D-Penicillamine in the Neonatal Period: Past (!), Present (!?) and Future (?!)

Abstract

D-penicillamine (D-PA) was first recognized as a potential benefit for neonatal hyperbilirubinemia (NHBI) caused by hemolytic diseases of the newborn infant or immaturity of UDP-glucuronyltransferase enzyme. During a long-term follow up study there was a remarkedly low incidence of retrolental fibroplasia (RLF) in the infants treated with D-PA in their neonatal period. Then, all infants < 1500 g birthweight were treated with D-PA to prevent retinopathy of prematurity (ROP). This preventive intervention was associated with elimination of all stages of ROP in this randomized, singlecentered comparison analysis (trial or RCT). The 14-day course of D-PA administration were replicated in other institutes in the USA and India. It is important to note that there was no intolerance or shortor long-term toxicity of the medication, in spite of the fact that D-PA was used 1020 times higher doses in the newborn period, than those in adult age. To our concept, the bilirubin-induced neurologic dysfunction (BIND), ROP and Autism Spectrum Disorders (ASD) are neurodegenerative and neurodevelopment diseases (NDs) of immature brain caused by accumulation of free metals and other neurotoxic formations, respectively, in the basal ganglia (BG) and other parts of the central nervous system (CNS) relevant to the above mentioned conditions. The main factor is the hemolysis of neonatal red blood cells. This process is going with the induction of a great amount of heavy metals (mainly iron and copper) and producing reactive oxygen an nitrogen species (ROS and (RNS). These elements are circulating in the bloodstream, and pass through the immature blood-brain-barrier (BBB), finding entrance into the central nervous system (CNS). The author hope that this review will be able to call the attention of neonatologists and the drug manufacturers’ onto this promising intravenous drug treatment.