Women who served in The U.S. Military in Vietnam may have experienced adverse pregnancy outcomes. The risk of having children with moderate-to-severe'' birth defects was signi(r)cantly associated with mother's military service in Vietnam.
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Original Title
Agent Orange Pregnancy Outcomes Among Us Women Vietnam Veterans1097-0274(200010)38!4!447--AID-AJIM11-3.0
Women who served in The U.S. Military in Vietnam may have experienced adverse pregnancy outcomes. The risk of having children with moderate-to-severe'' birth defects was signi(r)cantly associated with mother's military service in Vietnam.
Women who served in The U.S. Military in Vietnam may have experienced adverse pregnancy outcomes. The risk of having children with moderate-to-severe'' birth defects was signi(r)cantly associated with mother's military service in Vietnam.
AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 38:447454 (2000)
Pregnancy Outcomes Among U.S.
Women Vietnam Veterans Han K. Kang, DrPH, 1 Clare M. Mahan, PhD, 1 Kyung Y. Lee, PhD, 1 Carol A. Magee, PhD, 1 Susan H. Mather, MD, MPH, 1 and Genevieve Matanoski, MD, DrPH 2 Background Since the 19651975 Vietnam War, there has been persistent concern that women who served in the U.S. military in Vietnam may have experienced adverse pregnancy outcomes. Methods We compared self-reported pregnancy outcomes for 4,140 women Vietnam veterans with those of 4,140 contemporary women veterans who were not deployed to Vietnam. As a measure of association, we calculated odds ratios (OR) and 95% condence intervals (CI) using logistic regression adjusting for age at conception, race, education, military nursing status, smoking, drinking and other exposures during pregnancy. Result There was no statistically signicant association between military service in Vietnam and index pregnancies resulting in miscarriage or stillbirth, low birth weight, pre-term delivery, or infant death. The risk of having children with ``moderate-to-severe'' birth defects was signicantly elevated among Vietnam veterans (adjusted OR1.46, 95% CI 1.062.02). Conclusion The risk of birth defects among index children was signicantly associated with mother's military service in Vietnam. Am. J. Ind. Med. 38:447454, 2000. Published 2000 Wiley-Liss, Inc. y KEY WORDS: women veterans; Vietnam war; pregnancy outcomes INTRODUCTION The possibility of long-term health effects including adverse reproductive health outcomes resulting from military service in Vietnam has been a subject of research interest in the United States over the past two decades [CDC Vietnam Experience Study, 1988; Stellman et al., 1988]. The U.S. Congress, responding to concerns of many women Vietnam veterans, legislatively mandated a comprehensive health study of women Vietnam veterans. This mandate led to three separate but related epidemiologic studies of women Vietnam era veterans: (1) post-Vietnam service mortality follow-up; (2) assessment of psychologic health outcomes; and (3) reproductive health outcomes. Results of the rst two studies were published or submitted to Congress previously [Thomas et al., 1991; Dalager and Kang, 1996]. The present report deals with the third study. The studies of reproductive outcomes among male veterans have been mostly negative in that service in Vietnam was not associated with the risk of fathering a child with birth defects, spontaneous abortion, stillbirth or neonatal death [Erickson et al., 1984; Donovan et al., 1984; Aschengrau and Monson, 1989, 1990]. However, in the recent ``Ranch Hand study'', neural tube defects (spina bida, anencephaly) were reported in four children of U.S. Air Force personnel who sprayed Agent Orange and other 1 Environmental Epidemiology Service, Veterans Health Administration Department of Veterans Affairs, Washington, DC 20036-3406. 2 Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland Contract grant sponsor: Medical Research Service, Office of Research and Development, Department of Veterans Affairs. *Correspondence to: Dr. Han K. Kang, Environmental Epidemiology Service, Department of Veterans Affairs, 1120 20th Street N.W., Suite 950, Washington, D.C. 20036-3406. E-mail: han.kang@mail.va.gov Accepted 23 May 2000 Published 2000 Wiley-Liss, Inc. y This article is a US Government work and, as such, is in the public domain in the United States of America. herbicides in Vietnam, while none was observed among children of control veterans [Wolfe et al., 1995]. Further- more, when the CDC birth defects study