What is the difference between physiological and pathological jaundice in newborns?

Distinguishing Physiological from Pathological Neonatal Jaundice

The critical distinction is timing and trajectory: jaundice appearing in the first 24 hours of life is pathological until proven otherwise and demands immediate investigation, while jaundice appearing after 24 hours with gradual rise and resolution by 2 weeks is typically physiological. 1, 2

Physiological Jaundice

Physiological jaundice is a benign, self-limited condition affecting most newborns that requires monitoring but rarely intervention. 1, 3

Defining Characteristics:

• Onset after 24 hours of life (typically days 2-3) 1, 2
• Peak bilirubin levels by days 3-5 in term infants, with gradual decline thereafter 3, 4
• Total serum bilirubin (TSB) typically remains below 15 mg/dL (257 μmol/L) in healthy term infants 1
• Resolution by 2 weeks in term infants (may persist up to 3-4 weeks in breastfed infants) 1, 3
• Infant appears well, feeding adequately, with normal weight loss pattern (less than 10% by day 3) 1
• Jaundice progresses cephalocaudally (face → trunk → extremities) 1

Underlying Mechanism:

Physiological jaundice results from the normal developmental immaturity of hepatic conjugation combined with increased bilirubin production from red blood cell breakdown and enhanced enterohepatic circulation in newborns 3, 4. This is an expected transitional phenomenon, not a disease state 5.

Management Approach:

• Monitor routinely every 8-12 hours during nursery stay 1, 2
• Support breastfeeding with 8-12 feedings per day to enhance bilirubin excretion 1, 2
• Avoid water or dextrose supplementation in non-dehydrated infants, as this provides no benefit 1
• Measure TSB or transcutaneous bilirubin (TcB) if jaundice appears excessive for infant's age 1, 2
• Plot bilirubin levels on hour-specific nomograms to assess risk trajectory 2
• Phototherapy is indicated only if TSB crosses treatment thresholds based on age and risk factors 2

Pathological Jaundice

Pathological jaundice represents an underlying disease process requiring urgent investigation and treatment to prevent kernicterus and neurologic injury. 1, 3

Red Flags Demanding Immediate Evaluation:

• Jaundice within the first 24 hours of life (always pathological) 1, 2, 3
• Rapidly rising TSB (crossing percentiles on nomogram or increasing >0.2 mg/dL/hour) 1, 2
• TSB exceeding the 95th percentile for age in hours 1, 2
• Jaundice persisting beyond 2-3 weeks in term infants 1, 2
• Elevated direct/conjugated bilirubin (suggests cholestasis or biliary atresia) 1, 2, 3
• Infant appears ill: lethargy, poor feeding, excessive weight loss (>10%), fever, or signs of sepsis 1
• Clinical signs of acute bilirubin encephalopathy: lethargy, hypotonia, poor suck, high-pitched cry, irritability, hypertonia, retrocollis, opisthotonos 1

Common Pathological Causes:

• Hemolytic disease: ABO/Rh incompatibility, G6PD deficiency, hereditary spherocytosis 1, 2
• Infection: sepsis, urinary tract infection, TORCH infections 3, 5
• Metabolic disorders: galactosemia, hypothyroidism 1, 2
• Cholestasis/biliary obstruction: biliary atresia (requires urgent surgical evaluation) 1, 2, 3
• Polycythemia, cephalohematoma, significant bruising (increased bilirubin load) 1

Mandatory Investigations for Pathological Jaundice:

• Blood type and Rh of mother and infant, direct Coombs' test (if not obtained from cord blood) 1, 2
• Complete blood count with smear to assess hemolysis 1
• Total and direct/conjugated bilirubin (especially if jaundice >3 weeks) 1, 2
• Reticulocyte count, G6PD level if hemolysis suspected 1
• Newborn screening results (thyroid, galactosemia) 1, 2

Treatment Imperatives:

• Initiate phototherapy immediately if TSB approaches treatment thresholds 2
• Intensive phototherapy (irradiance >30 μW/cm²/nm) should decrease TSB by >2 mg/dL within 4-6 hours 2
• Exchange transfusion is indicated if TSB reaches exchange levels or phototherapy fails to adequately lower bilirubin 2
• Treat underlying cause: antibiotics for sepsis, cessation of breastfeeding if breast milk jaundice suspected (though this is controversial), surgical referral for biliary atresia 3, 5

Critical Pitfalls to Avoid:

Never rely on visual assessment alone to estimate bilirubin levels, especially in darkly pigmented infants—always obtain objective measurements 1. Visual estimation leads to dangerous underestimation of severity 1.

Do not wait to "confirm" an elevated capillary TSB with a venous sample before initiating treatment, as this delays critical intervention 1. Capillary values are acceptable for clinical decision-making 1.

Any jaundice in the first 24 hours requires immediate TSB measurement and investigation—this is never physiological 1, 2. Early-onset jaundice suggests hemolytic disease and carries high risk for severe hyperbilirubinemia 2.

Infants with prolonged jaundice (>2-3 weeks) must have direct/conjugated bilirubin measured to rule out cholestasis and biliary atresia, which require urgent intervention 1, 2, 3. Missing biliary atresia has devastating consequences for liver function and survival 3.

Breastfed infants and late preterm infants (35-37 weeks) are at higher risk for severe hyperbilirubinemia and require closer monitoring with lower thresholds for intervention 2, 4.