Nestle Nutrition Workshop Series
Pediatric Program Volume 47 Supplement
Infant Formula:
Closer to the Reference
Editors
Niels C. R. Raiha Firmino F. Rubaltelli
N U T R I T I O N
Infant Formula:
Closer to the Reference
The Nestle Nutrition Workshop, Infant Formula: Closer to the Reference, was held in Sardinia, Italy, 13-16 June 2000.
Nestle Nutrition Workshop Series
Pediatric Program Volume 47 Supplement
Infant Formula:
Closer to the Reference
Editors
N i e l s C . R. R a i h a Department of Pediatrics, University of Lund, Malmo, Sweden
F i r m i n o F. Rubaltelli Department of Critical Care Medicine and Surgery, Section of Neonatology, Careggi University Hospital, Florence, Italy
Nestle
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© 2002 by Nestec Ltd., and Lippincott Williams & Wilkins. All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright.
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Library of Congress Cataloging-in-Publication Data
Infant formula : closer to the reference / editors, Niels C. R. Raiha, Firmino F. Rubaltelli.
p. ; cm.—(Nestie Nutrition workshop series. Pediatric Program ; v. 47 supplement)
Includes bibliographical references and index.
ISBN 0-7817-3620-X
1. Infant formulas—Health aspects—Congresses. 2.
Infants—Nutrition—Requirements—Congresses. I. Raiha, Niels C. R. II. Rubaltelli, Firmino F. III. Nestle Nutrition workshop series. Pediatric Program ; v. 47 supplement.
[DNLM: 1. Infant Nutrition—Congresses. 2. Infant Food—Congresses.
WS 115 1434 20021 RJ216.1499 2002 6!3.2'083—dc21
2001038384
Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, Nestec, and Lippincott Williams & Wilkins are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of this information in a particular situation remains the professional responsibility of the practitioner.
The authors, editors, Nestec, and Lippincott Williams & Wilkins have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice.
10 9 8 7 6 5 4 3 2 I
Preface
Eighty-six years ago, the first commercially manufactured infant formula, called
"Synthetic Milk Adapter" (SMA), was developed by Dr. Henry Gestenberger at Western Reserve University in Cleveland, Ohio, USA. At that time, in 1915, Dr.
Gestenberger had already stated as his goal: "The future will hopefully bring my goal to completion: to produce an infant formula with a composition nutritionally and bi- ologically equivalent to that of human milk."
We have come a long way on this development since 1915 and the body of scientific literature on infant nutrition is growing rapidly. New and interesting chapters focused on achieving an artificial nutritional model increasingly similar to that provided by Mother Nature are added every year. A fascinating challenge is at hand with today's strong and justifiable emphasis on the importance of breast feeding. Working with infant formula requires being aware that the superiority of maternal milk lies not only in nutritive ca- pacities, which are altogether suitable for achieving normal physical growth, but also in the capacity of breast milk to guarantee the best intellectual development and the lowest morbidity on a short-, medium-, and long-term basis. In the formulation of artificial milk, it is imperative that the objective be to obtain the same results as maternal milk feeding, independent of the strict and precise adherence to the structure and composition of human milk. This will ensure the development of important functions, such as the im- mune system and intestinal ecosystem, the prevention of some childhood and adult ill- nesses, and psychomotor development in accordance with genetic capacity.
In recent years, our increased knowledge of the biological functions of maternal milk has allowed us to look beyond its purely nutritional values. The optimal nour- ishment of an infant means not only providing a quantity of nutrients that meet food requirements, but also guaranteeing the supply of the nutrients themselves. The com- mitment and responsibility of achieving the best possible quality of life for each in- dividual must be greater for those who care for human beings at the beginning of their existence. It is at this age when the organism is particularly sensitive and when early programming of metabolic processes occurs. At the root of much debilitating adult pathology lies the failure of proper feeding during infancy. In this way, each small scientific advance concerning the early stages of life can have great positive conse- quences later in life. The challenge becomes even more complex, and for this reason more fascinating, when dealing with preterm infants, because terms of reference are lacking and maternal milk is incapable of meeting all the nutritional needs of these infants. Preterm birth is accompanied by incomplete and immature structural and functional development that affects adaptation to extrauterine life. Our task is to try to prevent this initial disadvantage from becoming a permanent handicap.
