HYPERBILIRUBINEMIA

DEF: Elevated serum bilirubin.
ETIOL: In the first 3 to 4 postnatal days, healthy term infants can experience a physiologic increase in unconjugated serum bilirubin from cord levels of 1.5 mg/dL or less at birth to a mean value of 6.5 ± 2.5 mg/dL, with means of 7.3 ± 3.9 mg/dL and 5.7 ± 3.3 mg/dL for breast-fed infants and formula-fed infants, respectively. Although most new-borns have hyperbilirubinemia by adult standards, physiologic jaundice is linked to normal development and is usually benign and self-limited. It arises from a developmental delay in the conjugation and excretion of bilirubin; thus, preterm infants can have maximum serum bilirubin levels 30% to 50% higher than term babies, with elevated levels persisting for 6 to 7 days postnatally. Unconjugated or indirect hyperbilirubinemia is also caused by isoimmune hemolytic disease (e.g., ABO, Rh, or minor blood group incompatibilities); structural or metabolic abnormalities of RBCs (e.g., G6PD deficiency, hereditary spherocytosis); hereditary defects in bilirubin conjugation (e.g., Crigler-Najjar syndrome, Gilbert disease); bacterial sepsis; poly-cythemia; hypothyroidism; hemorrhage/hematoma; and breast milk jaundice. Conjugated, or direct, hyperbilirubinemia can be caused by congenital biliary atresia, extrahepatic biliary obstruction, neonatal hepatitis, inspissated bile syndrome, postasphyxia, a1-antitrypsin deficiency, and neonatal hemosiderosis.
CLIN: Jaundice in the first day of life is pathologic and mandates a thorough evaluation. Neonates who are not clinically jaundiced do not require routine bilirubin level determination. Visible cutaneous and scleral jaundice in the newborn is noted when the bilirubin level exceeds 7 to 8 mg/dL. Jaundice progresses from the head downward with increaseing severity of hyperbilirubinemia (i.e., scleral and facial icterus, 6 to 8 mg/dL; shoulder and trunk, 8 to 10 mg/dL; lower body, 10 to 12 mg/dL;generalized, > 12 to 15 mg/dL). When visible jaundice is detected, the rapidity of onset, the presence of blood group incompatibilities between mother and infant, the presence of hematomas or signs of infection, the method of feeding, and the duration and clinical course of jaundice beyond the third day should be noted. Daily inspection of the baby, undressed and in adequate light, is required for monitoring the progression of jaundice. A thorough abdominal examination includes palpation of the liver and spleen to evaluate for hepatosplenomegaly. Clinical manifestations of bilirubin toxicity include opisthotonos, extensor rigidity, tremors, oculomotor paralysis, and hearing loss (i.e., manifestations of basal ganglia and cranial nerve involvement). Fatal cases in the new-born period are characterized by a loss of the suck response and lethargy, followed by hyperirritability, seizures, and death.
STUDIES: A serum bilirubin concentration is obtained when significant visible jaundice is detected on the physical examination. When the indirect bilirubin is ³10 mg/dL and the calculated rate of increase exceeds 0.2 mg/dL/hour, repeat levels should be determined every 12 hours until the levels stabilize or a clear indication for treatment exists. Important studies to review include maternal blood type, infant's blood type, Coombs tests, hematocrit, hemoglobin, reticulocyte count, RBC indices, and RBC smear. Elevation of direct bilirubin (above 1.5 to 2.0 mg/dL) should prompt evaluation for intrinsic liver disease or biliary tract obstruction.
TX: Most cases of neonatal hyperbilirubinemia are developmental, benign, and self-limited, and therefore can be managed with observation, serial bilirubin determinations, and reassurance. For more severe or complicated cases, a specific diagnosis should be sought after initial stabilization of the neonate. Phototherapy can be used to stabilize indirect hyperbilirubinemia resulting from any cause and is generally used to manage hyperbilirubinemia of greater than 15 to 20 mg/dL. When the levels of bilirubin exceed 25 to 30 mg/dL or are rising rapidly in association with hemolysis, exchange transfusion (with phototherapy) is the treatment of choice. Hyperbilirubinemia occurring within the first 3 to 5 days of life in breast-fed infants may be a result of infrequent feedings and/or delayed production of adequate milk (breast-feeding jaundice); continued, frequent feedings usually lead to resolution. Prolonged hyperbilirubinemia in breast-fed infants may be caused by specific factors in breast milk (breast milk jaundice) and resolves with temporary cessation of nursing (24 to 48 hours); serum bilirubin level usually declines promptly (2 to 4 mg/dL), and nursing is subsequently resumed with little or no further increase in bilirubin.