was reanalyzed using the exposure opportunity index based upon interview data, the risk of spina bida was signicantly associated with the highest estimated level of Agent Orange exposure [Erickson et al., 1984]. Based on these data and others, an Institute of Medicine panel suggested an association between herbicide exposure in Vietnam and an increased risk of spina bida in children [IOM, 1996]. Although results of studies of male Vietnam veterans are potentially useful in assessing health consequences of Vietnam service for women, a further study of gender- specic health outcomes for women was desired. Maternal exposures to toxicants are more directly associated with adverse pregnancy outcomes, while evidence for the effects of paternal exposure on pregnancy outcomes is very limited and indirect [Ofce of Technology Assessment, 1985; Moore and Persaud, 1998]. Many potential risk factors for abnormal reproductive outcomes existed in Vietnam for women veterans, including psychological stresses of war, various infections, substance abuse, and Agent Orange contaminated with dioxin [Baker et al., 1989; Bates et al., 1990; Jordan et al., 1991]. Other potential risk factors associated with military hospital nursing conditions in Vietnam included physical stress, and exposure to waste anesthetic gases and ethyleneoxide [Custis, 1990; Rowland et al., 1996; Biovin, 1997]. We conducted a historical cohort study of 8,280 women veterans, comparing the pregnancy outcomes of 4,140 women Vietnam veterans with those of 4,140 non-Vietnam veterans in the military during the same era. Due to difculty in identifying a large number of women exposed to any particular aspect of Vietnam service with any degree of certainty, the study was a ``Vietnam experience'' type of study rather than of specic exposures. MATERIAL AND METHODS Study Subjects The U.S. Army and Joint Services Environmental Support Group compiled manually a list of Army women veterans who served in Vietnam. The Air Force provided a computer listing of all Air Force women known to have served in Vietnam, as did the Navy and Marine Corps. A total of 5,230 names were compiled as potential Vietnam veteran study subjects. Military personnel records of these women were retrieved from various locations and their military service data were extracted. Women Vietnam veterans for this study were dened as those women in the U.S. Military whose permanent tour of duty included service in Vietnam during the period from July 4, 1965 through March 28, 1973, a period of signicant U.S. military involvement in Vietnam. After the record review, 4,643 women met the eligibility criteria; of these 4,390 women were found alive as of January 1, 1992. Women non-Vietnam veterans for the study were dened as those women assigned to a military unit in the U.S. during the Vietnam War and whose tour of duty did not include service in Vietnam. Potential control subjects from each branch of service were selected using the same procedures as for Vietnam veterans. A pool of 6,657 women were eligible for controls; of these 4,390 women were randomly selected among the living members of this pool as of January 1, 1992 [SAS, 1990]. To determine the feasibility of the present study, we conducted a pilot study on 500 of these women (250 Vietnam veterans and 250 non-Vietnam controls), leaving 8,280 women (4,140 Vietnam and 4,140 non-Vietnam) available for the study. Survey Methods Instrument A structured health questionnaire was administered using a computer-assisted telephone interview software package to obtain information concerning demographic background, general health, lifestyle, menstrual history, pregnancy history, pregnancy outcomes, military experience including nursing occupation and combat exposure. For each pregnancy, information such as smoking, drinking, complications, infections, medications, exposure to x-ray, occupational history, exposure to anesthetic gases, ethyle- neoxide, herbicides and pesticides was collected. Location Strategies Names and social security numbers of the 8,280 veterans were rst passed through the Internal Revenue Service records and VA's Beneciary Identication Records Locator Subsystem. Those not located were also searched in the Defense Manpower Data Center records. Several nationwide commercial databases such as Telematch, TRW/ Experian, and Equifax proprietary databases, and national telephone directory CD-ROMs were searched for new addresses and telephone numbers. State nursing boards and nursing associations were also contacted