What is the appropriate management and treatment for jaundice and hyperbilirubinemia in patients, including newborns and adults, with various underlying causes?

Management of Jaundice and Hyperbilirubinemia

Neonatal Jaundice (≥35 Weeks Gestation)

Use total serum bilirubin (TSB) plotted on hour-specific nomograms as the definitive diagnostic test to guide all treatment decisions, and initiate intensive phototherapy immediately when TSB reaches age- and risk-factor-specific thresholds. 1

Distinguish Physiological from Pathological Jaundice

Physiological jaundice:

• Onset after 24 hours of life, peaks at days 3-5, resolves by 2 weeks 2
• TSB remains below 15 mg/dL in healthy term infants 2
• Infant appears well, feeding adequately, normal weight loss (<10% by day 3) 2
• Progresses cephalocaudally (face → trunk → extremities) 2

Pathological jaundice (requires urgent evaluation):

• Jaundice within first 24 hours of life—this is NEVER physiological 2
• Rapidly rising TSB (≥0.3 mg/dL per hour in first 24 hours or ≥0.2 mg/dL per hour thereafter) 1
• TSB exceeding 95th percentile for age in hours 2
• Jaundice persisting beyond 2-3 weeks in term infants 2

Risk Assessment and Monitoring

Prenatal and immediate postnatal testing:

• Test all pregnant women for ABO and Rh(D) blood types with serum screen for unusual isoimmune antibodies 1
• If mother is Rh-negative or lacks prenatal blood grouping, obtain direct antibody test (Coombs'), blood type, and Rh(D) type on infant's cord blood 1
• If maternal blood is group O, Rh-positive, cord blood testing is optional but requires appropriate surveillance and follow-up 1

Routine monitoring:

• Assess jaundice whenever vital signs are measured, minimum every 8-12 hours 1
• Never rely on visual assessment alone, especially in darkly pigmented infants—always obtain objective measurements 2
• Measure TSB if transcutaneous bilirubin (TcB) is within 3.0 mg/dL of phototherapy threshold, exceeds threshold, or is ≥15 mg/dL 1
• Plot all bilirubin measurements on hour-specific nomograms to assess risk 1, 3

Major risk factors for severe hyperbilirubinemia (in order of importance):

• Predischarge TSB/TcB in high-risk zone 1
• Jaundice observed in first 24 hours 1
• Blood group incompatibility with positive direct antiglobulin test or other hemolytic disease (e.g., G6PD deficiency) 1
• Gestational age 35-36 weeks 1
• Previous sibling received phototherapy 1
• Cephalohematoma or significant bruising 1
• Exclusive breastfeeding with poor intake and excessive weight loss 1
• East Asian race 1

Prevention Strategies

Breastfeeding support:

• Advise mothers to nurse 8-12 times per day for the first several days 1, 3
• Do NOT routinely supplement nondehydrated breastfed infants with water or dextrose water—this will not prevent hyperbilirubinemia 1, 3
• Assess adequacy of breastfeeding intake at every visit 1

Treatment Thresholds and Phototherapy

Initiate intensive phototherapy:

• Use hour-specific nomograms based on gestational age, neurotoxicity risk factors, and infant age in hours 1
• Use special blue fluorescent tubes or LED lights delivering irradiance >30 mW/cm²/nm 3
• Expect TSB decrease of >2 mg/dL within 4-6 hours of effective phototherapy 3
• Change infant's posture every 2-3 hours to maximize light exposure 3
• Avoid physical obstruction by equipment, large diapers, head covers, or electrode patches 3

Home phototherapy option:

• For infants already discharged with TSB above phototherapy threshold, home LED-based phototherapy is an option if specific criteria are met 1
• This helps avoid hospital readmission 2

Monitoring during phototherapy:

• Measure TSB to verify efficacy after starting phototherapy, with timing guided by TSB trajectory and infant age 1
• Assess hydration and temperature control during treatment 1
• Discontinue phototherapy when TSB has declined 2-4 mg/dL below hour-specific threshold at initiation 1
• Individualize discontinuation based on TSB level at initiation, cause of hyperbilirubinemia, and rebound risk 1

Post-phototherapy follow-up:

• For infants treated <48 hours of age, gestational age <38 weeks, positive DAT, or suspected hemolytic disease: measure TSB 8-12 hours after discontinuation and the following day 1
• All other infants: measure TSB within 1-2 days after discontinuation 1
• Use TSB (not TcB) unless ≥24 hours since phototherapy stopped 1

Escalation of Care

When TSB is at or within 0-2 mg/dL below exchange transfusion threshold:

• Provide intravenous hydration and emergent intensive phototherapy immediately 1
• Measure TSB at least every 2 hours until escalation period ends 1
• If TSB continues rising despite intervention, consult neonatologist about NICU transfer 1
• Consider exchange transfusion if TSB remains in intensive phototherapy range and phototherapy fails to promptly lower TSB 3
• Do NOT subtract direct bilirubin from TSB when making exchange transfusion decisions 3

Diagnostic Evaluation

Evaluate underlying cause in infants requiring phototherapy:

• Measure G6PD enzyme activity in any infant with jaundice of unknown cause whose TSB rises despite intensive phototherapy, rises suddenly after initial decline, or requires escalation of care 1
• For sick infants or those jaundiced at/beyond 3 weeks: measure total and direct/conjugated bilirubin to identify cholestasis 3
• Check newborn thyroid and galactosemia screening results in prolonged jaundice 3

Mandatory investigations for pathological jaundice:

• Blood type and Rh of mother and infant 2
• Direct Coombs' test 2
• Complete blood count with smear 2
• Total and direct/conjugated bilirubin 2
• Reticulocyte count 2
• G6PD level 2
• Newborn screening results 2

Discharge Planning and Follow-up

Before discharge:

• Provide written and verbal information explaining jaundice, monitoring needs, and when to seek care 1
• Perform predischarge TSB or TcB measurement and plot on nomogram 1

Post-discharge follow-up schedule:

• Discharged before 24 hours: see by 72 hours 1
• Discharged between 24-47.9 hours: see by 96 hours 1
• Discharged between 48-72 hours: see by 120 hours 1
• Follow-up should assess weight, percent change from birth weight, adequacy of intake, voiding/stooling pattern, and presence/absence of jaundice 1

Critical Pitfalls to Avoid

• Do NOT wait to confirm elevated capillary TSB with venous sample before initiating treatment—this delays critical intervention 2
• Any jaundice in first 24 hours requires immediate TSB measurement and investigation 2
• Infants with prolonged jaundice (>2-3 weeks) MUST have direct/conjugated bilirubin measured to rule out cholestasis and biliary atresia 2
• Breastfed infants and late preterm infants (35-37 weeks) require closer monitoring with lower thresholds for intervention 2

Adult Jaundice

Organize the diagnostic approach by measuring fractionated bilirubin to determine if hyperbilirubinemia is conjugated or unconjugated, then proceed with cause-specific evaluation based on prehepatic, intrahepatic, or posthepatic etiology. 4

Initial Evaluation

Clinical assessment:

• Jaundice becomes apparent when serum bilirubin exceeds 2.5-3 mg/dL 5
• Obtain comprehensive history focusing on alcohol use, medications, viral hepatitis exposure, autoimmune disorders, hemolysis risk factors, and biliary symptoms 4
• Perform focused physical examination for signs of chronic liver disease, hepatomegaly, splenomegaly, and abdominal masses 4

Initial laboratory testing:

• Total and fractionated bilirubin (conjugated and unconjugated) 4
• Complete blood count 4
• Aspartate transaminase (AST) and alanine transaminase (ALT) 4
• Alkaline phosphatase 4
• Gamma-glutamyltransferase 4
• Albumin 4
• Prothrombin time and international normalized ratio 4
• Urine test for bilirubin (indicates conjugated hyperbilirubinemia) 6

Differential Diagnosis by Bilirubin Type

Unconjugated (indirect) hyperbilirubinemia—prehepatic causes:

• Hemolysis 6
• Hematoma resorption 6
• Gilbert syndrome 7
• Crigler-Najjar syndrome types 1 and 2 7

Conjugated (direct) hyperbilirubinemia—intrahepatic causes:

• Alcoholic liver disease 4
• Infectious hepatitis 4, 6
• Drug-induced liver injury 4
• Autoimmune disorders 4, 6
• Dubin-Johnson syndrome 7
• Rotor syndrome 7
• Wilson disease 7

Conjugated hyperbilirubinemia—posthepatic causes:

• Choledocholithiasis (most common benign cause) 6
• Biliary strictures 4
• Biliary tract infection 6
• Pancreatitis 6
• Malignancies 4, 6

Imaging Studies

First-line imaging options (select based on suspected etiology):

• Abdominal ultrasonography 4, 6
• Computed tomography with intravenous contrast 4, 6
• Magnetic resonance cholangiopancreatography 4

When alkaline phosphatase is elevated:

• Proceed with hepatobiliary imaging to evaluate for obstruction 5
• Assess hepatic synthetic function to formulate treatment plan 5

If etiology remains unclear:

• Consider more invasive procedures such as cholangiography 6
• Liver biopsy may be required to establish diagnosis, prognosis, and management 4