Development of Jaundice in Newborns
Jaundice in newborns primarily develops due to increased bilirubin production from red blood cell breakdown combined with immature liver function that limits bilirubin conjugation and excretion. 1, 2
Pathophysiology of Neonatal Jaundice
Bilirubin Production and Metabolism
- Increased bilirubin production: Newborns have higher red blood cell turnover (shorter RBC lifespan) compared to adults 2
- Immature liver function: Limited ability to conjugate bilirubin due to:
- Enterohepatic circulation: Increased reabsorption of bilirubin from the intestines due to:
- Delayed passage of meconium
- Increased β-glucuronidase activity in the intestine 2
Types of Hyperbilirubinemia
Physiologic jaundice:
- Appears after 24 hours of life
- Peaks at 3-5 days in term infants
- Usually resolves by 7-10 days 4
Pathologic jaundice:
Breast milk jaundice:
- Appears after 3-5 days
- May persist for 3-12 weeks
- Associated with substances in breast milk that inhibit bilirubin conjugation 1
Risk Factors for Developing Severe Hyperbilirubinemia
Major Risk Factors
- Jaundice appearing within first 24 hours of life 4
- Blood group incompatibility (ABO, Rh) 4, 1
- Predischarge bilirubin level in high-risk zone 4
- G6PD deficiency (affects 11-13% of African Americans) 4
- Gestational age 35-36 weeks 1
Additional Risk Factors
- Previous sibling with jaundice 1
- Cephalohematoma or significant bruising 1
- Exclusive breastfeeding, especially with poor feeding 4
- East Asian, Mediterranean, or Middle Eastern ethnicity 1
- Maternal diabetes 1
Clinical Manifestations
Progression of Jaundice
- Jaundice typically progresses in a cephalocaudal direction (head to toe)
- First appears on the face and sclera when bilirubin levels reach 5-7 mg/dL
- Extends to the trunk at levels of 10-12 mg/dL
- Reaches the extremities at levels >15 mg/dL 1
Warning Signs of Severe Hyperbilirubinemia
- Jaundice appearing within 24 hours of birth
- Rapidly increasing bilirubin levels (>0.5 mg/dL/hour)
- Total serum bilirubin approaching exchange transfusion levels
- Signs of acute bilirubin encephalopathy (lethargy, poor feeding, high-pitched cry) 4, 1
Complications of Severe Hyperbilirubinemia
Acute Bilirubin Encephalopathy
- Early signs: lethargy, hypotonia, poor feeding
- Intermediate signs: irritability, hypertonia, high-pitched cry
- Advanced signs: retrocollis, opisthotonus, seizures 4
Kernicterus
- Permanent neurologic damage from bilirubin toxicity to basal ganglia and brainstem nuclei
- Can result in cerebral palsy, hearing loss, visual impairments, and intellectual disability 4, 5
Prevention and Management
Prevention
- Early and frequent breastfeeding (8-12 times per day) 4
- Avoiding routine supplementation with water or dextrose water 4
- Systematic assessment of risk factors before discharge 4, 1
- Predischarge bilirubin screening 4, 1
Diagnostic Evaluation
- Total and direct (conjugated) bilirubin levels
- Blood type and Coombs' test
- Complete blood count with differential and peripheral smear
- G6PD testing in high-risk populations 4, 1
Treatment
- Phototherapy based on hour-specific nomograms and risk factors
- Intravenous immunoglobulin for isoimmune hemolytic disease
- Exchange transfusion for severe cases not responding to phototherapy 1
Common Pitfalls in Management
Visual estimation of jaundice: Can lead to errors, particularly in darkly pigmented infants; always measure bilirubin levels when in doubt 4
Inadequate follow-up: Infants discharged before 72 hours require close follow-up within 1-2 days 4
Failure to recognize pathologic causes: Always investigate jaundice appearing within 24 hours of birth 4
Overlooking G6PD deficiency: Consider testing, especially in African American infants 4
Delayed recognition of cholestasis: Measure direct bilirubin if jaundice persists beyond 2 weeks 1
Understanding the pathophysiology of neonatal jaundice allows for appropriate risk assessment, early intervention, and prevention of severe complications such as kernicterus.