Summary of the Association of Birth Defect Children’s reports made to House Committee on Veterans’ Affairs and National Academy of Science Committee (1992)

The National Vietnam Veterans Birth Defects/Learning Disabilities Project

The National Vietnam Veterans’ Birth Defects/Learning Disabilities Project is a cooperative effort between the Association of Birth Defect Children (ABDC) and the New Jersey Agent Orange Commission (NJAOC).  The project is part of ABDC’s, National Birth Defect Registry (NBDR).

The NBDR was created to fill an important area of data deficiency in the reporting of birth defects and developmental birth defects in the United States.  According to an October 1991 General Accounting Office report, estimates of the rate of birth defects in the United States range widely. Very poor data are at the center of the uncertainty.  For example, one study found that approximately 2 to 3 percent of a group of children were diagnosed with a detectable physical or functional disorder at birth, but follow-up of the same children found that the actual rate of disorders reached 16 %.  (Chung, et al 1975)

This dearth of nationwide information limits our knowledge about reproductive and developmental disease. (GAO, 1991)

According to the GAO report, the cause of 60% of reproductive and developmental disease is unknown, but 74% of a group of experts surveyed by the National Research Council predicted that up to 25% or more of these reproductive problems will be found to have been environmentally induced.

Several states and the Center for Disease Control currently use hospital discharge data to evaluate the incidence and types of reproductive problems occurring in the nation.  This type of monitoring may fail to record from one-half to two-thirds of birth defects and developmental disabilities. (Chung, et al 1975)  Hospital discharge data does not record developmental delay, learning and attention problems, immunological problems, autism, and other functional problems that may cause more childhood functional disabilities than structural birth defects.

The NBDR was developed to gather more comprehensive data on structural birth defects and functional disabilities by collecting information directly from the parents of infants and older children with birth defects.  The reporting parent(s) is also asked about the prenatal environmental exposures of the mother and pre-conceptual exposures of the father.  Information is collected through a questionnaire designed in a standardized testing format with bubble-in categories. All data are entered by hand in a customized computer form that models the questionnaire.  Information typed into the program automatically goes into more than twenty separate tables that can be queried in multiple ways for data analysis.

The development of the questionnaire took more than a year and went through several revisions after review by outside experts.  During the pilot testing of the project, 5,000 questionnaires were distributed and more than 1,200 were returned and entered into the registry database.  This testing revealed the need for only minor changes in the questionnaire, which performed remarkably well with a large group of individuals from varied educational backgrounds.  The project has also been well received by the academic and professional communities.

The first distribution of NBDR questionnaires was to the entire ABDC mailing list of 5,000.  This population represents families of children with birth defects; professionals working with these families; birth defect support groups; hospitals; colleges; universities; public and private libraries and state or federal agencies working with developmental disabilities.  In addition, ABDC has approximately 1000 families of Vietnam veterans on its mailing list.

Since 1988, ABDC and the New Jersey Agent Orange Commission have discussed the feasibility of using the NBDR to collect data on the incidence of various birth defects and disabilities reported in the children of Vietnam veterans.  In April of 1991, the state of New Jersey approved a contract with ABDC to collect data on disabilities in the children of Vietnam veterans through the NBDR.  The NJAOC developed an additional page of questions to add to the NBDR questionnaire and a new cover letter describing the collaborative project.  These new components were added to the second printing of the questionnaire.

Both NJAOC and ABDC have distributed the new questionnaires.  At the time of this report, a total of 1,200 questionnaires have been entered into the NBDR.  Vietnam veterans 800 of the questionnaires other families on ABDC’s mailing list have returned 400.

Preliminary Data Analysis

ABDC and NJAOC have undertaken an early analysis of the data on disabilities in Vietnam veterans’ children compared to non-veterans’ children in the registry to facilitate the National Academy of Sciences’ review of the possible effects of herbicides/dioxin on reproductive outcomes.  Although Vietnam veterans have returned 800 questionnaires, over 65,000 veterans reported various adverse reproductive outcomes to the court during the Agent Orange litigation.  These initial findings may be modified as more data are collected.

Current data comparison has revealed no increases in any major category of structural birth defects, but a pattern of functional problems in Vietnam veterans’ children is emerging.  This pattern includes significant increases in the following conditions: all areas of learning and attention disorders; chronic skin disorders (eczema, psoriasis, acne-like rash, skin fungus and other skin problems); benign tumors and cysts; allergic disorders (hives, asthma, hay fever, food intolerance and others); growth disorders; immune problems; emotional/behavioral problems and a range of miscellaneous conditions including: tinnitus, frequent headaches, heat/cold sensitivity, fatigue, muscle pain or weakness, joint pain, unexplained fevers, hair loss, tooth problems and chronic stomach disorders.

