Correspondence

Birth Defects among Children of Persian Gulf War Veterans

N Engl J Med 1997; 337:1175-1176October 16, 1997

Article

To the Editor:

As coordinators of the national study of reproduction and children's health among Gulf War veterans in the United Kingdom, we were interested in the report by Cowan et al. (June 5 issue)1 on birth defects in similarly deployed U.S. service personnel. The results of this well conducted and clearly presented study are largely negative, but as the authors discuss, there are some limitations of the study design. Since the study included only live births, the true risk of congenital anomalies could not be assessed. Indeed, the fact that data on fetal death and termination of pregnancy because of fetal abnormalities were not included is apparent in the pattern of malformations reported. Serious and life-threatening conditions, such as central nervous system defects, had a low prevalence, since, it must be assumed, a large proportion resulted in late fetal death or were detected prenatally and led to the termination of the pregnancy. Thus, comparison of all identifiable birth defects in the offspring of Gulf War veterans with those in the offspring of nondeployed veterans, and whether there was an excess number of birth defects in the Gulf War group, remains unknown.

In addition, the study was restricted to veterans who were still in the service two to three years after the Gulf War. An estimated one third of U.S. veterans of the Gulf War were excluded from the study because they had left the service. As in many occupational-cohort studies, it is possible that the exposures and health outcomes among the veterans who left the armed forces are different from those among the veterans still in the service. It is extremely difficult and expensive to trace the people who have left the service, but without information on representative samples of all Gulf War veterans, the conclusion that there has been no increase in the risk of birth defects should be considered tentative. Because of our concern about the methodologic issues, we are attempting to survey all 52,000 Gulf War veterans in the United Kingdom and will be collecting data on all reproductive outcomes, including termination of pregnancies for medical reasons, fetal losses, and infertility.

Pat Doyle, Ph.D.
London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom

Eve Roman, Ph.D.
Centre for Clinical Epidemiology at Leeds University, Leeds LS2 9NG, United Kingdom

Noreen Maconochie, Ph.D.
London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom

1 References

1. 1

   Cowan DN, DeFraites RF, Gray GC, Goldenbaum MB, Wishik SM. The risk of birth defects among children of Persian Gulf War veterans. N Engl J Med 1997;336:1650-1656
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Doyle et al. recapitulate the limitations that we pointed out in our article, and we acknowledge that data on defects among aborted fetuses and stillbirths could not be included in the analysis. However, our study was not designed to document such data. Whatever the extent of prenatally diagnosed defects that resulted in elective termination of pregnancy or stillbirth, it is worth noting that there was no apparent adverse effect on live births in the original cohorts: as compared with the nondeployed veterans, the Gulf War veterans, both male and female, had slightly higher proportions of live births identified. The lack of information on the service members who had left the military was a concern, but it was not possible to identify births or birth defects among children of this group of veterans as part of our study. However, during the early portion of the follow-up period, when the effects of exposures during the war may have been greatest, the cohorts were largely intact. As we report in our article, we found no association between the risk of birth defects and the interval between the return from the Persian Gulf region and the birth of offspring.

The research on reproductive issues continues. A number of comprehensive, federally sponsored epidemiologic studies are in progress to examine these limitations. These large, controlled studies involve all types of Gulf War veterans: active and reserve personnel, as well as those who have left the military.1-3 The studies involve numerous research institutions, both federal and nonfederal.

The Naval Health Research Center in San Diego, California, is conducting two of these studies.1,2 In one study, investigators are obtaining postwar data on fetal deaths, infertility, miscarriage, and other difficult-to-quantify reproductive outcomes among 16,000 military couples. Another group of investigators is collaborating with seven states that maintain data on fetal deaths and conduct active surveillance for birth defects. These scientists will review data from an estimated 80,000 postwar pregnancies. These and several other reproductive studies are summarized in recent external review reports.1-3

David N. Cowan, Ph.D., M.P.H.
Office of the Assistant Secretary of Defense for Health Affairs, Falls Church, VA 22041

Gregory C. Gray, M.D., M.P.H.
Naval Health Research Center, San Diego, CA 92186

Robert F. DeFraites, M.D., M.P.H.
Office of the Surgeon General of the Army, Falls Church, VA 22041

3 References

1. 1

   Institute of Medicine. Health consequences of service during the Persian Gulf War: recommendations for research and information systems. Washington, D.C.: National Academy Press, 1996.
   

2. 2

   The Research Working Group of the Persian Gulf Veterans Coordinating Board. Annual report to Congress: federally sponsored research on Persian Gulf veterans' illnesses. Washington, D.C.: Department of Veterans Affairs, 1997.
   

3. 3

   Gulf War illnesses: improved monitoring of clinical progress and reexamination of research emphasis are needed. Washington, D.C.: General Accounting Office, 1997.
   

Citing Articles (3)

Citing Articles

1. 1

   Amy Iversen, Trudie Chalder, Simon Wessely. (2007) Gulf War Illness: Lessons from medically unexplained symptoms. Clinical Psychology Review 27:7, 842-854
   CrossRef

2. 2

   P. Doyle, N. Maconochie, M. Ryan. (2006) Reproductive health of Gulf War veterans. Philosophical Transactions of the Royal Society B: Biological Sciences 361:1468, 571-584
   CrossRef

3. 3

   Larry J. Dlugosz, William J. Hocter, Kevin S. Kaiser, James D. Knoke, Jack M. Heller, Nadia A. Hamid, Robert J. Reed, Kenneth S. Kendler, Gregory C. Gray. (1999) Risk Factors for Mental Disorder Hospitalization after the Persian Gulf War. Journal of Clinical Epidemiology 52:12, 1267-1278
   CrossRef