II. Epidemiology

  1. Jaundice Incidence in full term infants: 60%
  2. Jaundice Incidence in Preterm Infants: 80%

III. Physiology: Physiologic Jaundice

  1. See Breast Feeding Jaundice
  2. Neonatal Bilirubin starts to increase days 2 to 5 and returns to normal by 3 weeks of life
  3. Mechanisms of physiologic Neonatal Jaundice
    1. Increased Bilirubin production (2-3 fold over older infants)
      1. High fetal Hemoglobin turn-over (short Half-Life)
    2. Impaired Bilirubin conjugation
      1. Immature hepatic glucuronosyl transferase
    3. Decreased Bilirubin excretion
      1. Bilirubin requires conjugation to become water soluble and able to be excreted in the urine and stool
      2. Most Neonatal Jaundice is due to accumulation of unconjuigated Bilirubin (indirect Hyperbilirubinemia)
      3. Decreased excretion of Conjugated Bilirubin (direct Hyperbilirubinemia) is much less common
  4. Physiologic Jaundice
    1. Transient limitation of Bilirubin conjugation (immature hepatic glucuronosyl transferase)
    2. Increased Hemolysis
      1. Hemoglobin drops from 20 to 12 in first week
  5. Exaggerated Physiologic Jaundice
    1. Low glucuronyl transferase (Hepatic immaturity)
    2. Risk factors
      1. Breast Feeding Jaundice
      2. Prematurity
      3. Asian ethnicity
      4. Weight loss

IV. Signs: Jaundice

  1. General
    1. Visual Jaundice indicates Total Bilirubin >4 mg/dl
    2. Physiologic Jaundice is not present on Day 1
      1. Jaundice on the first day of life suggests Hemolysis
    3. Visual inspection is not an accurate screening tool
      1. Misses cases of severe Hyperbilirubinemia (esp. in darker skin tones)
      2. Visual estimated Bilirubin can differ from actual Serum Bilirubin by as much as 15 mg/dl
    4. Observe for signs of Jaundice beyond the skin exam
      1. Scleral Icterus
      2. Mucous membranes (e.g. beneath the Tongue)
  2. Level of Jaundice correlates with Bilirubin level (inexact)
    1. Jaundice above nipple line
      1. Reliably predicts Bilirubin <12 mg/dl
    2. Less accurate landmarks for estimation of Bilirubin
      1. Head and neck Jaundice: 6 mg/dl Bilirubin
      2. Trunk to Umbilicus: 9 mg/dl Bilirubin
      3. Trunk to knees: 12 mg/dl Bilirubin
      4. Wrists and Ankles: 15 mg/dl Bilirubin
      5. Hands and Feet: >15 mg/dl Bilirubin

V. Differential Diagnosis

VI. Labs: Bilirubin

  1. See Neonatal Bilirubin
  2. Transcutaneous Bilirubin (TcB) Meter
    1. Do not use to monitor infants on Phototherapy
    2. Correlates well with lower total Serum Bilirubin levels in most infants regardless of ethnicity
      1. Confirm with total Serum Bilirubin at >15 mg/dl (or when within 3 mg/dl of Phototherapy threshold)
      2. May overestimate Neonatal Bilirubin in black infants
      3. Holland (2009) Am J Clin Pathol 132(4): 555-61 [PubMed]
      4. Bhutani (2000) Pediatrics 106(2): E17 [PubMed]
      5. Campbell (2011) Paediatr Child Health 16(3): 141-5 [PubMed]
  3. Transcutaneous Bilirubin (TcB) level at >=12 hours of life (typical first universal screening time)
    1. Hour specific threshold for Phototherapy is based on age and Severe Neonatal Hyperbilirubinemia Risk Factors
    2. Obtain total Serum Bilirubin if TcB >15 mg/dl (or when within 3 mg/dl of Phototherapy threshold)
  4. Transcutaneous Bilirubin (TcB) level at 6 hours of life (Transcutaneous Bilirubin or TcB)
    1. Bilirubin <3 mg/dl): Unlikely to require Phototherapy in first 24 hours of life
    2. Bilirubin >5.3 mg/dl (90.6 umol/L): Likely to require Phototherapy in first 24 hours of life (and close monitoring)

