National Academies Press: OpenBook
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Adverse Effects of Pertussis and Rubella Vaccines

A Report of the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines

Christopher P. Howson, Cynthia J. Howe,
and Harvey V. Fineberg, Editors

Division of Health Promotion and Disease Prevention

Institute of Medicine

NATIONAL ACADEMY PRESS
Washington, D.C. 1991

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page ii

NATIONAL ACADEMY PRESS · 2101 Constitution Avenue, N.W. • Washington, D.C. 20418

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this the Institute acts under the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Samuel O. Thier is President of the Institute of Medicine.

The project was supported by funds coordinated through the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (contract no. NOI-AI-95041).

Library of Congress Cataloging-in-Publication Data

Institute of Medicine (U.S.). Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines.
Adverse effects of pertussis and rubella vaccines : a report of the
Committee to Review the Adverse Consequences of Pertussis and
Rubella Vaccines / Christopher P. Howson, Cynthia J. Howe, and
Harvey V. Fineberg, editors.
p. cm.
Includes bibliographical references and index.
ISBN 0-309-04499-5
1. Pertussis vaccines—Side effects—Congresses. 2. Rubella
vaccines-—Side effects—Congresses. 3. Whooping cough—Preventive
inoculation—Complications and sequelae—Congresses. 4. Rubella—
Preventive inoculation—Complications and sequelae—Congresses.
I. Howson, Christopher Paul. II. Howe, Cynthia J. III. Fineberg,
Harvey V. IV. Title.
[DNLM: 1. Pertussis Vaccine—adverse effects. 2. Rubella Vaccine—
adverse effects. WC 340 159r]
QR 189.5.P46156 1991
615'.372—dc20
DNLM/DLC
for Library of Congress          91-25665
                         CIP

Copyright © 1991 by the National Academy of Sciences

No part of this book may be reproduced by any mechanical, photographic, or electronic procedure, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purpose of official use by the United States government.

Printed in the United States of America

The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemusseen in Berlin.

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page iii

COMMITTEE TO REVIEW THE ADVERSE CONSEQUENCES OF PERTUSSIS AND RUBELLA VACCINES

HARVEY V. FINEBERG (Chairman), Dean, Harvard School of Public Health, Boston, Massachusetts

JOHN C. BAILEY, Director, Bear River District Health Department, Logan, Utah

MARY LUZ COADY, Director, Department of Pediatrics, Bryn Mawr Hospital, Bryn Mawr, Pennsylvania

LINDA D. COWAN, Associate Professor, Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma, Oklahoma City, Oklahoma

MARIE R. GRIFFIN, Associate Professor, Department of Preventive Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

RICHARD B. JOHNSTON, JR., William H. Bennett Professor of Pediatrics, University of Pennsylvania School of Medicine, and Childrens' Hospital of Philadelphia, Philadelphia, Pennsylvania

MICHAEL KATZ, Reuben S. Carpentier Professor and Chairman, Department of Pediatrics, College of Physicians and Surgeons, and Professor of Public Health (Tropical Medicine), School of Public Health, Columbia University, New York, New York

DARWIN R. LABARTHE, James W. Rockwell Professor of Public Health, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas

DAVID A. LANE, Professor, Department of Theoretical Statistics, University of Minnesota, Minneapolis, Minnesota

FREDERICK MOSTELLER, Roger I. Lee Professor of Mathematical Statistics, Emeritus, Director, Technology Assessment Program, Harvard University, Boston, Massachusetts

BENNETT A. SHAYWITZ, Professor of Pediatrics, Neurology, & Child Study Center, Yale University School of Medicine, New Haven, Connecticut

Project Staff

CHRISTOPHER P. HOWSON, Project Director

CYNTHIA J. HOWE, Program Officer

DOROTHY R. MAJEWSKI, Project Assistant

MICHAEL A. STOTO, Senior Program Officer

CYNTHIA H. ABEL, Financial Associate

MICHAEL K. HAYES, Contract Editor

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page iv

Institute of Medicine

SAMUEL O. THIER, President

ENRIQUETA C. BOND, Executive Officer

GARY B. ELLIS, Director, Division of Health Promotion and Disease Prevention

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page v

Preface

Although vaccines have markedly reduced the toll of many childhood illnesses, the practice of vaccination is not always without risk. Minor side effects are common, and serious side effects, although less numerous, have been observed on rare occasions with certain vaccines. Whether there are increased risks of serious adverse events following whole-cell pertussis and rubella vaccines, however, is controversial. The fact that pertussis and rubella vaccination is mandatory in many states has heightened public awareness of controversy and concern about the safety of the two vaccines.