for new addresses because most women veterans serving during the Vietnam era were nurses. Outcome Assessment To satisfy the basic statistical requirement of indepen- dence of observations, i.e., one pregnancy per woman, an index pregnancy was identied for each woman. For the Vietnam veterans, it was dened as the rst pregnancy after 448 Kang et al. entrance date to Vietnam service. If the Vietnam experience did have any effect, it would more likely be manifest in the rst pregnancy following the exposure (Vietnam service). For the non-Vietnam veterans, it was dened as the rst pregnancy after July 4, 1965, the starting date for the U.S. ground troops involvement in Vietnam, or the entrance date into military service, whichever was later. The outcomes studied and their denitions are as follows: Fetal loss including spontaneous abortion and stillbirth was dened as any loss of fetus regardless of gestational age; a low birth weight infant was dened as a baby born alive and weighing less than 2500 g or 5 pounds 8 ounces; pre-term delivery was dened as a baby born alive with a gestational age of 37 weeks or less or 8 months or less, if reported in months; ``likely'' birth defects were dened as congenital anomalies and included structural, functional, metabolic or hereditary defects. For this study in which the index pregnancy would have occurred as far back as 30 years, the relevant medical records were very difcult to retrieve. As an alternative method, maternally reported data on children with any reported defects were reviewed by a pediatric epidemiologist while blinded regarding Vietnam service status of mothers. These data included maternal description of defect(s); birth weight; gestational length; any history (yes/no) of surgery, medical treatment, or functional limitations due to defect; age at diagnosis; and if deceased, age and cause of death. After the review, the reported birth defects were grouped hierarchically into one of 11 groups as follows: likely congenital birth defects, groups 17; unlikely congenital birth defects, groups 811 (Table I). The ``likely'' congenital birth defects were further restricted to ``moderate-to-severe'' birth defects for analyses of signi- cant, potentially teratogenic defects. The ``moderate-to- severe'' birth defects only included conditions characterized by the serious nature of the diagnosis (if explicitly stated by the mother), or conditions having any history of surgical or medical treatment, functional impairment, or death from the defect or a related cause. Medical Records Review In order to document reported incidents of birth defects, an attempt was made to retrieve records on all likely congenital birth defects with ``moderate-to-severe'' condi- tions. The type of medical records sought were further restricted to hospital records because of the difculty locating a private physician or clinic in practice as far back as three decades ago. Women veterans were contacted again to gain consent for obtaining medical records, and to gather specic information about health care providers. Upon receipt of the signed release form from the mother or the adult child, a request for the records was sent to each hospital. Statistical Analysis As a measure of association for dichotomous outcomes, the odds ratio (OR) and 95% condence interval (CI) were calculated using a multivariate logistic regression model with adjustment for covariates [Selvin, 1991]. Analyses were based on self-reported interview data. Logistic TABLEI. Description of Generic Classes of Reported Birth Defects Group Description Likely birth defects 1. Chromosomal abnormality Abnormal chromosome number or size 2. Multiple anomalies Two or more defects in different organ systems except identifiable heritable syndromes 3. Isolated anomaly One or more defects within same organ system 4. Congenital neoplasms a Early childhoodtumors 5. Heritable genetic diseases/syndromes Identifiable single-allele disorders (dominant, recessive, or sex-linked) 6. Unspecifiedheart abnormality Undescribedisolatedheart defects or mumurs 7. Poorly specifiednon-cardiac defect Defect(s) with inadequate description to classify further Unlikely birth defects 8. Developmental disorders Learningand attention deficits, or epilepsy diagnosedbeyond infancy 9. Perinatal complications All delivery, newborn, or prematurity relatedconditions 10. Miscellaneous pediatric illnesses Food allergy, asthma, etc 11. Not classifiable No description of defect, or ``unknown'' a Some neoplasms are genetic defects. Women Vietnam Veterans' Pregnancy Outcomes 449 modeling was carried out using STATA and SAS [SAS Windows, 1991; Epi Inf, 1997; STATA, 1997]. RESULTS Overall, 6,430 women (78% of total; 85% of living and located veterans) completed a full telephone interview. Of the remaining 1,850 women (22.3% of total), 370 were never located (4.5%), 775 refused to participate in the study (9.4%), 339 were deceased (4.1%) and 366 completed only a short written questionnaire (4.4%). 