Overview
Definition:
Neonatal jaundice is a common condition characterized by elevated serum bilirubin levels in newborns, leading to yellowing of the skin and sclera
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked inherited disorder that predisposes red blood cells to oxidative stress and hemolysis, making newborns with this deficiency particularly vulnerable to severe hyperbilirubinemia and its complications when exposed to certain triggers.
Epidemiology:
G6PD deficiency is the most common human enzyme defect globally, affecting an estimated 400 million people
Its prevalence is highest in malaria-endemic regions, including parts of Africa, Asia, and the Mediterranean
In India, prevalence varies significantly by region, with higher rates in certain tribal populations and North Eastern states
Neonatal hyperbilirubinemia occurs in up to 60% of term and 80% of preterm infants
The incidence of severe hyperbilirubinemia leading to kernicterus in G6PD deficient neonates is higher compared to the general population.
Clinical Significance:
G6PD deficiency is a critical factor to consider in the evaluation of neonatal jaundice, especially in infants presenting with significant hyperbilirubinemia or rapid bilirubin rise
Failure to identify and manage G6PD deficiency appropriately can lead to acute hemolytic anemia, severe jaundice, acute bilirubin encephalopathy (kernicterus), and long-term neurodevelopmental sequelae
Early diagnosis and tailored management are crucial for preventing these devastating outcomes and are a key area of focus for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Jaundice appearing within the first 24-48 hours of life
Progressive worsening of jaundice
Lethargy and poor feeding
Irritability
High-pitched cry
Fever
Vomiting
Dark urine
Pale stools
In severe cases: opisthotonos, apnea, seizures, coma.
Signs:
Generalized icterus extending beyond the face and trunk
Pallor of skin and mucous membranes (due to hemolysis)
Hepatomegaly and splenomegaly may be present
Signs of kernicterus: retrocollis, opisthotonos, oculomotor abnormalities (sunset sign), lethargy, poor suck, seizures.
Diagnostic Criteria:
Diagnosis of G6PD deficiency is confirmed by biochemical assay for G6PD enzyme activity in red blood cells
However, this test can be falsely negative during an acute hemolytic episode due to the presence of younger, more enzyme-rich red cells
Neonatal screening for G6PD deficiency is recommended in populations with high prevalence
For jaundice, diagnostic criteria include a history of jaundice within the first 24-48 hours, rising bilirubin levels, and exclusion of other causes of hyperbilirubinemia.
Diagnostic Approach
History Taking:
Detailed family history of jaundice, anemia, or splenectomy
History of neonatal jaundice, especially if treated with phototherapy or exchange transfusion
Maternal history of G6PD deficiency or favism
Exposure to known triggers like certain drugs (sulfonamides, antimalarials, nitrofurantoin), fava beans, or naphthalene-containing substances
Gestational age at birth
Feeding history
Signs of hemolysis (pallor, dark urine).
Physical Examination:
Assess the extent of jaundice using Kramer's rule
Evaluate for pallor
Examine for hepatosplenomegaly
Assess for neurological signs of bilirubin encephalopathy (lethargy, poor suck, abnormal tone, seizures)
Assess hydration status.
Investigations:
Total and direct serum bilirubin levels: Hyperbilirubinemia (often predominantly unconjugated)
Complete blood count (CBC) with differential: May show anemia, elevated reticulocyte count, spherocytes, or bite cells on peripheral smear
G6PD enzyme assay: Performed preferably after the acute episode has resolved
Reticulocyte count: Elevated in hemolytic anemia
Direct Coombs test: Usually negative in G6PD deficiency-related hemolysis
Blood smear: May reveal bite cells, blister cells, or spherocytes.
Differential Diagnosis:
Physiological jaundice
Breast milk jaundice
Pathological jaundice due to ABO/Rh incompatibility
Sepsis
Hereditary spherocytosis
Other enzyme deficiencies (e.g., pyruvate kinase deficiency)
Gilbert's syndrome
Neonatal hepatitis
Biliary atresia.