VII. Labs: Secondary Cause

  1. See Nonphysiologic Neonatal Jaundice for additional evaluation

VIII. Evaluation: Jaudice Monitoring BEFORE Hospital Discharge

  1. Visually inspect skin with Vital Signs (at least every 8 hours)
    1. Visual inspection alone has low Test Sensitivity (misses cases of severe Hyperbilirubinemia)
    2. Confirming observation with transcutaneous or Serum Bilirubin is preferred
    3. Moyer (2000) Arch Pediatr Adolesc Med 154:391-4 [PubMed]
  2. Obtain Transcutaneous Bilirubin or Serum Bilirubin
    1. Obtain Neonatal Bilirubin based on risk (preferred method)
      1. See Risk Score for Neonatal Hyperbilirubinemia (score of 8 or more indicates testing)
    2. Often part of hospital directed universal screening (e.g. all newborns at 24 hours)
      1. Universal screening is controversial, but recommended at 24 to 48 hours of life and before hospital discharge
      2. Estimated to cost >$5 million in U.S. annually to prevent a single case of Kernicterus
      3. Increases Phototherapy rates without evidence that it decreases the risk of Bilirubin Encephalopathy
      4. Trikalinos (2009) Pediatrics 124(4): 1162-71 [PubMed]
    3. Obtain for Jaundice
      1. Neonatal Jaundice in the first 24 hours
      2. Neonatal Jaundice that appears excessive (e.g. below nipple line)
      3. Neonatal Jaundice that is difficult to assess on exam
      4. Do not rely solely on appearance of Jaundice as a screening indication (misses cases of severe Hyperbilirubinemia)

IX. Evaluation: Jaundice Monitoring AFTER Hospital Discharge

  1. Monitoring in newborns who received Phototherapy during hospitalization
    1. Phototherapy before 48 hours or Hemolysis history or risk (e.g. Direct Antiglobulin Test positive)
      1. See Severe Neonatal Hyperbilirubinemia Risk Factors
      2. Recheck total Serum Bilirubin in 12 to 24 hours
    2. Other infants who received Phototherapy during hospitalization
      1. Recheck total Serum Bilirubin (TSB) or Transcutaneous Bilirubin (TcB) in 1 to 2 days
  2. Monitoring in newborns who have NOT received Phototherapy
    1. Phototherapy Threshold minus TSB or TcB <1.9 mg/dl
      1. Age <24 hours
        1. Delay discharge, consider Phototherapy and recheck TSB in 4 to 8 hours
      2. Age >24 hours
        1. Recheck total Serum Bilirubin (TSB) in 4 to 24 hours
        2. Consider home Phototherapy or delayed discharge for inpatient Phototherapy
    2. Phototherapy Threshold minus TSB or TcB 2.0 to 3.4 mg/dl
      1. Recheck total Serum Bilirubin (TSB) or Transcutaneous Bilirubin (TcB) in 4 to 24 hours
    3. Phototherapy Threshold minus TSB or TcB 3.5 to 5.4 mg/dl
      1. Recheck total Serum Bilirubin (TSB) or Transcutaneous Bilirubin (TcB) in 1 to 2 days
    4. Phototherapy Threshold minus TSB or TcB 5.5 to 6.9 mg/dl
      1. Discharge <72 hours of age
        1. Follow-up in 2 days
        2. Consider total Serum Bilirubin (TSB) or Transcutaneous Bilirubin (TcB) at follow-up based on evaluation
      2. Discharge >72 hours of age
        1. Apply clinical judgment based on exam, Severe Neonatal Hyperbilirubinemia Risk Factors
    5. Phototherapy Threshold minus TSB or TcB >7.0 mg/dl
      1. Discharge <72 hours of age
        1. Follow-up in 3 days
        2. Consider total Serum Bilirubin (TSB) or Transcutaneous Bilirubin (TcB) at follow-up based on evaluation
      2. Discharge >72 hours of age
        1. Apply clinical judgment based on exam, Severe Neonatal Hyperbilirubinemia Risk Factors
  3. References
    1. Kemper (2022) Pediatrics 150(3): e2022058859 [PubMed]

X. Management

XI. Prevention

  1. Adequate early nutrition and hydration
    1. See Breast Feeding Technique
    2. See Infant Feeding
    3. See Formula Feeding
    4. Do not supplement with dextrose water or plain water
  2. Monitoring
    1. See Evaluation above

XII. Complications

  1. Kernicterus is most linked to nonphysiologic causes
  2. Kernicterus has been associated with physiologic causes
    1. Physiologic Jaundice
    2. Exaggerated Jaundice
    3. Breast Feeding Jaundice

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Related Studies

Ontology: Neonatal Jaundice (C0022353)

