Tài liệu Nutrition in Pediatrics Basic Science and Clinical Applications - THIRD EDITION docx

T HIRD E DITION
Nutrition
in Pediatrics
Basic Science and Clinical Applications
W. A LLAN WALKER, MD
Division of Nutrition
Harvard Medical School
Boston, Massachusetts
JOHN B. WATKINS, MD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
CHRISTOPHER DUGGAN, MD, MPH
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
2003
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© 2003 W. Allan Walker, MD, John B. Watkins, MD, Christopher Duggan, MD, MPH
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Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs and drug
dosages, is in accord with the accepted standard and practice at the time of publication. However, since research and regulation constantly change
clinical standards, the reader is urged to check the product information sheet included in the package of each drug, which includes recommended
doses, warnings, and contraindications. This is particularly important with new or infrequently used drugs. Any treatment regimen, particularly one
involving medication, involves inherent risk that must be weighed on a case-by-case basis against the benefits anticipated. The reader is cautioned
that the purpose of this book is to inform and enlighten; the information contained herein is not intended as, and should not be employed as, a
substitute for individual diagnosis and treatment.
DEDICATIONS
To the memory of Myriam Puig, MD, PhD, a contributor to the second and third editions
of this textbook. Dr. Puig succumbed to cancer in September 2002. Her professional life
was dedicated to the nutritional health of underprivileged Venezuelan children and her
publications to the benefit of nutrition for children everywhere.
— W. A
LLAN WALKER
To my colleagues, students, residents, and fellows, who continue to provide me with the
stimulation and inspiration to learn and ask new questions, and to my daughters, Sarah
Watkins and Leah Watkins Beane, and my wife, Mary Watkins, for their continued love
and support.
— J
OHN B. WATKINS
To Catherine and John Duggan, who nourished me from the beginning and inspired a career
in medicine; to Michael, Brendan, and Emily Duggan, and the rest of the world’s children,
for their optimal nutrition; and to Deborah Molrine, for constant love and support.
—C
HRISTOPHER DUGGAN
This page intentionally left blank
v
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
I GENERAL CONCEPTS

1 Pediatric Nutrition: A Distinct Subspecialty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
William C. MacLean Jr, MD, Alan Lucas, MD, FRCP, FMed.Sci
2 Clinical Assessment of Nutritional Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Irene E. Olsen, PhD, RD, Maria R. Mascarenhas, MD, Virginia A. Stallings, MD
3 Laboratory Assessment of Nutritional Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Clifford W. Lo, MD, MPH, ScD, Aime O’Bryan, RD, LD, CNSD
4 Body Composition and Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Lori J. Bechard, MEd, RD, LD, Myriam Puig, MD, PhD
5.1 Macronutrient Requirements for Growth: Fat and Fatty Acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Christine L. Williams, MD,MPH, Richard J. Deckelbuam, MD
5.2 Macronutrient Requirements for Growth: Carbohydrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Jonathan E. Teitelbaum, MD, Susan B. Roberts, PhD
5.3 Macronutrient Requirements for Growth: Protein and Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . 73
Leticia Castillo, MD
6 Trace Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Nancy F. Krebs, MD, MS, K. Michael Hambidge, MD, ScD
7 Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Eduardo Villamor, MD, DrPH, Roland Kupka, BS, Wafaie Fawzi, MD, DrPH
8 The Prudent Diet: Preventive Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Ronald M. Lauer, MD, Linda G. Snetselaar, RD, LD, PhD
9.1 Community Nutrition and Its Impact on Children: Developed Countries . . . . . . . . . . . . . . . . . . . . 142
Johanna Dwyer, DSc, RD, Melanie A. Stuart, MS, RD, Kristy M. Hendricks, DSc, RD
9.2 Community Nutrition and its Impact on Developing Countries (The Chilean Experience) . . . . . . . 161
Gerardo Weisstaub, MD, MSc, Magdalena Araya, MD, PhD, Ricardo Uauy, MD, PhD
10 Protein-Energy Malnutrition: Pathophysiology, Clinical Consequences, and Treatment . . . . . . . . . . 174
Mary E. Penny, MB, ChB
11 International Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Benjamin Caballero, MD, PhD, Asim Maqbool, MD
CONTENTS
vi Contents

12 Nutritional Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Carine M. Lenders, MD, MS, Walter Willett, MD, DrPH
13 Food Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Catherine E. Woteki, PhD, RD, Brian D. Kineman, MS
14 Drug Therapy and the Role of Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Kathleen M. Gura, PharmD, BCNSP, FASHP, Lingtak-Neander Chan, PharmD, BCNSP
II PHYSIOLOGY AND PATHOPHYSIOLOGY
15 Gene Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Mona Bajaj-Elliott, BSc, PhD, Ian R. Sanderson, MD, MSc, MRCP
16 Humoral Regulation of Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
William E. Russell, MD, J. Marc Rhoads, MD
17 Energy Metabolism and Requirements In Health and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Jean-Louis Bresson, MD, Jean Rey, MD, FRCP
18 Gastrointestinal Development: Implications for Infant Feeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Robert K. Montgomery, PhD, Richard J. Grand, MD
19 Immunophysiology and Nutrition of the Gut . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Elizabeth E. Mannick, MS, MD, Zili Zhang, MD, PhD, John N. Udall Jr, MD, PhD
20 Malnutrition and Host Defenses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Susanna Cunningham-Rundles, PhD, David F. McNeeley, MD, MPHTM
21 Brain Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
Maureen M. Black, PhD
22 Nutrition and the Behavior of Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Kathleen S. Gorman, PhD, Elizabeth Metallinos-Katasaras, PhD, RD
23 Energy and Substrate Regulation in Obesity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
Susan B. Roberts, PhD, Daniel J. Hoffman, PhD
III PERINATAL NUTRITION
24 Maternal Nutrition and Pregnancy Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
Theresa O. Scholl, PhD, MPH
25 Fetal Nutrition and Imprinting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Hilton Bernstein, MD, Donald Novak, MD

26 Development of the Fetus: Carbohydrate and Lipid Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
William W. Hay Jr, MD
27 Amino Acid Nutrition in Utero: Placental Function and Metabolism . . . . . . . . . . . . . . . . . . . . . . . . 471
Timothy R. H. Regnault, PhD, Frederick C. Battaglia, MD
28 The Low Birth Weight Infant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
Richard J. Schanler, MD
29 The Term Infant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
Ekhard E. Ziegler, MD, Samuel J. Fomon, MD, Susan J. Carlson, MMSc, RD, CSP, LD, CNSD
Contents vii
30 Weaning: Pathophysiology, Practice, and Policy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528
Kristy M. Hendricks, DSc, RD
31 Human Milk: Nutritional Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Jenifer R. Lightdale, MD, Jill C. Fulhan, MPH, RD, LD, IBCLC, Clifford W. Lo, MD, MPH, ScD
32 Protective Properties of Human Milk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
Armond S. Goldman, MD, Randall M. Goldblum, MD, Frank C. Schmalstieg Jr, MD, PhD
33 Approach to Breast-Feeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562
Ruth Lawrence, MD, Robert M. Lawrence, MD
IV NUTRITIONAL ASPECTS OF SPECIFIC DISEASE STATES
34 Developmental Disabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580
Babette S. Zemel, PhD, Virginia A. Stallings, MD
35 Inborn Errors of Fasting Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
Jon Oden, MD, William R. Treem, MD
36 Persistent Renal Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
Rita D. Swinford, MD, Ewa Elenberg, MD, Julie R. Ingelfinger, MD
37 Inflammatory Bowel Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
Robert B. Heuschkel, MBBS, MRCPCH, John Walker-Smith, MD, FRCP, FRACP, FRCPCH
38 Pediatric HIV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653
Tracie L. Miller, MS, MD, Colleen Hadigan, MD, MPH
39 Exocrine Pancreatic Disease Including Cystic Fibrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
Kevin J. Gaskin, MD, FRACP, Jane Allen, PhD, DipNutrDiet

