Veterans and Agent Orange Update 1998 (1999) / Chapter Skim
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9 Reproductive Effects
9 Reproductive Effects
Pages 434-465
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From page 434... ...
(IOM, 1994) and Update 1996 included a number of environmental, occupa tional, and Vietnam veteran studies that evaluated herbicide and dioxin exposure and the risk of adverse reproductive outcomes, including spontaneous abortion, birth defects, stillbirths, neonatal and infant mortality, low birthweight, and semen quality and infertility.
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From page 435... ...
Improvements in study design, especially exposure assessment, should allow for a more definitive evaluation of the relationship between herbicide exposure and adverse reproductive outcomes among women. The remainder of this chapter discusses the following specific categories of reproductive effects: birth defects, fertility, stillbirth, neonatal and infant death, and low birthweight and preterm birth.
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From page 436... ...
, including studies in VAO, Update 1996, and more recent publications reviewed in this report. Results of the analysis of birth defects among the offspring of Ranch Hands and other Vietnam veterans suggested the possibility of an association between dioxin exposure and risk of neural tube defects.
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From page 437... ...
13 1.1 (0.6-2.3) Neural tube defects among Ranch HandsC 4 Neural tube defects among comparison 0 Vietnam Experience Study Spina bifida among Vietnam veterans 9 Spina bifida among non-Vietnam veterans Anencephaly among Vietnam veterans Anencephaly among non-Vietnam veterans Birth Defects Study Vietnam veteran: spine bifida Vietnam veteran: anencephaly EOI-5: spine bifida EOI-5: anencephaly 1.7 (0.6-5.0)
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From page 438... ...
CFour neural tube defects among Ranch Hand offspring include 2 spine bifida (high dioxin level) , 1 spine bifida (low dioxin)
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From page 439... ...
However, neural tube defects (spine bifida, anencephaly) were in excess among offspring of Ranch Hands, with 4 total (rate of 5 per 1,000)
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From page 440... ...
. Several birth defects were associated with estimated chlorophenate exposure including cataracts, anencephaly or spine bifida, and anomalies of genital organs.
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From page 441... ...
County pesticide use data also provided interesting information for a regional ecologic analysis. The study had several limitations including the use of birth vital statistics to ascertain birth defects, use of a small number of confounders, lumping of birth defects into broad system groups, ecologic rather than individual-level pesticide data, and inability to separate the possible effects of multiple pesticides.
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From page 442... ...
Data were collected on a number of potentially confounding factors including medication use, maternal diabetes, parity, family history of neural tube defects, and parental smoking and alcohol consumption. Overall, the prevalence of paternal pesticide use did not differ between cases and controls (11 case fathers, 35 control fathers; OR = 0.9, CI 0.4-1.9~.
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From page 443... ...
(1997) provide some additional support for the association of herbicide exposure with this specific birth defect, although concerns remain, including the control of confounding, exposure determination, statistical imprecision, and isolation of exposure to specific herbicides and TCDD.
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From page 444... ...
A more thorough discussion of biologic plausibility with respect to exposure to TCDD or herbicides and reproductive and developmental disorders is contained in Chapter 3; a summary is presented in the conclusion to this chapter. Increased Risk of Disease Among Vietnam Veterans Since there are some data suggesting that the highest risks occur in those veterans estimated to have had exposure to Agent Orange (e.g., Ranch Hands)
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From page 445... ...
For FSH, a pattern of increasing risk with increasing serum dioxin was also found, but the test for trend was not statistically significant (p = 0.10~. The adjusted odds ratios forlow testosterone were more elevated (2nd dioxin quartile = 3.9; 3rd = 2.7; 4th = 2.1)
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From page 446... ...
A recent Ranch Hand publication addressed the relationship between serum dioxin and reproductive hormones (Henriksen et al., 1996~. The investigators measured serum testosterone, FSH, LH, and testicular abnormality during clinic visits by Ranch Hand and comparison participants in 1982, 1985, 1987, and 1992.
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From page 447... ...
No Ranch Hands in the low- or high-exposure categories had a high percentage of abnormal sperm. The odds ratio for low sperm count was 0.9 (CI 0.7-1.2)
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From page 448... ...
has suggested that a reduction in testosterone and high gonadotropin levels after dioxin exposure would result in an excess of female offspring. Potential confounding factors for altered sex ratio are uncertain, but parental age, social class, illness, race, smoking, and stress have been considered.
