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Agent Orange Pregnancy Outcomes Among Us Women Vietnam Veterans1097-0274(200010)38!4!447--AID-AJIM11-3.0

Agent Orange Pregnancy Outcomes Among Us Women Vietnam Veterans1097-0274(200010)38!4!447--AID-AJIM11-3.0

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Published by: Children Of Vietnam Veterans Health Alliance on Aug 01, 2012
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AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 38:447±454 (2000)
Pregnancy Outcomes Among U.S.Women Vietnam Veterans
Han K. Kang,
DrPH
,
1
Ã
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 1965±1975 Vietnam War, there has been persistent concernthat 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 Vietnamveterans with those of 4,140 contemporary women veterans who were not deployed toVietnam. As a measure of association, we calculated odds ratios (OR) and 95%con®dence 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 signi®cant association between military service inVietnam 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 signi®cantly elevated among Vietnam veterans (adjusted OR
1.46,95% CI 
1.06±2.02).
Conclusion
The risk of birth defects among index children was signi®cantly associated with mother's military service in Vietnam.
Am. J. Ind. Med. 38:447±454, 2000.
Published 2000 Wiley-Liss, Inc.
y
 KEY WORDS: women veterans; Vietnam war; pregnancy outcomes
INTRODUCTION
The possibility of long-term health effects includingadverse reproductive health outcomes resulting frommilitary service in Vietnam has been a subject of researchinterest in the United States over the past two decades [CDCVietnam Experience Study, 1988; Stellman et al., 1988].The U.S. Congress, responding to concerns of many womenVietnam veterans, legislatively mandated a comprehensivehealth study of women Vietnam veterans. This mandate ledto three separate but related epidemiologic studies of women Vietnam era veterans: (1) post-Vietnam servicemortality follow-up; (2) assessment of psychologic healthoutcomes; and (3) reproductive health outcomes. Resultsof the ®rst two studies were published or submitted toCongress previously [Thomas et al., 1991; Dalager andKang, 1996]. The present report deals with the thirdstudy.The studies of reproductive outcomes among maleveterans have been mostly negative in that service inVietnam was not associated with the risk of fathering a childwith birth defects, spontaneous abortion, stillbirth orneonatal death [Erickson et al., 1984; Donovan et al.,1984; Aschengrau and Monson, 1989, 1990]. However, inthe recent ``Ranch Hand study'', neural tube defects (spinabi®da, 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 ofVeteransAffairs,Washington,DC 20036-3406.
2
JohnsHopkinsSchool of Hygiene andPublic Health,Baltimore,MarylandContractgrantsponsor:Medical Research Service,Office of Researchand Development,DepartmentofVeteransAffairs.*Correspondenceto:Dr.HanK.Kang,EnvironmentalEpidemiologyService,DepartmentofVeterans Affairs, 1120 20th Street N.W., Suite 950,Washington, D.C. 20036-3406. E-mail:han.kang
@
mail.va.govAccepted 23May 2000
Published 2000 Wiley-Liss, Inc.
y
This article is a USGovernment work and, as such, isin the public domainintheUnitedStatesofAmerica.
 
herbicides in Vietnam, while none was observed amongchildren of control veterans [Wolfe et al., 1995]. Further-more, when the CDC birth defects study was reanalyzedusing the exposure opportunity index based upon interviewdata, the risk of spina bi®da was signi®cantly associatedwith the highest estimated level of Agent Orange exposure[Erickson et al., 1984]. Based on these data and others, anInstitute of Medicine panel suggested an associationbetween herbicide exposure in Vietnam and an increasedrisk of spina bi®da in children [IOM, 1996].Although results of studies of male Vietnam veteransare potentially useful in assessing health consequences of Vietnam service for women, a further study of gender-speci®c health outcomes for women was desired. Maternalexposures to toxicants are more directly associated withadverse pregnancy outcomes, while evidence for the effectsof paternal exposure on pregnancy outcomes is very limitedand indirect [Of®ce of Technology Assessment, 1985;Moore and Persaud, 1998].Many potential risk factors for abnormal reproductiveoutcomes existed in Vietnam for women veterans, includingpsychological stresses of war, various infections, substanceabuse, and Agent Orange contaminated with dioxin [Bakeret al., 1989; Bates et al., 1990; Jordan et al., 1991]. Otherpotential risk factors associated with military hospitalnursing 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 womenveterans, comparing the pregnancy outcomes of 4,140women Vietnam veterans with those of 4,140 non-Vietnamveterans in the military during the same era. Due todif®culty in identifying a large number of women exposedto any particular aspect of Vietnam service with any degreeof certainty, the study was a ``Vietnam experience'' type of study rather than of speci®c exposures.
MATERIAL AND METHODSStudy Subjects
The U.S. Army and Joint Services EnvironmentalSupport Group compiled manually a list of Army womenveterans who served in Vietnam. The Air Force provided acomputer listing of all Air Force women known to haveserved in Vietnam, as did the Navy and Marine Corps. Atotal of 5,230 names were compiled as potential Vietnamveteran study subjects. Military personnel records of thesewomen were retrieved from various locations and theirmilitary service data were extracted. Women Vietnamveterans for this study were de®ned as those women in theU.S. Military whose permanent tour of duty includedservice in Vietnam during the period from July 4, 1965through March 28, 1973, a period of signi®cant U.S.military involvement in Vietnam. After the record review,4,643 women met the eligibility criteria; of these 4,390women were found alive as of January 1, 1992.Women non-Vietnam veterans for the study werede®ned as those women assigned to a military unit in theU.S. during the Vietnam War and whose tour of duty did notinclude service in Vietnam. Potential control subjects fromeach branch of service were selected using the sameprocedures as for Vietnam veterans. A pool of 6,657 womenwere eligible for controls; of these 4,390 women wererandomly selected among the living members of this pool asof January 1, 1992 [SAS, 1990].To determine the feasibility of the present study, weconducted a pilot study on 500 of these women (250Vietnam veterans and 250 non-Vietnam controls), leaving8,280 women (4,140 Vietnam and 4,140 non-Vietnam)available for the study.
Survey Methods
Instrument 
A structured health questionnaire was administeredusing a computer-assisted telephone interview softwarepackage to obtain information concerning demographicbackground, general health, lifestyle, menstrual history,pregnancy history, pregnancy outcomes, military experienceincluding nursing occupation and combat exposure. Foreach 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 8,280veterans were ®rst passed through the Internal RevenueService records and VA's Bene®ciary Identi®cation RecordsLocator Subsystem. Those not located were also searchedin the Defense Manpower Data Center records. Severalnationwide commercial databases such as Telematch, TRW/ Experian, and Equifax proprietary databases, and nationaltelephone directory CD-ROMs were searched for newaddresses and telephone numbers. State nursing boardsand nursing associations were also contacted for newaddresses because most women veterans serving duringthe Vietnam era were nurses.
Outcome Assessment 
To satisfy the basic statistical requirement of indepen-dence of observations, i.e., one pregnancy per woman, anindex pregnancy was identi®ed for each woman. For theVietnam veterans, it was de®ned as the ®rst pregnancy after
448 Kang et al.
 
