J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from
Journal of Medical Genetics 1988, 25, 819-826
Reproductive behaviour and consistent patterns of abnormality in offspring of Vietnam veterans
BARBARA FIELD AND CHARLES KERR From the Departments of Paediatrics (Westmead Centre) and Preventive and Social Medicine, University of Sydney, New South Wales, Australia.
SUMMARY In view of the persistent claim of Australian Vietnam veterans that their health and that of their children were adversely affected, aspects of reproductive behaviour and the distribution of disease and disability in family units were investigated in a sample of Tasmanian veterans and another group chosen for comparison of selected characteristics. One third of veterans reported serious health problems and their reproductive behaviour differed with more marital breakdowns, increased use of reproductive alternatives, and more complications of pregnancy. Patterns of malformation and disease among veterans' children involved predominantly the central nervous, skeletal, and cardiovascular systems. A similar pattern was detected on review of the three other major investigations on veterans' offspring in the USA and Australia. Although plausible mechanisms remain unknown, the evidence from all available studies supports a causal contribution to defects in veterans' children from a paternally mediated by copyright. genetic effect.
Vietnam veterans have claimed consistently that war theless, claims persist that veterans experienced service produced adverse effects on their health. serious reproductive problems. In Australia, the Symptoms they describe closely resemble those matter has not been clarified by a Royal Commis- observed in veterans of the first and second world sion which rejected any association between Viet- wars which are usually categorised as 'post-stress nam service and birth abnormalities and whose neurosis'. However, Vietnam veterans are unique in treatment of scientific evidence has been criticised.6 claiming that war service affected their reproductive We have examined two aspects which have not http://jmg.bmj.com/ patterns and health of their offspring. Such consequ- been previously addressed: the reproductive be- ences have been ascribed to the use in Vietnam of haviour of Vietnam veterans and the patterns of the defoliant, Agent Orange. However, no definite disease and disability among their children. association has been detected between exposure of military personnel and increase in congenital mal- Material and methods formations among their offspring. 1 Major
epidemiological investigations on the reproductive We did not consider that a formal case control study on September 24, 2021 by guest. Protected outcome of Vietnam veterans exposed to Agent of parents and children would provide sufficient Orange have been the US Air Force Ranch Hand information to address our research objectives. Project (Ranch Hand2),2 the Centre for Disease Accordingly we constructed an analytical approach Control Study (CDC), and the Australian Govern- centred on family structure and interactions. The ment's Veterans Study (AVS).4 Yet doubts remain study was based on information provided by families about the negative conclusions of these retrospec- living in Tasmania, an island state to the south of the tive studies and there are additional uncertainties Australian mainland, with an area of 68 300 km2 about the existence of male transmission of chemi- and a population of 390 000 in 1977. cally induced fetal detriment. We agree with Hatch A total of 1395 Tasmanian servicemen was offi- and Stein5 that epidemiological methods have cially listed as having served in Vietnam between reached the limits of resolving any consequences of 1965 and 1972; 705 men were conscripts and 690 defoliant exposure on reproductive events. Never- served in the regular army. The majority were stationed at Nui Dat in Phuoc Toy Province. The Received for publication 20 August 1987. term of duty was up to 12 months for conscripts and Revised version accepted for publication 7 March 1988. longer for some regular army personnel. 819 J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from
820 Barbara Field and Charles Kerr
