Clinical Gradation of Icterus
Icterus follows a predictable cephalocaudal (head-to-toe) progression pattern, with jaundice appearing first in the face, then advancing to the chest and abdomen, and finally extending to the arms and legs—each stage indicating progressively higher bilirubin levels. 1
Anatomical Progression Zones
The clinical gradation system is based on the anatomical extent of visible jaundice:
Zone 1 (Face only): Jaundice limited to the face and head represents the earliest stage of icterus, typically corresponding to lower bilirubin levels 1
Zone 2 (Chest and abdomen): Progression of jaundice to the trunk indicates higher bilirubin levels than facial jaundice alone 1
Zone 3 (Arms and legs): Extension of jaundice to the extremities suggests more significant hyperbilirubinemia 1
Conjunctival icterus: When present, conjunctival icterus is consistently associated with total serum bilirubin (TSB) >14.9 mg/dL (255 μmol/L), typically placing infants in the 76th-95th percentile or >95th percentile on the Bhutani nomogram 2
Critical Assessment Principles
Visual estimation alone is unreliable and leads to errors, particularly in darkly pigmented infants—objective measurement with transcutaneous bilirubin (TcB) or TSB must be performed for any jaundice in the first 24 hours of life or when jaundice appears excessive. 1
TcB measurements generally provide values within 2-3 mg/dL of TSB for levels <15 mg/dL 1
Phototherapy "bleaches" the skin, rendering both visual assessment and TcB measurements unreliable during treatment 1
Jaundice assessment should occur at least every 8-12 hours in at-risk infants 1
Risk Stratification by Bilirubin Levels
The Bhutani hour-specific nomogram provides objective risk assessment based on measured bilirubin levels:
High-risk zone: 39.5% risk of developing TSB >95th percentile 1
High intermediate-risk zone: 12.9% risk of progression 1
Low intermediate-risk zone: 2.26% risk of progression 1
Low-risk zone: 0% risk of significant hyperbilirubinemia 1
Physiological vs. Pathological Thresholds
Physiological jaundice typically peaks at 5-6 mg/dL (86-103 μmol/L) at 72-96 hours of age and does not exceed 17-18 mg/dL (291-308 μmol/L) 3
Levels may not peak until seven days of age in Asian infants or those born at 35-37 weeks' gestation 3
Bilirubin levels exceeding these physiological ranges are considered pathological and require evaluation 3
Common Pitfalls to Avoid
Never rely on visual assessment alone, especially in infants with darker skin pigmentation 1
Do not use TcB measurements during or immediately after phototherapy 1
Any jaundice appearing in the first 24 hours of life mandates immediate objective measurement, as this is never physiological 1
Conjunctival icterus should trigger immediate TSB measurement and evaluation, as it indicates clinically significant hyperbilirubinemia 2