NEONATAL JAUNDICE New Trends in Phototherapy
NEONATAL JAUNDICE New Trends in Phototherapy Edited by Firmino F. Rubaltelli Department of Pediatrics University of Padua Padua, Italy and Giulio Jori Department of Biology University of Padua Padua, Italy Springer Science+Business Media, LLC
Library of Congress Cataloging in Publication Data Meeting on New Trends in Phototherapy (1983: Padua, ltaly) Neonatal jaundice. "Proceedings of a meeting on New Trends in Phototherapy, held June 9-11, 1983, in Padua, Italy."-T.p. verso. Includes bibliographical references and index. 1. Jaundice, Neonatal-Treatment-Congresses. 2. Phototherapy-Congresses. 1. Rubaltelli, Firmino F. Il. Jori, Giulio. III. Title. [DNLM: 1. Jaundice, Neonatal Therapy-Congresses. 2. Phototherapy-In infancy and childhood-congresses. WH 425 M495n 1983] RJ276.M43 1983 618.92'01 84-3365 ISBN 978-1-4684-7519-7 ISBN 978-1-4684-7517-3 (ebook) DOI 10.1007/978-1-4684-7517-3 Proceedings of a meeting on New Trends in Phototherapy, held June 9-11, 1983, in Padua, ltaly 1984 Springer Science+Business Media New York Originally pub1ished by P1enum Press, New York in 1984 Softcover reprint ofthe hardcover 1st edition 1984 AII rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher
PREFACE Hyperbilirubinemia of the neonate and the related risk of brain damage with conseguent important alterations in motor development, particularly in sick preterm babies, remains a major problem in nurseries throughout the world. Since its introduction in the 1950's phototherapy has been used for reducing serum bilirubin concentrations in the newborn with hyperbilirubinemia; however, only recently the photoprocesses invoked by light on various substrates including bilirubin have been clarified in sufficient detail. Light treatment actually exemplifies the intimate relationship between the clinical and basic sciences: the better understanding of the mechanism of phototherapy as a result of investigations initiated in the laboratory has been extended to the bedside as new types of lamps or new schedules of treatment. As a consequence, phototherapy of hyperbilirubinemia has emerged as a well-established branch of photomedicine, based on molecular photobiology, scientific method, and creative use of physics and sophisticated electrooptical capabilities. The collaboration and exchange of information between workers in different basic and clinical disciplines is likely to stimulate a further optimization of phototherapy. The purpose of this monograph is to discuss some of the new aspects of bilirubin metabolism and phototherapeutic treatment. Bilirubin conjugation in the fetal and early neonatal life, the mechanism of bilirubin entry into the brain, the measurements of bilirubin concentration in the skin and serum bilirubin binding capacity are discussed by a number of prominent neonatologists. The chemistry and photochemistry of bilirubin, as well as novel develop~ ments in the phototherapy of neonatal jaundice are presented by distinguished scientists from the clinical and basic sciences. v
PREFACE We hope that the present monograph will contribute to a more precise understanding of the possible risk of bilirubin encephalo~ pathy, especially in preterm newborn infants, and the appropriate treatment. Firmino F. Rubaltelli, M. D. Giulio Jori, Ph. D.
ACKNOWLEDGEMENTS This symposium was sponsored by the National Research Council (CNR), the University of Padova, the Province Administration of Padova, and the Regional Government of Veneto. The organization of the symposium was made possible by the financial support obtained from Nestle-Guigoz, Monico Farmaceutici, Olympic Medical Corporation, Cassa di Risparmio di Padova and Banca Popolare di Padova. vil
CONTENTS BILIRUBIN METABOLISM Bilirubin metabolism in the newborn: its mechanisms and relationship to kernicterus L Stern Serum bilirubin mono- and diconjugates in human newborns M Muraca, N Blanckaert, J Fevery, F F Rubaltelli, V Carniellie and G Pettena Mechanism of bilirubin entry into the brain in an animal model D Bratlid 13 23 The importance of serum binding and the blood-brain barrier in the development of acute bilirubin neurotoxicity 35 R P Wennberg, A J Hance and J Jacobsen Distribution of bilirubin between serum and cerebrospinal fluid in newborn infants 45 P Meisel, D Jahrig, I Weinke and K Jahrig ASSESSMENT OF THE RISK OF BILIRUBIN TOXICITY The chemical nature of fetal albumin R Brodersen, C Jacobsen, H Iverson and F Lundquist Estimation of reserve albumin equivalent concentration for binding of bilirubin R Brodersen Postnatal changes in the ability of plasma albumin to bind bilirubin F Ebbesen and J Nyboe ix 51 55 63
X CONTENTS Interactions of bilirubin and drugs W J Cashore and M Funato Estimation and clinical significance of bilirubin binding status T Valaes Factors affecting the transcutaneous measurement of bilirubin: influence of race, gestational age, phototherapy and albumin binding capacity A K Brown, M H Kim, G Valencia, P Nuchpuckdee and G Boyle 79 95 CHEMISTRY AND PHOTOCHEMISTRY OF BILIRUBIN Recent advances in the chemistry of bile pigments 111 R Bonnett Solution conformations, photophysics and photochemistry of Bilirubin and biliverdin dimethyl esters 125 K Schaffner Photophysical properties of bile pigments 141 E J Land, R W Sloper and T G Truscott In vitro and in vivo bilirubin-sensitized photoeffects at the molecular and cellular levels 149 J D Spikes Photooxygenation products of bilirubin in the urine of jaundiced phototherapy neonates 161 D A Lightner, W P Linnane III and C E Ahlfors PHOTOTHERAPY OF NEONATAL JAUNDICE Molecular mechanisms of phototherapy of neonatal jaundice 173 A F McDonagh Mechanisms of action of phototherapy: new concepts 187 J F Ennever and W T Speck Laser-oriented search of the optimum light for phototherapy G P Donzelli, M G Migliorini, R Pratesi, G Sbrana and C Vecchi 197 A mathematical description of the phototherapy-effect: an investigation of the dose-response relationship under high irradiances 215 G Wiese
CONTENTS The Gunn rat: a model for phototherapy L Ballowitz, F Hanefeld and G Wiese Light dose-response relationship in phototherapy K L Tan Prediction of the effect of phototherapy in newborns G Wiese 225 235 xi 245 Reducing the duration of phototherapy for neonatal jaundice by cholestyramine administration 257 D Nicolopoulos, E Hadjigeorgiou, A Malamitsi-Puchner and N Kalpoyannis Bronze baby syndrome: new insights on bilirubinphotosensitization of copper-porphyrins 265 F F Rubaltelli, G Jori, E Rossi and G Garbo Effect of light and various concentrations of oxygen on the retina of the newborn pig 277 T R C Sisson, S C Glauser, E M Glauser, G Chan and N Romayananda Effect of phototherapy on hepatic microsomal drug metabolism in heterozygous and homozygous Gunn rats 291 B R Sonawane, B Granati, L Chiandetti, F F Rubaltelli, T R C Sisson and S J Yaffe ~ong term outcome of phototherapy; selected aspects of the NICHHD cooperative phototherapy study 303 A K Brown, M H Kim and D Bryla Index 315