Definition (NCI) Jaundice that appears during the neonatal period. In the majority of cases, it appears in the first week of life and is classified as physiologic due to accelerated destruction of erythrocytes and liver immaturity. In a minority of cases it is classified as non-physiologic, appearing in the first twenty four hours after birth, and is associated with underlying diseases including hemolytic disorders, polycythemia, and cephalohematoma.
Definition (MSH) Yellow discoloration of the SKIN; MUCOUS MEMBRANE; and SCLERA in the NEWBORN. It is a sign of NEONATAL HYPERBILIRUBINEMIA. Most cases are transient self-limiting (PHYSIOLOGICAL NEONATAL JAUNDICE) occurring in the first week of life, but some can be a sign of pathological disorders, particularly LIVER DISEASES.
Concepts Sign or Symptom (T184)
MSH D007567
ICD10 P59.9
SnomedCT 299968002, 206474007, 111470007, 276549000, 387712008, 31482007, 30235009
English Jaundice, Neonatal, ICTERUS NEONATORUM, JAUNDICE NEONATAL, JAUNDICE OF NEWBORN, Icterus neonatorum unspecified, Icterus neonatorum, unspecified, Neonatal jaundice, unspecified, Jaundice, neonatal, neonatal jaundice (diagnosis), neonatal jaundice, Jaundice in baby, Jaundice neonatal, Jaundice of newborn, Jaundice, Neonatal [Disease/Finding], babies jaundice, infant jaundice, newborn jaundice, infants jaundice, jaundice baby, jaundice neonatal, baby jaundice, of newborn jaundice, Jaundice;infant, Jaundice;newborn, babys jaundice, jaundice in baby, jaundice newborns, icterus neonatorum, jaundice newborn physiologic, physiologic jaundice in newborn, jaundice infant, jaundice newborn, Neonatal jaundice (finding), Icterus neonatorum, unspecified (disorder), Icterus neonatorum, Neonatal jaundice, Neonatal jaundice (disorder), icterus; neonatorum, neonatorum; icterus, Neonatal jaundice, NOS, Neonatal Jaundice, infantile jaundice, jaundice of the newborn
French ICTERE NEONATAL, Jaunisse du nouveau-né, ICTERE DU NOUVEAU-NE, JAUNISSE DU NOUVEAU-NE, Ictère des nouveau-nés, Ictère néonatal, Ictère du nouveau-né, Jaunisse néonatale
Portuguese ICTERICIA NEONATAL, Icterícia em bebé, Icterícia do recém-nascido, ICTERICIA DO RECEM-NASCIDO, Icterícia Grave do Recém-Nascido, Icterícia neonatal, Icterícia Neonatal
Spanish ICTERICIA NEONATAL, Icterus neonatorum, Ictericia del recién nacido, Ictericia en bebé, ICTERICIA DEL RECIEN NACIDO, ICTERUS NEONATORUM, icterus neonatorum, ictericia neonatal (trastorno), ictericia neonatal, Ictericia neonatal, Ictericia Neonatal
Italian Ittero neonatale, Ittero dei neonati, Ittero del neonato
Dutch geelzucht baby, geelzucht pasgeborene, icterus neonatorum, icterus; neonatorum, neonatorum; icterus, Neonatale geelzucht, niet gespecificeerd, neonatale geelzucht, Hyperbilirubinemie, neonatale, Icterus neonatorum
German neonatale Gelbsucht, Gelbsucht beim Neugeborenen, Icterus neonatorum, Gelbsucht beim Baby, GELBSUCHT NEUGEBORENES, ICTERUS NEONATORUM, IKTERUS NEUGEBORENES, Neugeborenenikterus, nicht naeher bezeichnet, Gelbsucht Neugeborenes, Ikterus, Neugeborenen-, Neugeborenenikterus
Swedish Gulsot hos nyfödda
Japanese シンセイジオウダン, 黄疸-新生児, 新生児生理的黄疸, 新生児黄疸, 生理的黄疸
Finnish Vastasyntyneen ikterus
Russian ZHELTUKHA NOVOROZHDENNYKH, ZHELTUKHA NEONATAL'NAIA, ЖЕЛТУХА НЕОНАТАЛЬНАЯ, ЖЕЛТУХА НОВОРОЖДЕННЫХ
Czech Ikterus u novorozence, Icterus neonatorum, Novorozenecký ikterus, novorozenecká žloutenka, žloutenka novorozenců, žloutenka novorozenecká
Korean 상세불명의 신생아 황달
Croatian ŽUTICA, NEONATALNA
Polish Żółtaczka noworodków
Hungarian Neonatalis icterus, Neonatalis sárgaság, Sárgaság a csecsemőben, Sárgaság, neonatalis, Icterus neonatorum
Norwegian Neonatal icterus, Neonatal ikterus, Neonatal gulsott, Icterus neonatarum, Gulsott hos nyfødt

Ontology: Hyperbilirubinemia, Neonatal (C0857007)

