II. Causes: Time of onset in a term infant

  1. Jaundice onset within first 24 hours
    1. Neonatal Sepsis
      1. Pneumonia
      2. Meningitis
      3. Urinary Tract Infection
    2. Necrotizing Enterocolitis (NEC)
    3. Streptococcal or Staphylococcal Skin Infections
    4. Herpes simplex viremia
    5. Toxoplasmosis
    6. Rubella
    7. Occult Hemorrhage
    8. Erythroblastosis Fetalis
  2. Jaundice onset within first 2 weeks of life
    1. See causes below
  3. Jaundice onset after 2 weeks of life
    1. Persistent Late-Onset Breast Milk Jaundice
    2. Sepsis
    3. Hypothyroidism and other metabolic disorders

III. Causes: Normal Physiologic Neonatal Jaundice

  1. Normal Physiologic Jaundice
  2. Exaggerated Physiologic Jaundice
  3. Breast Milk Jaundice

IV. Causes: Overproduction of Bilirubin (Indirect Hyperbilirubinemia)

  1. Increased Hemolysis Causes (Anemia and Reticulocytosis)
    1. Coombs positive (common)
      1. Fetal hydrops from Rh Sensitization
      2. Anti-Kell
      3. Anti-Duffy
      4. ABO incompatibility
    2. Coombs negative (uncommon except G6PD Deficiency)
      1. Red Blood Cell membrane defect (e.g. Spherocytosis)
      2. Abnormal Red Blood Cell (Thalassemia and other Hemoglobinopathy)
      3. Red Blood Cell enzyme defect (e.g. G6PD Deficiency, pyruvate kinase)
        1. Consider G6PD in newborns of Asian, African or Middle Eastern descent
        2. Some Newborn Screen panels now include G6PD Deficiency
  2. Non-hemolytic causes (No Reticulocytosis)
    1. See Decreased conjugation causes below
    2. Common
      1. Breast Milk Jaundice or Physiologic Jaundice
      2. Maternal Diabetes Mellitus
      3. Birth Trauma
        1. Intraventricular Hemorrhage in Preterm Infants
        2. Cephalohematoma
      4. Polycythemia
        1. Fetal-maternal transfusion
        2. Twin-Twin Transfusion
    3. Uncommon
      1. Ileus
      2. Cystic Fibrosis
      3. Pyloric Stenosis

V. Causes: Decreased Conjugation (Indirect Hyperbilirubinemia, no Hemolysis)

  1. Common
    1. Prematurity
    2. Breast Milk Jaundice
  2. Uncommon
    1. Familial nonhemolytic Jaundice: Crigler-Najjar Syndrome (Type 1 and type 2)
    2. Gilbert's Disease (Gilbert Syndrome)
    3. Hypothyroidism

VI. Causes: Decreased Excretion (Direct Hyperbilirubinemia)

  1. Infection (Common)
    1. Sepsis
    2. Tuberculosis
    3. Toxoplasmosis
    4. Herpes Simplex Virus
    5. Rubella
    6. Syphilis
    7. Hepatitis
    8. Urinary Tract Infection
  2. Metabolic Causes
    1. Hyperalimentation-induced cholestasis (common in Premature Infants)
    2. Maternal Diabetes Mellitus (common)
    3. Hypopituitarism
    4. Inborn Errors of Metabolism
      1. Galactosemia
      2. Glycogen Storage Diseases
      3. Tyrosinosis
      4. Hypermethioninemia
  3. Genetic disorders
    1. Turner's Syndrome
    2. Trisomy 18
    3. Trisomy 21
  4. Medications
    1. Antibiotics
      1. Sulfa
      2. Rifampin
      3. Erythromycin
      4. Tetracycline
    2. Metabolic agents
      1. Novobiocin
      2. Pregnanediol
      3. Lucey-Driscoll Syndrome
    3. Miscellaneous
      1. Aspirin
      2. Acetaminophen
      3. Alcohol
      4. Corticosteroids
  5. Intestinal Obstruction
    1. Biliary atresia
    2. Dubin-Johnson Syndrome
    3. Rotor's Syndrome
    4. Choledochal cyst
    5. Cystic Fibrosis
    6. Tumor or amniotic band

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