Professor Niels C. R. Raiha, Sweden Professor Firmino F. Rubaltelli, Italy
Foreword
Coming closer to the reference in infant feeding is a challenge for all infant formula manufacturers. There might be a chance to copy breast milk in the future by means of modern technology, but the question "which breast milk?" remains. Mothers pro- duce milk individually for their baby and its composition changes with the duration of lactation as well as during the course of a feed. Milk composition also depends on the mother's dietary habits. It is therefore logical to consider the metabolic outcome of the breast-fed infant as the reference.
Clinical trials comparing a new infant formula with "tailor-made protein" for younger infants are available now. They indicate that growth and key metabolic in- dices in infants fed those formulas are similar to the breast-fed reference group. In particular, the profile of essential amino acids, long-chain polyunsaturated fatty acids, and variables reflecting iron nutritional status are now very close in breast-fed and formula-fed infants. Feeding the new formulas also results in a lower renal so- lute load.
The data presented during this Nestle Nutrition Workshop will be the basis for es- tablishing safety and efficacy of new formulas taking the breast-fed infant as refer- ence. We thank the chairmen Professor Niels Raiha and Professor Firmino Rubaltelli for establishing the program together, the speakers and all the participants for their invaluable contribution, and Nestle Italy for their excellent organization and warm hospitality.
PROFESSOR FERDINAND HASCHKE, M.D.
Nestle South Africa Randburg, South Africa
ANNE-LISE CARRIE FASSLER, PH.D.
Nestec Ltd.
Vevey, Switzerland
Contents
Probiotics and Immune Function: Insights into Mechanisms of
Modulation of Mucosal Immunity by Selected Lactobacilli 1 A. Pfeifer, E. J. Schiffrin, D. Holler, T. Von Der Weid, and S. Blum
Probiotic Agents: Clinical Applications in Infants and Children 15 J. M. Saavedra
The Role of Probiotics in Gastrointestinal Disorders of Infancy and
Childhood 29 S. Guandalini and P. Gupta
Potential Role of Probiotics in the Prevention of Necrotizing
Enterocolitis 47 C. Dani, R. Biadaioli, and F. F. Rubaltelli
Iron Requirements During Infancy and Early Childhood 53 F. Haschke
Iron Requirements in Infant Formulas During the First 6 Months
of Life 71 O. Hernell, M. Domellof, and T. hind
Iron: A Potent Pro-oxidant 85 G. Buonocore and S. Perrone
Protein Requirements in Infancy 97 E. E. Ziegler
Protein Quantity and Quality in Infant Formula: Closer
to the Reference I l l N. C. R. Raihd, A. Fazzolari Nesci, C. Cajozzo, G. Puccio, I. Minoli,
G. E. Mom, A. Monestier, E. Haschke-Becher, A.-L. Carrie, and F. Haschke
Plasma Amino Acid Concentrations in Breast-fed and Formula-fed
Infants and Reference Intervals 121 C. Bachmann and E. Haschke-Becher
Protein Requirements in Preterm Infants 139 G. E. Moro and I. Minoli
Nutrition of Preterm Infants on Discharge from Hospital 149 M. De Curtis, C. Pieltain, and J. Rigo
ix
v CONTENTS
Role and Function of Nucleotides in Infant Nutrition 165 J. J. Boza and O. Martinez-Augustin
Role and Function of Growth Factors in Infant Nutrition 185 L. C. Read, I. A. Penttila, G. S. Howarth, J. M. Clarke, and
G. O. Regester
Role and Function of Long-chain Polyunsaturated Fatty Acids in
Infant Nutrition 197 C. Agostoni and E. Riva
Fatty Acid Profiles of Infants Fed Formulas Supplemented with
Long-chain Polyunsaturated Fatty Acids 211 E. Haschke-Becher, A. Fazzolari Nesci, I. Minoli, N. C. R. Rdihd,