In response to concerns about possible adverse consequences of legally mandated vaccines, the U.S. Congress in 1986 passed the National Childhood Vaccine Injury Act (Public Law 99-660), followed by the Vaccine Compensation Amendments of 1987 (Public Law 100-203). The core of the legislation was the establishment of a federal compensation scheme for persons potentially injured by vaccines, to be funded by excise taxes imposed on manufacturers of vaccines. In addition, Section 312 of Public Law 99-660 also called for a review of scientific and other information on possible adverse consequences of the pertussis and rubella vaccines. The Institute of Medicine (IOM) was specifically asked to conduct this review, and funds coordinated by the National Institute of Allergy and Infectious Diseases were made available for this purpose in September 1989.

In November 1989, IOM established the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines. The specific charge

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page vi

to the committee, as outlined in Section 312 of the National Childhood Vaccine Injury Act, was to:

· identify and review all available medical and scientific literature on the nature, circumstance, and extent of the relationship, if any, between vaccines containing pertussis (including whole cells, extracts, and specific antigens) and the following illnesses and conditions: hemolytic anemia, hypsarrhythmia, infantile spasms, Reye syndrome, peripheral mononeuropathy, deaths classified as sudden infant death syndrome (SIDS), aseptic meningitis, juvenile diabetes, autism, learning disabilities, hyperactivity, and other such illnesses as recommended by the committee or the Advisory Commission on Childhood Vaccines, and inquire into the possible association between pertussis vaccines and permanent neurologic damage;

· conduct a similar review of the potential relationship between rubella vaccines (including the measles-mumps-rubella combination vaccine) and radiculoneuritis;

· sponsor a workshop on pertussis and rubella vaccines that shall include invited researchers and experts on vaccine-related illness and conditions;

· conduct a public meeting covering both pertussis and rubella vaccines to obtain information from a variety of interested parties; and

· prepare a report that presents the committee's assessment of evidence and conclusions about the possible association between pertussis and rubella vaccines and these specific adverse events.

At its first meeting in January 1990, the committee voted to add chronic arthritis to the list of adverse events to be examined with respect to rubella vaccines. In May 1990, at the request of the Advisory Commission on Childhood Vaccines, the committee agreed to consider seven additional adverse events: anaphylaxis; erythema multiforme or other rashes; GuillainBarrè syndrome (polyneuropathy); protracted inconsolable crying or screaming; thrombocytopenia; and shock and "unusual shock-like state" with hypotonicity, hyporesponsiveness, and short-lived convulsions (usually febrile), with respect to pertussis vaccines; and thrombocytopenic purpura, with respect to rubella vaccines.

The 11-member interdisciplinary committee appointed to conduct the study included individuals with expertise in infectious diseases, pediatrics, internal medicine, neurology, epidemiology, biostatistics, decision analysis, biologic mechanisms of vaccines, immunology, and public health. During the course of the 20-month study, the committee examined a wide range of information sources, including case series and individual case reports published in peer-reviewed journals and reported by vaccine manufacturers; unpublished case reports from physicians, parents, and other concerned persons; epidemiologic studies; studies in animals; and other laboratory studies. Whenever possible, the committee examined primary sources of data.

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page vii

Other works, for example, the Report of the Task Force on Pertussis and Pertussis Immunization—1988 published in 1988 by the American Academy of Pediatrics, DPT: A Shot in the Dark published in 1985 by Coulter and Fisher, and the 1985 Institute of Medicine report Vaccine Supply and Innovation provided secondary sources of information. The committee also considered a variety of other data sources, including conference and symposium proceedings, legal judgments, and academic dissertations. By drawing on a variety of information sources, the committee has attempted to ensure a comprehensive and critical review.

The committee held five meetings during which it evaluated the literature and prepared its general review and summary. A public meeting convened at the outset of the study served as a forum for open discussion and presentation of views and information by individual scientists and by representatives of medical specialty organizations, parent groups, vaccine manufacturers, and the legal community.

The committee also conducted one workshop during which it interacted with and shared the expertise and research findings of a larger community of scientists representing a range of views on topics pertinent to the committee's charge. The workshop provided an opportunity for the committee members to consider new or controversial data and various points of view and to identify gaps in knowledge. The subjects considered in the workshop included the time course of events following pertussis or rubella vaccination, variations in pertussis and rubella vaccine compositions and their implications for evaluating possible adverse events following vaccination, evidence concerning the possible relationship of pertussis vaccines to irreversible encephalopathy and sudden infant death syndrome, and evidence concerning any relationship of rubella vaccines to radiculoneuritis, peripheral neuropathy, and chronic arthritis.

