Abstract
Objective:
To identify clinical and genetic risk factors for moderate hyperbilirubinemia during the first week of life.
Study Design:
Using univariate and multivariate multiple regression analyses, the RR for clinical factors, the African variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency (G202A/A376G), and (TA)n UGT1A1 polymorphisms were established in a cohort of 608 Brazilian newborn infants. Hyperbilirubinemia was monitored until 134.5±49.8 h of life (IQR, 111.0 to 156.7). The dependent variable was total bilirubinemia (TB)⩾12.9 mg per 100 ml estimated by transcutaneous or plasma bilirubin measurements.
Result:
The African variant of G6PD deficiency and (TA)7/(TA)7 and (TA)7/(TA)8 polymorphisms present in 6.1 and 12.0% of newborns, respectively, were not risk factors for moderate hyperbilirubinemia. Coexpression of G6DP deficiency and UGT1A1 polymorphisms occurred in 0.49% of the subjects. Independent clinical predictors for TB⩾12.9 mg per 100 ml were gestational age <38 weeks and reference curve percentiles >P40th.
Conclusion:
In this study, G6PD deficiency and UGT1A1 gene promoter polymorphisms were not risk factors for moderate hyperbilirubinemia. Genetic factors may vary considerably in importance among different populations.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM . Clinical report from the pilot USA kernicterus registry (1992 to 2004). J Perinatol 2009; 29 (Suppl 1): S25–S45.
Manning D, Todd P, Maxwell M, Platt MJ . Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed 2007; 92 (5): 342–346.
American Academy of Pediatrics: Clinical practice guideline. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (1): 297–316.
Kaplan M, Abramov A . Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in sephardic-jewish neonates: incidence, severity, and effect of phototherapy. Pediatrics 1992; 90 (3): 401–405.
Agrawal SK, Kumar P, Rathi R, Sharma N, Das R, Prasad R et al. UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia. Pediatr Res 2009; 65 (6): 675–680.
Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK . A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics 2008; 121 (1): e170–e179.
Kaplan M, Herschel M, Hammerman C, Hoyer JD, Stevenson DK . Hyperbilirubinemia among African-American, glucose-6-phosphate dehydrogenase-deficient neonates. Pediatrics 2004; 114 (2): e213–e219.
WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989; 67 (6): 601–611.
Kaplan M, Hammerman C . The need for neonatal glucose-6-phosphate dehydrogenase screening: a global perspective. J Perinatol 2009; 29 (Suppl 1): S46–S52.
Lin Z, Fontaine J, Watchko JF . Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics 2008; 122 (1): e156–e162.
Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E . Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci USA 1997; 94 (22): 12128–12132.
Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA et al. The genetic basis of the reduced expression of bilirubin UDP-glucoronosyltransferase 1 in Gilbert’ syndrome. N Engl J Med 1995; 333 (18): 1171–1175.
Kaplan M, Herschel M, Hammerman C, Karrison T, Hoyer JD, Stevenson DK . Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates. Clin Chim Acta 2006; 365 (1–2): 177–182.
Saad STO, Salles TSI, Carvalho MHM, Costa FF . Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Brazil. Hum Her 1997; 47 (1): 17–21.
Facchini FP, Mezzacappa MA, Rosa IR, Mezzacappa Filho F, Aranha-Netto A, Marba ST . Follow-up of neonatal jaundice in term and late premature newborns. J Pediatr (Rio J) 2007; 83 (4): 313–318.
American Association of Blood Banks.. Elution procedures. Technical Manual 9th edn, AABB: Arlington, VA, 1985; p: 429–433.
Bhutani VK, Johnson L, Sivieri EM . Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999; 103 (1): 6–14.
Facchini FP . Standardizing the calibration of phototherapy devices-a proposal. J Pediatr (Rio de J) 2001; 77 (2): 67–74.
Brewer GJ, Tarlov AR, Alving AS . The methemoglobin reduction test for primaquine-type sensitivity of erythrocytes. A simplified procedure for detecting a specific hypersusceptibility to drug hemolysis. JAMA 1962; 180: 386–388.
