Can G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency cause hyperbilirubinemia in neonates?

G6PD Deficiency and Neonatal Hyperbilirubinemia

Yes, G6PD deficiency is a significant cause of hyperbilirubinemia in neonates and requires early screening and more aggressive management to prevent kernicterus. 1

Mechanism and Prevalence

G6PD deficiency leads to impaired production of reduced glutathione, which predisposes red blood cells to damage by oxidative metabolites, resulting in hemolysis 2. This hemolysis contributes to hyperbilirubinemia in affected neonates through:

• Increased bilirubin production from hemolyzed red blood cells
• Impaired bilirubin clearance

The prevalence varies by population:

• 11-13% of African Americans 1
• Higher rates in Mediterranean, Middle Eastern, and Asian populations

Clinical Presentation and Risk Assessment

G6PD-deficient infants with hyperbilirubinemia typically present with:

• Jaundice appearing on day 2 onwards 2
• Higher serum bilirubin levels (mean 17.2 ± 4.4 mg/dL in G6PD deficient cases) 2
• Risk of sudden, unpredictable increases in total serum bilirubin (TSB) 3
• More severe hyperbilirubinemia requiring intervention 4

Important Risk Factors

The American Academy of Pediatrics identifies G6PD deficiency as a major risk factor for severe hyperbilirubinemia, listing it among conditions requiring closer monitoring 3. G6PD deficiency is particularly concerning because:

• It can cause sudden increases in TSB levels 3
• It was identified as the cause of hyperbilirubinemia in 31.5% of infants who developed kernicterus in one report 3
• Preterm infants with G6PD deficiency are at even higher risk 5

Diagnostic Considerations

Important diagnostic challenges:

• G6PD levels can be falsely elevated during active hemolysis 3, 1
• A normal G6PD level in a hemolyzing neonate does not rule out G6PD deficiency 3, 1
• If G6PD deficiency is strongly suspected despite normal levels, repeat testing at 3 months of age is recommended 3, 1

Management Approach

Screening and Monitoring

• Screen for G6PD deficiency in infants with significant hyperbilirubinemia 3, 1
• Plot TSB levels on hour-specific nomograms to assess risk 3
• Monitor more frequently as G6PD-deficient infants may develop sudden increases in TSB 3, 1

Treatment

• Intervene at lower TSB levels for G6PD-deficient infants 3, 1
• Phototherapy is the first-line treatment, with longer duration often required (3.76 ± 1.93 days vs. 3.13 ± 2.14 days in non-G6PD deficient infants) 6
• Exchange transfusion may be required in severe cases (needed in 50.9% of G6PD-deficient infants in one study) 6

Medications to Avoid

• Methylene blue (contraindicated as it may cause hemolysis) 1
• Dapsone and other oxidative drugs 1
• Any known triggers of hemolysis in G6PD deficiency

Prevention and Follow-up

• Risk assessment before discharge is essential for all newborns 3, 1
• Early detection through screening programs in populations with high prevalence 4
• Educate parents about:
  • Monitoring for jaundice
  • Avoiding triggers of hemolysis
  • Importance of prompt medical attention if jaundice develops 1

Prognosis

Without proper management, G6PD-deficient neonates with hyperbilirubinemia are at risk for:

• Kernicterus and its sequelae 7
• Hearing loss 7
• Developmental delays 7

With appropriate screening and early intervention, these complications can largely be prevented.