Table 9.1 includes a summary of the studies that have reported results specifically for neural tube defects (typically anencephaly and/or spina bifida), including studies in VAO and more recent publications. Unfortunately, some studies (e.g., Seveso), particularly the occupational and environmental studies, do not have results specific for individual birth defects, usually because of the small number of cases. A number of studies of veterans appear to show an elevated relative risk for either service in Vietnam or estimated exposure to herbicides or dioxin and neural tube defects (anencephaly and/or spina bifida) in their offspring. Many of the estimates are imprecise, and chance cannot be ruled out. Nonetheless, the pattern of association warrants further evaluation. The CDC Birth Defects Study (Centers for Disease Control, 1988), the CDC Vietnam Experience Study (Centers for Disease Control, 1989), and the Ranch Hand Study (Wolfe et al., 1992) are of the highest overall quality. The CDC VES cohort study found that more Vietnam veterans reported that their children had a central nervous system anomaly (OR = 2.3; 95 percent CI 1.2-4.5) than did non-Vietnam veterans (Centers for Disease Control, 1989). The odds ratio for spina bifida was 1.7 (CI 0.6-5.0). A substudy was conducted in an attempt to validate the reported cerebrospinal defects (spina bifida, anencephaly, hydrocephalus) by examination of hospital records. A difference was detected, but its interpretation was limited by differential participation between the veteran groups and failure to validate negative reported—i.e., the veterans not reporting their children having a birth defect. Thus, the issue of a recall bias remains a major concern with this study.

The CDC Birth Defects Study utilized the population-based birth defects registry system in the metropolitan Atlanta area (Centers for Disease Control, 1988). There was no association between overall Vietnam veteran status and the risk of spina bifida (OR = 1.1, CI 0.6-1.7) or anencephaly (OR = 0.9, CI 0.5-1.7). However, the exposure opportunity index based on interview data was associated with an increased risk of spina bifida; for the highest estimated level of exposure (EOI-5), the OR was 2.7 (CI 1.2-6.2). There was no similar pattern of association for anencephaly. This study has a number of strengths, including the use of a population-based birth defects registry system and adjustment for a number of potentially confounding factors. Two study limitations include the relatively low response proportions among the case and control subjects (approximately 56 percent) and the lag between birth and interview for some cases and controls.

Thus, all three epidemiologic studies (Ranch Hand, VES, CDC Birth Defects Study) suggest an association between herbicide exposure and an increased risk of spina bifida in offspring. Although the studies were judged to be of relatively high-quality, they suffer from methodologic limitations, including possible recall bias, nonresponse bias, small sample size, and misclassification of exposure. In addition, the failure to find a similar association with anencephaly, an embryologically related defect, is of concern.

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