• Clinical science

Neonatal jaundice


Neonatal jaundice is one of the most common conditions occurring in newborn infants and is characterized by elevated levels of bilirubin in the blood (total serum bilirubin concentration > 5 mg/dL). The most common cause of neonatal jaundice is a physiological rise in unconjugated bilirubin, which results from hemolysis of fetal hemoglobin and an immature hepatic metabolism of bilirubin. Physiological jaundice is harmless and occurs in most infants between the third and the eighth day of life. Pathologic neonatal jaundice can be conjugated or unconjugated and is typically a symptom of an underlying disease. Possible conditions include hemolytic anemias, blood group incompatibilities, Gilbert and Crigler–Najjar syndromes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and congenital biliary flow obstructions. Hyperbilirubinemia can cause drowsiness and poor feeding in the newborn, and in severe cases, unconjugated bilirubin can cross the blood-brain barrier and cause permanent neurological damage (kernicterus). The degree of hyperbilirubinemia can be measured by transcutaneous and/or serum bilirubin measurements. Treatment modalities include phototherapy, intravenous immune globulin (IVIG), and exchange transfusion, in addition to specific therapies for the respective underlying conditions. Treatment is targeted at reducing the risk of kernicterus and hence permanent neurological sequelae.


Physiological neonatal jaundice Pathological neonatal jaundice
  • Always unconjugated hyperbilirubinemia
    • Peak total serum bilirubin : < 15 mg/dL (in the case of a full-term, breastfed infant)
    • Daily rise in bilirubin levels < 5 mg/dL/day
  • Can be either conjugated or unconjugated hyperbilirubinemia
    • Peak total serum bilirubin can rise > 15 mg/dL
    • Daily rise in bilirubin levels > 5 mg/dL/day
  • Risk factors for pathological jaundice:

Etiology of conjugated hyperbilirubinemia

Etiology of unconjugated hyperbilirubinemia



Physiological hyperbilirubinemia

Pathological hyperbilirubinemia

  • Can be caused by multiple mechanisms:
    • Increased production of bilirubin
    • Decreased hepatic uptake
    • Decreased conjugation
    • Impaired excretion
    • Increased enterohepatic circulation

Subtypes and variants

Breastfeeding jaundice

  • Pathophysiology: insufficient breast milk intake; → lack of calories and inadequate quantities of bowel movements to remove bilirubin from the body → ↑ enterohepatic circulationincreased reabsorption of bilirubin from the intestines
  • Clinical features: onset within 1 week
  • Treatment: increase breastfeeding sessions, rehydration

Breast milk jaundice

  • Pathophysiology: increased concentration of β-glucuronidase in breast milk → ↑ deconjugation and reabsorption of bilirubin → persistence of physiologic jaundice
  • Clinical features: onset within 2 weeks after birth; lasts for 4–13 weeks
  • Treatment
    • Continued breastfeeding and supplementation with formula feeds
    • Phototherapy if required

Clinical features



  1. Physical examination for icterus
  2. Bilirubin tests
    • Transcutaneous bilirubin measurement (TcB)
    • Serum bilirubin measurement
      • Total serum bilirubin (TSB) measured
      • Differentiation of direct (conjugated) and indirect (unconjugated) bilirubin (see “Classification”)
      • Assessment of degree of jaundice based on nomogram → infants > 95th percentile must be evaluated for pathological jaundice (see tests below)
  3. Other laboratory tests

Physiological neonatal jaundice is a diagnosis of exclusion! Laboratory tests should first rule out all pathological causes of neonatal jaundice!

Jaundice in a term newborn less than 24 hours old is always pathologic!




Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia.

