Agent Orange and Birth Defects

By Betty Mekdeci, Executive Director

The soldiers are dying.  But, even more tragic…the children they have left behind are suffering.  Sometimes we hear from the veterans, but it is usually the wives and children that send us these poignant messages.

“I lost my husband from a cancerous brain tumor 13 months ago.  My son has many disabilities including Tourette’s syndrome, mental retardation, mild Cerebral Palsy, hydrocephalus and he is profoundly deaf. He will never be able to live on his own.”

“My father passed away in 1998.  He had many health problems including type II diabetes.  He was only 50 years old.  Agent Orange has been a part of my life from the moment I was born.  I was born without my right leg, several of my fingers and my big toe on my left foot.  My mother had three miscarriages. My younger brother (age 29) has to wear bifocals and suffers from chronic joint pain.”

“I was in the infantry in the area where the highest concentrations of Agent Orange were used. My oldest daughter had Chronic Mylogenous Leukemia.”

“I served four tours in Vietnam.  We have three children…one daughter with a heart defect, another daughter with scoliosis and digestive problems and a son born with a defective optic nerve in his right eye that has left him blind in that eye.  There is no history of birth defects on either side of our family.”

“I am a 57 year old Vietnam vet who was exposed to Agent Orange.  At age 41, I had to have an emergency heart bypass.  I have had six heart attacks since my surgery.   Our youngest daughter suffered with learning disabilities through grade school and high school.  Her first child was born in 2002 with complex congenital heart disease and fetal hydrops.  He only lived five hours.  I feel that I passed on something to our daughter because I was exposed to Agent Orange.”

Since 1991, Birth Defect Research for Children has recorded thousands of cases like these reported by Vietnam veterans in our National Birth Defect Registry.

Approximately 2.6 million veterans served in Vietnam.  Statistically 3-6% of all children are born with some kind of birth defect.  Are these just unfortunate coincidences or has Agent Orange exposure left a legacy of disabilities in Vietnam veterans’ children that may possibly extend into future generations?  There is now an impressive body of scientific evidence showing increases in birth defects and developmental problems in the children of Vietnam veterans and others exposed to dioxin-like chemicals.

Agent Orange was a combination of two defoliants, 2-45T and 2-4D contaminated by dioxin (TCDD), a toxic byproduct of the chemical production process.  Over 19 million gallons of herbicides were sprayed in Vietnam between 1962-1971 to destroy crops and ground cover.  Over 11.2 million gallons sprayed after 1965 were dioxin-contaminated Agent Orange.  Agents Purple, Pink and Green used before 1965 were even more highly contaminated with dioxin.

According to Barry Commoner and Thomas Webster in Dioxins and Health (Schecter & Gasiewicz 2003), “the current scientific evidence argues not only that dioxin is a potent carcinogen, but that the non-cancer health and environmental hazards of dioxin may be more serious than believed previously.” These authors report  “that dioxin appears to act like a persistent synthetic hormone interfering with important physiological signaling systems that can lead to altered cell development, differentiation and regulation.  The most troubling consequence is the possibility of reproductive, developmental and immunological effects at the levels of dioxin-like compounds present in the bodies of the average person”.

Since studies of Vietnam veterans exposed to herbicides in Vietnam have found much higher levels of dioxin in their bodies than the average person, these effects should be detected at an even greater frequency in the veterans and their children.

In 1996, the national Academy of Sciences found “limited/suggestive” evidence of an association between Agent Orange exposure and spina bifida, a neural tube defect, in all veterans’ children.  In 2000, Dr. H.K. Kang with the Environmental Epidemiology Service of the Veterans Health Administration published a study that found that the risk of moderate-to-severe birth defects was significantly associated with the mother’s military service in Vietnam.  These findings resulted in the Veterans Administration funding assistance programs for spina bifida in the children of male or female Vietnam veterans and for all birth defects without other known causes in the children of female veterans.

The Australian Department of Veterans Affairs (without acknowledging a link to Agent Orange exposure) provides treatment to children of Vietnam veterans with spina bifida, cleft lip or palate, acute myeloid leukemia and adrenal gland cancer.

Additional studies provide evidence that many more birth defects may be associated with dioxin-contaminated herbicide exposure in Vietnam.  In 1990, an independent scientific review of the literature was sponsored by the American Legion, the Vietnam Veterans of America, and the National Veterans Legal Services Project.  Seven prominent, independent scientists and physicians on this Agent Orange Scientific Task Force concluded that elevated incidences of specific birth defects in the children of Vietnam veterans were found in several studies.  These included spina bifida, oral clefts, cardiovascular defects, hip dislocations and hypospadias.  In addition, defects of the digestive tract and “other” neoplasms like neuroblastoma were also higher in Vietnam veterans’ children.

Aschengrau & Monson from the Harvard School of Public Health conducted a study  (American Journal of Public Health 1990) on paternal military service and the risk of late pregnancy outcomes. The scientists reported that Vietnam veterans’ risk of fathering an infant with one or more major malformations was increased at a statistically significant level.

