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Michael Kaplan - One of the best experts on this subject based on the ideXlab platform.
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hemolysis and glucose 6 phosphate dehydrogenase deficiency related neonatal Hyperbilirubinemia
Neonatology, 2018Co-Authors: Michael Kaplan, Ronald J. Wong, David K. StevensonAbstract:Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency affecting more than 300 million individuals worldwide. Extreme neonatal Hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death, is the most devastating manifestation of G6PD deficiency. In a recent review of Favism, Luzzatto and Arese state that the pathophysiology of jaundice in G6PD-deficient neonates is different from that of favism, as there is little evidence of hemolysis in these infants. Objectives To explore the role of hemolysis in neonatal Hyperbilirubinemia associated with G6PD deficiency. Methods Previously published works including studies of endogenous production of carbon monoxide (CO), an index of heme catabolism, in hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of hemolysis in this condition. Results Three studies demonstrated that endogenous CO production is elevated in G6PD-deficient neonates with extreme Hyperbilirubinemia. Conclusions Hemolysis is an important pathogenetic factor in G6PD deficiency-associated neonatal Hyperbilirubinemia.
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Bilirubin and the Genome: The Hereditary Basis of Unconjugated Neonatal Hyperbilirubinemia
2013Co-Authors: Michael Kaplan, Cathy HammermanAbstract:Abstract: Severe neonatal unconjugated Hyperbilirubinemia, with the risk of bilirubin encephalopathy or kernicterus in severe, untreated cases, occurs when bilirubin production exceeds the body's ability to eliminate it. The causes of neonatal Hyperbilirubinemia are multifactorial and comprise increased hemolysis on the one hand, and diminished bilirubin conjugation on the other. In recent years, many of these etiologies have been found to have a genetic origin. Sometimes hereditary factors act independently, but in other circumstances, single mutations which ordinarily do not produce disease in and of themselves, may result in severe Hyperbilirubinemia as a result of interaction with other mutated genes. Of cardinal importance to this discussion is the concept of the human genome, whereby the thousands of genes of which it is comprised may interact one with the other, or with the environment, exacerbating the severity of jaundice in certain individuals, and protecting against Hyperbilirubinemia in others. Genetic interactions have been demonstrated combining increased bilirubin production with diminished bilirubin conjugation, resulting in severe Hyperbilirubinemia. Appreciation of the multiplicity of genetic interactions is of importance in our evaluation of the neonate with severe Hyperbilirubinemia, in our attempts to prevent future cases of kernicterus, and in genetic counseling of families who have had an infant with severe neonatal Hyperbilirubinemia. Gene therapy for the most severe of these inherited defects of bilirubin conjugation, Crigler-Najjar syndrome type 1, might become a reality in future years
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neonatal Hyperbilirubinemia in african american males the importance of glucose 6 phosphate dehydrogenase deficiency
The Journal of Pediatrics, 2006Co-Authors: Michael Kaplan, Cathy Hammerman, Marguerite Herschel, James D Hoyer, Gillian Z Heller, David K. StevensonAbstract:Objective To perform risk factor analysis for the prediction of Hyperbilirubinemia in an African American male neonatal cohort. Study design A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for Hyperbilirubinemia. Factors studied included birth weight ≥4.0 kg, gestational age ≤37 weeks, breast-feeding, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and predischarge bilirubin ≥75 th percentile. Hyperbilirubinemia was defined as any bilirubin value ≥95 th percentile on the hour-of-life–specific bilirubin nomogram. Results Forty-three (8.6%) neonates developed Hyperbilirubinemia. At 48 ± 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75 th percentile 10.0 mg/dL, and 95 th percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin ≥75 th percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P Conclusions African American male neonates may be at higher risk for Hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in Hyperbilirubinemia prediction in these newborns.