This pattern of disability is very similar to symptoms reported in children with Chronic Fatigue Immune Dysfunction Syndrome or CFIDS.  (CFIDS Chronicle 1991)  Discrete immunological defects have been noted in several studies of patients with CFIDS and in research at the National Institutes of Health. (CFIDS Chronicle, 1993) Although most veteran families have not had comprehensive immunological evaluations of their children, some of the most seriously affected children have been tested and have immune markers similar to those reported in CFIDS patients.  In a study of teenagers with CFIDS, over half had a history of recurrent infections, allergic disorders, colic, spitting up and stomach cramps during the first 5 years of life.  This symptom complex was twice what was expected in a normal, healthy population and parallels NBDR findings in Vietnam veterans’ children.  Some of the major difficulties reported in older children and teenagers with CFIDS are neurocognitive deficits that seem to mirror the learning, attention and emotional/behavioral problems reported in Vietnam veterans’ children.

Can Prenatal Damage to the Immune System Cause a Syndrome of Immune Dysfunction?

The development of the human immune system begins late in the fetal period, is functioning at birth and reaches maximum capacity around the time of puberty. (Paul, 1984; Claman, 1987)  The immune system is susceptible to chemical injury from a variety of agents.  The developing fetus is unable to recognize and react to a wide range of foreign substances, and it is more susceptible to long-term immunotoxic effects than is the adult. (Lewis et al, 1978; Bick, 1985; Hausman and Wekler, 1985)  Exposure in utero, when the immune system is developing could have long-term effects on the ability of an individual to generate an immune response. (Osburn and Schultz, 1973)  The effects of the dioxin TCDD (a contaminant of Agent Orange) on the thymus and on immune system responses are more severe and long-lasting if TCDD is administered before and after birth rather than only at birth. (Vos and Moore, 1974; Faith and Moore, 1977; Luster et al, 1979)  Thymic atrophy and cell-mediated immunosuppression are also extensive after perinatal exposure when the immune system is being developed in utero.  (Thomas and Hinsdill, 1979; Fine et al, 1989)  Upon perinatal exposure to TCDD, there is a significant reduction in early lymphopoiesis.  These studies show that in the developing fetus or neonate, the immune system could be at greater risk of suppression if it is exposed to environmental toxicants. (NRC, 1992)

Because the cellular events responsible for immune processes are also involved in embryogenesis, many immunosuppressive xenobiotics would be expected to be developmental toxicants. (NRC, 1992)  A review of the literature has revealed that most of the recognized teratogens are also immunotoxicants. (Mekdeci, 1991)  Although no pattern of major structural anomalies has been identified in Vietnam veterans’ children reported to the NBDR, there is new research suggesting that some learning disabilities and attention disorders may be related to differences in the size and shape of certain areas of the brain.  (Hynd, et al, 1990)  These studies suggest that something disrupts the normal growth patterns in the brain’s cortex during fetal development.

Male-Mediated Birth Defects

Since male Vietnam veterans have reported the majority of children with disabilities to the NBDR, it is important to consider whether birth defects and disabilities can be related to a father’s exposures to chemicals. Dr. Donald Mattison, from the School of Public Health at the University of Pittsburgh, has reported that animal studies have identified more than 100 chemicals that can produce spontaneous abortions or birth defects in offspring fathered by exposed males.  Some of these chemicals include alcohol, anesthetic gases, lead, solvents, pesticides and a variety of industrial chemicals.  (Harris, 1991)  Paternal use of noxious agents may exert deleterious effects directly by genetically altering the sperm, or indirectly by exerting modifying effects on the environment surrounding the mating germ cells (Pollard & Smallshaw, 1988)  Dr. Robert Dixon, former chief of the Laboratory of Reproductive and Developmental Toxicology at the National Institute of Environmental Health Sciences contends that semen, like breast milk, may be a collecting point for some toxic agents. (Emmett, 1980)  The human sperm cell has a moderate fat content and a high nucleic acid content, both of which are quite efficient in binding chemicals such as chlorinated or brominated chemicals. (Jansson, 1980)  A study of men working with lead has found twice the concentration of lead in their semen as in their blood.  Dr. Ralph Dougherty reported high levels of four toxic chemicals in the seminal fluid of 132 male students at Florida State University.  (Dougherty, 1990)

