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At least 19 recordsLinked to original sources
PubMed2005

Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate-glucuronosyltransferase gene: the common -3263T > G mutation of phenobarbital response enhancer module is not associated with the neonatal hyperbilirubinemia in Japanese.

BACKGROUND: Neonatal hyperbilirubinemia is frequent and severe in Japanese newborns. Previously, it has been reported that half of the Japanese neonates with severe hyperbilirubinemia carried the 211G > A (p.G71R) mutation of the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene causing Gilbert syndrome. Recently, it was reported that the -3263T > G mutation in the phenobarbital response enhancer module in UGT1A1 was associated with the majority of cases of Gilbert syndrome. The gene frequency of the -3263T > G mutation was determined and the relation with neonatal hyperbilirubinemia in Japanese was studied. METHODS: UGT1A1 in 119 neonates born at Yamagata University Hospital, Yamagata, Japan, and 26 subjects who had undergone phototherapy due to severe hyperbilirubinemia at four other hospitals were studied. The gene frequency of -3263T > G mutation in Japanese, Korean, Chinese and German healthy adult controls was also determined. Hyperbilirubinemia was assessed with a Jaundice Meter and UGT1A1 was analyzed by sequence determination or restriction enzyme method. RESULTS: The gene frequency of the -3263T > G mutation was 0.26 in Japanese subjects and was similar to the prevalence in Korean, Chinese and German populations. However, there was no significant increase in the gene frequency of the mutation in the neonates who required phototherapy for hyperbilirubinemia compared to that in the neonates without severe hyperbilirubinemia. In addition, neonates with or without the mutation did not show a significant change in the level of bilirubin and the mutation also did not show a synergic effect with the 211G > A mutation on the level of bilirubin. CONCLUSION: The -3263T > G mutation is not likely to be associated with the neonatal hyperbilirubinemia in Japanese.

Asian People↗
PubMed1997

[Hyperbilirubinemia in healthy full-term neonates: guidelines for diagnosis and treatment. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics].

In healthy full-term neonates without haemolytic disease, hyperbilirubinaemia is not associated with neurological, auditory or cognitive disorders later in life. Therefore, the new threshold levels of hyperbilirubinaemia at which further diagnosis and treatment are indicated, are higher than the former ones.

Bilirubin↗
PubMed1997

[Hyperbilirubinemia in full-term neonates: sequelae for long-term development better than expected. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics].

OBJECTIVE: Critical evaluation of guidelines for treatment of hyperbilirubinaemia in healthy full-term newborns, based on literature data concerning effects of hyperbilirubinaemia on later development. DESIGN: Structured literature survey. SETTING: Groningen, the Netherlands. METHODS: By electronic and hand searching of literature according to published guidelines data were collected on the relation between the peak total serum bilirubin concentration (TSB) in the first week of life and later development. RESULTS: One large study, the Collaborative Perinatal Project (CPP), showed statistically significant negative associations of TSB in the first week of life with Bayley development score at age 8 months, intelligence quotient (IQ) at age 4 years, and unspecified neurological abnormalities at age 7-8 years. In other studies, with considerable less power than the CPP, no such findings were made. In the original analyses of the CPP no correction was made for confounders and effect modifiers; after correction for such variables, a relation between TSB in the first week of life and later development was no longer found. At the age of 6 years, no statistically significant differences in IQ, hearing, and neurological abnormalities were found between children who, as newborns, had or had not been treated with phototherapy because of hyperbilirubinaemia. CONCLUSION: Treatment for jaundice in healthy full-term newborns is only indicated at considerably higher serum bilirubin levels than those recommended previously.

Bilirubin↗
PubMed2003

Management of hyperbilirubinemia in newborns: measuring performance by using a benchmarking model.