Veterans were asked to nominate for comparative There were 281 families in the comparison group purposes a family living in the same suburb or area and they contained 726 children, 11 born before with a father of similar age to the veteran and 1965. There was no difference between the Vietnam containing children. This sample was required to veteran and comparison groups (table 1) in the identify any significant discrepancies in demo- following respects: fathers' and mothers' ages and graphic, social, reproductive, and general health social class, parental age at marriage or at the birth variables between the families of veterans and those of the first child, use of contraception, difficulty in of similarly aged men with children who lived in the conceiving, or the number of families reporting one same locality. Such descriptive data are not avail- or more miscarriages. Nor were differences detected able in Australia, and although it was recognised in the average number of children per family, the that the method of selecting a comparison group male/female ratio, and birth weight below 2500 g of may introduce a sample bias, this risk was minimised living children. However, the comparison families by the wide range of variables being investigated reported more occupational exposure to chemicals and the veteran being informed only in general (p<001) and a greater but less significant frequency terms about a study into 'family health' until he had of disease among relatives other than parents and nominated a comparison family. Interviews with 281 offspring (OO5>p>0.01). comparison families were completed. Some could The veterans' families reported more health not be contacted, others declined to provide in- problems in both father and mother, more marital formation. Some veterans did not know of a family breakdown and use of reproductive alternatives which met the requirements and others did not wish (adoption, AID, and IVF, not significant), and to nominate one. more frequent complications of pregnancy A questionnaire covering 22 aspects of reproduc- (p<0-01). The veterans' reproductive outcome con- tion and child health was completed on veteran and
comparison families by telephone interview. Addi- by copyright. tional information was obtained on veterans' service TABLE 1 Comparison ofcharacteristics of veteran and experience in Vietnam, family history of disease, non-veteran groups and the fathers' exposure to chemicals in civilian Parents Veteran Non-veteran life. (n=357) (n=281) All major medical problems and stillbirths in Father's age 37-3 37 NS children were confirmed or clarified by the attend- Mother's age 34-6 34-62 NS ing physician. Samples of veterans and members of Father's age at marriage 24-1 23-8 NS Mother's age at marriage 21.4 21.4 NS comparison families were examined to determine Father's age at birth whether each group was similar in basic characteris- of first child 26-5 26-0 NS Mother's age at birth http://jmg.bmj.com/ tics. of first child 23-7 23-6 NS Analysis of the type of health problems in Use of contraception 280 225 NS veterans' children was then carried out. Interactions Difficulty conceiving 89 43 NS Miscarriages 103 74 NS between parental characteristics and reproductive Average number of children 2-5 2-9 NS behaviour and the patterns of disease among Father's health problems 123 12 <0-01 Mother's health problems 18 2 <0-01 offspring were analysed by assessing the number of Marital breakdown 32 6 <0-01 families reporting an adverse outcome, the total Reproductive alternatives 5 1 NS Occupational exposure to number of children, and the first born children. chemicals 61 64 <0-01 on September 24, 2021 by guest. Protected Parental characteristics were examined in 47 fami- Family history of disease 63 66 <0-05 lies which contained 53 children who had died or Complications of pregnancy 141 46 <0-01 who were surviving with a major illness or malig- Children Veteran Non-veteran nancy. (832 cases) (726 cases) Fetal loss Definite 199 108 <0-01 Results Suspected 26 8 Adopted 17 2 NS (12 families) (1 family) A total of 436 veterans was located by telephone. Birth weight <2500 g 48 27 NS Twenty-three did not wish to participate, 18 had 37 Not known 13 Not known Deaths 33 11 <0-01 completed their families before service in Vietnam, Major disease 39 3 <0-01 38 had not had children, and 357 conceived one or Malignancy 4 0 NS Minor abnormality 137 41 <0-01 more children since completion of service, a total of Health problems 308 145 <0-01 832 children. Learning problems 83 20 <0-01 one or more Behaviour problems 65 12 <0-01 Thirteen of these families had Sensory and other problems 66 37 <0-01 children born before service, a total of 52 children. J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from