40 Acute and Chronic Liver Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 686
Deirdre A. Kelly, MD, FRCP, FRCPI, FRCPCH
41.1 Cancer Prevention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699
Richard S. Rivlin, MD, Susanna Cunningham-Rundles, PhD
41.2 Cancer Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 709
Sarah J. Schwarzenberg, MD, Sally Weisdorf-Schindele, MD
42 Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 722
Joseph I. Wolfsdorf, MB, BCh, Maryanne Quinn, MD, Roberta D. Laredo, RD, LD, CDE
43 Acute Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 738
Caleb K. King, MD, PhD, Christopher Duggan, MD, MPH
44 Chronic Diarrhea and Intestinal Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 752
Olivier Goulet, MD, PhD
45 Short-Bowel Syndrome, Including Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771
Jon A. Vanderhoof, MD
46 The Critically Ill Child . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 790
Patrick J. Javid, MD, Tom Jaksic, MD, PhD
47 Hyperlipidemia and Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 799
Sarah D. deFerranti, MD, MPH, Ellis Neufeld, MD, PhD
viii Contents
48 Carbohydrate Absorption and Malabsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811
Martin H. Ulshen, MD
49 Nutritional Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 830
Paul Harmatz, MD, Ellen Butensky, RN, MSN, PNP, Bertram Lubin, MD
50 Function and Nature of the Components in the Oral Cavity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 848
James H. Shaw, DMD, PhD, Linda P. Nelson, DMD, MScD, Catherine Hayes, DMD, DMSc
51.1 Adolescence: Healthy and Disordered Eating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 861
Ellen S. Rome, MD, MPH, Isabel M. Vazquez, MS, RD, LD, Nancy E. Blazar, RD, LD
51.2 The Adolescent Athlete: Performance-Enhancing Drugs and Dietary Supplements. . . . . . . . . . . . . . 878
Jordan D. Metzl, MD
51.3 Adolescence: Bone Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883

Keith J. Loud, MD, CM, Catherine M. Gordon, MD, MS
52 Failure to Thrive: Malnutrition in the Pediatric Outpatient Setting. . . . . . . . . . . . . . . . . . . . . . . . . 897
Robert Markowitz, MD, Christopher Duggan, MD, MPH
53 Protein-Energy Malnutrition in the Hospitalized Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910
Susan S. Baker, MD, PhD
54 Evaluation and Management of Obesity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917
Carine M. Lenders, MD, MS, Alison G. Hoppin, MD
V APPROACH TO NUTRITIONAL SUPPORT
55 Standard and Specialized Enteral Formulas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 935
Tien-Lan Chang, MD, Ronald E. Kleinman, MD
56 Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 945
Maria-Luisa Forchielli, MD, MPH, FACG, Julie Bines, MD, FRACP
57 Parenteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 957
John A. Kerner Jr, MD
58 Dietary Supplements (Nutraceuticals) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 986
Steven H. Zeisel, MD, PhD, Karen E. Erickson, MPH
59 Special Diets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 997
Sherri Utter, MS, RD, LD, CNSD, Sharon B. Collier, MEd, RD, LD
APPENDIX
I Nutritional Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1017
Gina Hardiman, RD, LD
II Nutritional Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
Gina Hardiman, RD, LD
III Enteral Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Gina Hardiman, RD, LD
ix
B
ecause the field of nutrition is actively evolving and creating major new principles in the care of the
pediatric patient, we have embarked on the third edition of this textbook. The editors continue to support
the premise that a comprehensive text as a reference source in pediatric nutrition is essential for the proper care

of infants and children. As medical care in the twenty-first century is predicated on prevention of disease, the
discipline of pediatric nutrition becomes that much more important. For example, we now know from the
Barker hypothesis that intrauterine nutrition and weight gain during the first year of life are important
predictors of chronic diseases of adulthood (cardiovascular disease, diabetes, and hypertension). In addition,
as we attempt to cope with the worldwide epidemic of obesity and its concomitant “syndrome X,” we recognize
that a healthful diet and attention to weight gain must begin in early childhood before “bad” eating habits are
established. Furthermore, as parents seek a more healthful lifestyle for themselves and their children, they are
assessing conventional approaches to treatment of disease and are seeking alternative forms of treatment and
prevention. An example of this alternative approach is the use of probiotics to treat diarrhea, prevent daycare
infections, and cope with the “hygiene hypothesis” for the development of atopic disease. Therefore, an
updated access to clinical research-based information on the appropriate use of nutrition as an alternative form
of therapy is essential for the practicing physician.
As with the first edition, we commissioned a comprehensive review of the second edition of this textbook to
ensure the most updated and extensive coverage of nutrition. This review led to the addition of several chapters
to each major section of the book. In the “General Concepts” section, the macronutrient requirement for growth
chapter has been expanded to three chapters separately dealing with fat, carbohydrate, and protein. We have
added new chapters on nutritional epidemiology, food safety, and international nutrition. In a newly added section
entitled “Physiology and Pathophysiology,” we have considered the role of nutrition in major body functions and
dysfunctions including gene expression, immunophysiology, brain development, obesity, and behavior. The
“Perinatal Nutrition” section, added to the second edition, has been expanded further to include chapters on
maternal nutrition and pregnancy outcome and fetal nutrition and imprinting. The section on specific disease
states has been expanded to include “The Adolescent Athlete and Dietary Supplements,” “Nutrition and the
Prevention of Cancer in Childhood,” and “Evaluation and Management of Obesity.” In keeping with the changing
approach of care to pediatric patients, chapters have been added in dietary supplements (nutraceuticals) and
special diets in the “Nutrition Support” section. Finally, the Appendix has been expanded to provide a more
comprehensive resource for nutritional assessment and requirements and updated information on enteral
products. As in previous editions, authors have been newly selected or retained based on their expertise in the
topic of their chapter and their willingness to provide the most updated views on the subject.
In general, we believe that the third edition will provide a comprehensive resource for the health care
provider for children entering the twenty-first century.

For this edition, Dr. Christopher Duggan has been added as an editor. His comprehensive knowledge of
clinical care for the hospitalized patient, experience in nutritional issues in developing countries, and extensive
experience in clinical nutrition research have been welcomed by the editors.
The editors wish to again thank Ms. Suzzette McCarron for her organizational talents and her ability to
liaison between authors, editors, and the publisher. Without her extensive efforts this textbook would never
have been possible. We also thank Ms. Carlotta Hayes for her many contributions
The editors are also grateful to Mr. Brian Decker, Ms. Jamie White, and the able staff of BC Decker Inc for
their help and support in further developing this edition and in the publication of this textbook.
W. Allan Walker
John B. Watkins
Christopher Duggan
PREFACE
T
he importance of nutrition in pediatrics has become more apparent in recent years as a result of significant
observations that have helped both to define the specific needs of young infants to attain optimal growth
and development and to prevent the expression of nutritionally related diseases at a later age. Of particular
importance to industrialized societies is the awareness of subtle malnutrition present in pediatric patients in
general as well as in underprivileged children of large cities and the hospitalized pediatric patient population.
We now know that specific nutrient deficiency (e.g., zinc essential fatty acids) can occur in virtually any pedi-
atric patient as well as in unique patient populations such as premature infants, food faddists, or families
obsessed with weight reduction. Thus, the increased awareness of nutrition as an important component of the
practice of pediatrics has prompted the creation of this book.
The purpose of this text is to offer a comprehensive review of general concepts of nutrition as they pertain
to pediatrics as well as relevant information on the nutritional management of specific disease states. Accord-
ingly, the text is divided into four major sections. In the first, general concepts of nutrition, such as nutrient
requirements, nutritional assessment, and prevention of disease, are presented. In the second section, a sys-
temic approach to the pathophysiology of nutrition as it pertains to other disciplines—immunology,
endocrinology, pharmacology, and gastroenterology—is developed. The third and largest section comprehen-
sively covers specific disease states and is directed at the nutritional management of these conditions, which
include diabetes, cystic fibrosis, and anemias. A special effort has been made to provide updated information

