Treatment of neonatal hyperbilirubinemia
|PhD ceremony:||Ms L.W.E. (Lori) van der Schoor|
|When:||September 23, 2019|
|Supervisors:||prof. dr. H.J. (Henkjan) Verkade, prof. dr. J.W. (Hans) Jonker|
|Co-supervisor:||dr. C.V. Hulzebos|
|Where:||Academy building RUG|
|Faculty:||Medical Sciences / UMCG|
Neonatal jaundice, characterized by a yellow colorization of the skin and eyes, is a common disease in infants. Especially in preterm infants it occurs frequently; up to 80% experiences a certain level of jaundice. The yellow colorization is caused by elevated levels of the yellow pigment bilirubin, leading to the name hyperbilirubinemia. When hyperbilirubinemia is severe, bilirubin can deposit in the brain, where it can cause damage. This damage can cause irreversible cerebral palsy (spasticity) and/or hearing and sight problems. Severe untreated hyperbilirubinemia has even been described to cause death. In order to prevent this neurological damage, it is essential to timely diagnose and treat neonatal hyperbilirubinemia. This thesis describes studies on treatment options of this disease, using both animal models and preterm infants. Neonatal hyperbilirubinemia is treated by blue light phototherapy. Conventionally, this blue light is emitted by fluorescent tube devices. However, these devices emit significant heat and have been described to cause DNA damage in infants. Currently, fluorescent tube devices are gradually being replaced by light-emitting-diode (LED) devices. In this thesis, we tested the effect of these devices on DNA damage and oxidative stress in both jaundiced rats and premature infants, showing that LED phototherapy is not associated with these negative side effects. Furthermore, we describe two therapeutic bile acids, ursodeoxycholic and obeticholic acid, as potential treatment options for neonatal hyperbilirubinemia. Both compounds decrease bilirubin in both blood and brain in jaundiced neonatal mice and rats. The mechanism by which these compounds work, includes enhancing intestinal bilirubin detoxification.