The committee's report is presented in seven chapters and six appendixes. The report also includes a glossary of terms and a bibliography of information sources. Chapter 1 provides an executive summary of the report. Chapter 2 offers a brief history of the development of pertussis and rubella vaccines and of the controversy concerning their possible associations with severe adverse events. Chapter 3 details the methodologic considerations of the committee in its evaluation of the evidentiary base. Chapters 4 through 6 present the evidence pertaining to pertussis vaccines and specific adverse events, and Chapter 7 presents evidence pertaining to rubella vaccine and specific adverse events. An afterword on research needs follows Chapter 7. Appendix A describes the strategies the committee used to gather its information. Appendix B provides a brief chronology of pertussis and rubella vaccines. Appendix C discusses animal models used in studying pertussis and in the testing of vaccines. Appendix D describes the technical details of the committee's power calculations and meta-analyses.

Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page viii

Appendix E discusses the possible involvement of aluminum salts in adverse events following pertussis immunization. Appendix F provides brief biographies of committee members. In preparing its report, the committee recognized that its charge was to focus on questions of causation and not broader, although important, topics, such as cost-benefit or risk-benefit analyses of vaccination.

We hope that this report will provide a foundation of evidence and methods that may also be useful to others concerned with assessing the safety of vaccines.

image

Harvey V. Fineberg, Chairman
Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page ix

Acknowledgments

The committee wishes to thank the many people who provided information to the committee, including Kenneth Bart, National Vaccine Program; Philip Berry, Berry & Berry; Thomas P. Bleck, Rush Memorial Hospital; Dean A. Blumberg, University of California, Los Angeles; E. Borst-Eilers, The Health Council of The Netherlands; James D. Cherry, University of California, Los Angeles; Richard V. Colan, pediatric neurologist; Harris L. Coulter, Center for Empirical Medicine; George Curlin, National Institute of Allergy and Infectious Diseases; Marie Valdes Dapena, University of Miami; Darryl DeVivo, Neurological Institute; Charles A. Dinarello, Tufts University School of Medicine; Mr. and Mrs. Donny Epps, Athens, Georgia; Barbara Loe Fisher, Dissatisfied Parents Together; Kay A. Fox, Chronic Rubella Viremia Support; Ronald Gabriel, University of California, Los Angeles; James L. Gale, University of Washington; Mark Geier, medical/ legal consultant; Marjorie Grant, Determined Parents to Stop Hurting Our Tots; Rajesh K. Gupta, Visiting Fellow, National Institute of Child Health and Human Development; Stephen C. Hadler, Centers for Disease Control; Joanne M. Hatem, York Gastroenterology; Rosemary Havill, Health Resources and Services Administration; Carole A. Heilman, National Institute of Allergy and Infectious Diseases; Erik L. Hewlett, University of Virginia School of Medicine; Alan R. Hinman, Centers for Disease Control; Ulla Hoikkala, Embassy of Finland; Michael R. Hugo, Schlichtmann, Conway, Crowley & Hugo; David L. Klein, National Institute of Allergy and Infec-

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page x

tious Diseases; Daniel Lahn, National Vaccine Program; Leonard P. Kurland, Mayo Clinic; John R. LaMontagne, National Institute of Allergy and Infectious Diseases; Stephan Lawton, Reed, Smith, Shaw & McClay; Charles R. Manclark, Food and Drug Administration; Cynthia McCormick, Vaccine Injury Compensation Program; David L. Miller, St. Mary's Hospital Medical School, London; John Mullen, Centers for Disease Control; J. Anthony Morris, The Bell of Atri, Inc.; Edward A. Mortimer, Jr., Case Western Reserve University School of Medicine; Yuth Nimit, National Vaccine Program; Walter A. Orenstein, Centers for Disease Control; Georges Peter, Rhode Island Hospital; Stanley A. Plotkin, Pasteur Mèrieux Connaught Company; Keith Redhead, National Institute for Biological Standards and Control; Joseph Reini, Embassy of Finland; Noel R. Rose, The Johns Hopkins School of Hygiene and Public Health; Jeffrey Schwartz, Jellinek, Schwartz, Connolly & Freshman, Inc.; John Sladky, Children's Hospital of Philadelphia; Martin Smith, pediatrician; Mark E. Thoman, Iowa Poison Control Center; Dirk Teuwen, SmithKline Biologicals; Puru Thapa, University of Washington; Aubrey Tingle, British Columbia Children's Hospital; Alexander Walker, Harvard School of Public Health; Steven G. Wassilak, Centers for Disease Control; Jeanette Wilkins, University of Southern California School of Medicine; and Arthur C. Zahalsky, Southern Illinois University.