BACKGROUND: Accreditors hold hospitals accountable for harm from serious newborn hyperbilirubinemia, yet standards for evaluating performance in prevention are lacking. OBJECTIVE: We confirmed prognostic variables for newborn hyperbilirubinemia and developed a benchmarking model for self-evaluation of hyperbilirubinemia management. METHODS: We conducted a 3-year prospective cohort study in the Henry Ford Health System (HFHS) on 5507 healthy newborns of >or=35 weeks' gestational age. HFHS follows a rigorous protocol for hyperbilirubinemia management. Defining hyperbilirubinemia as age-specific levels of total serum bilirubin exceeding American Academy of Pediatrics criteria for considering phototherapy and severe hyperbilirubinemia as total serum bilirubin >or=20 mg/dL, we used logistic and Poisson regressions to determine predictors and estimate parameters for a benchmarking model. We compared incidence rates for severe hyperbilirubinemia from HFHS to aggregate data from 11 hospitals reported to have less rigorous management. RESULTS: Newborns were 52.9% black, 14.4% white, 24.3% Latino, and 2.4% Asian; 30% were exclusively and 28% partially breastfed. Regression analyses revealed associations for hyperbilirubinemia and severe hyperbilirubinemia with black mothers (negative) and exclusive or partial breastfeeding and younger gestational age (positive). Male newborns and older mothers were also associated with severe hyperbilirubinemia. For all 5 variables, we found a lower risk for severe hyperbilirubinemia at HFHS than in the comparison hospital group. To compare hospitals, we developed a benchmarking model for incidence of hyperbilirubinemia adjusting for race, feeding method, and gestational age. CONCLUSIONS: Hospitals with access to newborns' inpatient and postdischarge data can use our benchmarking model to compare their management of hyperbilirubinemia with a reference population that received rigorous care.

Benchmarking↗
PubMed2001

Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah's Witness newborns as an alternative to exchange transfusion.

OBJECTIVE: The religious convictions of parents who are Jehovah's Witness adherents lead them to reject the use of exchange transfusions as therapy for severe hyperbilirubinemia in newborns in whom intensive phototherapy has failed to control this problem. Consequently, physicians caring for such infants may be obliged to initiate legal action to compel use of the procedure when severe hyperbilirubinemia not sufficiently responsive to phototherapy warrants an exchange transfusion. Our goal was to determine if we could use the potent inhibitor of bilirubin production, Sn-Mesoporphyrin (SnMP), to resolve the troubling medical-legal issues in such situations in 2 infants with hemolytic disease of the newborn who required exchange transfusions for severe hyperbilirubinemia but whose Jehovah's Witness parents rejected the procedure. SnMP was administered in a single dose, as in previous studies, at the time when exchange transfusion would have been initiated and plasma bilirubin levels were monitored at close intervals thereafter. METHODS: SnMP is a potent inhibitor of heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin. We found in earlier studies that in single doses of 6 micromol/kg birth weight, SnMP is extremely effective in moderating the course of hyperbilirubinemia and in eliminating the need for supplemental phototherapy in jaundiced newborns. In the 2 cases described, a single dose of SnMP (6 micromol/kg birth weight) was administered intramuscularly to severely jaundiced infants with immune hemolysis at a time when clinical circumstances dictated the need for exchange transfusion. CASE 1: This patient was a preterm male infant (gestational age: 35 5/7 weeks; birth weight: 2790 g) whose plasma bilirubin concentration (PBC) at 1 hour after birth was 5.0 mg/dL. Despite intensive phototherapy with 3 banks of lights and 1 biliblanket, the PBC increased steadily with no diminution in the rate of increase for 75 hours. In view of the problems of immune hemolysis, and prematurity, and the inability of phototherapy to stop progression of hyperbilirubinemia, a decision to carry out an exchange transfusion was made; the decision was, however, rejected by the Jehovah's Witness parents. Pending legal action to compel use of the procedure, a request to this (Rockefeller) laboratory for SnMP was made; its use was approved by the Food and Drug Administration; and the inhibitor was delivered to the physician-in-charge (D.P.M.) in Sioux Falls, South Dakota. The single dose of SnMP was administered to the infant at 75 hours after birth; the course of hyperbilirubinemia before and after the use of the inhibitor is shown in Fig 1. [figure: see text]. CASE 2: This female term infant (gestational age: 38-39 weeks; birth weight: 4140 g) with immune hemolysis was delivered by cesarean section and because of problems related to meconium aspiration required helicopter transfer to the Special Care Nursery in Abilene, Texas, where 10 hours after birth the first PBC was determined to be 18.0 mg/dL. Double-bank phototherapy plus a biliblanket was initiated; a third bank of lights was later ordered. The PBC fluctuated in the ensuing 2 days between 13.8 to 25.8 mg/dL during which suggestive clinical signs of possible bilirubin encephalopathy became manifest. In view of the clinical circumstances and the continued severe hyperbilirubinemia, permission for a double-exchange transfusion was requested. The parents, who were Jehovah's Witness adherents, refused the procedure. While preparing legal action to compel use of the exchange, a request was made to this (Rockefeller) laboratory for use of SnMP to attempt control of hyperbilirubinemia. With FDA approval, the SnMP was delivered to the attending neonatologist (J. R. M.) in Abilene and administered in a single dose (6 micromol/kg birth weight) at 56 hours after birth when the PBC was 19.5 mg/dL. The course of bilirubinemia before and after SnMP use is shown in Fig 2. [figure: see text]. RESULTS AND CONCLUSIONS: The use of SnMP to moderate or prevent the development of severe hyperbilirubinemia in newborns (preterm, near-term, term with high PBCs [15-18 mg/dL], ABO-incompatibility; glucose-6-phosphate dehydrogenase deficiency) has been extensively studied in carefully conducted clinical trials the results of which have been reported earlier. This inhibitor of bilirubin production has demonstrated marked efficacy in moderating the course of hyperbilirubinemia in all diagnostic groups of unconjugated neonatal jaundice. The 2 cases described in this report confirmed the efficacy of SnMP in terminating progression of hyperbilirubinemia in infants in whom phototherapy had failed to sufficiently control the problem and whose parents, for religious reasons, would not permit exchange transfusions. Interdiction of severe hyperbilirubinemia by inhibiting the production of bilirubin with SnMP can be an effective alternative to the use of exchange transfusion in the management of severe newborn jaundice that has not responded sufficiently to light treatment to ease concern about the development of bilirubin encephalopathy.