on the unique nutritional needs of patients with these diseases. These chapters are augmented by appropriate
appendix material describing special diets and requirements of patients. In the final section, which presents an
approach to nutritional support of pediatric patients, a major effort is directed at updating the reader on the
more recent information about breast-feeding. Following a practical discussion concerning problems of nurs-
ing mothers, this section addresses enteric and parenteral support of pediatric patients with special needs for
nutritional support. In short, this book serves as a comprehensive reference text for the practicing pediatrician,
pediatric trainee, and subspecialist requiring nutritional information.
We want to thank our many authors selected to write chapters on subjects for which they have special exper-
tise. By developing a specific format for the textbook and then selecting the most appropriate authors in their
fields to develop the topics, we have provided the most comprehensive and updated text on pediatric nutrition
presently available.
W. Allan Walker
John B. Watkins
PREFACE TO FIRST EDITION
xi
Jane Allen, PhD, DipNutrDiet
Department of Pediatrics and Child Health
University of Sidney
Sidney, Australia
Exocrine Pancreatic Disease Including Cystic Fibrosis
Magdalena Araya, MD, PhD
Instituto de Nutrición y Tecnología de los Alimentos
(INTA)
University of Chile
Santiago, Chile
Community Nutrition and its Impact on Developing
Countries (The Chilean Experience)
Mona Bajaj-Elliott, BSc, PhD
Department of Adult and Pediatric Gastroenterology
Queen Mary School of Medicine and Dentistry

London, England
Gene Expression
Susan S. Baker, MD, PhD
Digestive Diseases and Nutrition Center
Children’s Hospital of Buffalo
State University of New York at Buffalo
Buffalo, New York
Protein-Energy Malnutrition in the Hospitalized
Patient
Frederick C. Battaglia, MD
Department of Pediatrics
University of Colorado School of Medicine
Aurora, Colorado
Amino Acid Nutrition in Utero: Placental Function
and Metabolism
Lori J. Bechard, MEd, RD, LD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Body Composition and Growth
Hilton Bernstein, MD
Division of Gastroenterology and Nutrition
Department of Pediatrics
University of Florida
Gainesville, Florida
Fetal Nutrition and Imprinting
Julie Bines, MD, FRACP
Division of Gastroenterology and Nutrition
Royal Children’s Hospital
University of Melbourne

Melbourne, Australia
Enteral Nutrition
Maureen M. Black, PhD
Department of Pediatrics
University of Maryland School of Medicine
Baltimore, Maryland
Brain Development
Nancy E. Blazar, RD, LD
Private Practice
Cleveland, Ohio
Adolescence: Healthy and Disordered Eating
Jean-Louis Bresson, MD
Centre D’Investigation Clinique
Hôpital Necker des Enfants Malades
Paris, France
Energy Metabolism and Requirements In Health
and Disease
Ellen Butensky, RN, MSN, PNP
Department of Gastroenterology and Nutrition
Children’s Hospital and Research Center at Oakland
Oakland, California
Nutritional Anemias
Benjamin Caballero, MD, PhD
Center for Human Nutrition
Department of International Health
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland
International Nutrition
Susan J. Carlson, MMSc, RD, CSP, LD, CNSD
Department of Food and Nutrition Services

University of Iowa Hospital
Iowa City, Iowa
The Term Infant
CONTRIBUTORS
xii Contributors
Leticia Castillo, MD
Department of Anesthesia
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Macronutrient Requirements for Growth:
Protein and Amino Acids
Lingtak-Neander Chan, PharmD, BCNSP
Department of Pharmacy and Medicine
University of Illinois at Chicago
Chicago, Illinois
Drug Therapy and the Role of Nutrition
Tien-Lan Chang, MD
Division of Pediatric Gastroenterology and Nutrition
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Standard and Specialized Enteral Formulas
Sharon B. Collier, MEd, RD, LD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Special Diets
Susanna Cunningham-Rundles, PhD
Division of Immunology

New York Hospital
The Weill Medical College of Cornell University
New York, New York
Malnutrition and Host Defenses
Cancer Prevention
Richard J. Deckelbaum, MD
Institute of Human Nutrition
Columbia University College of Physicians and
Surgeons
New York, New York
Macronutrient Requirements for Growth:
Fat and Fatty Acids
Sarah D. deFerranti, MD, MPH
Department of Cardiology
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Hyperlipidemia and Cardiovascular Disease
Christopher Duggan, MD, MPH
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachuetts
Acute Diarrhea
Failure to Thrive: Malnutrition in the Pediatric
Outpatient Setting
Johanna Dwyer, DSc, RD
Frances Stern Nutrition Center
Department of Medicine
New England Mecical Center

Tufts University Schools of Medicine
Boston, Massachusetts
Community Nutrition and Its Impact on Children:
Developed Countries
Ewa Elenberg, MD
Division of Pediatric Nephrology
Massachusetts General hospital
Harvard Medical School
Boston, Massachusetts
Persistent Renal Failure
Karen E. Erickson, MPH
Department of Nutrition
University of North Carolina School of
Public Health
Chapel Hill, North Carolina
Dietary Supplements (Nutraceuticals)
Wafaie W. Fawzi, MD, DrPH
Department of Nutrition
Harvard School of Public Health
Boston, Massachusetts
Vitamins
Samuel J. Foman, MD
Foman Infant Nutrition Unit
University of Iowa
Iowa City, Iowa
The Term Infant
Maria-Luisa Forchielli, MD, MPH, FACG
Department of Pediatrics
University Bologna Medical School
Bologna, Italy

Enteral Nutrition
Jill C. Fulhan, MPH, RD, LD, IBCLC
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Human Milk: Nutritional Properties
Contributors xiii
Kevin J. Gaskin, MD, FRACP
Department of Pediatrics and Child Health
University of Sidney
Sidney, Australia
Exocrine Pancreatic Disease Including Cystic Fibrosis
Randall M. Goldblum, MD
Division of Allergy/Immunology/Rheumatology
Department of Pediatrics
University of Texas Medical Branch
Galveston, Texas
Protective Properties of Human Milk
Armond S. Goldman, MD
Division of Allergy/Immunology/Rheumatology
Department of Pediatrics
University of Texas Medical Branch
Galveston, Texas
Protective Properties of Human Milk
Catherine M. Gordon, MD, MSc
Divisions of Adolescent Medicine and Endocrinology
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Adolescence: Bone Disease

Kathleen S. Gorman, PhD
Feinstein Center for a Hunger Free America
University of Rhode Island
Providence, Rhode Island
Nutrition and the Behavior of Children
Oliver Goulet, MD, PhD
Department de Pediatric
Gastroenterology et Nutrition
Hôpital Necker Enfants Malades
Paris, France
Chronic Diarrhea and Intestinal Transplantation
Richard J. Grand, MD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Gastrointestinal Development: Implications for
Infant Feeding
Kathleen M. Gura, PharmD, BCNSP, FASHP
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Massachusetts College of Pharmacy and Health
Sciences
Boston, Massachusetts
Drug Therapy and the Role of Nutrition
Colleen Hadigan, MD, MPH
Division of Pediatric Gastroenterology and Nutrition
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts

Pediatric HIV Infection
K. Michael Hambidge, MD, ScD
Center for Human Nutrition
Department of Pediatrics
University of Colorado Health Science Center
Denver, Colorado
Trace Elements
Gina Hardiman, RD, LD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Nutritional Assessment
Nutritional Requirements
Enteral Products
Paul Harmatz, MD
Division of Gastroenterology and Nutrition
Children’s Hospital and Research Center at Oakland
Oakland, California
Nutritional Anemias
William W. Hay Jr, MD
Division of Perinatal Medicine
University of Colorado School of Medicine
Denver, Colorado
Development of the Fetus: Carbohydrate and
Lipid Metabolism
Catherine Hayes, DMD, DMSc
Department of Oral Health Policy and Epidemiology
Harvard University School of Dental Medicine
Boston, Massachusetts
Function and Nature of the Components in the

