical complications such as increased rate of cesarean sections, preeclampsia, and birth trauma, and perinatal morbidities, such as macrosomia, hypoglycemia, hypocalcemia, and hyperbilirubinemia. Therefore, screening for gestational diabetes mellitus and early diagnosis of this condition allows intervention to be carried out, thereby, the reduction of the untoward effects mentioned above can be minimized. METHODS: Screening for abnormal glucose metabolism was carried out in 489 pregnant women. A 50-g oral glucose load without regard to time of day or last meal, and a 1-hour plasma glucose determination with a threshold of 140mg/dl were used as a glucose screening test(GST). Patients with an abnormal GST underwent an oral glucose tolerance test(GTT). RESULTS: The overall incidence of gestational diabetes was 2.7%. The occurrence of this disorder was significantly related to the age of pregnant women, parity, or the presence of risk factors for gestational diabetes and obesity(Body Mass Index> or =26kg/m2). CONCLUSION: This study suggests that Korean pregnant women should be screened for gestational diabetes.
Blood Glucose ; Cesarean Section ; Diabetes, Gestational* ; Early Diagnosis ; Female ; Glucose Tolerance Test ; Glucose* ; Humans ; Hyperbilirubinemia ; Hypocalcemia ; Hypoglycemia ; Incidence ; Mass Screening* ; Meals ; Metabolism ; Parity ; Parturition ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Prenatal Diagnosis* ; Risk Factors

The aim of this study was to investigate antifactor Xa (aFXa) levels after once daily dose of 40 mg of enoxaparin and to evaluate factors influencing aFXa levels among Korean intensive care unit (ICU) patients. This prospective observational study was conducted between August and December 2011 in medical ICUs at Samsung Medical Center. AFXa levels between 0.1 and 0.3 U/mL were considered to be effective for antithrombotic activity. Fifty-five patients were included. The median aFXa levels were 0.22 (IQR 0.17-0.26) at 4 hr, 0.06 (IQR 0.02-0.1) at 12 hr, and 0 U/mL (IQR 0-0.03) at 24 hr. The numbers of patients showing effective antithrombotic aFXa levels were 48 (87.3%), 18 (32.7%), and 0 (0%) at 4, 12 and 24 hr, respectively. At 12 hr, higher sequential organ failure assessment (SOFA) scores and hyperbilirubinemia were significantly associated with low aFXa levels (OR, 0.58; 95% CI, 0.36-0.93; P = 0.02 and 0.06; 0.003-0.87; 0.04, respectively). Once daily dose of 40 mg of enoxaparin is inadequate for maintaining effective antithrombotic aFXa levels, and the inadequacy is more salient for patients with high SOFA scores and hyperbilirubinemia.
Aged ; Asian Continental Ancestry Group ; Critical Illness ; Enoxaparin/*therapeutic use ; Factor Xa/analysis/*antagonists & inhibitors ; Female ; Fibrinolytic Agents/*therapeutic use ; Humans ; Hyperbilirubinemia/metabolism ; Intensive Care Units ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Regression Analysis ; Republic of Korea ; Risk Factors ; Venous Thromboembolism/*drug therapy

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load