Overview
Definition:
Hyperbilirubinemia is a condition characterized by elevated levels of bilirubin in the blood, commonly presenting as jaundice, which is yellowing of the skin and sclera
In neonates, it is a frequent occurrence due to immature hepatic conjugation and increased bilirubin production.
Epidemiology:
Approximately 60% of full-term and 80% of preterm neonates develop jaundice
Severe hyperbilirubinemia, requiring intervention, occurs in about 10% of term infants
Prematurity, Asian ethnicity, and breastfeeding are associated with higher incidence.
Clinical Significance:
While most neonatal jaundice is physiological and resolves spontaneously, severe unconjugated hyperbilirubinemia poses a risk of acute bilirubin encephalopathy and chronic kernicterus, leading to irreversible neurological damage
Early identification and management are crucial for preventing these severe sequelae.
Age Considerations
Definition:
Neonatal hyperbilirubinemia is primarily defined by the timing of onset, duration, and rate of rise of serum bilirubin levels, as well as the infant's gestational age and postnatal age.
Gestational Age:
Preterm infants are at higher risk due to less mature hepatic function and potentially lower birth weight
Management thresholds are adjusted based on gestational age.
Postnatal Age:
The interpretation of bilirubin levels is critically dependent on the infant's age in hours
Levels that are benign at 72 hours can be dangerous at 24 hours.
Clinical Presentation
Symptoms:
Visible jaundice, often starting on the face and progressing caudally
Lethargy
Poor feeding
Irritability
High-pitched cry
Hypotonia
Fever or hypothermia
Seizures (in severe cases).
Signs:
Yellowing of sclera and skin (icterus)
Palpable liver or spleen (hepatosplenomegaly) in some cases
Signs of encephalopathy such as opisthotonos, poor Moro reflex, and abnormal eye movements.
Diagnostic Criteria:
Clinical jaundice: observed when total serum bilirubin (TSB) is >5 mg/dL in neonates
Pathological jaundice: Jaundice appearing within the first 24 hours of life
TSB rising by >5 mg/dL per day
TSB >15 mg/dL in term infants
Clinical signs of disease
Jaundice lasting >2 weeks in term infants.
Diagnostic Approach
History Taking:
Gestational age at birth
Birth weight
Maternal blood group and Rh status
History of G6PD deficiency or ABO incompatibility in previous siblings
Feeding method (breastfeeding vs
formula)
Onset and progression of jaundice
Infant's behavior (feeding, activity, cry).
Physical Examination:
Assess the extent of jaundice by blanching the skin
Examine for signs of encephalopathy (neurological status)
Evaluate for hepatosplenomegaly
Assess hydration status and vital signs.
Investigations:
Total serum bilirubin (TSB) measurement, including direct and indirect fractions
Direct Coombs' test if isoimmune hemolytic disease is suspected
Blood type and Rh for infant and mother
Complete blood count (CBC) with reticulocyte count
Glucose-6-phosphate dehydrogenase (G6PD) deficiency assay if indicated
Liver function tests if cholestasis is suspected.
Differential Diagnosis:
Physiological jaundice
Breast milk jaundice
Breastfeeding jaundice
Hemolytic disease (ABO, Rh, G6PD deficiency, hereditary spherocytosis)
Sepsis
Intrauterine infection (TORCH)
Gilbert's syndrome
Crigler-Najjar syndrome
Biliary atresia
Hypothyroidism
Inspissated bile syndrome.
Management
Initial Management:
Assess infant's gestational age, postnatal age, and TSB level
Identify risk factors for hyperbilirubinemia
Initiate appropriate monitoring and supportive care.
Phototherapy Thresholds Bhutani Nomogram:
The Bhutani nomogram plots TSB levels against post-natal age in hours and categorizes infants into low, intermediate, and high-risk zones
Phototherapy is indicated for infants in the intermediate-risk zone at higher TSB levels and in the high-risk zone at lower TSB levels
Specific thresholds vary based on risk zone and gestational age, but generally, phototherapy is initiated when TSB levels approach levels associated with a significant risk of neurotoxicity
For example, in a term infant, phototherapy might be initiated around 10-12 mg/dL in the low-risk zone, 12-15 mg/dL in the intermediate zone, and 15-18 mg/dL in the high-risk zone
Exchange transfusion is considered at much higher levels, typically above 20-25 mg/dL depending on risk factors.
Phototherapy Protocols:
Standard phototherapy uses blue-green light (wavelength 460-490 nm) to convert unconjugated bilirubin into water-soluble photoproducts excreted in bile and urine
The intensity of light (irradiance) should be at least 8-10 µW/cm²/nm
Infants should be undressed except for eye patches and diaper
Maintain adequate hydration and feeding
Monitor TSB levels every 4-8 hours during intensive phototherapy.
Exchange Transfusion:
Indicated for severe hyperbilirubinemia not responding to phototherapy, especially in cases of hemolytic disease, or when TSB levels are critically high (e.g., >20-25 mg/dL in term infants) to rapidly reduce bilirubin levels and prevent kernicterus
This involves removing infant's blood and replacing it with donor blood.
Complications
Acute Bilirubin Encephalopathy:
Early signs include lethargy, poor sucking, and high-pitched cry
Intermediate stage shows hypotonia, opisthotonos, and irritability
Advanced stage involves seizures, coma, and respiratory arrest.
Chronic Kernicterus:
Irreversible neurological sequelae characterized by extrapyramidal movement disorders (choreoathetoid cerebral palsy), auditory dysfunction (sensorineural hearing loss), oculomotor abnormalities (especially upward gaze palsy), and dental enamel dysplasia.
Prevention Strategies:
Early identification of at-risk infants
Frequent monitoring of TSB levels
Timely initiation of phototherapy and, if necessary, exchange transfusion
Adequate feeding and hydration
Screening for G6PD deficiency in at-risk populations.
Key Points
Exam Focus:
Understand the principles of bilirubin metabolism and breakdown products
Memorize the Bhutani nomogram and the risk stratification
Know the phototherapy thresholds for different risk zones and gestational ages
Recognize the signs and symptoms of acute bilirubin encephalopathy and kernicterus
Be aware of indications for exchange transfusion.
Clinical Pearls:
Always assess jaundice based on post-natal age in hours, not just days
Use the Bhutani nomogram as a guide, but clinical judgment is paramount
Ensure adequate light intensity and coverage for phototherapy
Monitor for signs of dehydration and monitor TSB trends, not just single values.
Common Mistakes:
Over-reliance on visual assessment of jaundice
Ignoring the infant's gestational and post-natal age
Delaying phototherapy in high-risk infants
Inadequate monitoring of TSB levels
Misinterpreting the Bhutani nomogram by not considering the risk zones.