In a study by Field and Kerr with the Department of Paediatrics at the University of Sydney (Journal of Medical Genetics 1988), the authors reported patterns of malformations among Vietnam veterans’ children involving the central nervous system, skeletal and cardiovascular systems.

The Ranch Hand study of Vietnam veterans who were involved in herbicide spraying has been analyzed several times for adverse reproductive outcomes.  The 1995 analysis found modest, but significant increases in spontaneous abortion, defects of the circulatory system and heart, all anomalies, major birth defects and some developmental delays in the Ranch Hand veterans’ children.  There was also an increase in spina bifida in the children of Ranch Hand veterans with high dioxin levels.

More recent studies have found additional support for increases in birth defects in the children of both male and female veterans.  Researchers from the University of Texas, the University of Queensland and the University of Sydney collaborated on a meta-analysis (a review of the combined data from many studies) of Agent Orange and birth defects (International Journal of Epidemiology 2006).  They identified all studies (1966-2002) that had examined an association between Agent Orange or dioxin and birth defects.  In total, the study authors identified 22 studies including 13 Vietnamese and 9 non-Vietnamese studies. They determined from their systematic review and meta-analysis of these studies that parental exposure to Agent Orange was associated with an increased risk in birth defects.  The association increased with greater degrees of exposure rated on intensity and duration of exposure. Although other researchers have pointed out weaknesses in the studies of birth defects from Vietnam, the birth defect association with Agent Orange exposure was statistically significant even when the Vietnamese studies were excluded.

Genetic damage in New Zealand Vietnam War veterans was investigated in a study (Cytogenetic & Genome Research 2007) by Rowland et al. from the Institute of Molecular Biosciences at Massey University in New Zealand.  A significantly higher frequency of genetic damage was found in New Zealand Vietnam War veterans compared to a matched control group. The study authors suggested that new Zealand Vietnam War veterans had been exposed to a harmful substance that could cause genetic damage. Although the study authors suggested that these results should be interpreted with caution as far as specific health outcomes, they went on to say that genetic damage to any degree has the potential to result in adverse health effects.  The greatest concern about genetic damage is that it can be passed on to future generations.

Important new research on birth defects in the children of Vietnam veterans was recently presented at the 2006 meeting of the Society of for Epidemiological Research in Boston, Massachusetts.  Drs. Del Junco, Sweeney and Papke conducted a case control study of neural tube defects (anencephaly, encephalocele, spina bifida) in the offspring of Vietnam veterans.   They found that paternal blood levels of TCDD were significantly associated with neural tube defects in their children and, although a small sample size with limited statistical power, that a particular paternal genotype (genetic predisposition) could enhance this association. A manuscript describing these findings is currently under preparation for submission.

Associations between Agent Orange and other dioxin-contaminated herbicides and structural birth defects like spina bifida, oral clefts, heart defects and hypospadias may be just the “tip of the iceberg”.   The more frequent outcomes of prenatal exposure to dioxin may be in the area of immunological, neurological and neuroendocrine outcomes.

Since 1990, Birth Defect Research for Children has collected data on birth defects and developmental disabilities in the children of Vietnam veterans through the National Birth Defect Registry.  The Registry was designed through a collaboration of seven prominent scientists to identify patterns of birth defects and disabilities in children with similar prenatal/pre-conceptual exposures.

When compared to non-veterans children in the registry, the children of Vietnam veterans have shown consistent increases in learning, attention and behavioral disorders; all types of skin disorders; problems with tooth development; allergic conditions and asthma; immune system disorders including chronic infections; some childhood cancers and endocrine problems including thyroid disorders and childhood diabetes. More and more studies of prenatal exposures to dioxins and similar chemicals are adding support for these associations.

According to Dr. Linda Birnbaum with the Environmental Protection Agency, dioxin can modulate growth and development.  In the embryo/fetus, dioxin-altered programming can result in malformations, anomalies, fetal toxicity and functional and structural deficits which are often not detectable until later in life.

In a paper published in Environmental Health Perspectives, Dr. Birnbaum also discusses research that demonstrates that prenatal exposures to Endocrine Disruptors (chemicals which can disrupt hormone activity) like TCDD can alter hormones, reproductive tissue development and increase susceptibility to potential carcinogen exposure in the adult.

Increased susceptibility to chronic childhood infections and cancers later in life may be a result of dioxin’s effects on the developing immune system. Weisglas-Kuperus et al. investigated the immunologic effects of background (everyday) exposures to  Polychlorinated Biphenyls (PCBs are chemicals with dioxin-like effects) and dioxins in preschool Dutch children (EHP 2000). The researchers found that prenatal exposure to these chemicals was associated with changes in the T-cell population.  They concluded that the effects of perinatal background exposure to PCBs  and dioxins persist into childhood and could be associated with a greater susceptibility to infectious disease.