Bilirubin↗
PubMed2006

Hyperbilirubinemia after extracorporeal circulation surgery: a recent and prospective study.

AIM: To clarify the incidence and nature of postoperative hyperbilirubinemia in patients after modern extracorporeal circulation, to analyze possible perioperative risk factors, and to elucidate the clinical significance of postoperative hyperbilirubinemia associated mortality and morbidity. METHODS: Between March 2005 and May 2006, three hundred and eighty six consecutive patients undergoing extracorporeal circulation surgery due to a variety of cardiac lesions were investigated prospectively. The incidence of postoperative hyperbilirubinemia was defined as a serum total bilirubin concentration of more than 51 micromol/L. Several perioperative parameters were compared by logistic regression between hyperbilirubinemia and non-hyperbilirubinemia patients to determine possible risk factors contributing to postoperative hyperbilirubinemia and mortality. RESULTS: Overall incidence of postoperative hyperbilirubinemia was 25.3% (98/386). In patients with postoperative hyperbilirubinemia, 56.2% reached peak total bilirubin concentration on the first postoperative day, 33.5% on the second day, and 10.3% on the seventh day. Eighty percent of the increase of total bilirubin resulted from an increase of both conjugated and unconjugated bilirubin. Development of postoperative hyperbilirubinemia was associated with a higher mortality (P<0.01), longer duration of mechanical ventilation (P<0.05) and longer ICU stay time (P<0.05). Preoperative total bilirubin concentration, preoperative right atrium pressure, numbers of valves replaced and of blood transfusion requirement were identified as important predictors for postoperative hyperbilirubinemia. CONCLUSION: Early postoperative hyperbilirubinemia after modern extracorporeal circulation is mainly caused by an increase in both conjugated and unconjugated bilirubin, and is associated with a high mortality. Important contributing factors are the preoperative total bilirubin concentration, preoperative severity of right atrial pressure, numbers of valve replacement procedures, and the amount of blood transfusion requirement during and shortly after surgery. We suggest that postoperative hyperbilirubinemia is a multifactorial process, which is caused by both the impaired liver function of bilirubin transport and the increased production of bilirubin from haemolysis.

Adolescent↗
PubMed2002

An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility.

