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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
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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
. . .
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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
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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
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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
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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
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Adverse Reproductive Outcomes in
Families of Atomic Veterans:
The Feasibility of
Epidemiologic Studies
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