  • Indications
  • Contraindication: direct (conjugated) bilirubin → danger of “bronze baby” syndrome
  • Procedure
    • Exposure to blue light; (wavelength: 420–480 nm) → conversion of unconjugated (hydrophobic) bilirubin in skin to water-soluble form → excretion of water-soluble form in urine and/or bile
    • Continued until total bilirubin levels < 15 mg/dL
    • Adequate fluid supplementation to prevent dehydration
    • Eye protection against UV light
  • Side effects

Exchange transfusion

  • Most rapid method for lowering serum bilirubin concentrations
  • Indications
    • Threshold in a 24-hour-old term baby is a total serum bilirubin value > 20 mg/dL
    • Inadequate response to phototherapy, or a rapid rise in the total serum bilirubin level (> 1 mg/dL/hour in less than 6 hours)
    • Acute bilirubin encephalopathy
    • Hemolytic disease, severe anemia
  • Implementation
  • Side effects: higher mortality and morbidity from infections, acidosis, thrombosis, hypotension, and electrolyte imbalances

IV immunoglobulin

  • Used in cases with immunologically mediated conditions, or in the presence of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice
  • Dose range for IVIG: 500–1000 mg/kg



  • Favorable in most cases
  • In rare cases kernicterus may occur, resulting in permanent neurological sequelae.


  • Interruption of enterohepatic circulation through adequate enteral nutrition
    • Frequent feeds with breast milk
    • Protein-rich nutrition in the form of breast milk or special formula feeds
    • In the case of dehydration, protein-rich feeding solutions are preferred over glucose or water.
  • 1. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education; 2015.
  • 2. Kaplan. USMLE Step 2 CK Lecture Notes 2017: Pediatrics. New York, NY: Kaplan; 2016.
  • 3. Porter ML, Dennis BL. Hyperbilirubinemia in the term newborn. Am Fam Physician. 2002; 65(4): pp. 599–606. pmid: 11871676.
  • 4. Woodgate P, Jardine LA. Neonatal jaundice: phototherapy. BMJ Clin Evid. 2015; 2015. pmid: 25998618.
  • 5. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004; 114(1): pp. 297–316. pmid: 15231951.
  • 6. Springer SC. Kernicterus. In: Rosenkrantz T. Kernicterus. New York, NY: WebMD. http://emedicine.medscape.com/article/975276. Updated April 2, 2014. Accessed May 11, 2017.
  • 7. Maisels MJ, Kring E. Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of > or = 35 weeks' gestation. Pediatrics. 2006; 117(4): pp. 1169–1173. doi: 10.1542/peds.2005-0744.
  • 8. Sawyer TL. Phototherapy for Jaundice. In: Rosenkrantz T. Phototherapy for Jaundice. New York, NY: WebMD. http://emedicine.medscape.com/article/1894477. Updated December 6, 2015. Accessed May 11, 2017.
  • Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. New York, NY: McGraw-Hill Education; 2015.
  • Gottesman LE, Del Vecchio MT, Aronoff SC. Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects. BMC Pediatr. 2015; 15(1). doi: 10.1186/s12887-015-0506-5.
  • Wong RJ, Bhutani VK. Pathogenesis and Etiology of Unconjugated Hyperbilirubinemia in the Newborn. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-and-etiology-of-unconjugated-hyperbilirubinemia-in-the-newborn. Last updated October 23, 2017. Accessed January 27, 2018.
  • Yaworski A, Van Meer A, Wong E. Neonatal Hyperbilirubinemia. http://www.pathophys.org/neonatal-hyperbilirubinemia/. Updated January 1, 2018. Accessed January 27, 2018.
  • Deshpande PG. Breast Milk Jaundice. In: Aslam M. Breast Milk Jaundice. New York, NY: WebMD. https://emedicine.medscape.com/article/973629. Updated December 8, 2017. Accessed January 27, 2018.
  • Wickremasinghe AC, Kuzniewicz MW, Grimes BA, McCulloch CE, Newman TB. Neonatal phototherapy and infantile cancer. Pediatrics. 2016; 137(6): pp. e20151353–e20151353. doi: 10.1542/peds.2015-1353.
  • Hansen TWR. Neonatal Jaundice. In: Aslam M. Neonatal Jaundice. New York, NY: WebMD. https://emedicine.medscape.com/article/974786. Updated December 28, 2017. Accessed January 28, 2018.
  • Fox G, Watts T, Hoque N. Oxford Handbook of Neonatology. Oxford, UK: Oxford University Press; 2017.
last updated 08/02/2018
{{uncollapseSections(['wtYhfI', 'jLc_x10', 'AtYRTI', 'ztYrTI', '_tY5TI', 'ZFYZgI', 'YFYngI', 'XFY9gI', 'cFYaSI'])}}