Chelation Therapy in the Neonatal Period: D-penicillamine Can Exert Neuroprotective Effects in Kernicterus and Retinopathy of Prematurity

This review covers of the results of previously conducted retrospective and prospective clinical trials and data of Cochrane reviews to examine the effects of Dpenicillamine (DPA) for neonatal hyperbilirubinemia and associated low incidence of retinopathy of prematurity (ROP). In the ABOand Rh-Hemolytic Disease of the Newborn (HDN) DPA significantly reduced the need for both initial and repeated exchange transfusions (ET). In Rh-HDN, almost the half of cases, no ET was performed in the DPA-treated group. Furthermore, this treatment was associated with elimination of all stages of ROP in two trials conducted between 1984 and 1986 in the Department of Pediatrics, Medical University of Debrecen. DPA-therapy of newborn infants may have significant neuroprotective effects in cases jeopardized by bilirubin-induced neurologic dysfunction (BIND) or ROP, which may be related to its capability to alter the nitric oxide (NO) system and to its strong antioxidant effects. It can be assumed that in preventing and treating hyperbilirubinemia, ROP and oxygen toxicity, the mechanism of action of DPA is identical: the protection of biomembranes against lipid peroxidation caused by free oxygen radical. Conclusion: It is important to note that there was no intolerance or shortor long-term toxicity of the medication, in spite of the fact that in the newborn period DPA was used 10-20 times higher doses than those in adult. INTRODUCTION: Chelation therapy is routinely performed for cases of heavy metal overload in the clinical practice. The use of chelation therapy for non-overload indications continues to be investigated. This review addresses the medical necessity of chelation therapy in the neonatal period. The idea that DPA might be a suitable drug to act as a copper-binding agent for use to control icterus neonatorum occurred, serendipituously, to one of us (L.L.), while reflecting on the similarity of copper storage in Wilson ’ s disease and neonates 1, 2 . QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.6(10).4269-76 Article can be accessed online on: www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.6(10).4269-76 It is well known that all neonates have increased concentration of copper in their liver and in their brain (particularly in the basal ganglia), and a decreased concentration of a specific plasma copper-protein, coeruloplasmin, in comparison with individuals over one year old. D-Penicillamine: [β, β-dimethyl-D-cysteine] Fig.1: Shows the DPA molecule which was discovered among the hydrolysis products of penicillin by Abraham et al. In 1942 3 . FIG.1: STRUCTURAL FORMULA OF D-PENICILLAMINE