Oral Cavity
Kristy M. Hendricks, DSc, RD
Department of Community Health and Nutrition
Tufts University School of Medicine
Boston, Massachusetts
Community Nutrition and Its Impact on Children:
Developed Countries
Weaning: Pathophysiology, Practice, and Policy
Robert B. Heuschkel, MBBS, MRCPCH
Department of Pediatric Gastroenterology
Royal Free Hospital
University College Medical School
London, England
Inflammatory Bowel Disease
xiv Contributors
Daniel J. Hoffman, PhD
Department of Nutritional Science
Rutgers University
New Brunswick, New Jersey
Energy and Substrate Regulation in Obesity
Alison G. Hoppin, MD
Division of Gastroenterology and Nutrition
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Evaluation and Management of Obesity
Julie R. Ingelfinger, MD
Division of Pediatric Nephrology
Massachusetts General Hospital
Harvard Medical School

Boston, Massachusetts
Persistent Renal Failure
Tom Jaksic, MD, PhD
Department of Surgery
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
The Critically Ill Child
Patrick J. Javid, MD
Department of Surgery
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
The Critically Ill Child
Deirdre A. Kelly, MD, FRCP, FRCPI, FRCPCH
The Liver Unit
Birmingham Children’s Hospital, NHS Trust
University of Birmingham School of Medicine
Birmingham, England
Acute and Chronic Liver Disease
John A. Kerner Jr, MD
Division of Pediatric Gastroenterology and Nutrition
Lucille Salter Packard Children’s Hospital
Stanford University School of Medicine
Palo Alto, California
Parenteral Nutrition
Brian D. Kineman, MS
Food Science and Human Nutrition
Iowa State University
Ames, Iowa

Food Safety
Caleb K. King, MD, PhD
Division of Pediatric Gastroenterology and Nephrology
University of North Carolina
Chapel Hill, North Carolina
Acute Diarrhea
Ronald E. Kleinman, MD
Division of Pediatric Gastroenterology and Nutrition
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Standard and Specialized Enteral Formulas
Nancy F. Krebs, MD, MS
Center for Human Nutrition
Department of Pediatrics
University of Colorado Health Science Center
Denver, Colorado
Trace Elements
Roland Kupka, BS
Department of Nutrition
Harvard School of Public Health
Boston, Massachusetts
Vitamins
Roberta D. Laredo, RD, LD, CDE
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Diabetes Mellitus
Ronald M. Lauer, MD
Division of Pediatric Cardiology

University of Iowa School of Medicine
Iowa City, Iowa
The Prudent Diet: Preventive Nutrition
Robert M. Lawrence, MD
Department of Pediatrics
University of Florida
Gainesville, Florida
Approach to Breast-Feeding
Ruth Lawrence, MD
Breastfeeding and Human Lactation Study Center
University of Rochester Medical Center
Rochester, New York
Approach to Breast-Feeding
Carine M. Lenders, MD, MS
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Nutritional Epidemiology
Evaluation and Management of Obesity
Contributors xv
Jenifer R. Lightdale, MD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Human Milk: Nutritional Properties
Bertram Lubin, MD
Children’s Hospital and Research Center at Oakland
Oakland, California

Nutritional Anemias
Clifford W. Lo, MD, MPH, ScD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Laboratory Assessment of Nutritional Status
Human Milk: Nutritional Properties
Keith J. Loud, MD, CM
Division of Adolsescent Medicine
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Adolescence: Bone Disease
Alan Lucas, MD, FRCP, FMed.Sci
Medical Research Council – Childhood Nutrition
Research Center
Institute of Child Health
Great Ormond Street Hospital for Children
London, England
Pediatric Nutrition: A Distinct Subspecialty
William C. MacLean Jr, MD
Department of Pediatrics
The Ohio State University School of Medicine
Columbus, Ohio
Pediatric Nutrition: A Distinct Subspecialty
Elizabeth E. Mannick, MS, MD
Division of Pediatric Gastroenterology and Nutrition
Louisiana State University Health Sciences Center
New Orleans, Louisiana

Immunophysiology and Nutrition of the Gut
Asim Maqbool, MD
Center for Human Nutrition
Department of International Health
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland
International Nutrition
Robert Markowitz, MD
Division of General Pediatrics
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Failure to Thrive: Malnutrition in the Pediatric
Outpatient Setting
Maria R. Mascarenhas, MD
Division of Gastroenterology and Nutrition
Children’s Hospital of Philadelphia
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania
Assessment of Nutritional Status for Clinical Care
David F. McNeeley, MD, MPHTM
Division of Infectious Diseases
New York Presbyterian Hospital
Cornel University Medical Center
New York, New York
Malnutrition and Host Defenses
Elizabeth Metallinos-Katasaras, PhD, RD
Department of Nutrition
Simmons College
Boston, Massachusetts

Nutrition and the Behavior of Children
Jordan D. Metzl, MD
Sports Medicine Institute for Young Athletes
Hospital for Special Surgery
Cornell Medical College
New York, New York
The Adolescent Athlete: Performance-Enhancing
Drugs and Dietary Supplements
Tracie L. Miller, MS, MD
Division of Pediatric Gastroenterology and Nutrition
University of Rochester Medical Center
Rochester, New York
Pediatric HIV Infection
Robert K. Montgomery, PhD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Gastrointestinal Development: Implications for
Infant Feeding
Linda P. Nelson, DMD, MScD
Department of Pediatric Dentistry
Harvard University School of Dental Medicine
Boston, Massachusetts
Function and Nature of the Components in the
Oral Cavity
Ellis Neufeld, MD, PhD
Division of Hematology
Children’s Hospital Boston
Harvard Medical School

Boston, Massachusetts
Hyperlipidemia and Cardiovascular Disease
Donald Novak, MD
Division of Pediatric Gastroenterology
University of Florida
Gainesville, Florida
Fetal Nutrition and Imprinting
Amie O’Bryan, RD, LD, CNSD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Laboratory Assessment of Nutritional Status
Jon Oden, MD
Division of Pediatric Endocrinology
Duke University School of Medicine
Durham, North Carolina
Inborn Errors of Fasting Adaptation
Irene E. Olsen, PhD, RD
Division of Gastroenterology and Nutrition
Children’s Hospital of Philadelphia
University of Pennsylvania School of Medicine
Philadelphia, Philadelphia
Assessment of Nutritional Status for Clinical Care
Mary E. Penny, MB, ChB
Instituto de Investigación Nutricional
Lima, Perú
Protein-Energy Malnutrition: Pathophysiology,
Clinical Consequences, and Treatment
Myriam Puig, MD, PhD
Centro Medico Docente La Trinidad

Caracas, Venezuela
Body Composition and Growth
Maryanne Quinn, MD
Division of Endocrinology
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Diabetes Mellitus
Timothy R. H. Regnault, PhD
Department of Pediatrics
University of Colorado School of Medicine
Aurora, Colorado
Amino Acid Nutrition in Utero: Placental Function
and Metabolism
Jean Rey, MD, FRCP
Department of Pediatrics
Hôpital Necker des Enfants Malades
Paris, France
Energy Metabolism and Requirements In Health
and Disease
J. Marc Rhoads, MD
Division of Pediatric Gastroenterology
Ochsner Clinic for Children
Tulane University School of Medicine
New Orleans, Louisiana
Humoral Regulation of Growth
Richard S. Rivlin, MD
Clinical Nutrition Research Center
American Health Foundation
Memorial Sloan-Kettering Cancer Center

New York, New York
Cancer Prevention
Susan B. Roberts, PhD
Energy Metabolism Laboratory
USDA Human Nutrition Research Center
Tufts University School of Medicine
Boston, Massachusetts
Macronutrient Requirements for Growth: Carbohydrates
Energy and Substrate Regulation in Obesity
Ellen S. Rome, MD, MPH
Section of Adolescent Medicine
Cleveland Clinic
Ohio State University
Cleveland, Ohio
Adolescence: Healthy and Disordered Eating
William E. Russell, MD
Division of Pediatric Endocrinology
Vanderbilt University Medical Center
Nashville, TN
Humoral Regulation of Growth
Ian R. Sanderson, MD, MSc, MRCP
Department of Pediatric Gastroenterology
St. Bartholomew’s Hospital
The London School of Medicine and Dentistry
London, England
Gene Expression
Richard J. Schanler, MD
Division of Neonatology
Schneider Children’s Hospital at Northshore
Albert Einstein College of Medicine

