Genetics and the Risk of Neonatal Hyperbilirubinemia: Commentary on the article by Huang et al. on page 682

Watchko, Jon F.

doi:10.1203/01.pdr.0000142588.65045.25

Cited by 24 publications

(5 citation statements)

References 15 publications

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“…Hemolytic diseases like ABO incompatibility, Rh incompatibility, spherocytosis and G6PD deficiency can increase bilirubin production while Crigler-Najjar syndrome, hypothyroidism and prematurity can reduce conjugation2). Breast milk feeding may also act as a modifier that predisposes the risk for development of severe NIH with a specific genotype14). Unconjugated bilirubin is mainly produced by erythrocytes turnover15).…”

Section: Discussionmentioning

confidence: 99%

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency

Isa

Mohamed

et al. 2017

Korean J Pediatr

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PurposeThis study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus.MethodsThis is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients.ResultsOf 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male (P<0.0001), and had lower Hb levels (P<0.0001) and higher maximum bilirubin levels (P=0.001). More G6PD-deficient patients needed ET (P<0.0001). G6PD deficiency (P=0.006), lower Hb level (P=0.002), lower hematocrit count (P=0.02), higher bilirubin level (P<0.0001), higher maximal bilirubin level (P<0.0001), and positive blood culture result (P<0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus (P=0.021) and independently related to ET (P=0.03).ConclusionG6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

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Section: Discussionmentioning

confidence: 99%

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency

Isa

Mohamed

et al. 2017

Korean J Pediatr

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“…Breast‐fed infants have higher serum bilirubin levels on each of the first 5 days of life and this hyperbilirubinaemia can persist for weeks to months (15–17). Breast milk feeding may act as an environmental modifier for selected genotypes and thereby potentially predispose to the development of marked neonatal jaundice (5,6). Hyperbilirubinaemia risk increases when breast milk feedings were combined with the UGT1A1 and SLCO1B1 variants (7).…”

Section: Discussionmentioning

confidence: 99%

“…As reviewed elsewhere (4), many pathophysiological theories have arisen to explain this prolonged nonconjugated hyperbilirubinaemia associated with human milk feedings in otherwise healthy infants. Breast milk feeding is a modifier for selected genotypes and thereby potentially affects the development of obvious neonatal jaundice (5,6). A recent report lends credence to this possibility, demonstrating that the risk of developing a TSB level of 20 mg/dL or higher associated with breast milk feeding was enhanced 22‐fold when combined with expression of a coding sequence gene polymorphism of the bilirubin conjugating enzyme UGT1A1 (the G211A missense mutation UGT1A1A*6) or solute carrier organic anion transporter 1B1 (SLCO1B1, also known as organic anion transporter polypeptide 2 [OATP‐2]; the A388G missense variant SLCO1B1*1b) (7).…”

Section: Introductionmentioning

confidence: 99%

Prolonged unconjugated hyperbilirubinaemia associated with the haem oxygenase‐1 gene promoter polymorphism

et al. 2010

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“…For example, a severe, chronic and nonhemolytic unconjugated hyperbilirubinemia (serum bilirubin levels of 15-38 mg/dl) is experienced in individuals with Crigler-Najjar syndrome (CNS). Patients with CNS type 1 have complete loss of UGT1A1 activity and often develop kernicterus (182,183) whereas CNS type 2 (7-15 mg/dl) is characterized by a missense mutation in the same gene and causes partial inactivation of the enzyme (68,79). The pathological phenotype of jaundice develops in these patients due to excessive bilirubin accumulation and increases the risk of neurological dysfunction occurring, which is associated with neuronal apoptosis (83).…”

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confidence: 99%

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

Boon

Bulmer

Coombes

et al. 2014

American Journal of Physiology-Renal Physiology

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Unconjugated bilirubin is an endogenous circulating antioxidant, bound to albumin, and therefore is retained in the vascular compartment. Bilirubin has well-documented neurotoxic effects in infants; however, current evidence indicates mildly elevated bilirubin is associated with protection from cardiovascular disease and all-cause mortality in adults. Recent clinical studies show mildly elevated bilirubin is associated with protection from kidney damage and dysfunction, in addition to cardiovascular events and all-cause mortality in patients undergoing hemodialysis. This is the first review to examine the clinical evidence and summarize the potential mechanisms of action that link bilirubin to protection from kidney damage, subsequent kidney failure, and dialysis-related mortality. With this understanding, it is hoped that new therapies will be developed to prevent renal dysfunction and mortality from cardiovascular disease in at-risk individuals.

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Genetics and the Risk of Neonatal Hyperbilirubinemia: Commentary on the article by Huang et al. on page 682

Cited by 24 publications

References 15 publications

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency

Prolonged unconjugated hyperbilirubinaemia associated with the haem oxygenase‐1 gene promoter polymorphism

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

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