Management
Initial Management:
Immediate assessment of bilirubin levels and rate of rise
Identify and discontinue any potential offending agents or exposures
Ensure adequate hydration and caloric intake
Monitor vital signs and neurological status closely.
Medical Management:
Phototherapy: The primary treatment for hyperbilirubinemia
Bilirubin levels should be compared to established nomograms considering gestational age, postnatal age, and risk factors (including G6PD deficiency)
Intensive phototherapy with high irradiance is often required
Exchange Transfusion: Indicated for extremely high bilirubin levels, rapid bilirubin rise despite phototherapy, or signs of kernicterus
Specific thresholds for exchange transfusion in G6PD deficient infants are often lower than in non-deficient infants due to the risk of rapid hemolysis
Common guidelines suggest exchange transfusion if bilirubin reaches levels above 20-25 mg/dL or shows a rapid rise of >0.5 mg/dL/hour despite intensive phototherapy.
Surgical Management:
Not applicable for neonatal jaundice itself, but management of kernicterus complications may involve long-term supportive care.
Supportive Care:
Maintain adequate hydration and nutrition
Monitor fluid balance
Continuous neurological assessment
Provide supportive care for symptoms of kernicterus
Long-term follow-up for neurodevelopmental deficits.
Complications
Early Complications:
Acute hemolytic anemia
Severe unconjugated hyperbilirubinemia
Acute bilirubin encephalopathy (kernicterus) characterized by lethargy, poor feeding, opisthotonos, seizures.
Late Complications:
Chronic bilirubin encephalopathy (cerebral palsy, auditory neuropathy, gaze abnormalities, intellectual disability)
Persistent anemia.
Prevention Strategies:
Universal or targeted neonatal screening for G6PD deficiency in at-risk populations
Educating parents and healthcare providers about triggers (drugs, fava beans, mothballs)
Early recognition and prompt management of hyperbilirubinemia with appropriate use of phototherapy and exchange transfusion based on evidence-based thresholds
Close monitoring of infants with G6PD deficiency.
Prognosis
Factors Affecting Prognosis:
Severity of G6PD deficiency (class of deficiency)
Presence and severity of hemolysis
Timeliness and efficacy of treatment (phototherapy, exchange transfusion)
Peak bilirubin levels and duration of hyperbilirubinemia
Development of kernicterus.
Outcomes:
With prompt and appropriate management, most infants with G6PD deficiency and neonatal jaundice can achieve good outcomes
Infants who develop kernicterus are at risk for permanent neurological damage, with outcomes varying significantly in severity.
Follow Up:
Infants treated for severe hyperbilirubinemia, especially those with suspected or confirmed G6PD deficiency, require close pediatric follow-up
This includes monitoring for anemia, hearing deficits (auditory neuropathy), and neurodevelopmental assessment
Genetic counseling for affected families may be indicated.
Key Points
Exam Focus:
Remember that G6PD deficiency is an X-linked recessive disorder predisposing to hemolytic anemia
Triggers are crucial
Bilirubin thresholds for phototherapy and exchange transfusion are often lower in G6PD-deficient neonates compared to their non-deficient counterparts due to the risk of rapid hemolysis
Neonatal screening is important in endemic areas
Differentiating between acute and chronic bilirubin encephalopathy is tested.
Clinical Pearls:
Always consider G6PD deficiency in a jaundiced neonate with a rapid rise in bilirubin, anemia, or a history of hemolysis
Avoid prescribing oxidant drugs or recommending fava bean consumption to infants or mothers breastfeeding infants with known or suspected G6PD deficiency
Perform G6PD assay after the acute episode to avoid false negatives
The "bite cells" on peripheral smear are pathognomonic of oxidative damage.
Common Mistakes:
Delaying intervention in hyperbilirubinemia in G6PD deficient infants due to adherence to general bilirubin nomograms without considering the enzyme deficiency
Prescribing medications known to cause hemolysis in G6PD deficiency
Not performing a G6PD assay or performing it during the acute phase leading to false-negative results
Underestimating the risk of kernicterus in G6PD deficient neonates.