Reproductive behaviour and consistentpatterns ofabnormality in offspring of Vietnam veterans 821 tained a greater fetal loss, more stillbirths and chronic health problems, and learning, behavioural, neonatal, infant, and child deaths, and more chil- sensory, and other relatively minor problems dren with major and minor abnormalities, tumours, (p<001). Details are given in tables 2 and 3. Health TABLE 2 Deaths and major health problems in children problems of children from the non-veteran compan- of Vietnam veterans. son group are listed in tables 4 and 5. The average age of the 357 veterans with children Gestation Sex Year of was 37-3 years at the time of interview. The average death age of their wives was 34*6 years. Only 53 of the Stillbirths veterans were less than 20 years old on embarkation Intrauterine death 34 wk F 1970 Intrauterine death 31 wk F 1970 Hydrocephalus, Down's syndrome 41 wk F 1971 TABLE 3 Relatively minor health problems in children of Intrauterine death 22 wk F 1971 Vietnam veterans. Hydrocephalus 40 wk F 1972 Cerebral teratoma 40 wk F 1972 Sex Intrauterine death 26 wk Indeterminate 1973 Intrauterine death 32 wk F 1973 Neurological Intrauterine death 39 wk M 1973 Epilepsy 3M, IF Intrauterine death 26 wk M 1973 Epilepsy, cerebral palsy M Intrauterine death 40 wk M 1974 Epilepsy, short stature M Neonatal deaths Epilepsy, hyperactivity M F Cerebral haemorrhage I d M 1970 Clonus hyperreflexia, hyperactivity M Spina bifida, omphalocele 1 h Indeterminate 1971 Ataxia, 6th nerve palsy Prematurity, hydrops 15 h F 1972 Megalencephaly, learning problems M Prematurity 2 h F 1973 Muscular hypotonia M M Prematurity, septicaemia 4 d M 1974 Facial palsy Prematurity, hyaline membrane disease, intraventricular Skeletal Spina bifida occulta, ureteric reflux haemorrhage 1 d M 1974 2F Hydrocephalus, cleft palate, fused Deformity of chest wall and ribs by copyright. Pigeon chest M cervical vertebrae I h M 1977 Osgood-Schlatter disease M Cervical meningomyelocele Id M 1980 Congenital heart disease, joint Scheuermann disease M deformities 4d Ft 1975 Sacral dimple M Congenital heart disease, joint Hypoplastic jaw F deformities 3d Ft 1977 Palatal hypoplasia 2F Congenital heart disease, joint Talipes 10M, 14F deformities, cataract 14 d Ft 1984 Cardiac Cerebrocostomandibular syndrome 3 wk M 1983 Patent ductus arteriosus iF, 1M Infant deaths Pulmonary stenosis M Cot death 2 mth M 1979 Mitral valve prolapse F Congenital heart disease, scoliosis F Benign cardiac murmur 10M, 8F 3 mth 1973 http://jmg.bmj.com/ Down's syndrome, congenital heart disease, renal hypoplasia 4 mth M 1970 Skin Down's syndrome, congenital heart Haemangioma disease 6 mth F 1970 Mid-frontal M Upper lip F Child deaths Anus M Anoxic brain damage 20 mth F* 1972 Strawberry haemangioma Anoxic brain damage 7y F 1972 Face F Multiple cranial and vertebral Arm M malformations, epilepsy 5y Ft 1970 Vascular hamartoma M Werdnig-Hoffmann syndrome 1Iy Mt 1974 Multiple pigmented naevi 2M, IF Degenerative neurological disease 8y Ft 1971 Facial pigmentation 2F on September 24, 2021 by guest. Protected Drowning 5y M 1971 Ichthyosis M children Giant hairy naevus F Surviving Date of Lipoblastoma F birth Central nervous system Meningomyelocele, hydrocephalus F 1973 Other Cerebral arteriovenous Hemia malformation F 1972 Single inguinal 15M. IOF Porencephalic cyst F 1971 Bilateral inguinal 5M, IF Degenerative neurological disease Ft 1979 Umbilical IM, 3F 2M Thalamic tumour M 1975 Umbilical and inguinal Hydrocele, undescended testes 12M Skeletal Heterochromia iridis M Short femur, absent fibula M 1979 Enamel dysplasia M Amputation deformity of fingers F 1975 Breast deformity F Scoliosis (progressive) F 1969 Anus malformation M Darwinian tubercles 2M Other Cataracts M Mosaic Down's syndrome F 1975 Colour blindness 4M Diabetes F 1976 Strabismus 15M, 9F Ear deformity 2M *, t, t refer to sibs identified in three families. J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from
822 Barbara Field and Charles Kerr for Vietnam. Ninety were regular soldiers and 28 were non-commissioned officers, and 77 were served for more than 12 months. The majority were officers. Forty-three veterans embarked for Viet- in Vietnam for less than one year. Two hundred and nam during 1965 and 1966, 278 between 1967 and four men had duties in jungle areas, 130 were solely 1970, and 36 between 1971 and 1972. in administrative posts, and 23 had served in both situations. PARENTAL ILLNESS A total of 214 was based solely in Nui Dat (jungle Eighteen families reported current health problems base), 63 were in Saigon or Vung Tau (urban or in both parents. non-jungle areas), and the remaining 80 served in both situations. Fifty-three men were privates, 227 Veterans' health problems Nearly two-thirds (63.6%) of veterans reported that their current health was good and specified no TABLE 4 Deaths and major health problems in children of problems. Forty-one described their health as fair non-veterans. and 86 had serious health problems: two resulting from war injury, five malignancies (lymphoma, Gestation Sex Year of Hodgkin's disease, melanoma of the eye, and birth laryngeal and skin cancer), 18 psychiatric and nerve Stillbirths problems, 19 skin rashes, eight bowel and peptic Toxaemia 38 wk F 1966 Twin 40 wk F 1968 ulcer problems, one epilepsy, two hypertension, one Intrauterine death, brain haemorrhage, one heart attack, two back placental separation 28 wk F 1971 Intrauterine death, twin 28 wk F 1972 problems, one asthma, and one Reiter's syndrome. Anencephaly 36 wk M 1973 Twenty-five had multiple problems. Intrauterine death 28 wk M 1973 Cord around neck 38 wk M 1973