New York, New York
The Low Birth Weight Infant
xvi Contributors
Frank C. Schmalstieg Jr, MD, PhD
Division of Immunology/Allergy/Rheumetology
Department of Pediatrics
University of Texas Medical Branch
Galveston, Texas
Protective Properties of Human Milk
Theresa O. Scholl, PhD, MPH
Department of Obstetrics and Gynecology
School of Osteopathic Medicine
University of Medicine and Dentistry of New Jersey
Stratford, New Jersey
Maternal Nutrition and Pregnancy Outcome
Sarah J. Schwarzenberg, MD
Division of Pediatric Gastroenterology and Nutrition
University of Minnesota
Minneapolis, Minnesota
Cancer Treatment
James H. Shaw, DMD, PhD
Department of Pediatric Dentistry
Harvard University School of Dental Medicine
Boston, Massachusetts
Function and Nature of the Components in the
Oral Cavity
Linda G. Snetselaar, RD, LD, PhD
Department of Internal Medicine
University of Iowa College of Medicine
Iowa City, Iowa

The Prudent Diet: Preventive Nutrition
Virginia A. Stallings, MD
Division of Gastroenterology and Nutrition
Children’s Hospital of Philadelphia
University of Pennsylvania School of Medicine
Philadelphia, Philadelphia
Assessment of Nutritional Status for Clinical Care
Developmental Disabilities
Melanie A. Stuart, MS, RD
Frances Stern Nutrition Center
New England Medical Center
Boston, Massachusetts
Community Nutrition and Its Impact on Children:
Developed Countries
Rita D. Swinford, MD
Division of Pediatric Nephrology
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Persistent Renal Failure
Jonathan E. Teitelbaum, MD
Pediatric Gastroenterology and Nutrition
Monmouth Medical Center
Long Branch New Jersey
Drexel University School of Medicine
Philadelphia, Pennsylvania
Macronutrient Requirements for Growth: Carbohydrates
William R. Treem, MD
Division of Pediatric Gastroenterology and Nutrition
Duke University School of Medicine

Durham, North Carolina
Inborn Errors of Fasting Adaptation
Ricardo Uauy, MD, PhD
Instituto de Nutrición y Tecnología de los Alimentos
(INTA)
University of Chile
Santiago, Chile
Community Nutrition and its Impact on Developing
Countries (The Chilean Experience)
John N. Udall Jr, MD, PhD
Division of Pediatric Gastroenterology and Nutrition
New Orleans Children’s Hospital
Louisiana State University Health Sciences Center
New Orleans, Louisiana
Immunophysiology and Nutrition of the Gut
Martin H. Ulshen, MD
Division of Pediatric Gastroenterology and Nutrition
Duke University Medical Center
Durham, North Carolina
Carbohydrate Absorption and Malabsorption
Sherri Utter, MS, RD, LD, CNSD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Boston, Massachusetts
Special Diets
Jon A. Vanderhoof, MD
Division of Gastrointestinal and Nutrition
University of Nebraska Medical Center
Omaha, Nebraska
Short-Bowel Syndrome, Including Adaptation

Isabel M. Vazquez, MS, RD, LD
Department of Pediatrics
Children’s Nutrition Research Center
Baylor College of Medicine
Houston, Texas
Adolescence: Healthy and Disordered Eating
Contributors xvii
Eduardo Villamor, MD, DrPH
Department of Nutrition
Harvard School of Public Health
Boston, Massachusetts
Vitamins
John B. Watkins, MD
Division of Gastroenterology and Nutrition
Children’s Hospital Boston
Harvard Medical School
Boston, Massachuetts
W. Allan Walker, MD
Division of Nutrition
Harvard Medical School
Boston, Massachusetts
John Walker-Smith, MD, FRCP, FRACP, FRCPCH
Department of Paediatric Gastroenterology
Royal Free Hospital
University College Medical School
London, England
Inflammatory Bowel Disease
Sally Weisdorf-Schindele, MD
Division of Pediatric Gastroenterology
and Nutrition

University of Minnesota School of Medicine
Minneapolis, Minnesota
Cancer Treatment
Gerardo Weisstaub, MD, MSc
Instituto de Nutrición y Tecnología de los Alimentos
(INTA)
University of Chile
Santiago, Chile
Community Nutrition and its Impact on Developing
Countries (The Chilean Experience)
Walter Willett, MD, DrPH
Department of Nutrition
Harvard School of Public Health
Boston, Massachusetts
Nutritional Epidemiology
Christine L. Williams, MD, MPH
Children’s Cardiovascular Health Center
Columbia University College of Physicians
and Surgeons
New York, New York
Macronutrient Requirements for Growth:
Fat and Fatty Acids
Joseph I. Wolfsdorf, MB, BCh
Division of Endocrinology
Children’s Hospital Boston
Harvard Medical School
Boston, Massachusetts
Diabetes Mellitus
Catherine E. Woteki, PhD, RD
College of Agriculture

Iowa State University
Ames, Iowa
Food Safety
Steven H. Zeisel, MD, PhD
Department of Nutrition
University of North Carolina School of Public Health
Chapel Hill, North Carolina
Dietary Supplements (Nutraceuticals)
Babette S. Zemel, PhD
Division of Gastroenterology and Nutrition
Children’s Hospital of Philadelphia
University of Pennsylvania School of Medicine
Philadelphia, Philadelphia
Developmental Disabilities
Zili Zhang, MD, PhD
Division of Gastroenterology and Nutrition
New Orleans’ Children’s Hospital
Louisiana State University Health Sciences Center
New Orleans, Louisiana
Immunophysiology and Nutrition of the Gut
Ekhard E. Ziegler, MD
Foman Infant Nutrition Unit
Department of Pediatrics
University of Iowa
Iowa City, Iowa
The Term Infant
xviii Contributors
1. General Concepts
CHAPTER 1
PEDIATRIC NUTRITION:

A DISTINCT SUBSPECIALTY
William C. MacLean Jr, MD, Alan Lucas, MD, FRCP, FMed. Sci
S
cientific interest in nutrition has a long history.
1,2
Bal-
ance studies were conceived by Sanctorius in the 1620s.
Lavoisier researched the oxidation of foods and Magendie
discovered that protein was necessary for survival two cen-
turies ago. In 1838, Franz Simon produced his classic dis-
sertation, in Latin, on human milk biochemistry, which for
the first time underpinned a rational basis for infant nutri-
tion. It was over 100 years ago, in the late nineteenth cen-
tury, that Rubner defined the energy content of foods and
constructed the first calorimeter for measuring energy
expenditure. By the early twentieth century, we already had
a broad understanding of nutrient needs and an increasing
understanding of micronutrients and of the effects of spe-
cific deficiencies (Funk coined the term “vitamines” in
1912). Sophisticated metabolic research on animals fed by
continuous intravenous infusion flourished in the first
three decades of the last century, and as early as 1944, we
saw the first case of a child, age 5 months, fed successfully
via the intravenous route.
In parallel with this long-term development of nutri-
tional science has been an equally long-term appreciation
of the clinical and public health importance of infant and
child nutrition. In the earliest part of the last century, and
well before, nutrition was a prominent and vital part of car-
ing for infants. Unquestionably, in the eyes of early clini-

cians, how and what the infant was fed during health and
illness were primary determinants of survival. The infant
mortality rate in the United States in 1900 was 165 per
1,000.
1
The unacceptably high rate and the variability from
one area of the country to the other related primarily to
mode of feeding in infancy.
At that time, pediatrics, both as an academic specialty
and in everyday practice, was in its own infancy. At the
turn of the nineteenth century, there were probably fewer
than a dozen practitioners in the United States who were
exclusively devoted to pediatrics.
2
In the first presidential
address to the American Pediatric Society in 1889, Abra-
ham Jacobi discussed the rationale for having the specialty
of pediatrics distinct from internal medicine: “Pediatrics
deals with the entire organism at the very period during
which it presents the most interesting features to the stu-
dent of biology and medicine there is scarcely a tissue or
an organ which behaves exactly alike at different periods
of life.”
2
A review of the topics covered in the annual presiden-
tial addresses to the American Pediatric Society during its
first 35 years shows a frequent return to nutrition and
nutrition-related subjects. In 1924, David M. Cowie sug-
gested that feeding in infancy was then sufficiently based
on sound physiologic principles and that pediatrics needed

