Healthcare utilization and mortality among veterans of the Gulf War

The authors conducted an extensive search for published works concerning healthcare utilization and mortality among Gulf War veterans of the Coalition forces who served during the 1990-1991 Gulf War. Reports concerning the health experience of US, UK, Canadian, Saudi and Australian veterans were reviewed. This report summarizes 15 years of observations and research in four categories: Gulf War veteran healthcare registry studies, hospitalization studies, outpatient studies and mortality studies. A total of 149728 (19.8%) of 756373 US, UK, Canadian and Australian Gulf War veterans received health registry evaluations revealing a vast number of symptoms and clinical conditions but no suggestion that a new unique illness was associated with service during the Gulf War. Additionally, no Gulf War exposure was uniquely implicated as a cause for post-war morbidity. Numerous large, controlled studies of US Gulf War veterans' hospitalizations, often involving more than a million veterans, have been conducted. They revealed an increased post-war risk for mental health diagnoses, multi-symptom conditions and musculoskeletal disorders. Again, these data failed to demonstrate that Gulf War veterans suffered from a unique Gulf War-related illness. The sparsely available ambulatory care reports documented that respiratory and gastrointestinal complaints were quite common during deployment. Using perhaps the most reliable data, controlled mortality studies have revealed that Gulf War veterans were at increased risk of injuries, especially those due to vehicular accidents. In general, healthcare utilization data are now exhausted. These findings have now been incorporated into preventive measures in support of current military forces. With a few diagnostic exceptions such as amyotrophic lateral sclerosis, mental disorders and cancer, it now seems time to cease examining Gulf War veteran morbidity and to direct future research efforts to preventing illness among current and future military personnel.     

The challenges of exposure assessment in health studies of Gulf War veterans

A variety of exposures have been investigated in Gulf War veterans' health studies. These have most commonly been by self-report in a postal questionnaire but modelling and bio-monitoring have also been employed. Exposure assessment is difficult to do well in studies of any workplace environment. It is made more difficult in Gulf War studies where there are a number and variety of possible exposures, no agreed metrics for individual exposures and few contemporary records associating the exposure with an individual. In some studies, the exposure assessment was carried out some years after the war and in the context of media interest. Several studies have examined different ways to test the accuracy of exposure reporting in Gulf War cohorts. There is some evidence from Gulf War studies that self-reported exposures were subject to recall bias but it is difficult to assess the extent. Occupational exposure-assessment methodology can provide insights into the exposure-assessment process and how to do it well. This is discussed in the context of the Gulf War studies. Alternative exposure-assessment methodologies are presented, although these may not be suitable for widespread use in veteran studies. Due to the poor quality of and accessibility of objective military exposure records, self-assessed exposure questionnaires are likely to remain the main instrument for assessing the exposure for a large number of veterans. If this is to be the case, then validation methods with more objective methods need to be included in future study designs.     

Birth prevalence and recurrence rates of neural tube defects in southern Alberta in 1970-81.

Given the observed variation in birth prevalence and recurrence rates of neural tube defects, it is important to obtain such data specific to a given locality for research and genetic counseling purposes. A review of hospital medical charts, the patient lists of the Medical Genetics and Myelomeningocele clinics at Alberta Children''s Hospital and data from the Canadian Congenital Anomalies Surveillance System revealed the annual birth prevalence rate of neural tube defects in southern Alberta in 1970-81 to be 1.62/1000 total births. This figure suggests southern Alberta to be a low-frequency area. There was no significant variation in the annual rates of spina bifida, encephalocele or all neural tube defects combined over the study period. A significant linear decline in the frequency of births of anencephalic infants, however, was noted (p = 0.025). Information on the total reproductive history of the mothers revealed that the empiric risk of recurrence of a neural tube defect was 2.2%, and the risk to all siblings was estimated to be 2.3%. In future prevalence studies multiple sources of case ascertainment should be used, including data on pregnancies terminated because of a fetal neural tube defect.     

