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

To the Editor.—We read with great interest the recent article by Keren et al,1 in which factors predictive of neonatal hyperbilirubinemia were sought. We found it particularly surprising that glucose-6-phosphate dehydrogenase (G6PD) deficiency did not reach significance as a risk factor and seemed to be nonpredictive of jaundice. This finding is contrary to those of previous studies in which G6PD deficiency was found to be a major factor in the pathogenesis of hyperbilirubinemia and was highly associated with extreme hyperbilirubinemia and kernicterus. Recent examples of this association emanate from the United States, Canada, and the United Kingdom and Ireland, countries not usually associated with a high overall frequency of G6PD deficiency.2–4Newborns are a group at particular risk of G6PD deficiency. Commonly, there is an increased risk of moderate hyperbilirubinemia that responds to phototherapy and should not endanger these newborns.5,6 Rarely, acute hemolytic crises may precipitate extreme and dangerous hyperbilirubinemia, with the devastating consequence of bilirubin encephalopathy and the long-term outcome of kernicterus. This form of extreme icterus is unpredictable, unfortunately, and may be the reason that kernicterus may not be completely eradicable.What could be the reasons for the discrepancy between the Keren et al findings and those previously reported? One factor may be that a molecular screen, rather than customary biochemical testing, was used to identify G6PD deficiency. The particular screen used by these authors studies 5 G6PD mutations that are prevalent in the United States and is, by design, estimated to identify ∼90% of G6PD-deficient individuals in the United States, including female heterozygotes who may be partially deficient.7 Had a simple biochemical screening test or a quantitative enzyme assay been used, virtually 100% of the G6PD-deficient boys should have been identified. Although the G6PD Mediterranean mutation has been predictive of hyperbilirubinemia, even in heterozygotes,5 this mutation accounts for only a portion of the US-based G6PD genotype. Because of possible differences between G6PD Mediterranean and other genotypes, we cannot be sure how many of the study subjects designated as G6PD deficient by the DNA method actually had low levels of G6PD enzyme activity. Pooling of boys and girls, thereby including many heterozygotes, may have resulted in dilution of the patient sample. Another difference between the present and past studies includes the definition of hyperbilirubinemia: the Keren et al definition was based on the criteria for commencing phototherapy from the 2004 American Academy of Pediatrics guidelines.8 Because these guidelines vary according to the presence or absence of risk factors, and because the G6PD status was available only 2 weeks after delivery, this important risk factor was not taken into account at the time of patient management.The results of the study in question ought not to let G6PD deficiency off the hook. Until this molecular method of screening for G6PD deficiency is evaluated further and the definitions used for determining hyperbilirubinemia are put to scrutiny, G6PD deficiency should continue to be regarded as a risk factor associated with severe neonatal hyperbilirubinemia.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.