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Adverse Reproductive Outcomes in Families of Atomic Veterans: The Feasibility of Epidemiologic Studies - Committee to Study the Feasibility of, and Need for, Epidemiologic Studies of Adverse Reproductive Outcomes in the Families of Atomic Veterans Medical Follow-up Agency INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1995
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 Govern- ing Board of the National Research Council, whose members are drawn from the eoun- eils of the National Aeademy of Sciences, the National Academy of Engineering, and the Institute of Medieine. The members of the committee responsible for the report were chosen for their special competencies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to proce- dures approved by a Report Review Committee consisting of members of the National Aeademy of Sciences, the National Aeademy of Engineering, and the Institute of Medi c~ne. The Institute of Medieine was chartered in 1970 by the National Aeademy of Sei- enees 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 both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medieine. Support for this project was provided by the Depa~l~ent of Veterans Affairs (contract no. V 101 -~93)P- 1469~. International Standard Book No. 0-309-05340-4 Additional copies of this report are available in limited quantities from: National Academy Press 2101 Constitution Avenue, N.W. P.O. Box 285 Washington, D.C. 20055 Call 800-624-6242 or 202-334-3313 (in the Washington Metropolitan AreaJ B669 Copyright 1995 by the National Academy of Sciences. All rights reserved. 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 serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.
COMMITTEE TO STUDY THE NEED FOR, AND FEASIBILITY OF, EPIDEMIOLOGIC STUDIES OF ADVERSE REPRODUCTIVE OUTCOMES IN THE FAMILIES OF ATOMIC VETERANS WILLIAM J. SCHOLL, Chair, Director, Center for Demographic and Popula- tion Genetics, School of Public Health, University of Texas, Houston, Texas FRED A. METTLER, JR., Chair-pro tem, Chair and Professor, Department of Radiology, University of New Mexico School of Medicine, Albuquerque, New Mexico ROBERT W. MILLER, Chair-pro tem, Scientist Emeritus, Genetic Epidemiol- ogy Branch, National Cancer Institute, Bethesda, Maryland GEORGE J. ANNAS, Chair and Professor, Health Law Department, School of Public Health, Boston University, Boston, Massachusetts JOHN A. AUXIER, President, Auxier & Associates, Inc., Knoxville, Tennessee GERTRUD BERKOWITZ, Associate Professor, Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, New York MICHAEL B. BRACKEN, Professor and Chair, Division of Chronic Disease Epidemiology, Yale University School of Medicine, New Haven, Connecticut CARTER DENNISTON, Professor and Chair, Laboratory of Genetics, Univer- sity of Wisconsin, Madison, Wisconsin JOHN J. MULVIHILL, Professor, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania ANDREW F. OLSHAN, Assistant Professor, Department of Epidemiology, - University of North Carolina at Chapel Hill, Chapel Hill, North Carolina LOWELL SEVER, Technical Group Leader-Epidemiology, Health Risk Assessment Department, Pacific Northwest Laboratory, Richland, Washington ALLEN J. WILCOX, Chief, Epidemiology Branch, National Institute of Envi- ronmental Health Sciences, Research Triangle Park, North Carolina Study Staff RICHARD N. MILLER, Study Director J. CHRISTOPHER JOHNSON, Associate Study Director JOHN D. ZIMBRICK, Associate Study Director ERIN M. BELL, Research Associate PAMELA C. RAMEY-McCRAY, Project Assistant . . .
Preface At the request of the Department of Veterans Affairs and mandated in Pub- lic Law 103-446, Section 508, enacted on November 2, 1994, the Medical Fol- low-up Agency (MFUA) of the Institute of Medicine (IOM) established a committee to review the available data and scientific literature on the health ef- fects of exposure to ionizing radiation and to prepare a report on the feasibility of studying veterans exposed to ionizing radiation and the risk of health effects in their spouses, children, and grandchildren. Specifically, the committee, which was established in January 1995, was asked to address the following three ques- t~ons: 1. Is it feasible to conduct an epidemiologic study to determine whether there is an increased risk of adverse reproductive outcomes in the spouses and of adverse health effects in the children and grandchildren of veterans who partici- pated in atmospheric weapons tests, served with the occupation forces of Hi- roshima or Nagasaki, Japan, prior to July 1, 1946, or were prisoners of war of Japan with an opportunity for exposure to ionizing radiation similar to that of the occupation forces (the Atomic Veterans)? 2. If such a study is feasible, how much time and money would be required to organize and implement it? 3. Are there other sources of information that would yield similar results at lower cost or in less time? v
Al PREFA CE The committee met in Washington, D.C., on three separate occasions, Janu- ary 23-24, March 2-3, and April 17-18, 1995. At the first meeting the commit- tee solicited comments oral, written, or both from members of the public and, in particular, representatives of the various concerned veterans groups. Com- ments were also sought from members of and spokespersons for the House and Senate Committees on Veterans Affairs and the U.S. Department of Veterans Affairs. This report sets forth the committee's assessment of the feasibility of studies of adverse reproductive outcomes in families of servicemen exposed to . . . . . Ionizing radiation. The committee is deeply appreciative of the comments and written submis- sions of the various concerned individuals and groups, and of the work of the staff of the Medical Follow-up Agency. In particular, we are indebted to Rich- ard Miller, J. Christopher Johnson, John Zimbrick, Erin Bell, and Pamela Ramey-McCray for staff support. We thank Michael Hayes for editorial review. William J. Schull, Chair
Contents EXECUTIVE SUMMARY 1; INTRODUCTION.......... Aims of this Report, 1 1 2. BASIC EPIDEMIOLOGIC ISSUES 3. FEASIBILITY AND DESIGN OF AN EPIDEMIOLOGIC STUDY Study Cohort, 18 Measurement of Exposure, 18 Defining the Disease and Ascertaining the Cases, 18 BASIC PRINCIPLES OF RADIATION BIOLOGY Biological Effects, 23 Sources of Radiation Exposure, 25 Potentially Sensitive Subgroups, 26 5. GENETIC PRINCIPLES AND ISSUES . . V11 13 .......... 17 .. 27
V111 6. CURRENT KNOWLEDGE AND ESTIMATION OF GENETIC RISK Basic Estimation Equation, 30 Data From Which Risk Estimates Have Been Made, 33 Estimating the Doubling Dose, 3 8 7. ADVERSE REPRODUCTIVE OUTCOMES General Remarks, 43 Male-Mediated Reproductive and Developmental Outcomes, 44 Infertility, 46 Spontaneous Abortions, 47 Pretend Delivery, 48 Stillbirths and Neonatal Deaths (Pennatal Deaths), 49 Birth Defects, 50 Maternal Illnesses, 54 Altered Sex Ratio, 56 Mortality Among the Children of Exposed Parents, 57 Cancer and Leukemia in Particular, 59 Immune Deficiency, 60 Neurologic Deficit, Including Mental Retardation, 60 8. FEASIBILITY OF THE STUDY OF ADVERSE REPRODUCTIVE OUTCOMES IN THE FAMILIES OF VETERANS EXPOSED TO IONIZING RADIATION ..................................... Definition of a Suitable Sample or Cohort, 62 Size of the Sample or Cohort Required, 63 Dosimetry of Atomic Veterans, 68 Identification of Adverse Reproductive Outcomes, 71 9. ALTERNATIVE APPROACHES 1 0. CONCLUSIONS GLOSSARY REFERENCES ....... CONTENTS ....29 .42 . 62 . 74 .79 . 81 91
Adverse Reproductive Outcomes in Families of Atomic Veterans: The Feasibility of Epidemiologic Studies