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understanding severe Hyperbilirubinemia and preventing kernicterus adjuncts in the interpretation of neonatal serum bilirubin
Clinica Chimica Acta, 2005Co-Authors: Michael Kaplan, Cathy HammermanAbstract:Abstract The serum total bilirubin concentration at any point in time represents the amount of bilirubin being produced minus that being excreted. Hyperbilirubinemia develops when bilirubin production exceeds the body's capacity to excrete it, primarily by conjugation. When extreme, Hyperbilirubinemia may lead to the development of free bilirubin, that form of bilirubin which may cross the blood–brain barrier and enter and damage the basal nuclei of the brain. This rare, though devastating complication, may result in irreversible bilirubin induced brain damage termed kernicterus. In this paper, adjuncts to the interpretation of the serum total bilirubin are discussed, with the purpose of singling out those few neonates in real danger of bilirubin encephalopathy. Interpretation of the serum total bilirubin should be performed in conjunction with factors unique to the particular infant being evaluated. Understanding the mechanisms and dangers of severe neonatal Hyperbilirubinemia should facilitate recognition of an emergency situation and optimize the speed with which bilirubin testing is performed and blood for exchange transfusion prepared. Hyperbilirubinemia is a condition of major importance and a source of concern to all involved in the management of the newborn. Its prevention and management should be based on the recently revised American Academy of Pediatric guidelines, with special attention paid to neonates manifesting risk factors for kernicterus. Close cooperation between the clinical laboratory and the medical team managing the newborn is an essential component in the management of a hyperbilirubinemic baby.
David K. Stevenson - One of the best experts on this subject based on the ideXlab platform.
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hemolysis and glucose 6 phosphate dehydrogenase deficiency related neonatal Hyperbilirubinemia
Neonatology, 2018Co-Authors: Michael Kaplan, Ronald J. Wong, David K. StevensonAbstract:Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency affecting more than 300 million individuals worldwide. Extreme neonatal Hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death, is the most devastating manifestation of G6PD deficiency. In a recent review of Favism, Luzzatto and Arese state that the pathophysiology of jaundice in G6PD-deficient neonates is different from that of favism, as there is little evidence of hemolysis in these infants. Objectives To explore the role of hemolysis in neonatal Hyperbilirubinemia associated with G6PD deficiency. Methods Previously published works including studies of endogenous production of carbon monoxide (CO), an index of heme catabolism, in hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of hemolysis in this condition. Results Three studies demonstrated that endogenous CO production is elevated in G6PD-deficient neonates with extreme Hyperbilirubinemia. Conclusions Hemolysis is an important pathogenetic factor in G6PD deficiency-associated neonatal Hyperbilirubinemia.
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association of hmox1 gene promoter polymorphisms with Hyperbilirubinemia in the early neonatal period
Pediatrics International, 2015Co-Authors: Yoshinori Katayama, Ronald J. Wong, David K. Stevenson, Hajime Nakamura, Hui Zhao, Tomoyuki Yokota, Mariko Taniguchiikeda, Kazumoto Iijima, Ichiro MoriokaAbstract:Background Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal Hyperbilirubinemia in a population of Japanese term neonates. Methods Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on Hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with Hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case–control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates. Results The prevalence of short alleles (<22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal Hyperbilirubinemia (OR, 3.1; 95%CI: 1.03–9.53). Conclusions Infants carrying short alleles (<22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal Hyperbilirubinemia.
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neonatal Hyperbilirubinemia in african american males the importance of glucose 6 phosphate dehydrogenase deficiency
The Journal of Pediatrics, 2006Co-Authors: Michael Kaplan, Cathy Hammerman, Marguerite Herschel, James D Hoyer, Gillian Z Heller, David K. StevensonAbstract:Objective To perform risk factor analysis for the prediction of Hyperbilirubinemia in an African American male neonatal cohort. Study design A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for Hyperbilirubinemia. Factors studied included birth weight ≥4.0 kg, gestational age ≤37 weeks, breast-feeding, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and predischarge bilirubin ≥75 th percentile. Hyperbilirubinemia was defined as any bilirubin value ≥95 th percentile on the hour-of-life–specific bilirubin nomogram. Results Forty-three (8.6%) neonates developed Hyperbilirubinemia. At 48 ± 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75 th percentile 10.0 mg/dL, and 95 th percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin ≥75 th percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P Conclusions African American male neonates may be at higher risk for Hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in Hyperbilirubinemia prediction in these newborns.
Cathy Hammerman - One of the best experts on this subject based on the ideXlab platform.
