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
BC Decker Inc
Hamilton • London
BC Decker Inc
P.O. Box 620, L.C.D. 1
Hamilton, Ontario L8N 3K7
Tel: 905-522-7017; 800-568-7281
Fax: 905-522-7839; 888-311-4987
E-mail:
www.bcdecker.com
© 2003 W. Allan Walker, MD, John B. Watkins, MD, Christopher Duggan, MD, MPH
Previous copyright BC Decker Inc 1996 under ISBN 1-55009-026-7.

Fax: 610-827-1671
E-mail:
Australia
Tel: 61 02 9517-8999
Fax: 61 02 9517-2249
E-mail:
www.harcourt.com.au
Mexico and Central America
ETM SA de CV
Calle de Tula 59
Colonia Condesa
06140 Mexico DF, Mexico
Tel: 52-5-5553-6657
Fax: 52-5-5211-8468
E-mail:
Argentina
CLM (Cuspide Libros Medicos)
Av. Córdoba 2067 - (1120)
Buenos Aires, Argentina
Tel: (5411) 4961-0042/(5411) 4964-0848
Fax: (5411) 4963-7988
E-mail:
Brazil
Tecmedd
Av. Maurílio Biagi, 2850
City Ribeirão Preto – SP – CEP: 14021-000
Tel: 0800 992236
Fax: (16) 3993-9000
E-mail:
Japan

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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:

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 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

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

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-

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

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

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

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.

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

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