Mothers' health problems by copyright. Neonatal deaths Eighteen veterans' wives reported health problems Diabetic 36 wk M 1972 (three related to stress, two cervical cancer, and one Infant deaths each of cancer of the ovary, cancer of the stomach, Cot death 1 mth M 1970 Cot death 8 mth F 1980 diabetes, attempted suicide, and cerebral haemor- Gastroenteritis 8 mth F 1969 rhage). There were eight with multiple problems. Sudden infant death 9 wk M (adopted) 1976 Surviving children Complications of pregnancy Bilateral cleft lip/palate F 1979 One hundred and forty-one veterans' wives (39.5%) Stroke at 5 years F 1974 reported serious complications of pregnancy requir- ing specialist attention (toxaemia, antepartum http://jmg.bmj.com/ haemorrhage, threatened miscarriage, prolonged TABLE 5 Relatively minor health problems in children of labour, and prematurity). non-veterans. Marital status and sterility Sex Of thirty-eight veterans who had not had children, Hereditary spherocytosis (splenectomy) F 15 were not married and had planned not to have Short stature, heart murmur F F children and three had been severely wounded in on September 24, 2021 by guest. Protected Congenital anaemia Vietnam. With 23 childless married couples, two Petit mal M had elected not to have children and two were Epilepsy M Epilepsy M delaying the decision because of anxiety. Eleven veterans (3%) were stated to be sterile. Two wives Perthes' disease Hirschsprung's disease M were unable to have children and in six instances the Pyloric stenosis M reason was not known. Hernia Three hundred veterans had married after service Single SM in Vietnam. The average age at marriage was 24-1 Bilateral 2M years for the father and 21-4 years for the mother. Umbilical iF, IM Thirty-two (9%) had divorced and were in second Colour blindness iM marriages or de facto relationships. Talipes 7M, IF Strabismus 6M, 3F Hydrocele, undescended testes 6M Reproductive practice
cardiac murmur 6M, 2F A total of 289 veterans (81%) practised contracep- Benign tion before the birth of the first child. Eighty-nine J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from
Reproductive behaviour and consistentpatterns ofabnormality in offspring of Vietnam veterans 823 (25%) reported difficulty in conceiving. There were reported as having no health problems or learning or 19 adopted children in 12 families; three pregnancies behavioural difficulties. were achieved by AID and two by IVF. One hundred and three (30%) families reported Child mortality and health problems in surviving one or more miscarriages, three reported one children ectopic pregnancy, and one a hydatidiform mole. Three of 52 children born before the father's service The total number of miscarriages reported was 195 in Vietnam had died during the neonatal period definite and 26 suspected, that is, 21-3% of concep- (two because of prematurity, one with interstitial tions resulted in fetal loss before 20 weeks. pneumonitis). One surviving female was physically One hundred and seventy-five men had their first handicapped because of birth trauma. child within three years of return from service. The Thirty-three (4%) of 832 children born after the average age of the father at the birth of the first child father's service in Vietnam had died. Causes of was 26-5 years and of the mother 23*7 years. Natural death and other details are shown in table 2. children per family averaged 2-5, but for veterans Eleven offspring were stillborn, 12 died within participating in the study the average was 2-1. one month, and 10 between two months and eight years. The sex ratio was 17 females:14 males and CHARACTERISTICS OF VETERANS' CHILDREN two were of indeterminate sex. Prematurity was associated with death in 10 General features instances. An abnormality of the central nervous Years of birth ranged from 1966 to 1984 with a peak system was recorded in 16 cases. The skeleton and in 1974. Sixty percent of children were born between heart were affected in 10 instances. One death was 1972 and 1977. The total male/female ratio was the result of drowning and another was recorded as 1:1*02 (for first births it was 1-03:1). A birth weight cot death.