Infertility among male UK veterans of the 1990-1 Gulf war: reproductive cohort study

Objectives To examine the hypothesis that, theoretically at least, exposure to toxicants of the type present in the Gulf war could affect spermatogenesis, which might be observed as increased levels of infertility.Design Retrospective reproductive cohort analysis.Setting Male UK Gulf war veterans and matched comparison group of non-deployed servicemen, surveyed by postal questionnaire.Participants 42 818 completed questionnaires were returned, representing response rates of 53% for Gulf veterans and 42% for non-Gulf veterans; 10 465 Gulf veterans and 7376 non-Gulf veterans reported fathering or trying to father pregnancies after the Gulf war.Main outcome measures Failure to achieve conceptions (type I infertility) or live births (type II infertility) after the Gulf war, having tried for at least a year and consulted a doctor; time to conception among pregnancies fathered by men not reporting fertility problems.Results Risk of reported infertility was higher among Gulf war veterans than among non-Gulf veterans (odds ratio for type I infertility 1.41, 95% confidence interval 1.05 to 1.89; type II 1.50, 1.18 to 1.89). This small effect was constant over time since the war and was observed whether or not the men had fathered pregnancies before the war. Results were similar when analyses were restricted to clinically confirmed diagnoses. Pregnancies fathered by Gulf veterans not reporting fertility problems also took longer to conceive (odds ratio for > 1 year 1.18, 1.04 to 1.34).Conclusions We found some evidence of an association between Gulf war service and reported infertility. Pregnancies fathered by Gulf veterans with no fertility problems also reportedly took longer to conceive.     

Birth defects in infants of diabetic mothers: A historical review

Background: Over the past 80+ years, outcomes in diabetic pregnancies have improved remarkably. In the preinsulin era, both fetal and maternal deaths were common. After insulin was discovered, the likelihood of a successful pregnancy increased, but fetal losses were still common. By the end of the 20th century, a number of medical advances allowed women with diabetes to reasonably expect to deliver a healthy infant, although the perinatal mortality rate was twice that reported for women without diabetes. The excess losses were attributable to birth defects.Objective: The purpose of this article was to use the recognition of, and approach to, birth defects in infants of mothers with diabetes as an example of the gradual evolution of clinical care and research from the dawn of the insulin era to the age of molecular biology.Methods: Archival material from the Joslin Diabetes Center (Boston, Massachusetts) was used to document the early history of the problem. Particular emphasis was given to the writings of Priscilla White, MD. Illustrative articles, especially those cited in textbooks, were chosen to highlight developments over the mid to late 20th century.Results: Before the discovery of insulin, maternal death was the primary issue in diabetic pregnancies. With the availability of insulin, the maternal death rate decreased sharply and fetal deaths became the preeminent problem. Many of these losses were due to iatrogenic prematurity complicated by respiratory distress syndrome; early deliveries avoided stillbirth in late gestation. In the last quarter of the 20th century, methods of assessing fetal well-being and lung maturity allowed pregnancies to proceed nearer to term. Birth defects then emerged as the leading cause of perinatal mortality. The risk for birth defects was linked to diabetes control early in the first trimester, and the mechanism was related to free oxygen radicals from excess glucose. Preconception programs have been shown to reduce the risk.Conclusions: Clinical advances often are not dramatic. This article illustrates how resolution of a problem may evolve incrementally over decades. Birth defects, once unnoticed in infants of diabetic mothers, became a leading concern. It is now possible to reduce the incidence of these defects to levels seen in nondiabetic pregnancies. Epigenetic mechanisms responsible for malformations have been elucidated.     

Use of prenatal diagnostic procedures in pregnancies affected with birth defects, Hawaii, 1986-2002

BACKGROUND: Information on the utilization of prenatal ultrasound (US), amniocentesis (AC), and chorionic villus sampling (CVS) in pregnancies affected by birth defects in the United States is limited. The intent of this study was to report on the utilization of these procedures in Hawaii. METHODS: Cases were all infants and fetuses of any pregnancy outcome with birth defects, included in a Hawaii birth defects registry, and delivered during 1986-2002. The rates of prenatal US, AC/CVS, and prenatal diagnosis were calculated. RESULTS: Prenatal US was performed in 76% of the cases and AC/CVS in 14% of the cases. Prenatal diagnosis of a birth defect was made in 16% of the cases. The prenatal US, AC/CVS, and prenatal diagnosis rates in 1998-2002 were 1.5, 1.5, and 1.7 times the rates in 1986-1991, respectively. Among all birth defects, the AC/CVS rate for women aged <35 years was 7% and for women aged > or =35 years was 48%. Among chromosomal abnormalities, the AC/CVS rate for women aged <35 years was 36% and for women aged > or =35 years was 66%. CONCLUSIONS: Only a fraction of the Hawaii birth defects cases was prenatally diagnosed. The rates for prenatal US, AC/CVS, and prenatal diagnosis among pregnancies affected by birth defects were higher in 1998-2002 than in 1986-1991. AC/CVS rates were lower for maternal age <35 years.     

