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Neonatal bilirubin production-conjugation imbalance: effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity
  1. M Kaplan1,2,
  2. M Muraca4,*,
  3. H J Vreman6,
  4. C Hammerman1,3,
  5. M T Vilei4,
  6. F F Rubaltelli5,
  7. D K Stevenson6
  1. 1Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
  2. 2Faculty of Medicine, Hebrew University, Jerusalem, Israel
  3. 3Faculty of Health Sciences, Ben Gurion University of the Negev, Be’er Sheva, Israel
  4. 4Department of Internal Medicine, University of Padua, Florence, Italy
  5. 5Department of Neonatology, University of Florence, Florence, Italy
  6. 6Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University Medical Center, Stanford, CA, USA
  1. Correspondence to:
    Dr Kaplan
    Department of Neonatology, Shaare Zedek Medical Center, PO Box 3235, Jerusalem 91031, Israel;


Objective: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates.

Methods: Term and borderline premature (35–37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration.

Results: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r  =  0.22, p  =  0.15). TCB did correlate inversely with STB (r  =  −0.42, p  =  0.004), and there was a positive correlation between the production-conjugation index and STB (r  =  0.45, p  =  0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n  =  8) than term neonates (2.31 (2.12–3.08) v 1.05 (0.53–1.81), p  =  0.003). This difference was the result of changes in TCB.

Conclusions: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at especial risk of bilirubin production-conjugation imbalance.

  • COHb, carboxyhaemoglobin
  • COHbc, COHb corrected for inspired (room air) CO
  • G6PD, glucose-6-phosphate dehydrogenase
  • HPLC, high performance liquid chromatography
  • STB, serum total bilirubin
  • TCB, total conjugated bilirubin
  • bilirubin
  • glucose-6-phosphate dehydrogenase
  • bilirubin conjugation
  • borderline prematurity
  • haemolysis

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  • * Present address: Clinical Chemistry Laboratory, Ospedale Pediatrico Bambino Gesu, Piazza Sant’ Onofrio 4, 00165 Rome, Italy

  • Competing interests: none declared

  • Presented in part at the Pediatric Academic Societies’ Annual Meeting, Seattle, WA, USA, 3–6 May, 2003.