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From page 449... ...
found reduced fertility rates among the worker cohort but could not consistently attribute this effect to chlorophenate exposure. Nonetheless, sufficient uncertainty remains because some studies had methodologic limitations including small sample sizes for higher exposure categories, failure to account for potential confounding factors, and exposure misclassification.
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From page 450... ...
210,0001,300 1.1 (0.9-1.2) VIETNAM VETERANS New Studies Henriksen et al., 1996 Ranch Hands Low testosterone High dioxin (1992)
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From page 451... ...
Summary of VAO and Update 1996 A statistical association of herbicide exposure with stillbirth, neonatal, and infant death has been inconsistently reported in the available occupational and environmental epidemiologic studies. The majority of studies did not have adequate statistical power, and the assessment of exposure was incomplete.
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From page 452... ...
No association was found for either stillbirths or infant deaths and any of the chlorophenate exposure measures. For the maximal index of exposure for any sawmill job held up to three months prior to conception the odds ratios were close to the null value (stillbirth OR = 1.0, CI 0.9-1.1; infant death OR = 1.0, CI 0.9-1.0)
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From page 453... ...
The new Ranch Hand report suggested an association between dioxin exposure and an increased risk of infant death; however, the association was not consistently related to level of exposure and was also found for the period prior to service in southeast Asia. The evidence remains inadequate because some studies were limited by small sample sizes for higher exposure categories, failure to account for potential confounding factors, and exposure misclassification.
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From page 454... ...
VIETNAM VETERANS Studies Reviewed in VAO Aschengrau and Monson, Stillbirth and paternal Vietnam service 1990 Vietnam veterans compared to men with no military service5 1.5 (0.4-3~9) Vietnam veterans compared to non Vietnam veterans5 3.2 (0.7-14.5)
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From page 455... ...
CDC, 1989 Vietnam Experience Study GBDS study early neonatal death 16 2.0 (0.8-4.9) Field and Kerr, 1988 Follow-up of Australian Vietnam veterans 12 18.1(2.4-134.4)
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From page 456... ...
Established risk factors for preterm birth include race, marital status, socioeconomic status, previous low birthweight or preterm birth, multiple gestations, cigarette smoking, and cervical, uterine, or placental abnormalities (Berkowitz and Papiernik, 1993~. Summary of VAO and Update 1996 Given the lack of available occupational and environmental studies, the evidence on low infant birthweight was considered inadequate.
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From page 457... ...
No association was found for either low birthweight, small for gestational age, or PTD and any of the chlorophenate exposure measures. For the maximal index of exposure for any sawmill job held up to three months prior to conception, the odds ratios were close to 1.0 (low birthweight OR = 0.99, CI 0.97-1.0; small for gestational age OR = 1.0, CI 0.9-1.0; preterm birth OR = 0.9, CI 0.9-1.0~.
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From page 458... ...
There is inadequate or insufficient evidence to determine whether an association exists between exposure to the herbicides and fertility, stillbirth, neonatal and infant death, birth defects (other than spine bifida) , and low birthweight and preterm birth.
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From page 459... ...
* 14 27 Intrauterine growth retardationpost-service in southeast Asia Background Low High Follow-up of Air Force Ranch Hands conceptions during or after Southeast Asian service with high current dioxin levels Vietnam Experience Study (GBDS)
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From page 460... ...
Research suggests that in utero and lactational TCDD exposure selectively impairs rat prostate growth and development without inhibiting testicular androgen production or consistently decreasing prostate DHT concentrations. Studies in female animals are limited but demonstrate in utero and lactational exposure reduced fertility, decreased ability to remain pregnant throughout gestation, decreased litter size, increased fetal death, impaired ovary function, and decreased levels of hormones such as estradiol and progesterone.
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From page 461... ...
The spatial and temporal expression of AhR and Arnt suggests that the developing myocardium and cardiac sepia are potential targets of TCDD induced teratogenicity, and such targets are also consistent with cardiac hypertrophy and septal defects observed following TCDD exposure. Evidence suggests that the endothelium lining of blood vessels is a primary target site of TCDD-induced cardiovascular toxicity.
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From page 462... ...
Research on biological mechanisms is burgeoning and subsequent Veterans and Agent Orange updates may have more and better information on which to base conclusions. Increased Risk of Disease Among Vietnam Veterans Under the Agent Orange Act of 1991, the committee is asked to determine (to the extent that available scientific data permit meaningful determinations)
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From page 463... ...
1984b. Vietnam veterans' risks for fathering babies with birth defects.
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From page 464... ...
1996. Serum dioxin, testosterone, and gonadotropins in veterans of Operation Ranch Hand.
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From page 465... ...
1995. Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand.
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