Definition (NCI) Increased levels of bilirubin in the blood during the neonatal period. In the majority of cases it is seen in the first week of life and usually there is no underlying disease, however, it may also occur in hemolytic diseases, infections, metabolic disorders, and liver abnormalities.
Definition (MSH) Accumulation of BILIRUBIN, a breakdown product of HEME PROTEINS, in the BLOOD during the first weeks of life. This may lead to NEONATAL JAUNDICE. The excess bilirubin may exist in the unconjugated (indirect) or the conjugated (direct) form. The condition may be self-limiting (PHYSIOLOGICAL NEONATAL JAUNDICE) or pathological with toxic levels of bilirubin.
Concepts Disease or Syndrome (T047)
MSH D051556
SnomedCT 111470007, 281610001, 30235009
Dutch hyperbilirubinemie neonataal, hyperbilirubinemie pasgeborene, hyperbilirubinemie; neonataal, neonataal; hyperbilirubinemie, hyperbilirubinemie, neonataal
German Hyperbilirubinaemie des Neugeborenen, Hyperbilirubinaemie, neonatal, Hyperbilirubinaemie Neugeborenes, Hyperbilirubinämie, Neugeborenen-, Hyperbilirubinämie, neonatale, Neonatale Hyperbilirubinämie, Neugeborenen-Hyperbilirubinämie
Portuguese Hiperbilirrubinemia do recém-nascido, Hiperbilirrubinemia neonatal, Hiperbilirrubinemia Neonatal
Spanish Hiperbilirrubinemia del recién nacido, hiperbilirrubinemia neonatal (trastorno), hiperbilirrubinemia neonatal, Hiperbilirrubinemia neonatal, Hiperbilirrubinemia Neonatal
Russian ГИПЕРБИЛИРУБИНЕМИЯ НЕОНАТАЛЬНАЯ, NOVOROZHDENNOGO GIPERBILIRUBINEMIIA, GIPERBILIRUBINEMIIA NOVOROZHDENNOGO, GIPERBILIRUBINEMIIA NEONATAL'NAIA, GIPERBILIRUBINEMIIA NOVOROZHDENNYKH, ГИПЕРБИЛИРУБИНЕМИЯ НОВОРОЖДЕННОГО, ГИПЕРБИЛИРУБИНЕМИЯ НОВОРОЖДЕННЫХ, НОВОРОЖДЕННОГО ГИПЕРБИЛИРУБИНЕМИЯ
Swedish Hyperbilirubinemi hos nyfödda
English Hyperbilirubinemia, neonatal, neonatal hyperbilirubinemia, neonatal hyperbilirubinemia (diagnosis), Hyperbilirubinaemia neonatal, Hyperbilirubinaemia newborn, Hyperbilirubinemia neonatal, Hyperbilirubinemia newborn, Hyperbilirubinemia, Neonatal [Disease/Finding], Hyperbilirubinemia During Infancy, Infancy, Hyperbilirubinemia During, During Infancies, Hyperbilirubinemia, newborn hyperbilirubinemia, hyperbilirubinemia newborns, hyperbilirubinemia neonatal, hyperbilirubinemia newborn, Neonatal hyperbilirubinaemia, Neonatal hyperbilirubinemia, Neonatal hyperbilirubinemia (disorder), hyperbilirubinemia; neonatal, neonatal; hyperbilirubinemia, Neonatal hyperbilirubinemia, NOS, Neonatal hyperbilirubinaemia, NOS, Hyperbilirubinemia, Neonatal, Neonatal Hyperbilirubinemia
Japanese シンセイジコウビリルビンケツショウ, シンセイジコウビリルビンケッショウ, 高ビリルビン血症-新生児, 新生児特発性高ビリルビン血症, 新生児高ビリルビン血症, 新生児特発性高ビリルビン血
Finnish Vastasyntyneen hyperbilirubinemia
Czech Novorozenecká hyperbilirubinemie, Novorozenecká žloutenka, novorozenecká hyperbilirubinémie, hyperbilirubinémie novorozenecká, hyperbilirubinemie novorozenců a kojenců
Croatian Not Translated[Hyperbilirubinemia, Neonatal]
French Hyperbilirubinémie des nouveau-nés, Hyperbilirubinémie néonatale, Hyperbilirubinémie du nouveau-né
Polish Hiperbilirubinemia noworodków
Hungarian újszülöttkori hyperbilirubinaemia, Hyperbilirubinaemia, újszülöttkori, Neonatalis hyperbilirubinaemia
Norwegian Nyfødthyperbilirubinemi, Neonatal hyperbilirubinemi, Hyperbilirubinemi hos nyfødte
Italian Iperbilirubinemia neonatale