What are the symptoms of hyperbilirubinemia?

Symptoms of Hyperbilirubinemia

The primary symptom of hyperbilirubinemia is jaundice, characterized by yellowing of the skin and sclera, but additional symptoms vary based on severity and may progress to neurological manifestations including lethargy, poor feeding, and in severe cases, seizures and coma. 1

Clinical Presentation

Common Symptoms

• Jaundice: Yellow discoloration of skin and sclera
  • Typically progresses in a cephalocaudal direction (face first, then trunk and extremities) 2
  • May be difficult to detect in infants with darker skin tones (requires careful examination of sclera) 3
• Changes in urine color: Dark or tea-colored urine
• Changes in stool color: Pale stools (particularly concerning as they may indicate cholestasis) 3

Symptoms Based on Severity

Mild to Moderate Hyperbilirubinemia

• Jaundice without other significant symptoms
• May have mild lethargy
• Poor feeding in some cases

Severe Hyperbilirubinemia

Symptoms of acute bilirubin encephalopathy progress through phases 2:

Early Phase:

• Lethargy
• Hypotonia
• Poor sucking

Intermediate Phase:

• Moderate stupor
• Irritability
• Hypertonia
• Fever
• High-pitched cry
• Alternating drowsiness and hypotonia
• Retrocollis (backward arching of neck)
• Opisthotonos (arching of the back)

Advanced Phase (Kernicterus):

• Pronounced retrocollis-opisthotonos
• Shrill cry
• Refusal to feed
• Apnea
• Fever
• Deep stupor to coma
• Seizures
• Death in severe cases

Long-Term Sequelae of Kernicterus

If severe hyperbilirubinemia progresses to kernicterus (chronic bilirubin encephalopathy), survivors may develop 2:

• Severe athetoid cerebral palsy
• Auditory dysfunction
• Dental-enamel dysplasia
• Paralysis of upward gaze
• Intellectual deficits

Special Considerations

Neonatal Hyperbilirubinemia

• Affects approximately 60% of term infants and 80% of preterm infants 4, 5
• Risk factors include family history of neonatal jaundice and exclusive breastfeeding 2
• Assessment of adequate intake in breastfed infants is important (weight loss >10% of birth weight, fewer than 4-6 wet diapers in 24 hours, or fewer than 3-4 stools per day by the fourth day may indicate inadequate intake) 2

Cholestatic Hyperbilirubinemia

• May develop bronze infant syndrome when exposed to phototherapy (dark, grayish-brown discoloration of skin, serum, and urine) 2
• Prolonged jaundice beyond 21 days of life warrants investigation for cholestasis 3

Diagnostic Considerations

When evaluating a patient with suspected hyperbilirubinemia:

• Visual assessment alone is unreliable for estimating bilirubin levels 2
• Transcutaneous bilirubin (TcB) measurements are useful for initial screening but have limitations:
  • Less accurate at higher bilirubin levels (>15 mg/dL)
  • Not reliable in infants undergoing phototherapy
  • May be affected by skin pigmentation 1
• Total serum bilirubin (TSB) measurement is necessary for confirmation 1
• Fractionation into direct (conjugated) and indirect (unconjugated) components helps determine the underlying cause 1

Clinical Pitfalls to Avoid

1. Delayed recognition: Jaundice may be difficult to detect in infants with darker skin tones; always examine the sclera 3
2. Overlooking conjugated hyperbilirubinemia: Always pathological and requires prompt investigation 1
3. Dismissing prolonged jaundice: Jaundice persisting beyond 21 days requires evaluation for cholestasis, even in breastfed infants 3
4. Underestimating severity: Not all infants with severe hyperbilirubinemia show obvious clinical signs before developing kernicterus 2
5. Overdiagnosis: Avoid unnecessary testing for mild indirect hyperbilirubinemia, which may represent benign variants like Gilbert's syndrome 1

Early recognition of symptoms and prompt intervention are crucial to prevent progression to kernicterus, which can cause permanent neurological damage despite its rarity (estimated at 0.9 per 100,000 live births) 2.