less than 2500 g was recorded in 48 surviving Reported health problems have been divided by copyright. children but was not known for an additional 37, 13 arbitrarily into major (life threatening or seriously of whom were premature and died. disabling) in table 2 and relatively minor in table 3. Nearly half (46%) of veterans' children were Five children had major central nervous system TABLE 6 Interaction between parental characteristics, reproduction, and children's health status.
Paternal Maternal Father Regular National Years Site Jungle Lowest Year ill ill <20 y army service of of duty rank embark- health health entry service service ation Vietnam http://jmg.bmj.com/ Parental characteristics Miscarriage - - - t - Problems conceiving ------Pregnancy complication t Contraception - § Stillbirths - - t ------Major disease - - t - - - t Malignancies - Total: Stillbirths - - t - - - - Major disease Malignancies on September 24, 2021 by guest. Protected Birth weight <2500 g - - t Minor malformations 1 t -- - - - 2 t 3 _ Health problems 1 t 2 t 3 t Behavioural problems 1 t t 2 t t 3 t t Learning problems 1 ------2 t 3 _ Sensory problems 1 2 3 *p 824 Barbara Field and Charles Kerr disease and seven were reported to have epilepsy of Discussion sufficient severity to warrant anticonvulsant ther- There is no dispute that the Vietnam war and the apy. Three children had a major skeletal deformity public response in Western countries which supplied and there were 57 instances of minor abnormalities armed forces were profoundly disturbing for some ranging from spina bifida occulta to flexion de- veterans. Relatively larger burdens of ill health were formity of the toe. Of 13 dermatological conditions, reported by Tasmanian veterans, their wives, and six were of vascular origin. Of four tumours, three offspring than a comparison group with similar were of embryonic cell origin (cerebral teratoma, demographic and social characteristics. It is not vascular hamartoma, and a recurrent lipoblas- clear how representative the Tasmanian group were toma). of all Australian Vietnam veterans. There seems There were 10 instances of congenital heart little likelihood that the sample was biased towards disease of which six proved fatal. They were over-ascertainment of those with personal or fami- atrioventricular canal defects (two), truncus arter- lial health problems because the veterans were iosus plus an aortic valve defect, coarctation of the selected from an official alphabetical list and not on aorta, and ventricular septal defect with patent grounds of ill health, concern about children, or ductus. Of the four who survived, two had patent membership of the Australian Vietnam Veterans' ductus and one each pulmonary valve stenosis and Association. On the other hand, the mode of mitral valve prolapse. selection, via telephone to those with a fixed Four instances of chromosomal defect were iden- residence, may have given some selective preference tified: two with trisomy 21, a ring C chromosome to those with a relatively greater socioeconomic and (all dead), and one female surviving with mosaic domestic stability. trisomy 21. One stillborn male with hydrocephalus This selection mode applied also to the compari- was said to resemble trisomy 21. son group who were unlikely to have had a biased Three hundred and eight children (37%) were distribution of problems although relatively minorby copyright. reported to have continuing health problems. abnormalities may have been under-represented Learning difficulties were frequent (83 children) as owing to lower anxiety levels among the group. were behavioural and emotional problems (65 chil- More than one-third of veterans in this study dren). reported that they had a serious health problem. A number of families had multiple problems. For Origins of this load remain unclear but to some example, in one family the parents had a stillborn extent may reflect the adverse consequences of female and female twins who both died after anoxic Vietnam service or some exposure to specific brain damage at birth. In another family, three harmful agents. Whatever the causes, health prob- females died at and 14 days lems of veterans affected the lifestyle, coping, and respectively three, four, http://jmg.bmj.com/ with skeletal and cardiac malformations. One veter- parenting skills in some families and indirectly an had a daughter with multiple malformations, contributed to illness or problems in children. epilepsy, and mental retardation who died aged five Reproductive practice was modified in several and a son from another marriage who died at 