The committee would also like to thank individuals within the IOM whose support was instrumental. Leading the list are Christopher P. Howson, Project Director, and Cynthia J. Howe, Program Officer, whose hard work and dedication ensured the completion of the report, and Michael A. Stoto, Senior Program Officer in the Division of Health Promotion and Disease Prevention, for invaluable assistance in developing and applying evaluative methods used in this report. We are grateful, also, to Dorothy R. Majewski, secretary to the project, who typed volumes, arranged travel, and assisted at meetings, and to Jane Durch for help with the graphics. Others within IOM and the National Academy of Sciences who were instrumental in seeing the project to completion were Samuel O. Thier, President of IOM; Enriqueta C. Bond, Executive Officer of IOM; Gary B. Ellis, Director of the Division of Health Promotion and Disease Prevention; and Sally S. Stanfield and Francesca T. Moghari, National Academy Press. We appreciate the editorial assistance of Michael Hayes, Leah Mazade, Betsy Turvene, and Wallace Waterfall. Finally, this report could not have been completed without the expert help of National Research Council librarians Pamela Pangburn, Janet Ewing, Valerie Foster, and Yauthary Keo and IOM librarian Samuel Johnson.

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page xi

Contents

1 Executive Summary

1

2 Histories of Pertussis and Rubella Vaccines

9

3 Methodologic Considerations in Evaluating the Evidence

32

4 Evidence Concerning Pertussis Vaccines and Central Nervous System Disorders, Including Infantile Spasms, Hypsarrhythmia, Aseptic Meningitis, and Encephalopathy

65

5 Evidence Concerning Pertussis Vaccines and Deaths Classified as Sudden Infant Death Syndrome (SIDS)

125

6 Evidence Concerning Pertussis Vaccines and Other Illnesses and Conditions

144

Anaphylaxis

144

Autism

151

Erythema Multiforme or Other Rash

152

Guillain-Barrè Syndrome (Polyneuropathy)

154

Peripheral Mononeuropathy

156

Hemolytic Anemia

157

Juvenile Diabetes

159

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

Page xii

Learning Disabilities and Hyperactivity

161

Protracted Inconsolable Crying and Screaming

165

Reye Syndrome

169

Shock and ''Unusual Shock-Like State" with Hypotonicity, Hyporesponsiveness, and Short-Lived Convulsions, Usually Febrile

171

Thrombocytopenia

177

7 Evidence Concerning Rubella Vaccines and Arthritis, Radiculoneuritis, and Thrombocytopenic Purpura

187

Afterword on Research Needs

206

Bibliography

208

Glossary of Terms

283

Appendixes

 

A. Strategies for Gathering Information: Adverse Effects of Pertussis and Rubella Vaccines

293

B. Pertussis and Rubella Vaccines: A Brief Chronology

320

C. Animal Models for the Study of Whooping Cough and the Testing of Vaccine Materials

333

D. Technical Details of Power Calculations and Meta-Analyses

337

E. Possible Involvement of Aluminum Salts in Erythema Multiforme, Encephalopathy, or Other Adverse Events After Pertussis Immunization

347

F Committee Biographies

349

Index

355

Page xiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

There was a problem loading page R13.

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×

There was a problem loading page R14.

Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R1
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R2
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R3
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R4
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R5
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R6
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R8
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R9
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R10
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R11
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R13
Suggested Citation:"Front Matter." Institute of Medicine. 1991. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: The National Academies Press. doi: 10.17226/1815.
×
Page R14
Next: 1 Executive Summary »
Adverse Effects of Pertussis and Rubella Vaccines Get This Book
×
Buy Paperback | $100.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Parents have come to depend on vaccines to protect their children from a variety of diseases. Some evidence suggests, however, that vaccination against pertussis (whooping cough) and rubella (German measles) is, in a small number of cases, associated with increased risk of serious illness.

This book examines the controversy over the evidence and offers a comprehensively documented assessment of the risk of illness following immunization with vaccines against pertussis and rubella. Based on extensive review of the evidence from epidemiologic studies, case histories, studies in animals, and other sources of information, the book examines:

  • The relation of pertussis vaccines to a number of serious adverse events, including encephalopathy and other central nervous system disorders, sudden infant death syndrome, autism, Guillain-Barre syndrome, learning disabilities, and Reye syndrome.
  • The relation of rubella vaccines to arthritis, various neuropathies, and thrombocytopenic purpura.

The volume, which includes a description of the committee's methods for evaluating evidence and directions for future research, will be important reading for public health officials, pediatricians, researchers, and concerned parents.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!