Last updated:
April 1, 2026
Table Of Contents
Overview
Neonatal jaundice refers to yellowness of the skin and mucous membranes due to elevated bilirubin within the first 28 days of life.
Ill-appearing babies with jaundice are more likely to have infections or metabolic disorders.
Well-appearing babies are more likely to have biliary atresia or anomalies of the biliary tree
Overview of causes of jaundice
| Classification | Examples |
|---|---|
| Increased production | Hemolysis, cephalohematoma, bruising |
| Reduced clearance | Genetic mutations, prematurity, medications, hypothyroidism, metabolic conditions |
| Increased uptake | Breastfeeding failure jaundice, breast milk jaundice |
Causes of indirect or unconjugated hyperbilirubinaemia
| Category | Laboratory | Causes |
|---|---|---|
| Autoimmune hemolysis | Coombs positive + Reticulocytosis | ABO incompatibility, Rh isoimmunization |
| Non-autoimmune hemolysis | Coombs negative + reticulocytosis | Hemoglobinopathies (spherocytosis, elliptocytosis), enzymatic deficiencies (G6PD deficiency, pyruvate kinase deficiency, hexokinase deficiency) |
| Non-autoimmune non-hemolytic (coombs negative, no reticulocyosis) | Coombs negative + no reticulocytosis | Neonatal sepsis, shock-liver (due to birth asphyxia), hepatitis, intrauterine infections (TORCHES), extravascular hemorrhage (e.g., cephalohematoma), twin-to-twin transfusion syndrome, maternal-fetal transfusion, infant of diabetic mother, Crigler-Najjar syndrome, Gilbert’s syndrome, exaggerated enterohepatic circulation (in breastfeeding jaundice, also consider ileus), breast-milk jaundice, polycythemia (infant of diabetic mother) |
Causes of conjugated or direct hyperbilirubinaemia
| Classification | Causes |
|---|---|
| Intrahepatic | Viral hepatitis (CMV, enteroviruses, HSV, etc.), Bacterial hepatitis (E. coli, T. pallidum, L.monocytogenes), Disorders of metabolism (tyrosemia, fructose intolerance, galactosaemia, etc.), Genetic disorders (cystic fibrosis, A1AT-deficiency, PF1C, Rotor, Dubin-Johnson, etc.), Endocrine disorders (hypothyroidism, hypopituitarism), paucity of interlobular bile ducts, autoimmune hepatitis |
| Extrahepatic | Biliary atresia, choledochal cyst, Caroli’s disease, Alagille syndrome, Inspissated bile, Cystic fibrosis |
- Bilirubin metabolism
- Heme degradation: 80% of heme comes from senescent RBCs, and 20% comes from other heme-containing proteins. Heme oxygenase converts heme → biliverdin (releasing Fe2+ and CO). Biliverdin reductase converts biliverdin → unconjugated bilirubin (lipophilic and insoluble). Bilirubin binds to albumin for transport to the liver
- Hepatic uptake: Unconjugated bilirubin is hepatocytes is bound by ligandins intracellulary preventing its efflux back into plasma. Ligandins also facilitate bilirubin’s transport to the smooth endoplasmic reticulum for conjugation
- Conjugation in the liver (glucuronidation): bilirubin is conjugated with glucuronic acid by UDP-glucuronosyltransferase (UGT1A1). It is converted into a hydrophilic form, enabling biliary excretion
- Biliary excretion into the gut: Conjugated bilirubin is actively secreted in bile via multidrug resistance-associated protein 2 (MRP2). Bile is stored in the gallbladder and released into the duodenum after food intake
- Intestinal fate: Bacteria metabolise bilirubin into urobilinogen (colorless). Some urobilinogen is reabsorbed via enterohepatic circulation and returned to the liver. The remainder is oxidized to stercobilin (brown pigment excreted in feces) and urobilin (yellow pigment excreted in urine)
- Enterohepatic circulation: gut flora is usually immature in neonates, leading to increased enterohepatic circulation of bilirubin**. B-glucuronidase in the intestines deconjugates bilirubin, allowing it to be reabsorbed and contribute to physiologic jaundice.
- Initial investigations
- Complete Blood Count and Reticulocyte count to determine whether there is haemolysis or infection
- Serum bilirubin: elevated in jaundice
- Direct Coomb’s test: is hemolysis immune-mediated (isoimmunization)
- LFTs
- Albumin: hypoalbuminaemia lowers the threshold for bilirubin toxicity
- TSH: for hypothyroidism
- PT and aPTT
- Inflammatory markers (pro-calcitonin, CRP)
- Other investigations for hyperbilirubinemia based on history and physical exam findings
- Abdominal sonography
- TORCH titres – including Hepatitis B, urine for CMV
- Cultures – blood, urine, CSF, and nasopharyngeal
- HIDA scan
- ERCP/MRCP
- Percutaneous liver biopsy
- Other tests: urine for reducing sugars, succinylacetone, and serum ferritin
Physiological jaundice
Most neonates will have some degree of physiologic jaundice (60-80%) – some yellow discolouration of the sclera may only be visible. This happens as the neonate transitions from reliance on the placenta to clear bilirubin onto the baby’s own hepatic system. Neonates also have a high hematocrit (of around 60%) and a lower RBC lifespan, which results in a high turnover.
Jaundice progresses from head to toe.
Characteristics of physiologic jaundice:
- NEVER visible on the first day of life
- TSB may rise to 5mg/dL per day until day 3-5
- Conjugated bilirubin never passes 2 mg/dL OR 20% of TSB (whichever is lower)
- TSB peaks around day 3-5
- Visible jaundice resolves by 1 week of age (7 days) in a full-term AND 2 weeks (14 days) in a premature infant (< 37 weeks gestation)
Characteristics that predispose newborns to develop physiologic jaundice
| Characteristic | Description |
|---|---|
| Increased production of bilirubin | Newborns have more RBCs with a shorter lifespan |
| Decreased clearance of bilirubin | Newborns have immature liver enzymes |
| Increased uptake | Newborns have more enterohepatic circulation |
Pathologic Jaundice
Pathologic jaundice is any jaundice that does not satisfy the criteria for physiologic jaundice AND has other symptoms of illness, such as difficulty feeding.
Characteristics of pathological jaundice:
- Visible jaundice on the first day of life
- TSB rapidly rises by 5mg/dL over a 24 hr period
- Conjugated bilirubin surpasses 2 mg/dL or 20% TSB (whichever is lower)
- TSB continues to rise after day 5