8.1% of Vietnam veterans (or 334 women) and 10.7% of non-Vietnam veterans (or 441 women) refused to participate in the study. Demographic and military characteristics of respondents, including age, branch, military occupation and duration of service, were not signicantly different from their respective groups of eligible veterans. The limited health outcome data collected from 366 women who only completed a short written questionnaire showed no signicant difference in the prevalence of selected outcomes in comparison to those who completed the telephone interview. They were not included in the analysis. The most important factor associated with completing the telephone interview was ability to contact the subject by telephone. Once reached, a high proportion of eligible women (Vietnam veterans, 87%; non-Vietnam veterans, 83%) completed the interview. The denominators of interest by Vietnam service status of respondents are listed in Table II. Relatively fewer women Vietnam veterans were ever married (66 vs. 77%); or became pregnant (52 vs. 66%). The reason for the relatively smaller number of Vietnam veterans reporting ``ever pregnant'' than non-Vietnam veterans (52 vs. 66%) was that more of them never tried to become pregnant than non-Vietnam veterans (43% vs. 30%). Excluding those women who did not try to become pregnant, the percentages of women ``ever pregnant'' for Vietnam and non-Vietnam veterans were 91 and 94%, respectively. The most frequent reasons for ``never tried to become pregnant'' were ``never married'' and ``never wanted children.'' The concern about birth defects among children was very small: Vietnam veterans,8; non Vietnam veterans, 2. Among those women who experienced pregnancy, the average number of pregnancies (2.7 vs. 2.7) and average number of live births per pregnancy (0.70 vs. 0.73) were not signicantly different by their Vietnam service status. Among those who tried to become pregnant for 12 months or more, 77.4% of Vietnam veterans and 77% of non- Vietnam veterans eventually became pregnant. An approxi- mately equal proportion of women trying to become pregnant sought medical care for their difculty in becoming pregnant: Vietnam veterans, 66%; non-Vietnam veterans, 68%. Table III describes characteristics of women who had an index pregnancy. In general the two groups were similar. Relatively small numbers of women had pregnancies predating the index pregnancy. However, in reection of women who were selected for the study in each group, there were relatively more military nurses in the Vietnam group and more Army veterans in the non-Vietnam group. These and other differences were used in the multivariate analyses. The outcomes of the index pregnancies are presented in Table IV. After adjustment for demographic and military characteristics of mothers and a number of factors associated with the pregnancy, no signicant differences were observed due to Vietnam experience for spontaneous abortions or stillbirths, low birth weight, pre-term delivery, and infant death. However, a statistically signicant difference was observed in the number of ``likely'' birth defects and more restricted ``moderate-to-severe'' birth defects among live born babies between Vietnam veterans and those of non-Vietnam veterans. The odds ratio was higher for non-nurse Vietnam veterans than nurse Vietnam veterans when each group was compared to the correspond- ing non-Vietnam group. Among the non-nurse group, adjusted ORs (95% CI) for ``likely'' birth defects and ``moderate-to-severe'' birth defects were 3.14 (1.775.57) and 2.60 (1.384.85), respectively. The distributions of 231 infants with likely birth defects by generic class of defect (Vietnam; non-Vietnam infants) were chromosomal abnormality (3;4), multiple anomalies (28;11), isolated anomaly (81;74) congenital malignancy (1;1), heritable genetic disease (4;4), undescribed isolated heart ab- normality (10;7), and other poorly described non-cardiac defect (2;1). Spina bida, a condition of particular interest stemming from studies of male Vietnam veterans, was reported