Short answer, exact mechanism for G6PD (glucose-6-phosphate dehydrogenase) deficiency predisposing to neonatal jaundice is as yet unclear. Exploring features of G6PD deficiency, neonatal jaundice and G6PD deficiency-associated neonatal jaundice reveal a likely but as-yet scientifically unproven hypothesis.

G6PD deficiency
The G6PD gene is on the X chromosome.

  • So males can be G6PD normal/deficient and females G6PD normal/intermediate (heterozygous)/deficient (homozygous).
  • G6PD is the most common human enzyme deficiency (enzymopathy), present in ~400 million people worldwide (1).
  • Ethnic background plays a role with higher propensity in black, Asian and Mediterranean babies (2).
  • Every year ~4,500,000 births worldwide with G6PD deficiency (3).
  • Most people with this deficiency remain asymptomatic (illness-free) throughout life (4).
  • So far, ~ 140 mutations of G6PD have been identified. Mostly point mutations, i.e., one amino acid difference from the normal/wild-type form of the protein. Physiological outcome?
    • Different mutations variably decrease this enzyme’s stability (5).
    • Mutations can affect either how the enzyme catalyses its reaction or its affinity for its substrate.
  • G6PD deficiency is an enzyme defect with important consequences for red blood cell (RBC, erythrocyte) metabolism.
  • According to Klowak and Wong (6), red blood cell (RBC, erythrocyte) diseases are of 3 types:
    • Hemoglobin: sickle cell disease, thalassemia
    • Membrane-cytoskeleton: hereditary spherocytosis
    • Metabolism: G6PD deficiency, i.e., glucose-6-phosphate dehydrogenase deficiency

Neonatal jaundice

  • Neonatal jaundice is also known as neonatal hyperbilurbinemia .
  • In other words, accumulation of unconjugated bilirubin in the blood.
  • Neonatal jaundice is clinically evident by 1 to 4 days after birth.
  • Certain key differences in basic physiology can predispose newborns to jaundice (physiologic jaundice).
  • For one (4), in adults, colonic bacteria rapidly reduce conjugated bilirubin to urobilinogens so little of it reverts back to the liver through the gut-hepatic (enterohepatic) circulation .
    • OTOH, in newborns, most of the conjugated bilirubin is converted back to unconjugated bilirubin by the intestinal mucosal enzyme, beta glucuronidase.
    • Unconjugated bilirubin is reabsorbed into the blood by enterohepatic circulation.
    • This increases the bilirubin load that needs to be cleared by the newborn’s liver.
  • For another (4, 7), newborn per se is already prone to hyperbilirubinemia (physiologic jaundice) because its liver now has to newly take on the task of clearing bilirubin that was being cleared by the placenta in utero.
  • Third, newborns’ bilirubin production is 2 to 3 times higher compared to adults.
    • Newborns have more blood cells and fetal RBC lifespan is shorter (~85 days compared to 120 days).
    • Increased newborn RBC turnover means more bilirubin production.
  • Fourth, newborn clearance of bilirubin is much less efficient.
    • Much lower newborn levels of the enzyme uridine diphosphogluconurate glucuronosyltransferase (UGT1A1), a key bilirubin metabolism enzyme.
    • A 7-day old infant’s liver has ~1% adult liver UGT activity and reaches adult levels only by ~14 weeks of age (8).

Features of G6PD deficiency-associated neonatal jaundice

  • ~1/3rd of male newborns with neonatal jaundice have G6PD deficiency while rate is lower in female newborns (9, 10).
  • Among G6PD deficient, it’s also more frequent and severe in premature compared to normal births (11).
  • G6PD-associated neonatal jaundice is rarely present at birth and peaks at days 2 to 3 post-birth (12).

Why G6PD deficiency could predispose to neonatal jaundice
Though exact mechanism is as-yet undeciphered, a number of triggers have been identified:

1. Medical literature suggests maternal/caregiving factors could increase a G6PD deficient baby’s chance of getting neonatal jaundice (1).

  • The mother taking certain drugs (13).
  • Using naphthalene-camphor balls to store baby’s clothes (14).

2. G6PD deficiency-associated neonatal jaundice differs in key aspects from physiologic jaundice (1, 3, 7, 15).

  • Increased hemolysis, i.e., breakdown of RBCs or anemia, isn’t the most common observation in G6PD deficiency-associated neonatal jaundice.
  • Rather than anemia, bilirubin clearance is the most common problem in G6PD deficiency-associated neonatal jaundice.
  • This implicates the bilirubin pathway in G6PD deficiency-associated neonatal jaundice (3, 4, 7).
    • Prevailing hypothesis is that bilirubin conjugates less efficiently with serum albumin.
    • In turn, impaired blilrubin-albumin conjugation leads to impaired bilirubin clearance by liver.
    • No direct scientific evidence yet that certain G6PD deficiencies have less efficient bilirubin-serum albumin conjugation (binding).


  1. Cappellini, Maria Domenica, and G. Fiorelli. “Glucose-6-phosphate dehydrogenase deficiency.” The lancet 371.9606 (2008): 64-74. Page on david-bender.co.uk
  2. Ratnavel, Nandiran, and N. Kevin Ives. “Investigation of prolonged neonatal jaundice.” Current Paediatrics 15.2 (2005): 85-91.
  3. Maisels, M. Jeffrey. “Neonatal jaundice.” Pediatrics in Review 27.12 (2006): 443. Page on yimg.com
  4. Frank, Jennifer E. “Diagnosis and management of G6PD deficiency.” American family physician 72.7 (2005): 1277-1282.
  5. Gómez-Manzo, Saúl, et al. “The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes.” International journal of molecular sciences 15.11 (2014): 21179-21201. The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes
  6. Glucose-6-phosphate dehydrogenase deficiency
  7. Mason, Philip J., José M. Bautista, and Florinda Gilsanz. “G6PD deficiency: the genotype-phenotype association.” Blood reviews 21.5 (2007): 267-283. Page on researchgate.net
  8. Kawade, Noboru, and S. Onishi. “The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver.” Biochem. J 196 (1981): 257-260. Page on nih.gov
  9. Matthay, K. K., and W. C. Mentzer. “Erythrocyte enzymopathies in the newborn.” Clinics in haematology 10.1 (1981): 31-55.
  10. Kaplan, Michael, et al. “Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase–deficient heterozygotes.” The Journal of pediatrics 139.1 (2001): 137-140.
  11. Lopez, Rafael, and Jack M. Cooperman. “Glucose-6-phosphate dehydrogenase deficiency and hyperbilirubinemia in the newborn.” American Journal of Diseases of Children 122.1 (1971): 66-70.
  12. Kaplan, Michael, and Cathy Hammerman. “Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus.” Seminars in perinatology. Vol. 28. No. 5. WB Saunders, 2004.
  13. Perkins, Richard P. “Hydrops fetalis and stillbirth in a male glucose-6-phosphate dehydrogenase-deficient fetus possibly due to maternal ingestion of sulfisoxazole; a case report.” American journal of obstetrics and gynecology 111.3 (1971): 379.
  14. Valaes, Timos, Spyros A. Doxiadis, and Phaedon Fessas. “Acute hemolysis due to naphthalene inhalation.” The Journal of pediatrics 63.5 (1963): 904-915.
  15. Kaplan, Michael, et al. “Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.” The Journal of pediatrics 128.5 (1996): 695-697.