Biochemical defects of RBCs (e.g., G6PD deficiency, pyruvate deficiency, hexokinase deficiency, congenital erythropoietic porphyria, α- and γ-thalassemias)
Structural defects of RBCs (e.g., hereditary spherocytosis, hereditary ellip
tocytosis, infantile pyknocytosis,
xerocytosis
)
Physiologic hemolysis of the newborn
Infection
PHYSIOLOGIC JAUNDICE
Definition
Transient unconjugated hyperbilirubinemia (physiologic jaundice) that occurs in almost all newborns resulting from physiologic hemolysis
Laboratory Findings
In a normal full-term neonate, average maximum serum bilirubin is 6 mg/dL (≤12 mg/dL is in physiologic range) that occurs during the 2nd to 4th day and then rapidly falls to approximately 2.0 mg/dL by 5th day (phase I physiologic jaundice). Declines slowly to <1.0 mg/dL during the 5th to 10th day but may take 1 month to fall to <2 mg/dL (phase II physiologic jaundice). Phase I due to deficiency of hepatic bilirubin glucuronyl transferase activity, and sixfold increase in bilirubin load presented to the liver. In Asian and Native American newborns, the average maximum serum levels are approximately double (10–14 mg/dL) the levels in non-Asians, and kernicterus is more frequent. Serum bilirubin >5 mg/dL during the first 24 hours of life is indication for further workup because of risk of kernicterus.
In older children (and adults), icterus is apparent clinically when serum bilirubin is >2 mg/dL, but in newborns, clinical icterus is not apparent until serum bilirubin is >5–7 mg/dL; therefore, only half of the full-term newborns show clinical jaundice during the first 3 days of life.
In premature infants—average maximum serum bilirubin is 10–12 mg/dL and occurs during the 5th to 7th day. Serum bilirubin may not fall to normal until 30th day. Further workup is indicated in all premature infants with clinical jaundice because of risk of kernicterus in some low birth weight infants with serum levels of 10–12 mg/dL.
In postmature infants and half of small-for-date infants—serum bilirubin is <2.5 mg/dL, and physiologic jaundice is not seen. When mothers have received phenobarbital or used heroin, physiologic jaundice is also less severe.
When a pregnant woman has unconjugated hyperbilirubinemia, similar levels occur in cord blood, but when the mother has conjugated hyperbilirubinemia (e.g., hepatitis), similar levels are
not
present in cord blood.