A.-L. Carrie, C. Bachmann, and F. Haschke
Conclusions 227 N. C. R. Rdihd and F. F. Rubaltelli
Subject Index 231
Contributing Authors
Speakers Carlo Agostoni
Department of Pediatrics San Paolo Hospital Milan, Italy
Claude Bachmann
Laboratoire Central de Chimie Clinique Centre Hospitaller Universitaire Vaudois
(CHUV)
Lausanne, Switzerland
Julio J. Boza
Research Scientist Department of Nutrition Nestle Research Center Lausanne, Switzerland
Giuseppe Buonocore
Associate Professor
Institute of Preventive Pediatrics and Neonatology
University of Siena Siena, Italy
Carlo Dani
Division of Neonatology Careggi University Hospital Florence, Italy
Mario De Curtis
Istituto Materno Infantile Universita di Palermo Napoli, Italy
Stefano Guandalini
Professor, Department of Pediatrics University of Chicago;
Director, Section of Pediatric Gastroenterologx, Hepatologx, and Nutrition
University of Chicago Children's Hospital
Chicago, Illinois USA
Elisabeth Haschke-Becher
Department of Clinical Chemistry- University Hospital of Lausanne
(CHUV)
Lausanne, Switzerland
Ferdinand Haschke
Nutrition Division Nestle South Africa Randburg, South Africa
OUe Hernell
Professor and Chair
Department of Clinical Sciences, Pediatrics
Umea University;
Consultant
Department of Pediatrics Umea University Hospital Umea, Sweden
Guido E. Moro
Center for Infant Nutrition
Macedonio Melloni Maternity Hospital;
Professor of Neonatology Department of Pediatrics University of Milan Milan, Italy
Andrea Pfeifer
Director
Nestle Research Center Lausanne, Switzerland
Niels C. R. Raiha
Department of Pediatrics University of Lund Malmo, Sweden
Leanna C. Read
Chief Executive Officer
CRCfor Tissue Growth and Repair Child Health Research Institute North Adelaide, Australia
XI
XII CONTRIBUTING A UTHORS
Firmino F. Rubaltelli Professor of Pediatrics University of Florence;
Director, Section of Neonatology Careggi University Hospital Florence, Italy
Jose M. Saavedra Children's Nutrition Center Johns Hopkins Hospital Baltimore, Maryland USA
Ekhard E. Ziegler Fomon Infant Nutrition Unit Department of Pediatrics University of Iowa Iowa City, Iowa
USA
Session Chairmen G. Chirico//ta/y A. Colombo//to/>' G. Rondini//ta/>' G. Zoppi/Italy V. Console/Ztafy F. Mosca//to/v A. Fazzolari//ta/y L. Ziino/Italy F. Chiappe//ta/y G. Serra/Italy A. Mautone/7/a/}1 C. Fabris//ta/v L. Tatb/Italy I. Barberi//to/>' M. Giovannini//ta/y Invited Attendees
Karl ZWiau&vlAustria Philip Alliet/B<?/£(Mm Micheline Bertrand/Belgium Patrick Bollen/Belgium Daniel Brasseur/'Belgium Philippe Dacier/Belgium Andre DepTettere/Belgium Thierry Devreker/Belgium Philippe Goyens/Belgium
Jacques Louis/Belgium Jan Mahcn/Belgium Guy Molitor/Belgium Stefaan Peeters/Belgium Catherine Pichain/Belgium Michel Pletincx/fie/^/wm
Anne-Marie Rentmeesters/Be/g(Mm Jacques Rigo/'Belgium
Eddy Robberecht/Be/g/M/w Michele ScaiUon/Belgium Jean Pierre Van Biervliet/Be/g(Mm Yvan Vandenplas/fie/^/M/n Gigi Veereman/'Belgium
Jadranka Franulovic Katalinic/CVoaf/a Hansjosef Bohles/'Germany
Thomai Karagiozoglou Lampoudi/Greece Judit Cholnoky/Hungary Massimo Agosti/Italy Gabriele Ambrosioni//to/y Stefano Anania//to/j Felice Arena/Italy Marcello Assumma//?a/v Ignazio Barberi//ta(y Roberto Besana//ta/y Giulio Bevilaqua//to/>' Giacomo Biasucci/Zto'y Gianpaolo Bisson//to/v Teresa Bogetti///a/y Antonio Boldrini//?a/>' Letizia Caccamo//to/v Vittorio Carnelli//to/v Franco Chiappe//to/v Gaetano Chirico//to/v Giuseppe Claps//?a/y Paolo Colleselli//to/>' Angelo Colombo//fa/y Gilberto Compagnoni//?a/>' Vito Console///a/v
