Treatment of neonatal hyperbilirubinemia: Phototherapy and beyond

Neonatal jaundice, characterized by a yellow colorization of the skin, mucosa and sclerae, is a common disease in newborn 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. Bilirubin is a breakdown product of heme in red blood cells. Premature newborns have a temporary high erythrocyte turnover during the first days of life, which causes a higher bilirubin production. When hyperbilirubinemia is severe, bilirubin can deposit in the brain (especially in the so-called basal nuclei), where it can cause damage. This damage can cause a variety of problems described as kernicterus spectrum disorders (KSD). The KSD can include 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.