OBJECTIVE: In the era of early discharge of newborns from the hospital, newborns with ABO incompatibility are at especially greater risk for developing a subsequent significant hyperbilirubinemia because some of these infants also may present with some degree of ABO isoimmune disease. In this study, we aimed to determine prospectively the critical serum total bilirubin level to predict significant hyperbilirubinemia and severe hemolytic disease in healthy term newborns with ABO incompatibility based on a serum bilirubin measurement made at a postnatal age at which all newborns are at the hospital before discharge and at which any therapeutic intervention, if necessary, could be started as early as possible. METHODS: A total of 136 healthy term newborns with ABO (O-A or O-B) blood group incompatibility were followed prospectively with daily serum total bilirubin measurements for the first 5 days of life. Newborns with serum total bilirubin levels of > or =5 mg/dL and an increase in serum total bilirubin concentration of >0.5 mg/dL/h in the first 24 hours, > or =12 mg/dL on day 2, > or =15 mg/dL on day 3, and > or =17 mg/dL on days 4 and 5 were defined to have significant hyperbilirubinemia and were started on phototherapy treatment. Additional treatment modalities, including intense phototherapy, intravenous immunoglobulin treatment, and exchange transfusion, were used when serum bilirubin concentrations exceeded 20 mg/dL or increased by >1 mg/dL/h despite a phototherapy treatment of at least 4 hours. The additional assessment of the predictive ability of the sixth-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia was made on the basis of the placement of any of the first 5 days' serum bilirubin measurements in the > or =90th percentile of the study population. On the basis of the percentile tracks constructed from the 10th, 35th, 50th, 60th, and 90th percentiles of serum total bilirubin values, a nomogram demonstrating the 3 percentile tracks as risk zone demarcators with divided risk zones was produced. RESULTS: Twenty-nine newborns (21.3%) had significant hyperbilirubinemia. There were significant differences between the newborns who did and the newborns who did not develop significant hyperbilirubinemia with respect to the reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal jaundice (6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour of life was determined to have the highest sensitivity (86.2%) and negative predictive value (94.5%) and a positive predictive value of 39.7% to predict the newborns who would develop significant hyperbilirubinemia. At the mean serum bilirubin level of 6 mg/dL, the sensitivity, specificity, and negative and positive predictive values were 100%, 91.5%, 100%, and 35.3%, respectively, in diagnosing 6 cases of severe ABO hemolytic disease. On the hour (age)-specific percentile-based nomogram, the zone above the 90th percentile was determined as high risk and that below the 35th percentile as low risk. CONCLUSIONS: The reticulocyte count, a positive direct antiglobulin test, and the presence of a sibling with neonatal jaundice were determined to be the good predictors for the development of significant hyperbilirubinemia and severe hemolytic disease of the newborn. A serum bilirubin measurement and the use of the critical bilirubin levels of 4 mg/dL and 6 mg/dL at the sixth hour of life will predict nearly all newborns who will have significant hyperbilirubinemia and those who will develop severe hemolytic disease of the newborn, respectively. An hour (age)-specific percentile-based nomogram can be used to predict which newborn is at high risk (> or =90th percentile), intermediate risk (35th-90th percentiles), and low risk (<35th percentile) for developing significant hyperbilirubinemia. The 35th and 90th percentile tracks, approximating the serum bilirubin levels of 3.3 mg/dL and 6.5 mg/dL at the sixth hour of life, respectively, can be used as safe risk demarcators in deciding about the time of discharge of ABO-incompatible newborns from the hospital.

ABO Blood-Group System↗
PubMed2004

Incidence, course, and prediction of hyperbilirubinemia in near-term and term newborns.