in ve infants among index children of the Vietnam group and three infants among non-Vietnam group. Four were children TABLEII. Reproductive History of WomenVeteran Respondents Non-Vietnam Vietnamveterans veterans Outcomes (N 3392) (N 3038) Ever married 2225 2351 Ever pregnant 1775 1993 Number of pregnancies 4778 5465 Total live births a 3347 3992 Total index pregnancies b 1665 1912 Total index live births 1229 1460 a For Vietnamveterans, all liveborn babies after Vietnamservice were included and for non-Viet- namveteransalllivebornbabiesresultingfrompregnanciesafter July4,1965or thestartingdateof military service, whichever waslater. b For Vietnam veterans, the first pregnancy after the entrance date of Vietnam service; for non- Vietnam veterans, the first pregnancy after July 4, 1965 or the starting date of military service, whichever waslater. 450 Kang et al. of Army nurses who served in Vietnam in the years between 1967 and 1972. The fth case was a child of an enlisted Marine Corps woman who served in 19691970. The proportions of reported birth defects excluded for lack of apparent congenital defects are essentially the same between Vietnam and non-Vietnam groups: 15.7% of Vietnam and 14.3% of non-Vietnam infants. Among the covariates, smoking during pregnancy was shown to be a signicant risk factor for fetal loss (OR1.66, 95% CI 1.342.05), low birth weight (OR2.12, 95% CI 1.512.99), and pre-term delivery (OR1.42, 95% CI 1.031.94). Mother's age at concep- tion (each year of age) was positively associated with risk of fetal loss (OR1.05, 95% CI 1.021.07) but not with low birth weight or pre-term delivery. There was a strong association between any pregnancy complication and risk of low birth weight (OR2.96, 95% CI 2.164.08), and pre-term delivery (OR3.14, 95% CI 2.384.16). Medical Records Review Of the 180 children (95 Vietnam: 85 non-Vietnam) with ``moderate-to-severe'' birth defects, 72 (41:31) were reportedly diagnosed at birth. Sixty-eight (38:30) of the 72 women agreed to release the relevant records; however, only 23 (13:10) women actually returned the signed released form. The hospital records for the 23 children were sought and records were received for 14 children (7:7). Of the 14 children with records, birth defects reported by the mother were documented in the hospital records for 13 children (6:7). The records could not be obtained for nine children because the hospital destroyed the records, could not locate the records, or could not release the record of an adult child without the child's consent, but the child was dead. There appears to be no disproportionately higher number of Vietnam veterans refusing to release the records or agreeing to release the records but not returning the signed form. DISCUSSION There are several important limitations of this study. First, the extensive effort to document birth defects reported by mothers was essentially unsuccessful. Some veterans did not return the signed release form after agreeing to do so on the phone. Many records were lost because many hospitals routinely destroyed records after a certain period (1015 years), changed names, were closed or merged with another facility. Our attempt to use birth certicates for validation was also largely unsuccessful. Either the information was not available on the birth certicate or we were denied access to the certicate. Only in recent years was information on congenital malformation recorded on birth certicates in a structured format. The index births for this study occurred in the early 1970s, a period when the use of part II was not widely practiced by states. Part II of the certicate captures information on conditions present during the pregnancy, obstetric procedures, type and conditions of labor, method of delivery, congenital malformations, birth weight, length of gestation, etc. A study using data from the TABLE III. Percent Distribution of Vietnam Veterans and non-Vietnam Veterans who had an Index Pregnancy by Selected Demographic and Other Characteristics Associated with the Pregnancy Non-Vietnam Vietnamveterans veterans Characteristics (N 1665) (N 1912) Age at pregnancy <25 27 45 25^29 46 36 30 27 19 Median age (years) (26) (25) Calendar Year at Pregnancy (P .25 ^P .75 ) (1970^1975) (1969^1975) Race White 95 94 Non-White 5 6 Education level <4 yr college 43 41 4 yr college 30 30 Post graduate 27 29 Branch Army 84 90 Air Force 11 7 Navy 5 3 Marine Corps <1 <1 Military Occupation Nursing 86 62 Other 14 38 Smoking duringpregnancy Yes 28 26 No 72 74 Drinking