entrance date to Vietnam service. If the Vietnam experiencedid 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 de®ned as the ®rstpregnancy after July 4, 1965, the starting date for the U.S.ground troops involvement in Vietnam, or the entrance dateinto military service, whichever was later.The outcomes studied and their de®nitions are asfollows: Fetal loss including spontaneous abortion andstillbirth was de®ned as any loss of fetus regardless of gestational age; a low birth weight infant was de®ned as ababy born alive and weighing less than 2500g or 5 pounds 8ounces; pre-term delivery was de®ned as a baby born alivewith a gestational age of 37 weeks or less or 8 months orless, if reported in months; ``likely'' birth defects werede®ned as congenital anomalies and included structural,functional, metabolic or hereditary defects.For this study in which the index pregnancy would haveoccurred as far back as 30 years,therelevantmedical recordswere very dif®cult to retrieve. As an alternative method,maternally reported data on children with any reporteddefects were reviewed by a pediatric epidemiologist whileblinded regarding Vietnam service status of mothers. Thesedata included maternal description of defect(s); birth weight;gestational length; any history (yes/no) of surgery, medicaltreatment, or functional limitations due to defect; age atdiagnosis; and if deceased, age and cause of death.After the review, the reported birth defects weregrouped hierarchically into one of 11 groups as follows:likely congenital birth defects, groups 7; unlikelycongenital birth defects, groups 11 (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 characterizedby the serious nature of the diagnosis (if explicitly stated bythe mother), or conditions having any history of surgical ormedical treatment, functional impairment, or death from thedefect 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 likelycongenital birth defects with ``moderate-to-severe'' condi-tions. The type of medical records sought were furtherrestricted to hospital records because of the dif®cultylocating a private physician or clinic in practice as far back as three decades ago. Womenveterans were contacted againto gain consent for obtaining medical records, and to gatherspeci®c information about health care providers. Uponreceipt of the signed release form from the mother or theadult child, a request for the records was sent to eachhospital.
Statistical Analysis
As a measure of association for dichotomous outcomes,the odds ratio (OR) and 95% con®dence interval (CI) werecalculated using a multivariate logistic regression modelwith adjustment for covariates [Selvin, 1991]. Analyseswere based on self-reported interview data. Logistic
TABLEI.
DescriptionofGenericClassesofReportedBirthDefects
Group Description
Likelybirthdefects1. Chromosomalabnormality Abnormalchromosomenumberorsize2. Multipleanomalies Twoormoredefectsindifferentorgansystemsexceptidentifiableheritablesyndromes3. Isolatedanomaly Oneormoredefectswithinsameorgansystem4. Congenitalneoplasms
a
Earlychildhoodtumors5. Heritablegeneticdiseases/syndromes Identifiablesingle-alleledisorders(dominant,recessive,orsex-linked)6. Unspecifiedheartabnormality Undescribedisolatedheartdefectsormumurs7. Poorlyspecifiednon-cardiacdefect Defect(s)withinadequatedescriptiontoclassifyfurtherUnlikelybirthdefects8. Developmentaldisorders Learningandattentiondeficits,orepilepsydiagnosedbeyondinfancy9. Perinatalcomplications Alldelivery,newborn,orprematurityrelatedconditions10. Miscellaneouspediatricillnesses Foodallergy,asthma,etc11. Notclassifiable Nodescriptionofdefect,or``unknown''
a
Someneoplasmsaregeneticdefects.
Women Vietnam Veterans' Pregnancy Outcomes 449

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