to focus more on nutrition and metabolism, among other
things, of the older child.
2
By 1940, when the eleventh edi-
tion of Holt’s Diseases of Infancy and Childhood was pub-
lished, the editors unhesitatingly stated, “Nutrition in its
broadest sense is the most important branch of pediatrics.
A knowledge of its fundamental principles is essential to
the physician if he is to apply preventive and corrective
measures intelligently.”
3
WHY HAS PEDIATRIC NUTRITION NOT
EMERGED AS A DISTINCT SUBSPECIALTY?
Given that nutrition is the oldest branch of pediatrics
based on centuries of major research, it seems paradoxical
that it has never emerged as a formal, distinct academic
discipline. Indeed, considering its roots in and fundamen-
tal relationships to that which makes pediatrics unique—
growth and maturation—why has nutrition taken a back
seat to other subspecialties? The decline in the importance
of nutrition in pediatrics can be explained in two ways.
First, the urgency that fostered nutrition research and
the illnesses that made nutrition a prominent part of pedi-
atric practice decreased progressively during the last cen-
tury. The causes of infantile scurvy and rickets and other
deficiency diseases were delineated during the early
decades of the twentieth century. In fact, with the excep-
tion of iron deficiency, primary nutritional deficiencies are
now virtually unknown in the United States and other
developed countries, and infant mortality rates relate more

to the general level of socioeconomic development than to
nutritional practices. With the advent of refrigeration and
appropriate milk processing technology, survival of artifi-
cially fed infants in clean environments is now routine.
Second, pediatrics has followed the path taken by inter-
nal medicine and surgery; the past 40 years have seen the
growth of “organ-based” subspecialties: pediatric cardiol-
ogy, neurology, nephrology, and so on, and, more recently,
gastroenterology. The result of this evolutionary course
was to imbed clinical nutrition in a variety of “focused”
subspecialty areas. This arguably fostered a disease-specific
orientation to nutrition and fragmentation of nutrition
practice and research. Thus, enteral feeding has come
under the wing of gastroenterologists, parenteral nutrition
has interested gastroenterologists and pediatric surgeons as
well, aspects of growth have fallen into the domain of
endocrinology, neonatal nutrition has been taken on by
neonatologists, eating disorders by psychologists and psy-
chiatrists, food allergy by allergists and physicians in respi-
ratory medicine, and so forth. This fragmentation and mul-
tiple ownership of pediatric nutrition have hindered
development of the field as a distinct entity.
WHY IS PEDIATRIC NUTRITION
RE-EMERGING IN IMPORTANCE?
In the past, the major focus in the field of nutrition has
been one of meeting nutrient needs and the prevention of
nutrient deficiencies. There has now been a fundamental
sea change in orientation in this field. The major current
interest in nutrition is its impact on health.
4

Our new
understanding of the potential biologic impacts of nutri-
tion on health has led us to frame two key new questions:
Does nutrition matter in terms of patients’ responses to
their disease? Does it matter for long-term health and
development?
With regard to the first, increasing evidence now indi-
cates that good nutritional care may improve the clinical
course of disease, reduce hospital stay, reduce the need for
more expensive treatments, and, indeed, result in major
reduction in health care costs. Such benefits of nutritional
care are emerging over a broad range of pediatric domains
such as gastroenterology (eg, Crohn’s disease, short-bowel
syndrome), surgery, renal medicine, care of disabled chil-
dren (eg, cerebral palsy), infectious disease (eg, human
immunodeficiency virus [HIV]), and oncology. Neonatol-
ogy provides good examples of the effects of good nutrition
on clinical course: nutritional practices may have a major
influence on the incidence of life-threatening diseases
(necrotizing enterocolitis and systemic sepsis),
5
may influ-
ence the need for expensive and potentially hazardous par-
enteral nutrition, and may significantly impact length of
hospital stay.
However, the factor that has most influenced the re-
emergence of interest in pediatric nutrition is the increasing
evidence for its effects on long-term health and develop-
ment. The idea that early nutrition could have long-term
consequences is part of a broader concept concerning the

impact of early life events in general. To focus attention in
this area, Lucas proposed using the term “programming,”
6
the idea that a stimulus or insult applied during a critical or
sensitive period of development could have a long-lasting
or lifetime impact on the structure or function of the organ-
ism. The first description of programming during a sensi-
tive or critical period of development was by Spalding, who
in 1873 defined the critical period for imprinting in new-
born chicks.
7
Since then, developmentalists have described
numerous examples of short-lived stimuli—both endoge-
nous and exogenous—that have had lifetime effects.
What is the evidence that nutrition may behave in this
programming way? Since the first studies by McCance in
the 1960s, the evidence for such programming in animals
is overwhelming. Brief periods of experimental nutritional
manipulation in early life influence in adult life many out-
comes of potential relevance to humans,
8
including blood
pressure, insulin resistance, blood lipids, vascular disease,
body fatness, bone health, gut function, endocrine status,
learning, behavior, and longevity.
8–11
Nutritional program-
ming effects have been seen in all species studied, includ-
ing nonhuman primates.
9,10

In the past 20 years, increasing evidence has shown
that humans, like other species, may be highly sensitive to
early nutrition in terms of later health outcomes. Defi-
ciencies of single nutrients at critical periods can have
long-lasting effects. Animal studies have documented the
role of zinc deficiency in the development of neural tube
defects in the fetus. Decreased folic acid intake in the peri-
conceptional period also has been linked to neural tube
defects in the human.
12
Iron is another trace element that appears to play a crit-
ical role in development. Iron deficiency in rats, for exam-
ple, produces reversed sleep cycles, altered pain threshold,
and difficulty in learning. Dopamine D
2
receptors also are
decreased. When the iron-deficient diet is begun at 10 days
of age, later iron repletion is unable to reverse these defects
completely.
13
In the human, the mechanisms of the detri-
mental effects of severe iron deficiency in early childhood
on subsequent mental development are yet to be eluci-
dated, but several studies suggest that such effects may be
permanent.
14,15
On a molecular level, it is possible that iron
is required at a critical time for the expression of one or
several genes, and if this opportunity is lost, iron suffi-
ciency is unable to reverse the path of development.

Many observational studies have linked growth, size, or
nutrition in early life to the types of health outcome influ-
enced by early nutrition in animals. Such observational
data might be confounded, but, in more recent years, there
has been long-term investment in randomized intervention
studies. These trials have now shown that early diet during
2 General Concepts
the first weeks or months may influence, thus far up to
20 years later, such outcomes as blood pressure, blood
lipids, insulin resistance, tendency to obesity, bone health,
and cognitive performance.
8,16–18
The effects of brief early nutritional interventions are
often surprisingly large. Studies in the preterm infant show
that feeding a standard versus preterm formula for just
1 month may result in a 12-point deficit in verbal IQ (in
males) and a more than doubling of motor or cognitive
impairment (both sexes) 7 to 8 years later.
15
In the same
population, random assignment to banked donated breast
milk rather than infant formula resulted in a reduction in
diastolic blood pressure 13 to 16 years later of a magnitude
greater than that induced by nonpharmacologic interven-
tions used to manage hypertension in adult life (weight
loss, exercise, salt restriction).
17
These new data have major biologic and public health
implications. They show that nutrition cannot simply be
seen in terms of meeting nutritional needs. Rather, nutri-