duringpregnancy Yes 42 35 No 58 65 Working Yes 85 83 No 15 17 Birth control use Yes 13 15 No 87 85 Illegal druguse Yes 0.5 0.5 No 99.5 99.5 Prior pregnancy a Yes 5 8 No 95 92 a Pregnancies predatingtheindex pregnancy. Women Vietnam Veterans' Pregnancy Outcomes 451 Metropolitan Atlanta Congenital Defects and birth certi- cates showed the birth certicates to have a sensitivity of only 14% for detecting all birth defects [Watkins et al., 1996]. In view of the limited sensitivity, we stopped trying to obtain the birth certicates. Second, information on an individual's pregnancy and birth outcomes can only be obtained by asking the person. There is no national central repository of these data from which a person's reproductive history can be obtained. The health history information relevant to the study spans almost 30 years with the possibility of selective recall by one or both groups of veterans. Vietnam veterans may have over- reported certain health outcomes because of continuing publicity about the cancer and reproductive health hazards related to Agent Orange and Vietnam service. Third, because of the absence of reliable exposure measures in Vietnam, the study was designed to be a Vietnam experience study. Women who served in Vietnam may have been exposed to a wide variety of potential health hazards that are probably not homogeneous. Studying all women Vietnam veterans as a group irrespective of their potential exposure could have reduced the chance for detecting any adverse health outcome related to a particular health hazard. In the past, a variety of approaches have been used to estimate herbicide exposure among Vietnam veterans: military service in Vietnam, branch of service, year and length of service in Vietnam, military occupation, location of unit in relation to aerial spray mission data and/ or ground spraying activity and biological marker such as dioxin (2,3,7,8-TCDD) in adipose tissue or serum. None of these approaches has been fully validated, and there is little consensus on what method should be used for retro- spectively reconstructing exposure levels for Vietnam veterans. A model (s) to characterize exposure of veterans to Agent Orange and other herbicides used in Vietnam is being developed under a contract with the National Academy of Science [IOM, 1999]. When a model is validated, it can be applied to this study in the future. A strength of the study is that virtually all women Vietnam veterans were studied and their entire reproductive period following their entry into Vietnam service was covered. The roster of 4,643 women veterans, developed and veried through a review of military personnel records for the study, is by far the most comprehensive and largest collection of women who served in Vietnam. Information on the primary exposure variable of interest, military service in Vietnam, is documented and is not dependent on self- reports. Another strength is the use of a sample of women non- Vietnam veterans as a comparison group. The health status of veterans is different from their civilian peers because of many factors including initial screening for military service, requirements to maintain a certain standard of physical well-being, and better access to medical care during and after military service [Rothberg et al., 1990; Kang and Bullman, 1996]. Furthermore, unlike their male counter- parts, all women in the military during Vietnam War volunteered to serve in the military. TABLEIV. Outcomes of 3,577Index Pregnancies Among 6,430 WomenVietnamVeterans and Non-VietnamVeterans Total number of events Percentage* Odds Ratio (95%C.I.) z Vietnam Non-Vietnam Outcomes (N 1665) (N 1912) Vietnam Non-Vietnam Crude Adjusted y Spontaneous Abortion or Stillbirth a 278 317 16.7 16.6 1.01 (0.84^1.21) 1.0 (0.82^1.21) Lowbirth weight ( <2,500 gm) b 78 97 6.3 6.6 0.95(0.69^1.31) 1.06 (0.76^1.48) Pre-termdelivery b 37 weeks or 8 months 112 125 9.1 8.6 1.07 (0.81^1.41) 1.18 (0.88^1.59) Birth defects b Likely 129 102 10.5 7.0 1.56 (1.18^2.07) 1.66(1.24^2.22) Moderate-to-Severe 95 85 7.7 5.8 1.36 (0.99^1.86) 1.46 (1.06^2.02) Infant death ( <1year) b 6 11 0.5 0.8 0.65(0.21^1.89) a Percent based ontotal number of index pregnancies by group (1,665 Vietnam,1,912 non-Vietnam). b Percent based ontotal number of live index singletonbirthsby group (1,229Vietnam,1,460 non-Vietnam). y Adjusted odds ratios (and95%confidence intervals) were derived froma logistic regressionmodel after adjustment for demographic ((age at conception, paternal age at conception (only birthdefect regression), education, race, marital status)) andmilitary characteristics (branch, rank, military nursing) and a number of factors associated with the pregnancy (smoking, drinking, average number of hours worked during pregnancy (except for birth defect regression), complications during pregnancy (except miscarriage or stillbirth regression)). Complication during pregnancy included toxemia, diabetes, highbloodpressure, bleedingor threatenedmiscarriage. z 95%Confidence interval. 