Ontogeny of bilirubin-binding capacity and the effect of clinical status in premature infants born at less than 1300 grams

BACKGROUND. Bilirubin is toxic to the brain and enters the brain in unbound form. Serum unconjugated, unbound bilirubin may be a good predictor of bilirubin encephalopathy. Unbound bilirubin levels may depend on the bilirubin-binding capacity of albumin, which has not been described for neonates of < 28 weeks' gestation. OBJECTIVE. The purpose of this work was to determine the ontogeny of bilirubin-binding capacity and the effect of clinical status in very preterm neonates. METHODS. A total of 152 neonates ( 23-31 weeks' gestational age; 440-1300 g) were enrolled prospectively. At 5 days of age, total serum bilirubin and unbound bilirubin were measured with the unbound bilirubin-A1 analyzer ( Arrows Co, Osaka, Japan) and albumin with the Bromocresol-purple method. Scatchard plots were used to estimate bilirubin-binding affinity and capacity. Clinical status for each infant was rated as high, moderate, or low risk by using a modified Score for Neonatal Acute Physiology model. Low risk was considered clinically stable. RESULTS. Unbound bilirubin has a significant, direct correlation to total bilirubin and is greater in unstable than in stable neonates. For the entire cohort, bilirubin-binding capacity had a direct relationship to gestational age. The bilirubin-binding capacities of infants in the low- and high-risk groups also had a direct relationship to gestational age. Bilirubin-binding capacity was greater in the low- risk group ( 20.8 +/- 4.6 mg/dL; 356 +/- 79 mu mol/L) than in the moderate- ( 17.8 +/- 3.5 mg/dL; 304 +/- 60 mu mol/L) or high- ( 17.3 +/- 3.4 mg/dL; 296 +/- 58 mu mol/L) risk groups. Bilirubin-binding affinity did not differ by clinical risk status or gestational age. CONCLUSIONS. In very preterm, very low birth weight infants, bilirubin-binding capacity is directly proportional to gestational age. Bilirubin-binding capacity is lower and unbound bilirubin higher in unstable than in stable neonates. These data may be useful in guiding the management of hyperbilirubinemia in very low birth weight infants.