OBJECTIVE: In this study, we investigated prospectively the incidence of significant hyperbilirubinemia and demographic and laboratory characteristics and pattern of serum bilirubin levels of near-term newborns (35-37 weeks' [245-265 days'] gestation) by comparing them with those of term newborns (38-42 weeks' [266-294 days'] gestation) longitudinally in the first 7 days of life; we also aimed to determine the value of an early (6th-hour) serum bilirubin measurement in predicting the development of significant hyperbilirubinemia later during the first week of life in near-term newborns. METHODS: Serum total bilirubin measurements were initially made at the 6th hour of life and repeated daily for the next 4 days, and a last measurement was performed on the 7th day (150th hour) in 219 term newborns (term group) and 146 near-term newborns (near-term group). Newborns with serum total bilirubin levels of > or =8 and > or =12 mg/dL on day 2, > or =12 and > or 15 mg/dL on day 3, and > or =14 and > or =17 mg/dL on days 4, 5, and 7 for birth weights 2000 to 2500 g and >2500 g, respectively, were defined to have significant hyperbilirubinemia, and phototherapy treatment was started. The predictive ability of the 6th-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia in the near-term group was assessed on the basis of the placement of any of the first week's serum bilirubin measurements in the > or =95th percentile of the study population. A Gaussian distribution curve, the 5th, 30th, 60th, and 95th percentiles, and 4 percentile tracks were obtained from mean serum total bilirubin values. On the basis of the percentile tracks with various sensitivity, specificity, and negative and positive predictive values, a nomogram demonstrating the 4 percentile tracks as risk-zone demarcators with divided risk zones was produced. RESULTS: Twenty-three newborns (10.5%) in the term group and 37 newborns (25.3%) in the near-term group had significant hyperbilirubinemia and required phototherapy. When the daily mean serum bilirubin levels of the 2 groups were compared, the first 4 days' values did not significantly differ between the 2 groups, whereas the 5th and 7th days' values were significantly higher in the near-term group. There were significant differences between the 2 groups with respect to the incidence of significant hyperbilirubinemia, hematocrit, Apgar score, and mode of delivery. On the age-specific nomogram, the zone >95th percentile was labeled as high risk, and that <5th percentile was labeled as low risk. Serum total bilirubin values between the 5th and 30th, 30th and 60th, and 60th and 95th percentiles were designated as being in the low-intermediate, intermediate, and high-intermediate risk zones, respectively. The 5th and 95th percentiles on the nomogram had the highest sensitivity (100%) and specificity (98.2%), respectively, in predicting the subsequent development of significant hyperbilirubinemia. CONCLUSIONS: Near-term newborns should not be treated as term newborns in the approach to management of hyperbilirubinemia, because infants of 35 to 37 weeks' gestation had significantly lower birth weights, significantly higher serum total bilirubin levels on days 5 and 7, and were 2.4 times more likely to develop significant hyperbilirubinemia than those of 38 to 42 weeks' gestation in the present study. In near-term newborns of 35 to 37 weeks' (245 to 265 days') gestation, the decision to diagnose and treat significant hyperbilirubinemia should be made on the basis of risk status (percentile distribution of the serum bilirubin values on postnatal age) rather than using birth-weight-based thresholds. A nomogram constructed from daily serum bilirubin values of each population, as we present herein, can be used in assessing the age (hour)-specific jaundice risk (high, intermediate, or low) of each near-term newborn.

Birth Weight↗
PubMed1994

Hyperbilirubinemia after cardiac operation. Incidence, risk factors, and clinical significance.

Three hundred and two consecutive patients who had undergone cardiac operation for various cardiac lesions were studied prospectively to evaluate the incidence, risk factors, and the associated mortality of postoperative hyperbilirubinemia after cardiopulmonary bypass. Concentrations of the serum total (conjugated and unconjugated) bilirubin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, albumin, globulin, and serum haptoglobin were measured before the operation and again on the first, second, and seventh postoperative days. Postoperative hyperbilirubinemia was defined as occurrence of a serum total bilirubin concentration of more than 3 mg/dl in any measurement during the postoperative period. Logistic regression was done to identify possible risk factors for postoperative hyperbilirubinemia. Overall incidence of postoperative hyperbilirubinemia was 35.1%; the incidence of postoperative hyperbilirubinemia was higher in patients whose valves were replaced with mechanical prostheses than in those without prostheses (p < 0.00001). In patients with postoperative hyperbilirubinemia, 70% of the increase of total bilirubin on the first postoperative day came about from an increase in unconjugated bilirubin. Serum haptoglobin decreased significantly at the same time (p < 0.01). Development of the postoperative hyperbilirubinemia was associated with a higher mortality (5.6% versus 0.5%, p < 0.01) and higher frequency of use of intraaortic balloon counterpulsation, especially for patients in whom the highest postoperative total bilirubin occurred after the first 2 days. The numbers of valves replaced, preoperative right atrial pressure, and preoperative total bilirubin concentration are the significant risk factors that, in combination, correctly predict the occurrence of postoperative hyperbilirubinemia in 80% of the patients. We concluded that postoperative hyperbilirubinemia results mainly from an increase in unconjugated bilirubin and is associated with higher mortality, especially for patients in whom highest postoperative total bilirubin occurred late after operation. Patients with the higher preoperative right atrial pressure and total bilirubin level who then underwent multiple valve replacement procedures are at greater risk for development of postoperative hyperbilirubinemia.

Cardiac Surgical Procedures↗