Another study by a team of researchers from Quebec (EHP 2003) reported their finding of a chemical imbalance that could be a marker for prenatal immune damage caused by organochlorines (which include dioxin-like compounds). The researchers found that the lymphocyte cells of newborns exposed to higher concentrations of these chemicals during prenatal development secreted fewer cytokines than those of control newborns.  These alterations of the immune system could lead to increased susceptibility to infection.

Dallaire et al.conducted a study on the incidence of acute respiratory infections in Inuit children who had prenatal exposure to PCBs (EHP 2006). The incidence rates of acute ear infections and of lower respiratory tract infections were positively associated with PCBs.

Children who were born in Yu-Cheng, Taiwan between July 1978 and June 1987 were exposed to PCBs/PCDFs (dioxin-like chemicals) when their mothers consumed rice bran oil contaminated with these chemicals during pregnancy.  The Yusho children have been reported to have higher frequencies of bronchitis, respiratory tract and ear infections.   Rogan et al. also reported (Science 1988) that the exposed children were shorter and weighed less than non-exposed children.  They had abnormalities of their gums, skin, nails, teeth and lungs and showed developmental delays and behavior problems.  The researchers reported that these findings were consistent with a disorder of ectodermal tissue.  The skin, nervous system and sense organs are developed from the ectoderm.

In a similar poisoning incident in Yusho, Japan, children had ectodermal dysplasia syndrome that includes toxicity to the skin and teeth.  They also had developmental delays, speech problems, behavioral difficulties, and impaired intellectual development.

Since the nervous system is derived from the ectoderm, it is not surprising that a growing body of evidence is linking prenatal exposures to dioxin-like chemicals to learning and behavioral deficits.  At a Children’s Health Meeting (2000) sponsored by the National Institute of Environmental Health Sciences, Dr. Jerry Heindel reported that several studies of pregnant women who had consumed several meals of PCB-contaminated fish per month during pregnancy gave birth to infants with small but detectable learning and behavioral deficits.  The children with the highest exposure exhibited an average drop of 6 points in IQ compared to children with lower levels of exposure.

A 2007 study from the Department of Preventive Medicine at Kyungpook University in Korea has reported associations between blood concentration of persistent organic pollutants (including dioxins) and increases in learning and attention disorders in children in the general population.

These alterations may be mediated by effects on thyroid hormones. Women with hypothyrodism in the second trimester of pregnancy have children with cognitive deficiencies.  There is increasing evidence that exposure to certain synthetic compounds, including dioxins and PCBs during the perinatal period can also impair learning, memory and attention.

Dr. Thomas Zoeller, an endocrinologist at the University of Massachusetts, has found that dioxin-like PCBs activate cellular machinery that can alter the structure of other, non-dioxin-like PCBs. Some of these “dioxin-induced” metabolites can act directly on the thyroid hormone receptor.  In the fetal brain, this could alter the course of development leading to learning and developmental disabilities.

The new research on dioxin and dioxin-like chemicals is exciting and holds promise to unravel the intricate ways that these chemicals can alter embryonic development.  The research should continue, but it is now 35 years since Agent Orange was first sprayed in Vietnam.  And the calls keep coming…

“I have two daughters.  One was born while I was in Vietnam.  She is healthy.  My other daughter was born three years after I returned.  She has Lupus, Sojourns and a disease that has destroyed the cartilage in her nose, hip and ankle.”

“My husband died two years ago from Agent Orange-related problems. He was a Navy Seal and served three tours in Vietnam. We have three children.  Our oldest was born with a congenital heart defect.  He has had 7 open heart surgeries.  Our daughter was born with a brownish birth mark on one of her legs.  Our youngest son is on Ritalin because he has attention disorder.”

“I am an Agent Orange widow.  My husband died 6 years ago.  Two of my three children were born after my husband returned from Vietnam.  Both are insulin dependant diabetics.  The youngest also suffers from gastric and thyroid problems.”

“I have two daughters.  One has spina bifida and is covered through the VA program.  My other daughter has had seizures since age 3 and recently has been diagnosed with a brain tumor.  The VA says her problems are not related to my service in Vietnam.”

“My husband is a 100% disabled service connected veteran of the Vietnam war. His disabilities are due to Agent Orange exposure. We have two sons ages 26 and 15 that are both ADD/ADHD and get skin rashes on their feet and hands.”

In Dioxins and Health,  Thomas Webster and Barry Commoner comment, “Much of the media coverage of the dioxin debate has consisted of trying to convince the public that their common sense is wrong and that experts know best.  In this case, the public’s view has been largely correct.  Dioxin is a dangerous and unwanted chemical pollutant.”

The Vietnam veterans are not scientists, but their “common sense” has told them that their children have disabilities because of their service and exposures in Vietnam.

Vietnam veterans who would like to add information about their children’s birth defects or disabilities to the National Birth Defect Registry sponsored by Birth Defect Research for Children can register online at www.birthdefects.org .

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