Gulf War and Health Volume 11: Generational Health Effects of Serving in the Gulf War (2018) / Chapter Skim
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Veterans who served in the 1990–1991 Gulf War, Post-9/11, and Vietnam conflicts, among others, were subject to a variety of exposures during deployment that have been associated with health effects in veterans and other exposed populations. In 1998, in response to the health concerns of Gulf War veterans, Congress passed two laws: P.L.
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The report also focuses on the assessment of the available evidence on the reproductive effects related to exposures that may have occurred during the Gulf War and Post-9/11conflicts as well as on the health of veterans' children. Finally, the report examines the mechanisms, methods, and feasibility issues of potential research approaches for determining if there are health effects in the children or grandchildren of veterans of any era related to their parents' or grandparents' deployment exposures.
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; • Multigenerational effects of the toxicants of concern in various animal species, if such effects have not already been well-established; • The feasibility of conducting a long-term epidemiologic study to assess the generational health effects of Veterans and the resources (technological, logistical) that would need to be available to support such research; • Develop a framework for monitoring and studying generational health effects over time, including post-exposure assessments, initial screening of Veterans and their descen dants, the frequency and duration of such screenings; • Based upon a careful assessment of available laboratory technologies, establish a pro cess for what is to be included in the screening including biomarkers and early symptoms; • The number of Veterans and their descendants who should be part of such a study(ies)
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A few studies in veterans were specific to deployment exposures such as studies of the effects of DU. Studies were categorized as reporting reproductive (including adverse pregnancy outcomes)
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Epigenetic and genetic effects, including • Markers of DNA oxidative stress; • DNA methylation in maternal blood, umbilical cord blood, placenta, or peripheral blood lymphocytes, sperm; • mRNA expression; • Histone modifications; and • Mitochondrial DNA content in umbilical cord blood. Inadequate/Insufficient Evidence to Determine Whether an Association Exists The available studies are of insufficient quantity, quality, validity, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association between an exposure and a reproductive or developmental effect in humans.
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Deployment-related exposures included deployment itself, vaccines, chemical warfare agents, infectious diseases, DU, hexavalent chromium, and PB. The committee's conclusions for each toxicant of concern are listed in Box S-3 (reproductive effects, adverse pregnancy outcomes, and developmental effects)
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HEALTH MONITORING AND RESEARCH PROGRAM To help determine if veterans' descendants are at risk for health effects resulting from the veterans' exposures during deployment, the committee has proposed creating a health monitoring and research program (HMRP) with three arms: monitoring the health of veterans and their descendants over time; epidemiologic studies to examine groups of veterans and their descendants for health outcomes of concern; and basic and translational research to help address data and knowledge gaps.
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8 GULF WAR AND HEALTH BOX S-3 Summary of Conclusions Regarding Categories of Association Between Gulf War Deployment Exposures and Reproductive Effects, Adverse Pregnancy Outcomes, or Developmental Effects Sufficient Evidence of a Causal Relationship • None Sufficient Evidence of an Association • Leishmaniasis infection during pregnancy and adverse pregnancy outcomes • Hexavalent chromium and reproductive effects in men • Prenatal exposure to hexavalent chromium and developmental effects • Prenatal exposure to organophosphate pesticides and neurodevelopmental effects • Carbamate pesticides and reproductive effects in men • Prenatal exposure to particulate matter and adverse pregnancy outcomes -- low birth weight and preterm birth • Prenatal exposure to benzene and childhood leukemia Limited/Suggestive Evidence of an Association • Sulfur mustard and reproductive effects in men • Hexavalent chromium and adverse pregnancy outcomes • Organophosphate pesticides and reproductive effects in men • Pyrethroid pesticides and reproductive effects in men • Lindane and reproductive effects in women • Prenatal exposure to pyrethroid pesticides and developmental effects • Prenatal exposure to particulate matter and pregnancy-induced hypertensive disorders • Prenatal exposure to particulate matter and respiratory or neurodevelopmental effects in children • Polycyclic aromatic hydrocarbons and reproductive effects in men • Prenatal exposure to polycyclic aromatic hydrocarbons and adverse birth outcomes -- low birth weight and preterm birth, or developmental effects -- birth defects, childhood cancer, neurodevel opmental effects, and respiratory outcomes in childhood • Benzene and reproductive effects in men • Trichloroethylene and reproductive effects in men, or adverse pregnancy outcomes • Prenatal exposure to trichloroethylene and developmental effects • Prenatal exposure to perchloroethylene and developmental effects • Glycols and glycol ethers and reproductive effects in men • Prenatal exposure to glycols or glycol ethers and birth defects
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• Polycyclic aromatic hydrocarbons and reproductive effects in women • Prenatal polycyclic aromatic hydrocarbons exposure and other developmental effects (other than birth defects, childhood cancer, neurodevelopmental effects, and respiratory outcomes in childhood) • Polychlorinated dibenzodioxins and polychlorinated dibenzofurans and reproductive or develop mental effects • Exhaust and reproductive or developmental effects • Fuels and reproductive or developmental effects • Benzene and reproductive effects in women, or adverse pregnancy outcomes • Prenatal exposure to benzene and other developmental effects in children (other than childhood leukemia)
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of children born in the TRICARE system, including information in the DoD Birth and Infant Health Registry. New methodologies and efficiencies are available for identifying the population to be sampled, issuing invitations, determining the what and how of data collection and analyses, using incentives for recruiting and retaining participants, and using reminders to increase response rates.
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Basic and translational research in model systems -- in vitro systems that use cells and tissues as well as whole animals -- where both genetics and exposures can be controlled as well as generational animal studies that can be conducted in days or months provide powerful opportunities to assess biological plausibility, gain mechanistic insights, and address the complexities inherent in human studies. Such studies may detect subtle effects; follow genetic or epigenetic changes at the cellular and whole-animal levels, including effects on germ cells; assess impacts on reproductive function; and identify susceptible phenotypes.
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of genetic and epigenetic effects is necessary to understand the impact of deployment exposures on veterans and their descendants. MOVING FORWARD As the committee completed its review of the epidemiologic and toxicologic literature on the Gulf War and Post-9/11 toxicants of concern, a framework for an HMRP was developed and an agenda for basic and translational research on generational effects laid out.
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There are numerous resource, methodologic, and organizational considerations that must be addressed across several governmental agencies -- and, likely, private organizations as well -- to implement a large-scale HMRP of the magnitude envisioned and recommended by the Volume 11 committee. Critical considerations include financial and human resource costs, the availability and expertise of adequately trained personnel, the time required for project completion, technologic competencies, ready access to well-curated data, the maintenance of confidential human health data, ethical considerations for investigations that include parents and children, and the implementation of appropriate health and risk communication strategies between and among organizations and veterans and their families.
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