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Bilirubin and the Genome: The Hereditary Basis of Unconjugated Neonatal Hyperbilirubinemia
2013Co-Authors: Michael Kaplan, Cathy HammermanAbstract:Abstract: Severe neonatal unconjugated Hyperbilirubinemia, with the risk of bilirubin encephalopathy or kernicterus in severe, untreated cases, occurs when bilirubin production exceeds the body's ability to eliminate it. The causes of neonatal Hyperbilirubinemia are multifactorial and comprise increased hemolysis on the one hand, and diminished bilirubin conjugation on the other. In recent years, many of these etiologies have been found to have a genetic origin. Sometimes hereditary factors act independently, but in other circumstances, single mutations which ordinarily do not produce disease in and of themselves, may result in severe Hyperbilirubinemia as a result of interaction with other mutated genes. Of cardinal importance to this discussion is the concept of the human genome, whereby the thousands of genes of which it is comprised may interact one with the other, or with the environment, exacerbating the severity of jaundice in certain individuals, and protecting against Hyperbilirubinemia in others. Genetic interactions have been demonstrated combining increased bilirubin production with diminished bilirubin conjugation, resulting in severe Hyperbilirubinemia. Appreciation of the multiplicity of genetic interactions is of importance in our evaluation of the neonate with severe Hyperbilirubinemia, in our attempts to prevent future cases of kernicterus, and in genetic counseling of families who have had an infant with severe neonatal Hyperbilirubinemia. Gene therapy for the most severe of these inherited defects of bilirubin conjugation, Crigler-Najjar syndrome type 1, might become a reality in future years
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neonatal Hyperbilirubinemia in african american males the importance of glucose 6 phosphate dehydrogenase deficiency
The Journal of Pediatrics, 2006Co-Authors: Michael Kaplan, Cathy Hammerman, Marguerite Herschel, James D Hoyer, Gillian Z Heller, David K. StevensonAbstract:Objective To perform risk factor analysis for the prediction of Hyperbilirubinemia in an African American male neonatal cohort. Study design A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for Hyperbilirubinemia. Factors studied included birth weight ≥4.0 kg, gestational age ≤37 weeks, breast-feeding, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and predischarge bilirubin ≥75 th percentile. Hyperbilirubinemia was defined as any bilirubin value ≥95 th percentile on the hour-of-life–specific bilirubin nomogram. Results Forty-three (8.6%) neonates developed Hyperbilirubinemia. At 48 ± 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75 th percentile 10.0 mg/dL, and 95 th percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin ≥75 th percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P Conclusions African American male neonates may be at higher risk for Hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in Hyperbilirubinemia prediction in these newborns.
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understanding severe Hyperbilirubinemia and preventing kernicterus adjuncts in the interpretation of neonatal serum bilirubin
Clinica Chimica Acta, 2005Co-Authors: Michael Kaplan, Cathy HammermanAbstract:Abstract The serum total bilirubin concentration at any point in time represents the amount of bilirubin being produced minus that being excreted. Hyperbilirubinemia develops when bilirubin production exceeds the body's capacity to excrete it, primarily by conjugation. When extreme, Hyperbilirubinemia may lead to the development of free bilirubin, that form of bilirubin which may cross the blood–brain barrier and enter and damage the basal nuclei of the brain. This rare, though devastating complication, may result in irreversible bilirubin induced brain damage termed kernicterus. In this paper, adjuncts to the interpretation of the serum total bilirubin are discussed, with the purpose of singling out those few neonates in real danger of bilirubin encephalopathy. Interpretation of the serum total bilirubin should be performed in conjunction with factors unique to the particular infant being evaluated. Understanding the mechanisms and dangers of severe neonatal Hyperbilirubinemia should facilitate recognition of an emergency situation and optimize the speed with which bilirubin testing is performed and blood for exchange transfusion prepared. Hyperbilirubinemia is a condition of major importance and a source of concern to all involved in the management of the newborn. Its prevention and management should be based on the recently revised American Academy of Pediatric guidelines, with special attention paid to neonates manifesting risk factors for kernicterus. Close cooperation between the clinical laboratory and the medical team managing the newborn is an essential component in the management of a hyperbilirubinemic baby.
Marlies Wallner - One of the best experts on this subject based on the ideXlab platform.