Patterns of chromosomal translocations identified by a birth defects registry, Hawaii, 1986-2000

Using a birth defects registry, this investigation examined the distribution of translocations by type of translocation, chromosomes involved in the translocation, pregnancy outcome, method of diagnosis, inheritance, and diagnosis of major structural birth defects. A total of 121 cases were identified through a statewide population-based birth defects registry. The translocations were reciprocal in 89 (73.6%) cases, Robertsonian in 32 (26.4%) cases, balanced in 86 (71.1%) cases, and unbalanced in 35 (28.9%) cases. Live births accounted for 76 (88.4%) of balanced translocations and 22 (62.9%) of unbalanced translocations. Diagnosis was made by amniocentesis or chorionic villus sampling in 72 (83.7%) of balanced translocations and 11 (31.4%) of unbalanced translocations. Of cases of known inheritance, the translocation was of maternal origin in 38 (46.3%) cases, paternal origin in 25 (30.5%) cases, and de novo in 19 (23.2%) cases. Major structural birth defects were diagnosed in 17 (19.8%) of balanced translocations and 20 (57.1%) of unbalanced translocations. Translocations were more likely to be reciprocal, balanced, and of maternal origin. Infants and fetuses with unbalanced translocations were less likely to be live births and diagnosed by amniocentesis or chorionic villus sampling and more likely to be diagnosed with major structural birth defects.     

Long term depleted uranium exposure in Gulf War I veterans does not cause elevated numbers of micronuclei in peripheral blood lymphocytes

Depleted uranium (DU) is a high density heavy metal that has been used in military munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic. Long term exposure can cause adverse health effects. This study assessed genotoxic effects in DU exposed Gulf War I veterans as a function of uranium (U) body burden. Levels of urine U were used to categorize the cohort into low and high exposure groups. Exposure to DU occurred during friendly fire incidents in 1991 involving DU munitions resulting in inhalation and ingestion exposure to small particles of DU and soft tissue DU fragments from traumatic injuries. All of these Veterans are enrolled in a long term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 36-59 years, then cultured and evaluated for micronuclei (MN) using the cytokinesis block method. The participants were divided into two exposure groups, low and high, based on their mean urine uranium (uU) concentrations. Poisson regression analyses with mean urine U concentrations, current smoking, X-rays in the past year and donor age as dependent variables revealed no significant relationships with MN frequencies. Our results indicate that on-going systemic exposure to DU occurring in Gulf War I Veterans with DU embedded fragments does not induce significant increases in MN in peripheral blood lymphocytes compared to MN frequencies in Veterans with normal U body burdens.     

Racial differences in infant mortality attributable to birth defects in the United States, 1989-2002

BACKGROUND: The objective is to study racial differences in infant mortality attributable to birth defects (IMBD) in the United States. METHODS: We analyzed 1989-1991 and 1995-2002 linked birth/death files for trends and racial differences in IMBD by selected categories of birth defects for infants of non-Hispanic white, non-Hispanic black, and Hispanic mothers. RESULTS: In 1989-2002, the IMBD rates declined. However, the decline in postneonatal mortality attributable to birth defects (PMBD) rate was significantly slower than that of overall postneonatal mortality. The adjusted rate ratio for non-Hispanic black and Hispanic versus non-Hispanic white for neonatal mortality attributable to birth defects (NMBD) remained unchanged from 1989-1991 through 2000-2002. For PMBD, it increased from 0.97 (95% confidence interval [CI], 0.90-1.13) in 1989-1991 to 1.12 (95% CI, 1.04-1.21) in 2001-2002 and from 1.08 (95% CI, 1.00-1.16) to 1.18 (95% CI, 1.10-1.27) for non-Hispanic black and Hispanic, respectively. Infant mortality due to cardiovascular and central nervous system defects were the main contributors to the increased racial disparities in PMBD rates. CONCLUSIONS: The disparity in PMBD between infants of non-Hispanic black and Hispanic mothers and infants of non-Hispanic white mothers increased significantly from 1989-1991 to 2000-2002. Further studies are needed to assess the extent to which delays in care or lack of access to care for infants with birth defects might be contributing to the disparity in IMBD.