452 Kang et al. The overall participation rate among the living and located women in the study (85%) was moderate. However, non-respondents did not differ signicantly from respon- dents with respect to demographic and military character- istics that may be associated with health outcomes. The limited health outcome data collected by mail from 366 non- respondents did not differ signicantly from the telephone interview respondents. Fetal loss was not found to be associated with Vietnam service. A separate analysis in this study for military nurses showed the same results. In several male Vietnam veterans' health studies, Vietnam veterans reported more frequently than non-Vietnam veterans that their spouses had miscarriages [CDC, 1988; Stellman et al., 1988]. Whether the difference in reported miscarriages among women veterans and spouses of male veterans is due to gender specic (male-mediated) reproductive outcomes or simply inaccurate recollection of events by males is not known. Vietnam service was signicantly associated with the risk of ``likely'' birth defects as well as more restricted ``moderate-to-severe'' birth defects. Separate analyses for nurses and non-nurse veterans showed similar results, although the magnitude of the risk was higher among non- nurse Vietnam veterans. The causes of most human congenital anomalies are unknown. A combination of genetic and environmental factors may contribute to 20 25% of anomalies [Moore and Persaud, 1998]. Over-reporting by women Vietnam veterans was considered an unlikely explanation for this nding for the following reasons. First, there has been widespread publicity concerning the risk of many types of cancers, adverse pregnancy outcomes (stillbirth, spontaneous abor- tion, low birth weight, pre-term births) and birth defects among offspring of Vietnam veterans. None of the a priori health outcomes selected for the study was found to be associated with Vietnam service, except for birth defects. If women Vietnam veterans were inuenced by publicity, over-reporting would have been expected for the other adverse health outcomes as well. Second, the reported rates of adverse pregnancy outcomes, spontaneous abortions and low birth weight infants in the Vietnam group are almost identical to rates in other studies [Armstrong et al., 1992; McDonald et al., 1992a, 1992b]. The prevalence of ``moderate-to-severe'' birth defects among the index babies of the non-Vietnam veterans (5.8%) was also consistent with about 6% prevalence of obvious major anomaly expected in live born infants within 2 years of birth [Moore and Persaud, 1998]. In this study, about 93% of ``moderate-to-severe'' birth defects was detected within 2 years of birth. The rate at birth was 2.1% (31 of the 1,460 index births). In a CDC Vietnam veteran study, the corresponding rate of ``major'' birth defects was 2.4% [Center for Disease Control, 1988]. Third, the effects of covariates (e.g., smoking, drinking) on adverse pregnancy outcomes observed in the study were in general agreement with those in other studies [Armstrong et al., 1992; McDonald et al., 1992a, 1992b]. Fourth, the medical record retrieval rate was poor; however, based on a small number of available records, positive documentation of maternally reported birth defects in babies was about 93%, and the documentation rates do not differ substantially between Vietnam veterans and non-Vietnam veterans. For the gynecological cancers, 99% of the self-reported breast cancer outcomes were documented in 146 medical records received, which was about 50% of the records requested. This may suggest that the ability to corroborate self-reported adverse birth outcomes depended more on the availability of the records than on Vietnam service status of women veterans. Finally, the proportions of birth defects reported by women veterans excluded for lack of apparent congenital defects are essentially the same between Vietnam and non- Vietnam veterans: Vietnam veterans, 15.7%; non-Vietnam veterans, 14.3%. 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