20 ways. Some men did not marry and reproduce either months with central nervous system disease des- by choice or because of ill health or anxiety and cribed as Werdnig-Hoffmann syndrome. Both his stress and the publicity surrounding them. Some wives had experienced multiple miscarriages. chose to adopt children or use alternative methods such as AID or IVF. on September 24, 2021 by guest. Protected INTERACTIONS BETWEEN PARENTAL Others married immediately on return and began CHARACTERISTICS, REPRODUCTION, AND their families against a background of high risk CHILDREN S HEALTH STATUS factors for perinatal loss, with superimposed factors Parental health problems correlated with reproduc- of combat stress, health and psychiatric problems, tive and child health problems (table 6) and most and socioeconomic difficulties. Marital breakdown strongly with minor malformations, health, be- was frequent. havioural, and learning problems in children, and Nearly half the men in this study had their first also with problems in conceiving and complications child within three years of return from Vietnam, of pregnancy. Cross correlations existed between although contraception was generally used before paternal ill health and maternal ill health, jungle the first child was conceived. Sterility in the male, duties in Vietnam, and regular army status. The difficulty in conceiving, and miscarriage within latter status, as opposed to being conscripted for families did not differ from non-veteran or Austra- national service, correlated with miscarriages in lian population rates. There was, however, a higher families and with major disease among offspring. proportion of conceptions which resulted in fetal Other associations are recorded in table 6. loss before 20 weeks. J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from Reproductive behaviour and consistentpatterns ofabnormality in offspring of Vietnam veterans 825 Births of veterans' children were clustered around Wilms' tumour, neuroblastoma, hepatoblastoma, a five year interval (1972 to 1977). This explains the and rhabdomyosarcoma). deficiency of veterans' children found by the authors The three previous investigations and the current of the Australian Study (AVS)4 because their one all yielded a similar pattern of abnormalities. selection of cases covered a longer period of time. Especially consistent were central nervous system Distinct patterns of severe malformations and defects, midline abnormalities, naevi, and tumours illness among veterans' children were detected in of embryonic cell origin. the present study. Three tissue systems were pre- Unfortunately, no data exist in Australia for dominantly affected: the central nervous, the skele- comparing the observed pattern of malformations in tal, and cardiovascular systems. Defects of neural veterans' offspring with that found in an age tube development or midline fusion7 and congenital matched sample of the general population. As to a heart lesions8 are held to originate from defective possible underlying mechanism, Fraser et allo have tissue migration or vascularisation. A common postulated a genetic embryonic influence to account characteristic of such malformations is that they for an aggregation of different fusion defects. Their carry a significant recurrence risk within families. conclusion was based on the association in a series of The aetiology is held to involve a polygenic compo- sibs of neural tube defects, cleft lip and palate, nent interacting with an environmental factor. tracheo-oesophageal fistula, exstrophy of the blad- Patterns of malformation comparable to those der, diaphragmatic hernia, and germ cell tumours.11 observed in the present study are evident also in the Especially with reference to Vietnam veterans, three other major studies. The US Ranch Hand there was speculation about the mechanisms by which investigation showed increased rates of neonatal exposure to toxins could give rise to abnormalities in death and physical handicap among 833 children of offspring.3 The relatively high frequency of abnor- American veterans.2 Spinal malformations, con- malities in the skull, brain, ribs, and vertebrae genital heart defects, and cleft lip and palate were detected in the present study resembles the pattern by copyright. prominent. in progeny produced by exposure of female rats The AVS study4 did not identify deaths of during pregnancy to toxic substances including offspring. Several diagnostic categories for condi- 2-4-5,T and trifluralin.12 Other possible mechan- tions found to be relatively frequent in the present isms could be germ cell mutation or some indirect study were excluded, among them multiple con- effect of increased susceptibility to environmental genital abnormalities, naevi, herniae, and tumours. mutagens.5 Whatever the mechanism, we believe In that study, 30 of the 127 veterans' children that the evidence in all available studies supports the classified as abnormal had spina bifida or central involvement of a paternally mediated genetic effect. nervous system abnormality. Failure to observe the consistent pattern of The CDC study of the US veterans' offspring malformations in previous studies stems from over- http://jmg.bmj.com/ concluded that risks for fathering babies with spina emphasis on statistical aspects, insufficient attention bifida were relatively greater for veterans who had to the nature of adverse effects in children, the higher exposure opportunities to Agent Orange.3 relatively small number of veterans studied within Although the question of exposure could not be the reproductive age group, and coverage of too directly examined in the present study, it should be long a time beyond the peak period of veteran child noted from table 6 that the group of Australian bearin,g years. We believe, along with Hatch and veterans with a relatively high potential for exposure that Stein, methodological barriers have prevented on September 24, 2021 by guest. Protected (regular soldiers on jungle duty) had a positive any definite conclusions on the statistical signifi- correlation with major diseases among their cance of associations between the health of veterans' offspring. Although no socioeconomic differences children and events during service in Vietnam. Nor could be detected between conscripts and regular is it likely that further retrospective studies would soldiers in the present study (nor are data available resolve the matter. from other sources), it cannot be excluded that We support the veterans' view that they and their regular soldiers could have other characteristics children are in certain ways different from others. which may predispose them towards more unfavour- Moreover, we think that the possibility of some able reproductive outcomes. American veterans adverse genetic event, reflected in patterns of with second higher exposure opportunity indices disease among veterans' offspring, warrants con- participating in the CDC study also had higher risks tinuing surveillence on the children and their for producing offspring with cleft lip (with or offspring. without cleft palate) and 'other neoplasms' (der- References moid and epidermoid cysts, teratoma, lipoma, Armstrong BK, Stanley FJ. Birth defects and Vietnam service. hamartoma, central nervous system tumours, Med J Aust 1984;140:388-9. J Med Genet: first published as 10.1136/jmg.25.12.819 on 1 December 1988. Downloaded from 826 Barbara Field and Charles Kerr 2 Lathrop GD, Wolfe WH, Albanese RA, Moynahan PM. Carter CO. Multifactorial inheritance revisited. Proceedings of Project Ranch Hand 11. An epidemiologic investigation ofhealth the Third International Conference on Congenital Malforma- effects in Air Force personnel following exposure to herbicides. tions, The Hague, Netherlands, 1969. New York: Excerpta San Antonio, Texas: Aerospace Medical Division, 1984. Medica Foundation, 1970: 227-32. Erickson JD, Mulinarei J, McClain PW, et al. Vietnam veterans' '° Fraser FC, Czeizel A, Hanson C. Increased frequency of neural risks for fathering babies with birth defects. JAMA tube defects in sibs of children with other malformations. Lancet 1984;252:903-12. 1982;ii: 144-5. 4 Donovan JW, Adena MA, Rose G, Batistutta D. Case control Birch M. Anencephaly in stillborn sibs of children with germ cell study of congenital anomalies and Vietnam service. Canberra: tumours. Lancet 1980;i:1257. Australian Government Publishing Services, 1983. 12 Beck SC. Assessment of adult skeletons to detect prenatal Hatch MC, Stein ZA. Agent Orange and risks to reproduction. exposure to 2-4-5,T or trifluralin in mice. Teratology The limits of epidemiology. Teratogenesis Carcinog Mutagen 1981 ;23:33-55. 1986;6:185-202. 6 Humphrey GF. Scientists and Royal Commissions. Search 1986;17:63-4. Correspondence and requests for reprints to Profes- 7Opitz J, Gilbert EF. CNS anomalies and the midline as a developmental field. Am J Med Genet 1982;12:443-55. sor C B Kerr, Department of Public Health, 8Clark E. Mechanisms in the pathogenesis of congenital heart University of Sydney, Sydney, NSW 2006, Austra- defects. Proc Greenwood Genetic Center 1985;4:80. lia. by copyright. http://jmg.bmj.com/ on September 24, 2021 by guest. Protected