Vietnam veterans' risks for fathering babies born with serious structural birth defects were assessed using a case-control study. Case-group babies--those with serious structural defects--were born during 1968 through 1980 and registered by CDC's Metropolitan Atlanta Congenital Defects Program (MACDP). This program registers babies born with structural defects to women who are residents of the five-county metropolitan Atlanta area. To be included in the registry, a baby's defects must have been diagnosed during the first year of life and recorded on a hospital chart by a physician. The use of MACDP as the source of cases precluded analysis of other reproductive outcomes in the fathers or functional deficits, such as mental retardation, in the babies.

Control-group babies--those born without defects--were chosen from among 323,421 babies who were born in the same metropolitan area to resident mothers during the same period. They were frequency-matched to the case-group babies by race, year of birth, and hospital of birth. A total of 7,133 case-group babies and 4,246 control-group babies were eligible for the study. The decision to include fewer control-group babies than case-group babies was based on a review of the anticipated statistical power of the study.

In all, 4,929 mothers of case-group babies and 3,029 mothers of control-group babies completed interviews; fewer fathers completed interviews--3,977 from the case group and 2,426 from the control group. The major reason for parents' not participating in the study was that they could not be located after extensive searching.

Information about paternal military service in Vietnam was obtained during 1982 and 1983 through telephone interviews with the parents of the case- and control-group babies. Vietnam veteran fathers were asked if they believed they had been exposed to herbicides, such as Agent Orange. In addition, a five-level "Exposure Opportunity Index" (EOI) was defined based on activities that may have provided an opportunity for exposure to Agent Orange. Vietnam veteran fathers were given subjective scores by the staff of the Army Agent Orange Task Force reflecting their presumed opportunities for exposure to Agent Orange; the EOI scores were assigned on the basis of times and places of service in Vietnam and occupational duties. Scores were assigned without knowledge of the case/control status of the fathers. Both parents were questioned about a wide variety of other potential risk factors for birth defects. In addition, Vietnam veteran fathers were asked whether they had contracted malaria in Vietnam and whether they had taken malaria chemoprophylaxis there.

Defects occurring among the case-group babies were divided into 96 diagnostic categories for data analysis. Most of the 96 categories were comprised of specific defects, such as anencephaly, ventricular septal defect, and Down syndrome. Some categories were formed by grouping specific types of defects; one comprised all types of defects combined (i.e., the complete case series).

For each of these 96 categories, four hypotheses were tested: (1) whether veterans, excluding Vietnam veterans, were at different risk than nonveterans for fathering babies with birth defects; (2) whether Vietnam veterans were at different risk for fathering babies with birth defects; (3) whether Vietnam veterans who were judged by the Army Agent Orange Task Force to have had greater opportunities for exposure to Agent Orange had different risks for fathering babies with defects; and (4) whether Vietnam veterans who said during the interview that they had been exposed to herbicides, such as Agent Orange, were at different risk. Testing the first hypothesis determined whether, for the tests of the remaining three hypotheses, Vietnam veterans' risks should be compared with those of other veterans or with those of other veterans and nonveterans combined. Testing the second hypothesis was the main focus of this study.

Fathers of 428 case-group babies were Vietnam veterans; fathers of 268 control-group babies were Vietnam veterans. Fathers of 4,387 case-group babies and fathers of 2,699 control-group babies were not Vietnam veterans.

The estimated relative risk of Vietnam veterans' fathering babies with defects when all types of defects are combined was 0.97 (95% confidence limits 0.83-1.14). With few exceptions, the estimated relative risks of Vietnam veterans' fathering babies with defects in the remaining 95 defect groups were similar. Similarly, there was little evidence of different risks for Vietnam veterans who had been assigned higher Agent Orange EOI scores or for Vietnam veterans who had stated during the interview that they believed they had been exposed.

It was determined that, for most defect groups, Vietnam veterans' risks were neither higher nor lower than those of other fathers. In any large study in which multiple statistical tests are done, some exceptions are expected. Some of this study's exceptions are noted below. The estimated risks for fathering babies with spina bifida (imperfectly formed spinal cord) were higher for Vietnam veteran fathers who received higher EOI scores. Vietnam veterans who had higher scores had higher estimated risks for fathering babies with cleft lip with or without cleft palate. Vietnam veterans who received higher scores had higher estimated risks for fathering babies with defects classified as "Other Neoplasms," which include teratomas, neuroblastomas, hamartomas, dermoid cysts, lipomas, central nervous system tumors, Wilms tumor, and miscellaneous benign tumors. Vietnam veterans, in general, had a lower risk for fathering babies with cardiovascular defects classified as "complex" defects (two or more cardiovascular defects). Vietnam veterans who stated they had contracted malaria while in Vietnam had a higher estimated risk for fathering babies born with hypospadias.

No associations between risks of defects and use of malaria chemoprophylaxis were found. Reported by Chronic Diseases Div, Center for Environmental Health, CDC.

Editorial Note

Editorial Note: The most important conclusion to be drawn from this study is that the data collected contain no evidence to indicate that Vietnam veterans have had a greater risk than other men for fathering babies with defects when all types of serious structural birth defects are combined. This study cannot prove that some factor associated with service in Vietnam was or was not associated with the occurrence of rare types of defects, defects in the babies of selected individuals, or defects in the babies of small groups of veterans. The conclusion, however, that Vietnam veterans in general have not fathered, at higher rates than other men, babies with defects when all types of birth defects are combined is based on relatively strong evidence.

All parents are at some risk of having a baby born with birth defects. Because this risk is always there, it is called a "background risk." All men, whether Vietnam veterans or not, who father babies, have the same background risk--about two or three chances out of 100 that their babies will have serious structural birth defects.

Assessing Vietnam veterans' risks associated with exposure to Agent Orange is difficult. The measures of exposure that can be obtained today are imperfect, at best. The ability of Vietnam veterans to give valid reports of exposure is unknown, and the records used for the assignment of EOI scores were made for military purposes, not for health studies. This limitation makes it particularly difficult to assess whether the few statistically significant associations found in this study between defects and greater opportunity for exposure to Agent Orange are likely to reflect true effects of exposure or whether they are merely chance occurrences.

Moreover, the estimated relative risks for the exceptions presented here are rather low. These exceptions could conceivably be due to unmeasured confounding factors and may not be biologically significant. The same reasoning can be applied to the statistically significant association of malaria and hypospadias and the statistically significant association observed for babies with complex cardiovascular defects being fathered by Vietnam veterans.

A summary report of this study has recently been published (1), and a more comprehensive report is available from CDC. Copies of these reports can be obtained from CDC's Chronic Diseases Division, Center for Environmental Health.

Reference

1. Erickson JD, Mulinare J, McClain PW, et al. Vietnam veterans' risks for fathering babies with birth defects. JAMA 1984:252;903-12.

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