Internal Medicine

Neonatal jaundice

Yellowish discoloration of the skin, conjunctiva and the sclera from elevated serum or plasma bilirubin in the newborn period.

  • 60% of term and 80% of preterm babies develop jaundice in the first week of life, and about 10% of breastfed babies are still jaundiced at 1 month of age


Bilirubin metabolism:




(Unconjugated) bilirubin

UDP-Glucoronyltransferase (UDP-GT)

(Conjugated) bilirubin

Enterohepatic circulation: Conjugated bilirubin → Unconjugated bilirubin → Liver

Stools: Stercobilinogen
Urine: Urobilinogen


Physiological jaundice (M/C type of newborn hyperbilirubinemia):

    • Only causes unconjugated hyperbilirubinemia
    • Never appears on day 1
    • Never exceeds day 7 (term)/day 14 (pre-term)
    • Never affects palms & soles
    • Bilirubin levels <15 mg/dl
    • Bilirubin rise ≤ 5 mg/day

Pathological jaundice:

  • Conjugated hyperbilirubinemia (dark urine staining the nappy)
    • M/C cause: Biliary atresia

Breastfeeding jaundice (↓ breastfeeding in 1st week of life):

    • ↓ breastfeeding → Dehydration
    • ↓ breastfeeding → ↓ Gut motility → ↑ enterohepatic circulation (as breastmilk stays in intestine for longer, resulting in increased absorption)

Breastmilk jaundice (↑ enteroheaphtic circulation, usually after 1st week)


Physiological jaundice:

  • ↑ Hemolysis → Jaundice
  • Immaturity of liver UDP-glucoronyltransferase

Pathological jaundice:

  • ↑ bilirubin production:
    • Polycythemia
    • Hemolytic jaundice:
      • Rh incompatibility (severe)
      • ABO incompatibility (common)
      • G6PD deficiency
      • Thalassemias
      • Hereditary spherocytosis
  • ↓ bilirubin conjugation:
    • Criggler-Najjar syndrome: Absent (type I) or deficient (type II) UDP-GT
      • Gilbert syndrome: Deficient UDP-GT (but usually presents after puberty

Clinical features

  • Jaundice: Cephalocaudal progression

Kramer’s criteria:

  • Serum levels of total bilirubin are approximately:
    • 4-6 mg/dl (zone 1)
    • 6-8 mg/dl (zone 2)
    • 8-12 mg/dl (zone 3)
    • 12-14 mg/dl (zone 4)
    • >15 mg/dl (zone 5)
Maisels, M. J., Clune, S., Coleman, K., Gendelman, B., Kendall, A., McManus, S., & Smyth, M. (2014). The Natural History of Jaundice in Predominantly Breastfed Infants. Pediatrics, 134(2), e340 LP-e345. Retrieved from


  • Seizures
  • Cerebral palsy

Bilirubin-induced neurological damage (BIND):

  • PathologyKernicterus: ↑↑↑ Unonjugated bilirubin (lipid soluble) → Crosses BBB → Basal ganglia
  • Acute symptoms: SLOW: Seizures, lethargic, opisthotonus, whiney (high-pitched) cry
  • Chronic symptoms: Extrapyramidal cerebral palsy, sensorineural deafness, dental dysplasia, upward gaze palsy
Yellow discoloration of the brain parenchyma, most prominent in the basal ganglia and hippocampus, is due to bilirubin accumulation associated with excess circulating bilirubin. The transition between postnatal/neonatal hemoglobin to hemoglobin A is often associated with jaundice caused by a transient increase in bilirubin which is in normal physiological ranges. However hemolytic disease of the new born (e.g. blood type incompatibility) may lead to excess bilirubin which in turn will results in accumulation of unconjugated bilirubin in the brain which can cause severe neurologic damage.


Transcutaneous bilirubinometer (TcB):

  • Placed over sternum to measure serum bilirubin


First-line tests (cord-blood):

  • Total serum bilirubin
  • Blood groups (mother & baby)
  • Direct Coombs test
  • Evidence of hemolysis: Hb < 10g, Bilirubin > 5mg, DCT (+)


Physiological jaundice

  • Mother should be encouraged to breastfeed frequently and exclusively

Pathological jaundice

Phototherapy (mainstay treatment):

  • Mode of actionConverts insoluble bilirubin (unconjugated) into soluble isomers that can be excreted in urine and feces
    • Configurational isomerization (reversible reaction)
      • Z-isomers → E-isomers  (forms 25% of TSB and is nontoxic, but excreted slowly so not a major mechanism for decrease in TSB)
    • Structural isomerization (irreversible reaction)
      • Bilirubin → Lumirubin (forms 2-6% of TSB which is rapidly excreted from body thus is mainly responsible for phototherapy induced decline in TSB)
    • Photooxidation (minor reaction)
  • Types:
    • CFL phototherapy (M/C in India)
    • Blue LED
  • Technique:
    • Minimum level: 30 microW/cm2/nm
    • Wavelength range: 460-490 nm
    • Distance of light: 30-45 cm
    • Temperature: 25-28°C
    • Maximal exposure of baby
    • Cover eyes with eye-patch
    • Ensure optimum breastfeeding
  • Adverse effects:
    • Dehydration
    • Hypocalcemia
    • Bronze baby syndrome

Exchange transfusion:

  • Double volume exchange transfusion (DVET): 160 ml/kg
  • Blood type: O (-)ve (absence of antibodies)

Medical management:

  • Phenobarbitone
  • Metalloporphyrin (inhibits heme oxygenase → ↓ Biliverdin, bilirubin)

Breastfeeding/breastmilk jaundice

  • Continue breastfeeding


  • Antenatal investigation:
    • Maternal blood grouping
  • Ensuring adequate breastfeeding
  • Parent education regarding danger signs
  • High-risk babies (eg. large cephalohematoma) or family history of should be followed up after 2-3 days of discharge

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