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bilirubin decreases macrophage cholesterol efflux and atp binding cassette transporter a1 protein expression
Journal of the American Heart Association, 2017Co-Authors: Dongdong Wang, Anela Tosevska, E Heis, Angela Ladurner, Christine Molzer, Marlies WallnerAbstract:Background Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low‐density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. Methods and Results Cholesterol efflux from THP‐1 macrophages was assessed using plasma obtained from normo‐ and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3–17.1 μmol/L) exogenously added to plasma‐ or apolipoprotein A1–supplemented media also decreased macrophage cholesterol efflux in a concentration‐ and time‐dependent manner. We also showed reduced protein expression of the ATP‐binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1–mediated cholesterol efflux, in THP‐1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP‐1 macrophages. Conclusions Cholesterol efflux from THP‐1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild Hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin9s impact on cholesterol transport and represent an important advancement in our understanding of bilirubin9s role in cardiovascular disease.
Finn Ebbesen - One of the best experts on this subject based on the ideXlab platform.
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extreme neonatal Hyperbilirubinemia acute bilirubin encephalopathy and kernicterus spectrum disorder in children with galactosemia
Pediatric Research, 2018Co-Authors: Laura Fuglsang Bech, Mette Line Donneborg, Allan M Lund, Finn EbbesenAbstract:Galactosemia has not been recognized as a cause of extreme neonatal Hyperbilirubinemia, although growing evidence supports this association. In a retrospective cohort study, we identified children with galactosemia due to GALT deficiency using the Danish Metabolic Laboratory Database. Among these, we identified children with extreme neonatal Hyperbilirubinemia or symptoms of ABE. Extreme neonatal Hyperbilirubinemia was defined as maximum total serum bilirubin (TSBmax)) level ≥450 µmol/L and a ratio of conjugated serum bilirubin/TSB <0.30. We identified 21 children with galactosemia (incidence:1:48,000). Seven children developed extreme neonatal Hyperbilirubinemia (median [range] TSBmax level: 491 [456–756] µmol/L), accounting for 1.7% of all extreme neonatal Hyperbilirubinemia cases. During the first 10 days of life, Hyperbilirubinemia was predominantly of unconjugated type. Four children developed symptoms of intermediate/advanced ABE. One additional child had symptoms of intermediate/advanced ABE without having extreme neonatal Hyperbilirubinemia. On follow-up, one child had KSD. Galactosemia is a potential cause of extreme neonatal Hyperbilirubinemia, ABE, and KSD. It is crucial that putative galactosemic children are treated aggressively with phototherapy to prevent ABE and KSD. Thus it is important that galactosemia is part of the work up for unconjugated Hyperbilirubinemia.
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extreme neonatal Hyperbilirubinemia acute bilirubin encephalopathy and kernicterus spectrum disorder in children with galactosemia
Pediatric Research, 2018Co-Authors: Laura Fuglsang Bech, Mette Line Donneborg, Allan M Lund, Finn EbbesenAbstract:BACKGROUND Galactosemia has not been recognized as a cause of extreme neonatal Hyperbilirubinemia, although growing evidence supports this association. METHODS In a retrospective cohort study, we identified children with galactosemia due to GALT deficiency using the Danish Metabolic Laboratory Database. Among these, we identified children with extreme neonatal Hyperbilirubinemia or symptoms of ABE. Extreme neonatal Hyperbilirubinemia was defined as maximum total serum bilirubin (TSBmax)) level ≥450 µmol/L and a ratio of conjugated serum bilirubin/TSB <0.30. RESULTS We identified 21 children with galactosemia (incidence:1:48,000). Seven children developed extreme neonatal Hyperbilirubinemia (median [range] TSBmax level: 491 [456-756] µmol/L), accounting for 1.7% of all extreme neonatal Hyperbilirubinemia cases. During the first 10 days of life, Hyperbilirubinemia was predominantly of unconjugated type. Four children developed symptoms of intermediate/advanced ABE. One additional child had symptoms of intermediate/advanced ABE without having extreme neonatal Hyperbilirubinemia. On follow-up, one child had KSD. CONCLUSIONS Galactosemia is a potential cause of extreme neonatal Hyperbilirubinemia, ABE, and KSD. It is crucial that putative galactosemic children are treated aggressively with phototherapy to prevent ABE and KSD. Thus it is important that galactosemia is part of the work up for unconjugated Hyperbilirubinemia.