Giovanni Coppa/Italy Adriano Comas/Italy Giovanni Corsello//?a/y Sergio De Marini//ra/y Umberto De Vonderweid//fa/y Pierluigi Duvina//fa/y
CONTRIBUTING AUTHORS xi u Claudio Fabris//ta/y
Giacomo Faldella//ta/y M. Pia Fantini//fa/v
Angela Fazzolari Nesci//ta/y Fabrizio Ferrari//ta/y Fabrizio Fusco/ltaly Luigi Gargantini//ta/y Mariaclara Gasparoni//to/>- Marina Gemelli//ta(y Paolo Giliberto//ta/;y Roberto Giorgetti//ta/>' Marcello Giovannini//to/v Liborio Giuffre//?a/>' Achille Iolascon//ta/y Nicola La Forgia/Italy Marialisa Leonessa//ta/y Giuseppe Licata//ta/>' Paolo Lionetti//fa/y Riccardo Longhi/Italy Raffaele Longo//to/v Gina hucci/Italy Franco Macagno/Italy Mario Maccabruni//?a/y Cristiana Magnani//to/>>
Luigi Magni//ta/y Antonio Marini//ta/y Stefano Martinelli//fa/>' Giovanni Marzetti/Zra/y Savino Mastropasqua//?a/)' Angela Mautone//ta/>' Francesco Messina/Zm/y Vito Miniello/Ztafy Manlio Moretti/Italy Fabio Mosca/Italy Gianpaolo Negrini//ta/>' Mirella Nicoletti//ta/_v
M. Ilda Manuela Perrazzina///a/y Carlo Pinto//to/v
Klaus Pittschieler//ta/>' Enrico Polito//ra/y Benedetto PolizzUItaly Nicola Principi///a/y Anna Quinto//to/v Giuseppe Ricciardi//to/y
Enrica Riva//?a/y Giorgio Rondini//?a/y Roberto Rossoni//?«/v Onofrio Sergio SaiaJItaly Sabrina Salvadori//to/v Giampaolo Salvioli//fa/y Daniela Sambugaro//ta/v Fabrizio Sandri//fa/v
Maria Giovanna Santangelo//ta/>' Francesco Schettini//?a/>'
Giovanni Sena/Italy Nicola Solfrini/Zfa/j1
Gianfranco Spennati//fa/y Bartolo Spinella//to/y Andrea Sterpa//to/y Mauro Stronati//ta/y Paolo Tagliabue//tofy Francesco Tancredi//to/y Luciano Tato/Italy Gianfranco Temporin//to/y Giuseppe Tortorolo//ta/y Vittorio Tripodi//ra/>' Alberto Vierucci//to/v Vittorio Vigi/Italy Rinaldo Zanini/Italy Silvia Zaverio/Italy Ludovico Zi'mo/Italy Giuseppe Zoppi/Italy Per H. Finne/iVorwoy Jacek Pietrzylc/Poland
Ana Gabriela Almeida/Portugal Manuel Goncalo Cordeiro
Ferreira/Por?Mga/
Antonio Candido Ferreira Lima/Portugal
Ana Serrao Neto/Portugal Jose Manuel Carvalho Tojal Federico Arguelles Martin/5/?«in Jaime Dalmau/5p«/«
Carlos Sierra SalinasAS/?am Juan Carlos Vitoria/S/ja/n Staffan Polberger/Sweden
XIV CONTRIBUTING A UTHORS
Nestle Representatives
Eddy Dehaen Michel Ek Yvan Leclercq Leo Wagemans Andrea Papamandjaris Lesley Z. Scharf
Louis Dominique Van Egro WolfTh. Endres
Hans-Jorgen Klett Lajos Hanzel Ekaterina Kotlyarova Ferdinand Haschke Javier Dorca Fornas Vicente Ramoneda Pericas Anne-Lise Carrie Fassler Marie-Christine Secretin Julio Boza
Andrea Pfeifer Linda Hsieh
Nestle Belgilux S.A., Bruxelles, Belgium
Nestle Belgilux S.A., Bruxelles, Belgium
Nestle Belgilux S.A., Bruxelles, Belgium
Nestle Belgilux S.A., Bruxelles, Belgium
Nestle Canada Inc., North York Ontario, Canada
Nestle Canada Inc., North York Ontario, Canada
Nestle France S.A., Paris, France Nestle Alete GMBH, Muenchen,
Germany
Nestle Alete GMBH, Muenchen, Germany
Nestle Hungaria Kft., Budapest, Hungary
Nestle Food LLC, Russia Nestle South Africa, Randburg,
South Africa
Nestle Espafia S.A., Barcelona, Spain Nestle Espafia S.A., Barcelona, Spain Nestec Ltd., Vevey, Switzerland Nestec Ltd., Vevey, Switzerland Nestle Research Centre, Lausanne,
Switzerland
Nestle Research Centre, Lausanne, Switzerland
Nestle USA, Inc, Glendale, CA, USA
Nestle Nutrition Workshop Series Pediatric Program
Volume 47
Supplement: Infant Formula: Closer to the Reference
Niels C. R. Raiha and Firmino F. Rubaltelli, Editors; 256 pp., 2002.