tion emerges as a major environmental influence on the
genome, influencing lifetime health. It is also apparent that
there is now a new onus on health professionals to ensure
proper nutrition to optimize the short- and long-term
health of sick individuals and healthy populations.
RATIONALE FOR A SEPARATE DISCIPLINE
Viewed in the historical context of a changing subspecialty
paradigm and a new appreciation of nutrition’s role at the
molecular level with profound implications for health, the
time would seem right for nutrition to be recognized as a
distinct area of pediatric practice. But what other criteria
should be fulfilled for nutrition to be formally developed as
a pediatric subspecialty? Two questions must be addressed:
Is there a defined area of pediatric care that requires specific
nutritional expertise and are there readily identifiable defi-
ciencies in current pediatric nutritional patient teaching
and research that would benefit from such a development?
DEFINED AREA OF EXPERTISE
There is a defined area of pediatric care that requires nutri-
tional expertise. Nutritional advice is probably the most
common category of advice sought by parents. Nutritional
management problems are possibly the most common
problems in pediatric hospital practice; virtually every sick
premature infant and a high proportion of sick older chil-
dren could benefit from specific and expert nutritional
attention. Walk on any general ward and the number of
patients needing advice from a pediatric cardiologist,
nephrologist, or gastroenterologist will be far exceeded by
those who would benefit from sound nutritional care.
However, beyond the routine practice of what we know,

there are potentially important areas of new expertise that
need to be sewn into nutrition practice. Just as a field such
as cardiology owes its specialty status in part to the devel-
opment of specialized techniques—catheterization, diag-
nostic imaging, etc—so could pediatric nutrition be under-
pinned by new tools awaiting exploitation in a clinical
setting.
6
Isotope probes are available for exploring meta-
bolic process and energy expenditure. Body composition
devices (dual x-ray absorptiometry, impedance, isotope
dilution, air displacement plethysmography, three-dimen-
sional photonic scanning, ultrasonography, magnetic reso-
nance imaging, etc) are ready to be pioneered in the com-
plex management of sick infants and children. They also
are likely to prove useful in the assessment of the impact of
public health policy on the nutritional status of the child-
hood population (for instance, the value of interventions
to reduce obesity, which are currently monitored by inap-
propriately nonspecific and crude methods). New tools are
also available to measure and plot growth that will make
the diagnosis and management of growth disorders, failure
to thrive, and overweight less arbitrary and more precise.
Such techniques require trained specialists.
DEFICIENCIES IN PATIENT CARE
Subspecialists trained in pediatric nutrition would improve
patient care. Specialty advice in nutrition is often sought
from physicians whose primary interest is in another
area.
19

This results in fragmentation of care and creates a
lack of uniformity in how conditions are managed. A
“standard of practice” does not exist. Nutrition knowledge
has exploded to the point where clinicians in individual
specialties no longer can be expected to have a compre-
hensive grasp even of all aspects relevant to their own prac-
tice. The fact that a high percentage of inpatients in any
general or pediatric hospital continues to be found to be
malnourished by “world-class” criteria suggests that care
could be improved. With efforts to contain costs and the
move to home care, patients are leaving hospital with more
profound nutritional deficits than before, and the situation
can be expected to become worse.
For many years in the United States, parenteral nutri-
tion support in many hospitals was overseen by the surgical
service, whereas enteral nutrition was handled by virtually
any pediatrician. Even with the advent of nutrition support
teams, most of the physicians involved have acquired their
nutritional skills in an ad hoc fashion. If consultation about
enteral nutrition is needed, the gastroenterologist, by
default, has assumed responsibility and is likely to be
called. To be sure, gastroenterology and nutrition are
closely linked, and most pediatric gastroenterologists have
considerable expertise in nutrition, especially as it affects
their “organ system.” But the pediatric gastroenterologist
should not be expected to be well versed in all areas of
nutrition because only a small part of nutrition science and
practice is related directly to gastroenterology.
DEFICIENCIES IN TEACHING
Teaching of nutrition in medical schools also is fragmented

at best: “To almost everyone expressing an opinion about
the teaching of nutrition in medical schools, it appears to be
entirely unsatisfactory. Rare successes prove to be
ephemeral and crucially dependent on individual commit-
ment and outside funding.”
20
In most medical schools, the
basic science pertaining to nutrition is imbedded in bio-
chemistry and, perhaps, physiology. Formal teaching of
clinical nutrition is nearly nonexistent. What teaching there
Pediatric Nutrition: A Distinct Subspecialty 3
is generally is done as part of primary care rotations or by
subspecialists in other areas in pediatrics. Many medical
students never observe breast-feeding and are never trained
to make up a formula feed. Most house staff leave training
with less than adequate understanding of the physiology
and management of breast-feeding, the composition and
appropriate use of standard or special infant formulas, or
the appraisal of simple feeding problems and the rationale
for nutrition advice or care during the second 6 months of
life and beyond. Public health and preventive nutrition are
equally neglected. McLaren has argued that were nutrition
“given its rightful place” in the basic sciences, there would
be no need for courses in nutrition or nutrition textbooks.
19
Clinical teaching would revolve around clinical dietetics.
This would still leave nutrition primarily relating to and
being practiced by organ-based specialties. Although this
may be acceptable from the point of view of clinical prac-
tice, from the point of view of research, it will ultimately

impede inquiry into the important areas.
DEFICIENCIES IN RESEARCH
The area that perhaps stands to gain most from the devel-
opment of nutrition as a distinct discipline is research.
Although basic laboratory and animal research in nutrition
has been active, the key clinical research questions in pedi-
atric nutrition are unlikely to be addressed as long as nutri-
tion is divided among the traditional specialties. This is so
because the orientation toward disease of most subspecial-
ties will favor research to answer questions related to ther-
apeutic dietetics (ie, treatment of disease). With infant sur-
vival from a nutritional point of view assured in most
Western countries, the issue of how early nutrition should
be optimized in terms of its effects on later health becomes
of paramount importance.
The objective for clinical research in any field of health
policy or clinical practice should be to prove outcome ben-
efits for recommended approaches to management, gener-
ally by use of formal clinical trials that test the safety and
efficacy of the intervention. This would be standard in
established clinical areas. Thus, whether or not a clinician
should treat high blood pressure, remove a malignancy
rather than give chemotherapy, or repair a heart defect at
birth rather than later in childhood and other decisions
depend on proven clinical benefit for each management
option. For example, physicians routinely treat high blood
pressure precisely because lowering blood pressure has
been shown to reduce morbidity and mortality from car-
diovascular disease.
Research in childhood nutrition has been largely unsat-

isfactory in this respect. Research over the past 50 years
has failed to address adequately whether adhering to the
nutritional recommendations made by ad hoc groups and
governmental bodies confers outcome benefits.
6
The criti-
cal issue of whether early nutrition, either in health or dis-
ease, influences long-term health or development has,
until recently, barely been approached in formal studies.
Thus, most recommendations of expert bodies on funda-
mental areas of practice are based largely on theoretic con-
siderations derived from short-term physiologic experi-
ments and epidemiologic studies rather than on outcome
findings from intervention trials. Both physiology and epi-
demiology can be useful in identifying questions and fram-
ing hypotheses for such outcome trials, but neither can
replace them.
The paucity of clinical outcome studies in pediatric
nutrition contrasts sharply with the major research invest-
ment that has been made in pediatric nutritional physiol-
ogy. Possibly more research effort has been applied here
than in any other area of pediatrics. For instance, as far
back as 1953, Macy and colleagues summarized the con-
tents of 1,500 publications on the composition of breast
milk—just one small area of infant nutrition.
21
The profu-
sion of pediatric nutritional studies in the face of the
paucity of outcome data justifying clinical practice sug-
gests that clinical pediatric nutritional research has lacked

