What are the causes of neonatal jaundice?

Causes of Neonatal Jaundice

Neonatal jaundice has multiple etiologies, with physiological jaundice being most common, but pathological causes must be identified early to prevent kernicterus and long-term neurological damage. 1

Classification of Causes

Physiological Jaundice

• Normal physiological process occurring in approximately 80% of newborns 2
• Results from:
  • Increased red blood cell breakdown (shorter RBC lifespan in newborns)
  • Immature hepatic bilirubin conjugation
  • Increased enterohepatic circulation

Pathological Causes (Unconjugated Hyperbilirubinemia)

Blood Group Incompatibilities

• ABO incompatibility (most common significant risk factor) 3
• Rhesus (Rh) incompatibility (now rare due to effective prenatal monitoring) 3
• Presents with jaundice within first 24 hours of life 1

Increased Bilirubin Production

• Cephalohematoma and bruising (significant risk factor) 3
• Hemolytic disorders:
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency (found in 11-13% of African Americans) 1
  • Hereditary spherocytosis
  • Other hemolytic anemias

Decreased Bilirubin Clearance

• Gilbert's syndrome (inherited disorder with impaired conjugation) 1
• Crigler-Najjar syndrome
• Hypothyroidism (requires thyroid screening) 1

Other Risk Factors

• Male gender (independent risk factor) 3
• Shorter gestational age 3
• Early discharge from hospital (<36 hours after birth) 3
• Relative weight loss in first 5 days of life 3
• Exclusive breastfeeding (breast milk jaundice)

Pathological Causes (Conjugated Hyperbilirubinemia)

• Indicates potential liver disease when conjugated bilirubin >25 μmol/L in neonates and infants 1
• Requires urgent pediatric assessment 1

Biliary Obstruction

• Biliary atresia (critical to diagnose early) 4, 5
• Choledochal cyst
• Bile duct stenosis

Hepatocellular Damage

• Infections:
  • TORCH infections (Toxoplasmosis, Other, Rubella, Cytomegalovirus, Herpes)
  • Sepsis (requires evaluation when indicated by history/exam) 1
  • Urinary tract infections 1
• Metabolic disorders:
  • Galactosemia (requires screening) 1
  • Alpha-1 antitrypsin deficiency
  • Tyrosinemia

Other Causes

• Parenteral nutrition-associated cholestasis in preterm infants 4
• Neonatal hepatitis

Diagnostic Approach

Early Jaundice (First 14 Days)

1. Assess timing of onset:

   • Jaundice in first 24 hours is always pathological and requires immediate evaluation 1
   • Jaundice appearing after 24 hours is more likely physiological

2. Laboratory evaluation based on clinical presentation:

   • For all jaundiced infants: TcB (transcutaneous bilirubin) and/or TSB (total serum bilirubin) measurement 1
   • For rapidly rising bilirubin or unexplained jaundice:
     • Blood type and Coombs' test
     • Complete blood count and smear
     • Direct/conjugated bilirubin measurement 1

Prolonged Jaundice (Beyond 14 Days)

• All infants with jaundice beyond 3 weeks require:
  • Total and direct/conjugated bilirubin measurement
  • Evaluation for cholestasis if direct bilirubin is elevated
  • Thyroid and galactosemia screening 1

Key Considerations for Clinicians

• Jaundice appearing within first 24 hours is always pathological and requires immediate investigation 1
• Visual assessment of jaundice is unreliable, especially in darkly pigmented infants 1
• Male infants are at higher risk for severe jaundice and may experience greater learning impairment from hyperbilirubinemia 3
• Conjugated hyperbilirubinemia is never physiological and always requires prompt evaluation 1, 5
• Early discharge (<36 hours) is a significant risk factor for severe jaundice and may lead to delayed diagnosis 3

By systematically evaluating the timing, pattern, and laboratory findings of neonatal jaundice, clinicians can distinguish between benign physiological jaundice and potentially harmful pathological causes that require urgent intervention.