Summary

Current analysis of data on Vietnam veterans’ children compared to the children of non-veterans in the NBDR has identified a pattern of disabilities that could be related to prenatal damage to the immune system.  Further investigation of this hypothesis could be facilitated through continued data collection from larger numbers of both Vietnam veterans and non-veterans to balance out any artifacts that might be inherent in limited data collection.  Focused case control studies could be designed to look at subsets of Vietnam veterans’ children with the typical pattern of disability identified by the registry. Comprehensive immunological and neurocognitive testing of these subsets could be used to identify markers similar to those found in children and teenagers with CFIDS.  Magnetic resonance imaging (MRIs) could confirm whether there are any anatomical differences in the size or symmetry of critical areas of the brain.  NBRD data on Vietnam veterans’ children could be compared with cases gathered at environmental sites where exposure to dioxin, herbicides and similar chemicals has been reported.

References

Bick, P. 1985, The immune system: organization and function.  Pp. 1-10 in Immunotoxicology and Immunopharmacology, J. Dean, M.J. Luster, A.E. Munson and H. Amos, eds. New York: Raven. 

CFIDS Chronicle, Fall 1991.  Journal of the Chronic Fatigue and Immune Dysfunction Syndrome Association. 

CFIDS Chronicle, Winter 1993.  Immune abnormalities found in chronic fatigue syndrome may lead to a better understanding of the disease.  News from NIAD, Feb. 5, 1993, p. 2. 

Chung, C.S., Myrianthoupoulos, N.C., 1975. Risks of Congenital Malformations.  The National Foundation March of Dimes Original Article Series, Vol. XI, No. 10. 

Claman, H.N. 1987.  The biology of the immune system. JAMA, 258:2834-2840. 

Dougherty, Ralph, 1990. (personal communication) 

Emmett, A. 1990.  The Sperm Scare.  The Week-Seattle’s News Magazine, July 23. 

Faith, R. E. and J.A. Moore, 1977. Impairment of thymus-dependent immune functions by exposure of the developing immune system to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J. Toxicol. Environ. Health.  3:451-464. 

General Accounting Office, 1991.  Report to the Chairman, Committee on Government Affairs, U.S. Senate.  Reproductive and Developmental Toxicants.  October. 

Harris, M. 1991.  U.S. Study Blames Toxins in Sperm for Some Birth Defects.  The Sydney Morning Herald.  Feb. 1. 

Hausman, P.B. and M.E. Weksler, 1985.  Changes in the immune response with age.  Pp. 414-432 in Handbook of the Biology of Aging.  C.E. Finch and E.I. Schneider, eds. New York.  Van Nostrand Reinhold. 

Hynd, G.W. and M. Semrud-Clikeman, 1990.  Brain morphology in developmental dyslexia and attention deficit disorder/hyperactivity.  (under final review by Archives of Neurology) 

Jansson, Eric. 1990.  The impact of hazardous substances upon fertility and birth defects among men in the United States.  Friends of the Earth White Paper.  November 17. 

Lewis,V.M.,Twomey, J.J.; et al. 1978.  Age, thymic involution and circulating thymic hormone activity.  J. Clin. Endocrinol. Metab. 47:145-150. 

Luster, M.I., R.E. Faith et al, 1979.  Laboratory studies on the immune effects of halogenated aromatics.  Ann. N.Y. Acad. Sci. 320: 473-486. 

Mekdeci, B. 1991.  Immunotoxins as Teratogens.  Association of Birth Defect Children Newsletter, Winter, Vol. 17. 

National Research Council, 1992.  Biologic Markers in Immunotoxicology.  National Academy Press, Washington, D.C. P. 79. 

Osborn, B.I. and Schultz, R.D.  1973.  Immune responsiveness in the fetus and neonate.  J. Am. Vet. Med. Assoc. 163:801-806. 

Paul, W.E. ed. 1984.  Fundamental Immunology, New York: Raven, p. 809. 

Pollard, I. and J. Smallshaw,  1988.  Male mediated caffeine effects over two generations of rats. J. of Dev. Physiology, 10:271-281. 

Thomas, P.T. and R. D. Hindsdill.  1979.  The effect of perinatal exposure to tetra-chlorodibenzo-p-dioxin on the immune response of young mice.  Drug. Chem. Toxicology. 2:77-98. 

Vos, J.G. and J. A. Moore, 1974.  Suppression of cellular immunity in rats and mice by maternal treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.  Int. Arch. Allergy Appl. Immunol. 47:777-794.