What are the causes of childhood onset jaundice in pediatric patients?

Causes of Childhood Onset Jaundice

Childhood jaundice must be categorized by age at presentation and conjugation status, as this determines both the differential diagnosis and urgency of intervention—jaundice in the first 24 hours is always pathologic and demands immediate evaluation, while jaundice persisting beyond 2-3 weeks requires measurement of direct bilirubin to identify life-threatening cholestatic conditions like biliary atresia.

Age-Based Classification

Neonatal Period (First 28 Days)

Early Jaundice (First 24 Hours)

This is always pathologic and requires immediate bilirubin measurement and workup 1:

• Isoimmune hemolytic disease (ABO or Rh incompatibility with positive Coombs test) - most common serious cause 1
• G6PD deficiency - particularly in infants of East Asian, Mediterranean, or African descent 2, 1
• Hereditary spherocytosis or other red cell membrane defects 1
• Sepsis - bacterial infection causing hemolysis and hepatic dysfunction 1
• Significant cephalohematoma or bruising from birth trauma causing excessive bilirubin load 2, 1

Physiologic Jaundice (Days 2-14)

• Physiologic hyperbilirubinemia - occurs in most newborns due to increased red blood cell breakdown, immature hepatic conjugation, and increased enterohepatic circulation 3, 4
• Breastfeeding jaundice - associated with inadequate intake (≤7 feedings daily), dehydration, and excessive weight loss (>7-10% of birth weight) 2, 5
• Breast milk jaundice - typically peaks at 10-14 days, related to substances in breast milk that increase enterohepatic circulation 5, 4

Prolonged Jaundice (Beyond 14-21 Days)

Any jaundice persisting beyond 3 weeks requires measurement of total and direct (conjugated) bilirubin to identify cholestasis 2, 1:

• Biliary atresia - progressive obliteration of extrahepatic bile ducts; requires surgical intervention (Kasai procedure) ideally before 60 days of age 6, 7
• Choledochal cyst - congenital cystic dilatation of bile ducts 6, 7
• Neonatal hepatitis - infectious or idiopathic inflammation 6, 7
• Inspissated bile syndrome - bile duct obstruction from thickened bile 6, 7
• Metabolic disorders - galactosemia, hypothyroidism, alpha-1 antitrypsin deficiency 2, 6
• Total parenteral nutrition-associated cholestasis - particularly in preterm infants 4, 6

Beyond Neonatal Period (>28 Days to Adolescence)

Hepatocellular Causes (Unconjugated Hyperbilirubinemia)

• Viral hepatitis (hepatitis A, B, C, EBV, CMV) - hepatitis A is the most common vaccine-preventable cause in travelers 3
• Autoimmune hepatitis - more common in older children and adolescents 3
• Drug-induced hepatotoxicity - acetaminophen, antibiotics, anticonvulsants 3
• Alcoholic liver disease - in adolescents 3
• Hemolytic anemias - sickle cell disease, thalassemia, G6PD deficiency 3, 7
• Gilbert syndrome - benign inherited disorder causing mild unconjugated hyperbilirubinemia 3

Obstructive Causes (Conjugated Hyperbilirubinemia)

• Choledocholithiasis (common bile duct stones) - associated with hemolytic anemia, short-gut syndrome, total parenteral nutrition 3, 7
• Choledochal cyst - may present later in childhood 6, 7
• Caroli disease - congenital intrahepatic bile duct dilatation 6
• Malignancy - hepatoblastoma, lymphoma causing biliary obstruction 3
• Pancreatitis - causing bile duct compression 3
• Cholangitis - ascending bacterial infection of bile ducts 3

Systemic Causes

• Sepsis or shock - causing hepatic hypoperfusion and dysfunction 3
• Cirrhosis - from chronic liver disease of any etiology 3
• Congestive heart failure - causing hepatic congestion 3

Critical Diagnostic Approach

Initial Laboratory Evaluation

• Total and direct (conjugated) bilirubin - to differentiate unconjugated vs conjugated hyperbilirubinemia 2, 1, 8
• Blood type and direct antibody test (Coombs) - for isoimmune hemolysis 2, 1
• Complete blood count with peripheral smear and reticulocyte count - to assess for hemolysis 1
• G6PD level - particularly in at-risk populations 2, 1
• Hepatic profile (ALT, AST, alkaline phosphatase, albumin) 3, 8
• Urinalysis and urine culture - if direct bilirubin elevated 2

Imaging

• Ultrasound is the first-line imaging modality to differentiate obstructive from non-obstructive causes, evaluate for choledochal cyst, biliary atresia, and stones 3, 7
• Hepatic scintigraphy may be needed to assess biliary excretion in suspected biliary atresia 7

Critical Pitfalls to Avoid

• Never rely on visual assessment alone - always obtain objective bilirubin measurement, especially in darkly pigmented infants 2, 1
• Do not miss biliary atresia - any infant with jaundice beyond 3 weeks requires direct bilirubin measurement; delayed diagnosis beyond 60 days significantly worsens surgical outcomes 2, 6
• Jaundice in first 24 hours is never physiologic - requires immediate TSB measurement and hemolysis workup 1
• Do not discharge high-risk neonates (gestational age 35-36 weeks, hemolytic disease, poor feeding) without explicit follow-up plan within 24-96 hours 2, 1
• Verify newborn screening results for thyroid and galactosemia in prolonged jaundice 2