TUCSON, AZ—A new report from the National Academies of Sciences, Engineering, and Medicine found that sufficient evidence supported an association between exposure to seven factors and detrimental reproductive effects in men or women who served in the Gulf War or developmental effects in their children.
Another 16 factors had limited or suggestive evidence of an association.
“The Veterans Administration wants to protect veterans, and its default has been to go as far down as limited/suggestive evidence to find presumptive association,” explained committee chair Kenneth S. Ramos, MD, PhD, PharmB, associate vice president for precision health science, professor of medicine and executive director of the Center for Applied Genetics and Genomic Medicine at the University of Arizona in Tucson.
VA Spokesperson Ndidi Mojay told U.S. Medicine that the VA “is engaged in a deliberative process to review the report’s findings. Within six months of the report, the VA will report to Congress.”
The conditions with sufficient evidence included:
- 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, and
- Prenatal exposure to benzene and childhood leukemia.
The National Academies noted that “no toxicant had sufficient evidence of a causal association between exposure and reproductive or developmental effects, nor did any toxicant have limited/suggestive evidence of no association between exposure and reproductive or developmental effects.”
Sufficient evidence is considered the highest level available to show likely linkage of an exposure to an outcome. “Be mindful that human epidemiological studies never establish causality,” Ramos told U.S. Medicine. Proving causality requires direct intervention over an extended period of time and a control population to see the impact on health, he noted.
“Sufficient evidence means that the literature is compelling enough, powerful enough to reach a conclusion about potential association based on multiple, well-designed studies of multiple groups,” he explained.
The committee found the following conditions had limited/suggestive evidence:
- 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, neurodevelopmental 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, and
- Prenatal exposure to glycols or glycol ethers and birth defects.
Adding an illness to VA’s presumptive list means that veterans applying for disability benefits do not need to prove a connection between their illness and their time in service. Instead, they only need to show that they served in the covered theater during the relevant period and that they now suffer from the conditions. When covered conditions are presumed to affect children of veterans, the biological children might be eligible to receive VA benefits.
The National Academies also called for the creation of a health monitoring and research program to better understand the effects of exposures on veterans, their children, grandchildren and great-grandchildren.
The report recommended that the HMRP focus on the “collection, storage and maintenance of comprehensive baseline and longitudinal data and biospecimens from veterans, their partners, and their descendants; detailed exposure characterization and assessment during and after deployment; and the development, evaluation, standardization, and interoperability of biomarkers of exposure, susceptibility, and biological effects.”
The goal is to more fully and accurately characterize the effects of various exposures on veterans and their descendants through genetic and epigenetic changes. “To understand the effect of exposure in combat, we need data from before the veteran was put in harm’s way,” said Ramos. “Then we need veterans’ continued engagement and participation in the design and execution of studies that look at their exposures.”
The committee provided a research agenda for the HMRO that would capture the genetic and epigenetic changes associated with exposures that impact subsequent generations and for which little information currently exists.
The creation and maintenance of an HMRP would require “unwavering commitment to the longitudinal nature of the study for two generations at a minimum. That’s 35 to 40 years, at least,” Ramos emphasized.
While the committee did not propose a budget for the HMRP, “that’s the big gorilla in the room,” Ramos said. The report noted that the cost would be “substantial,” as seen in other large epidemiology studies but could be implemented in a tiered approach.
A pilot program could investigate the most important hypotheses. “Designing studies to address specific questions would help investigators understand their complexity before tackling bigger questions and expanded populations,” Ramos said.
To get started, the committee recommended leveraging two existing VA studies, the Million Veteran Program and the Millennium Cohort Study, which already have large cohorts, developed infrastructure, extensive data sources and some protocols for collection of biological specimens and family participation.
“The VA was extremely receptive to using the MVP and Millennium Cohort Study and had a very positive response to the report generally,” Ramos said.
The current report is the 11th “Gulf War and Health” review since 1998. That was when Congress directed the VA to contract with the National Academies to assess the scientific and medical literature focused on potential associations between illness and exposure to the toxic agents, environmental and wartime hazards and preventive measures associated with service during the Gulf War of 1990-1991 and engagements in Afghanistan and Iraq after Sept. 11, 2001.
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