Therapies to prevent severe neonatal unconjugated
hyperbilirubinemia and
kernicterus are
phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated
bilirubin not bound to
albumin (free
bilirubin, Bf).
Human serum albumin (HSA) administration was suggested to increase plasma
bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor
bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated
hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without
phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency.
Albumin infusion increased plasma
bilirubin-binding capacity, mobilizing
bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum
bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of
albumin administration in severe acute
hyperbilirubinemia conditions to prevent or treat
bilirubin neurotoxicity in situations in which exchange transfusion may be required.