Published online July 1, 2008
PEDIATRICS Vol. 122 No. 1 July 2008, pp. 217-218 (doi:10.1542/peds.2008-1163)

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LETTER TO THE EDITOR

Neonatal Hyperbilirubinemia: Don't Let Glucose-6-phosphate Dehydrogenase Deficiency off the Hook: In Reply

Ron Keren, MD, MPH
Susan Friedman, MD
Division of General Pediatrics
Center for Pediatric Clinical Effectiveness
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Department of Pediatrics
University of Pennsylvania School of Medicine
Philadelphia, PA 19104

Vinod Bhutani, MD
Department of Neonatal and Developmental Medicine
Lucile Packard Children's Hospital
Stanford University
Palo Alto, CA 94304

We agree with Kaplan and Hammerman: there is substantial evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with neonatal hyperbilirubinemia.^1–4 And, our results do not contest that association. Rather, our findings raise questions about the utility of a particular DNA-based G6PD screening test⁵ as a predictor of neonatal hyperbilirubinemia. As we pointed out in our article,⁶ there are several reasons why a positive G6PD mutation analysis did not correlate with hyperbilirubinemia in our study sample: (1) some mutations may not result in inadequate G6PD enzyme levels; (2) some mutations may result in low enzyme activity levels but not hyperbilirubinemia; and (3) some mutations that result in low enzyme activity and hyperbilirubinemia may not be detected by this screening test.

Studies are needed to further evaluate the predictive accuracy of and relationship between alternative methods of G6PD-deficiency screening. Infants enrolled onto these studies should have the following tests performed: G6PD mutation analysis, G6PD enzyme level, UDPGT1 polymorphism analysis, and daily bilirubin levels. Investigators can then compare the predictive value of alternative screening tests for G6PD deficiency, determine reasons for divergent screening test results, and evaluate the contribution of glucuronidation defects to hyperbilirubinemia. Even more important is that these studies can inform us about the incremental predictive value of G6PD screening tests above and beyond the predictive information provided by the predischarge bilirubin level (expressed as a risk zone on the hour-specific bilirubin nomogram) and the infant's gestational age, the 2 factors shown to be most predictive of significant hyperbilirubinemia.

REFERENCES

1. Kaplan M, Herschel M, Hammerman C, Hoyer JD, Stevenson DK. Hyperbilirubinemia among African American, glucose-6-phosphate dehydrogenase-deficient neonates. Pediatrics.2004; 114 (2). Available at: www.pediatrics.org/cgi/content/full/114/2/e213
2. Atay E, Bozaykut A, Ipek IO. Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia. J Trop Pediatr.2006; 52 (1):56 –58[Abstract/Free Full Text]
3. Weng YH, Chou YH, Lien RI. Hyperbilirubinemia in healthy neonates with glucose-6-phosphate dehydrogenase deficiency. Early Hum Dev.2003; 71 (2):129 –136[CrossRef][Web of Science][Medline]
4. Abolghasemi H, Mehrani H, Amid A. An update on the prevalence of glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Tehran neonates. Clin Biochem.2004; 37 (3):241 –244[CrossRef][Web of Science][Medline]
5. Lin Z, Fontaine JM, Freer DE, Naylor EW. Alternative DNA-based newborn screening for glucose-6-phosphate dehydrogenase deficiency. Mol Genet Metab.2005; 86 (1–2):212 –219[CrossRef][Web of Science][Medline]
6. 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). Available at: www.pediatrics.org/cgi/content/full/121/1/e170

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Keren, R. Articles by Bhutani, V. Search for Related Content PubMed Articles by Keren, R. Articles by Bhutani, V. Related Collections Premature & Newborn Social Bookmarking                         What's this?