How should I recognize and manage glucose‑6‑phosphate dehydrogenase (G6PD) deficiency in a newborn?

Recognition and Management of G6PD Deficiency in Newborns

Recognition: Clinical Presentation

G6PD deficiency should be suspected in any newborn with jaundice appearing in the first 24 hours of life, rapidly rising bilirubin levels despite phototherapy, or severe hyperbilirubinemia requiring intervention at lower thresholds. 1, 2

High-Risk Populations Requiring Heightened Vigilance

• Screen infants of African American descent (11-13% prevalence), Mediterranean ancestry, or Asian backgrounds where G6PD deficiency rates are significantly elevated 2, 3
• Sephardic Jewish and Muslim Arab newborns show particularly high prevalence rates 4
• Male infants are predominantly affected due to X-linked inheritance, though heterozygous females with borderline deficiency (2-10 U/g Hb) also face increased risk 4, 5

Key Clinical Features to Recognize

• Jaundice onset within the first 24 hours of life is a critical red flag requiring immediate bilirubin measurement 2
• Bilirubin levels that fail to respond adequately to phototherapy 2
• Severe hyperbilirubinemia without obvious hemolytic signs - G6PD-related jaundice often presents without overt hemolysis markers like Heinz bodies, distinguishing it from acute hemolytic crises 3
• Higher bilirubin levels at nursery discharge compared to G6PD-normal infants 4
• Increased phototherapy requirements (22.2% of G6PD-deficient infants vs 7.6% of normal infants) 4

Diagnostic Approach

When to Test for G6PD Deficiency

Test immediately when: 1, 2

• TSB approaches exchange transfusion levels
• Bilirubin fails to respond to phototherapy
• Severe hyperbilirubinemia occurs in at-risk ethnic groups
• Family history, ethnicity, or geographic origin suggest risk
• Jaundice appears in the first 24 hours

Laboratory Testing Strategy

Measure total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) immediately if jaundice appears excessive or within the first 24 hours 2

For rapidly rising TSB or infants on phototherapy, obtain: 2

• Blood type and Coombs test
• Complete blood count with peripheral smear
• Direct or conjugated bilirubin
• Reticulocyte count
• G6PD enzyme activity assay

Critical Testing Considerations

• Standard semiquantitative fluorescent spot tests miss a significant proportion of cases, particularly heterozygous females with partial deficiency 6, 5
• Quantitative G6PD assays using a cutoff of 6.4 U/g Hb (rather than 2.1 U/g Hb) detect more at-risk infants 5
• Normal G6PD levels during active hemolysis can be falsely reassuring - reticulocytes have higher G6PD activity, potentially obscuring the diagnosis 1
• If G6PD deficiency is strongly suspected but initial testing is normal during hemolysis, repeat testing at 3 months of age 1
• Borderline G6PD activity (2-10 U/g Hb rather than 2-7 U/g Hb) should be considered deficient for clinical purposes 4

Management Strategy

Bilirubin Monitoring Using Hour-Specific Nomograms

Plot all bilirubin values on the Bhutani nomogram using the infant's age in hours (never days) to determine risk zone and guide intervention 2

• High-intermediate risk zone (75th-94th percentile): follow-up within 24-48 hours 2
• Low-intermediate risk zone (40th-74th percentile): follow-up within 48-72 hours 2
• Never rely on visual assessment alone - this leads to errors, especially in darkly pigmented infants 2

Phototherapy Thresholds

Initiate phototherapy at lower TSB levels in G6PD-deficient infants compared to normal infants 1

• Treatment thresholds are reduced because G6PD deficiency increases the risk of bilirubin neurotoxicity 1
• The specific threshold depends on the infant's age in hours, gestational age, and presence of other risk factors 1

Exchange Transfusion Considerations

Consider exchange transfusion at lower bilirubin levels in G6PD-deficient infants due to increased kernicterus risk 1

• Exchange transfusion carries mortality risk of approximately 3 per 1000 procedures, though lower in otherwise healthy term infants 1
• Significant morbidity (apnea, bradycardia, vasospasm, thrombosis, necrotizing enterocolitis) occurs in up to 5% of procedures 1

Preventive Measures and Parental Education

Counsel parents to avoid oxidant stressors: 3, 6

• Certain medications (antimalarials, sulfonamides, nitrofurantoin, aspirin in high doses)
• Fava beans and other legumes
• Naphthalene-containing mothballs
• Henna application

Close monitoring during intercurrent illnesses as infections can trigger hemolysis 3

Universal Screening Considerations

The WHO recommends screening all infants in countries with high G6PD deficiency prevalence to prevent kernicterus 3

• Universal screening concurrent with bilirubin screening has been successfully implemented in some regions 6, 4
• Automated quantitative assays processing 90 samples/hour are available for high-throughput screening 7
• The American Academy of Pediatrics currently recommends selective testing rather than universal screening, though this may miss cases 6

Critical Pitfalls to Avoid

• Never discharge infants with jaundice in the first 24 hours without measuring bilirubin 2
• Never use days instead of hours when plotting bilirubin values on the nomogram 2
• Never fail to obtain G6PD testing in high-risk ethnic groups with severe hyperbilirubinemia 2
• Never assume a normal G6PD level during active hemolysis rules out deficiency - repeat at 3 months if suspicion remains 1
• Never overlook borderline G6PD activity (2-10 U/g Hb) in females - these heterozygotes face increased hyperbilirubinemia risk 4, 5
• Never rely solely on semiquantitative screening tests as they miss partially deficient females 5