Neonatal Jaundice

Basics

Produced by an imbalance between rates of bilirubin production and bilirubin elimination:

  • Newborns have a high rate of bilirubin production because of increased RBC mass and shorter RBC life span
  • Newborns have rate limitations in hepatic conjugation and biliary excretion of bilirubin, increased enterohepatic circulation, and diminished bilirubin binding to albumin- and bilirubin-binding protein

Description

  • In most newborns, this is physiologic jaundice and is not pathologic:
    • Bilirubin normally increases from 1.5 mg/dL in cord blood to a mean of 6.5 mg/dL on day 3, followed by a gradual decline to levels of <1.5 mg/dL by day 10 or 12 of life
  • Serum bilirubin may rise to levels exceeding neuroprotective defenses, causing bilirubin tissue binding in the basal ganglia, hippocampus, brainstem nuclei, and cerebellum:
    • Bilirubin-induced neurologic dysfunction (BIND) due to increasingly severe hyperbilirubinemia from mild dysfunction to acute bilirubin encephalopathy (ABE), kernicterus:
      • ABE is the acute manifestations of bilirubin toxicity seen in the 1st wk after birth
      • Kernicterus: Chronic form of BIND, with significant mortality or permanent sequelae including choreoathetoid type of cerebral palsy, gaze abnormalities, hearing loss, and dental dysplasia
    • Progression to BIND depends on rate of increase of bilirubin levels, duration of hyperbilirubinemia, albumin-binding reserves, unbound bilirubin level, host susceptibility, and comorbidities
    • Death is due to respiratory failure and progressive coma or intractable seizures
  • Risk factors (RFs) for significant hyperbilirubinemia:
    • Lower gestational age (GA), risk increased each week less < 40 wk
    • Jaundice observed in 1st 24 hr
    • Predischarge TSB close to phototherapy (PT) threshold
    • PT before discharge
    • Rapid rate of increase in TSB or TcB >0.3 mg/dL per hr in the 1st 24 hr, or >0.2 mg/dL per hour thereafter
    • Hemolysis from any cause
    • Isoimmune or other hemolytic disease
    • Sibling with neonatal jaundice
    • FHx inherited RBC disorders, G6PD
    • Exclusive breastfeeding, esp if inadequate with excessive weight loss
    • Cephalohematoma or excessive bruising
    • Macrosomia from maternal diabetes
    • Down syndrome
  • Hyperbilirubinemia neurotoxicity RF:
    • GA <38 wk, risk increases with degree prematurity
    • Albumin <3 mg/dL
    • Isoimmune hemolytic disease (positive DAT), G6PD deficiency
    • Significant clinical instability in the previous 24 hr, ie, asphyxia, acidosis
    • Sepsis
  • Post-phototherapy (post-PT) bilirubin rebound to bilirubin levels of concern may occur:
    • At high risk are newborns <38 wk gestation, age <48 hr at start of PT, patients with hemolytic disease, patients treated <72 hr

Etiology

  • Unconjugated hyperbilirubinemia:
    • Physiologic jaundice
    • Jaundice in breastfed infants:
      • Breastfeeding failure jaundice: Exaggeration of physiologic jaundice due to inadequate ingestion/production of breast milk in the 1st wk of life. Neonates dehydrated. Peaks days 3–5
      • Breast milk jaundice: Begins days 3–5, peaks within 2 wk but lasts up to 8 wk; caused by increased β-glucuronidase in breast milk 20–30% of predominately breastfed newborns may be jaundiced at 4 wk of age; 30–40% of these infants may have bilirubin levels ≥5 mg/dL
      • May be exacerbated by dehydration
    • Specific hemolytic conditions:
      • Blood group isoimmunization due to ABO, Rh, and minor blood group incompatibility; ABO is most common: Rh disease is unusual (RhoGAM prevents it)
      • RBC enzyme deficiencies: G6PD deficiency
      • RBC membrane defects: Hereditary spherocytosis and elliptocytosis
    • Sepsis: Bacterial, viral, or protozoal
    • Birth trauma:
      • Increased heme load from resolving cephalohematoma or ecchymosis
    • Polycythemia:
      • Maternal–fetal transfusion
      • Fetal–fetal transfusion
      • Infants of diabetic mothers
    • Congenital hypothyroidism
    • Defective hepatic conjugation:
      • Gilbert syndrome (familial partial defect in glucuronyltransferase activity) is benign
      • Crigler–Najjar syndrome (congenital lack of glucuronyltransferase) lifelong unconjugated hyperbili
    • Intestinal obstruction such as ileus, functional or anatomic, increases enterohepatic circulation
  • Conjugated hyperbilirubinemia:
    • Failure of hepatic excretion of conjugated bilirubin
    • Causes: Neonatal hepatitis, congenital biliary atresia, extrahepatic biliary obstruction, shock liver from neonatal asphyxia, neonatal hemosiderosis

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