Beutler E . Glucose-6-phosphate dehydrogenase deficiency. In: Stanbury JB, Wyngarden JB, Fredrikson DS, Goldstein JL, Brown MS (eds). The Metabolic Basis of Inherited Disease, 5th edn, Mc Graw-Hill: New York, 1983, pp. 1629–1653.
Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985; 230 (4732): 1350–1354.
Capurro H, Korichzky S, Fonseca D, Caldeyro-Barcia R . A simplified method for diagnosis of gestational age in the newborn infant. J Pediatr 1978; 93 (1): 120–122.
Fertrin KY, Gonçalves MS, Saad STO, Costa FF . Frequencies of UDP-glucoronosyltransferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil. Am J Med Genetics 2002; 108 (2): 117–119.
Bertini G, Dani C, Tronchin M, Rubaltelli FF . Is breastfeeding really favoring early neonatal jaundice? Pediatrics 2001; 107 (3): e41.
Newman TB, Escobar GJ, Gonzales VM, Armstrong MA, Gardener MN, Folck BF . Frequency of neonatal bilirubin testing and hyperbilirubinemia in a large health maintenance organization. Pediatrics 1999; 104 (5 Part 2): 1198–1203.
Kaplan M, Bromiker E, Schimmel MS, Algur N, Hammerman C . Evaluation of discharge management in the prediction of hyperbilirubinemia: the Jerusalem experience. J Pediatr 2007; 150 (4): 412–417.
Minnuci A, Giardina B, Zuppi C, Capoluongo E . Glucose-6-phosphate dehydrogenase laboratory assay: how, when, and why? IUBMB Life 2009; 61 (1): 27–32.
Kaplan M, Beutler E, Vreman HJ, Hammerman C, Levy-Lahad E, Renbaum P et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics 1999; 104 (1 Part 1): 68–74.
Samilchuk E, Al-Suliman I, Usanga E, Al-Awadi S . Glucose-6-phosphate dehydrogenase (G6PD) mutations and UDP-glucoronosyltransferase promoter polymorphism among G6PD deficient Kuwaitis. Blood Cells Mol Dis 2003; 31 (2): 201–205.
Huang MJ, Kua KA, Teng HC, Tang KS, Weng HW, Huang CS . Risks factors for severe hyperbilirubinemia in neonates. Pediatr Res 2004; 56 (5): 682–689.
Newman TB, Liljestrand P, Escobar GJ . Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns. Arch Pediatr Adolesc Med 2005; 159 (2): 113–119.
Maisels MJ, DeRidder JM, Kring EA, Balasubramaniam M . Routine transcutaneous bilirrubin measurements combined with risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol 2009; 29 (9): 612–617.
Slaughter J, Annibale D, Suresh G . False-negative results of pre-discharge neonatal bilirubin screening to predict severe hyperbilirubinemia: a need for caution. Eur J Pediatr 2009; 168 (12): 1461–1466.
Watchko JF . Vigintiphobia revisited. Pediatrics 2005; 115 (6): 1747–1753.
Acknowledgements
The study was funded by the Research Support Foundation of the State of São Paulo (FAPESP), grant number 2006/60917-1. We thank Mrs Cleide Moreira Silva from the Research Division (FCM/UNICAMP) for offering assistance in statistical analysis.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Mezzacappa, M., Facchini, F., Pinto, A. et al. Clinical and genetic risk factors for moderate hyperbilirubinemia in Brazilian newborn infants. J Perinatol 30, 819–826 (2010). https://doi.org/10.1038/jp.2010.48
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/jp.2010.48
Keywords
This article is cited by
-
Influence of UGT1A1 promoter polymorphism, α-thalassemia and βs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort
Annals of Hematology (2021)
-
Uridine diphosphate glucuronosyl transferase 1A (UGT1A1) promoter polymorphism in young patients with sickle cell anaemia: report of the first cohort study from Nigeria
BMC Medical Genetics (2019)
-
Resistance of infection by Plasmodium vivax to chloroquine in Bolivia
Malaria Journal (2015)
-
Clinical complications of G6PD deficiency in Latin American and Caribbean populations: systematic review and implications for malaria elimination programmes
Malaria Journal (2014)
-
UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms vs. neonatal hyperbilirubinemia: is there an association?
Pediatric Research (2012)