Volume 47: Nutrition and Growth
Reynaldo Martorell and Ferdinand Haschke, Editors; 448 pp., 2001.
Volume 46: Gastrointestinal Functions
Edgard E. Delvin and Michael J. Lentze, Editors; 352 pp., 2001.
Volume 45: Nutrition, Immunity, and Infection in Infants and Children Robert M. Suskind and Kraisid Tontisirin, Editors; 464 pp., 2001.
Volume 44: Risk Assessment in the Food Chain of Children
Peter J. Aggett and Harry A. Kuiper, Editors; 304 pp., 2000.
Volume 43: Nutrition of the Very Low Birthweight Infant
Ekhard E. Ziegler, Alan Lucas, and Guido E. Moro, Editors;
288 pp., 1999.
Volume 42: Probiotics, Other Nutritional Factors, and Intestinal Microflora Lars A. Hanson and Robert H. Yolken, Editors; 320 pp., 1999.
Volume 41: Nutrition and Bone Development
Jean-Philippe Bonjour and Reginald C. Tsang, Editors; 304 pp., 1999.
Volume 40: Clinical Trials in Infant Nutrition
Jay A. Perman and Jean Rey, Editors; 304 pp., 1998.
Volume 39: Placental Function and Fetal Nutrition Frederick C. Battaglia, Editor; 288 pp., 1997.
Volume 38: Diarrheal Disease
Michael Gracey and John A. Walker-Smith, Editors; 368 pp., 1997.
Volume 37: Feeding from Toddlers to Adolescence Angel Ballabriga, Editor; 320 pp., 1996.
Volume 36: Long-Term Consequences of Early Feeding
John Boulton, Zvi Laron, and Jean Rey, Editors; 256 pp., 1996.
Volume 35: Diabetes
Richard M. Cowett, Editor; 320 pp., 1995.
Volume 34: Intestinal Immunology and Food Allergy
Alain L. de Week and Hugh A. Sampson, Editors; 320 pp., 1995.
Volume 33: Protein Metabolism During Infancy Niels C. R. Raiha, Editor; 264 pp., 1994.
Volume 32: Nutrition of the Low Birthweight Infant
Bernard L. Salle and Paul R. Swyer, Editors; 240pp., 1993.
Volume 31: Birth Risks
J. David Baum, Editor; 256 pp., 1993.
Volume 30: Nutritional Anemias
Samuel J. Fomon and Stanley Zlotkin, Editors; 232 pp., 1992.
WORKSHOP SERIES
Volume 29: Nutrition of the Elderly
Hamish N. Munro and Gtinter Schlierf, Editors; 248 pp., 1992.
Volume 28: Polyunsaturated Fatty Acids in Human Nutrition
Umherto Bracco and Richard J. Deckelbamn, Editors; 256 pp., 1992.
Volume 27: For a Better Nutrition in the 21 st Century
Peter Leathwood, Marc Horisberger, and W. Philip T. James, Editors; 272 pp., 1992.
Volume 26: Perinatology
Erich Sal ing, Editor; 208 pp., 1992.
Volume 25: Sugars in Nutrition
Michael Gracey, Norman Kretchmer, and Ettore Rossi, Editors; 304 pp., 1991.
Volume 24: Inborn Errors of Metabolism
Jtirgen Schaub, Francois Van Hoof, and Henri L. Vis, Editors; 320 pp., 1991.
Volume 23: Trace Elements in Nutrition of Children—II Ranjit Kumar Chandra, Editor; 248pp., 1991.
Volume 22: History of Pediatrics 1850-1950
BufordL. Nichols, Jr., Angel Ballabriga, and Norman Kretchmer, Editors;
320 pp., 1991.
Volume 21: Rickets
Francis H. Glorieux, Editor; 304 pp., 1991.