direction. This lack of research direction, not seen to
nearly the same extent in the recognized pediatric special-
ties, can be traced in part to the absence of guidance on
research priorities from specialists trained in nutrition and
from centers of excellence in pediatric nutrition.
CONCLUSION
Like the blind men approaching the elephant, each sub-
specialty comes up with a different view of nutrition. Each
subspecialty creates a paradigm that determines how ques-
tions are framed and results are interpreted. Depending on
one’s primary interest, taurine may be thought of as a crit-
ical nutrient for neural development and function, a pri-
mary determinant of bile acid conjugation, or an osmoreg-
ulator of the brain during dehydration. Someone needs to
see the elephant for what it is—to collate our knowledge in
the field of nutrition, understand its significance for devel-
opment, and apply it to clinical practice.
Functional specialties in medicine increasingly are
interacting in a matrix fashion with organ-based special-
ties. Clinical nutrition fits comfortably into this new para-
digm. The time appears to be right to foster clinical nutri-
tion within pediatrics as a unique discipline. Such a
development would address currently identifiable deficien-
cies in patient care, training, and, especially, research in
clinical nutrition.
REFERENCES
1. Cone TE Jr. History of American pediatrics. Boston: Little,
Brown; 1979.
2. Pearson HA. The centennial history of the American Pediatric
Society 1888–1988. New Haven (CT): Yale University Print-

ing Service; 1989.
3. Holt LE, McIntosh R. Holt’s diseases of infancy and childhood.
11th ed. New York: D. Appleton-Century; 1940.
4. Lucas A. Pediatric nutrition as a new subspecialty: is the time
right? Arch Dis Child 1997;76:3–6.
5. Lucas A, Cole TJ. Breast milk and neonatal necrotizing entero-
colitis. Lancet 1990;336:1519–23.
6. Lucas A. Programming by early nutrition in man. In: Bock G,
Whelan J, editors. The childhood environment and adult
disease. CIBA Foundation Symposium 156. Chichester
(UK): Wiley; 1991. p. 38–55.
4 General Concepts
7. Spalding DA. nstinct with original observations on young ani-
mals. Macmillan’s Magazine 1873;27:282–93; reprinted Br J
Anim Behav 1954;2:2–11.
8. Lucas A. Programming by early nutrition: an experimental
approach. J Nutr 1998;128(2 Suppl):401S–6S
9. Lewis DS, Mott GE, McMahan CA, et al. Deferred effects of
preweaning diet on atherosclerosis in adolescent baboons.
Arteriosclerosis 1988;8:274.
10. Mott GE, Jackson EM, McMahan CA, McGill HC Jr. Choles-
terol metabolism in adult baboons is influenced by infant
diet. J Nutr 1990;120:243–51.
11. Dobbing J. Vulnerable periods in developing brain. In: Dobbing
J, editor. Brain, behavior, and iron in the infant diet. New
York: Springer-Verlag; 1990. p. 1–18.
12. Centers for Disease Control and Prevention. Recommendations
for the use of folic acid to reduce the number of cases of
spina bifida and other neural tube defects. Morb Mortal
Wkly Rep, 1992;41:1–7.

13. Youdim MBH. Neuropharmacological and neurobiochemical
aspects of iron deficiency. In: Dobbing J, editor. Brain,
behavior, and iron in the infant diet. New York: Springer-
Verlag; 1990. p. 83–99.
14. Lozoff B. Has iron deficiency been shown to cause altered behav-
ior in infants? In: Dobbing J, editor. Brain, behavior, and iron
in the infant diet. New York: Springer-Verlag; 1990. p. 107–25.
15. Walter T. Iron deficiency and behavior in infancy: a critical
review. In: Dobbing J, editor. Brain, behavior, and iron in the
infant diet. New York: Springer-Verlag; 1990. p. 135–50.
16. Lucas A, Morley R, Cole TJ. Randomized trial of early diet in
preterm babies and later intelligence quotient. BMJ
1998;317:1481–7.
17. Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants
and later blood pressure: two cohorts after randomized tri-
als. Lancet 2001;357(9254):413–9.
18. Fewtrell MS, Prentice A, Jones SC, et al. Bone mineralization
and turnover in preterm infants at 8-12 years of age: the
effect of early diet. J Bone Miner Res 1999;14:810–20.
19. Committee on Clinical Practice Issues in Health and Disease. The
role and identity of physician nutrition specialists in medical
school–affiliated hospitals. Am J Clin Nutr 1995;61:264–8.
20. McLaren DS. Nutrition in medical schools: a case of mistaken
identity. Am J Clin Nutr 1994;59:960–3.
21. Macy IG, Kelly HJ, Sloan RE. The composition of milks. Washing-
ton (DC): National Research Council; 1953. Publ. No.: 254.
Pediatric Nutrition: A Distinct Subspecialty 5
N
utritional assessment is an integral part of patient care
because nutritional status affects a patient’s response

to illness. Attention to nutritional status is especially
important in pediatric patients because they are also
undergoing the complex processes of growth and develop-
ment, which are influenced by the genetic makeup of the
individual and coexisting medical illness in addition to
nutritional status. Thus, the assessment of nutritional and
growth status is an essential part of clinical evaluation and
care in the pediatric setting.
The assessment should allow for the early detection of
both nutrient deficiencies and excesses. There is no single
nutrition measurement that is best; therefore, a combina-
tion of different measures is required. Growth is an impor-
tant indicator of health and nutritional status of a child, and
a variety of growth charts are currently available to help
with the assessment of growth. These include the 2000
Centers for Disease Control and Prevention (CDC) growth
charts that represent the US population. Each growth mea-
surement performed needs to be accurate and obtained at
regular intervals. These longitudinal data will help identify
at-risk patients (eg, those who are malnourished, obese,
stunted; small-for-gestational-age infants; and those with
refeeding syndrome) and will allow the monitoring of a
patient’s clinical response to nutritional therapy.
During infancy, childhood, and adolescence, many
changes in growth and body composition occur. Therefore,
clinicians must understand normal growth to recognize
abnormal patterns. Clinicians also need to recognize the
nutritional changes that occur with acute and chronic dis-
ease. With the epidemic of pediatric obesity, the proper
identification of the overweight or obese patient is also

important. A brief nutritional screening assessment may be
used to identify patients in need of an in-depth assessment.
A typical nutritional screening includes a brief medical and
dietary history (including feeding ability), anthropometric
measurements (eg, weight, stature), and possibly labora-
tory data. A full nutritional assessment includes more
detailed medical and dietary histories (including a measure
of dietary intake), a complete physical examination, fur-
ther anthropometric and body composition measurements,
sexual and skeletal maturation, laboratory data, and the
estimation of nutritional requirements. A clinician’s global
assessment of the child based on these objective data and
his/her clinical judgment is also important to consider in
determining nutritional status.
1
Most often, health care
professionals work as a team in gathering the information
for the assessment of nutritional status of children.
MEDICAL HISTORY
Obtaining the medical history is central to the nutritional
assessment. Past and present medical information, includ-
ing the duration of the current illness, relevant symptoms,
diagnostic tests and therapies (eg, chemotherapy, radia-
tion), and medications, is documented. Because nutritional
abnormalities are often associated with certain disease
states, it is essential to identify underlying medical condi-
tions and the concomitant medication history. Medications
can cause nutritional deficiencies (eg, 6-mercaptopurine)
and drug–nutrient interactions (eg, phenytoin and tube
feedings; Table 2-1). Drug–nutrient interactions may occur

between drugs (prescription and nonprescription) and
foods, beverages, and dietary and vitamin/mineral supple-
ments. Alterations in drug metabolism and absorption by
food or pharmacologic interactions may be clinically signif-
icant.
2
Past medical history includes previous acute and
chronic illness, hospitalizations, and operations. The his-
tory of past growth patterns (with previous growth charts,
as possible), onset of puberty (for the child and other fam-
ily members), and a developmental history (including feed-
ing abilities) may also be included. Family history should
include a medical history as well as the family’s social and
cultural background, especially as related to diet therapy
and the use of alternative and complementary medicine.
The review of systems includes oral motor function, dental
development, and gastrointestinal symptoms such as vom-
iting, gastroesophageal reflux, diarrhea, and constipation.
CHAPTER 2
CLINICAL ASSESSMENT
OF NUTRITIONAL STATUS
Irene E. Olsen, PhD, RD, Maria R. Mascarenhas, MD,
Virginia A. Stallings, MD