Association between Agent Orange and birth defects: systematic review and meta-analysis

Background The association between parental exposure to Agent Orange or dioxin and birth defects is controversial, due to inconsistent findings in the literature. The principal aim of this study was to conduct a meta-analysis of relevant epidemiological studies that examined this association and to assess the heterogeneity among studies. Methods Relevant studies were identified through a computerized literature search of Medline and Embase from 1966 to 2002; reviewing the reference list of retrieved articles and conference proceedings; and contacting researchers for unpublished studies. A specified protocol was followed to extract data on study details and outcomes. Both fixed-effects and random-effects models were used to synthesize the results of individual studies. The Cochrane Q test and index of heterogeneity (I-2) were used to evaluate heterogeneity, and a funnel plot and Egger's test were used to evaluate publication bias. Results In total, 22 studies including 13 Vietnamese and nine non-Vietnamese studies were identified. The summary relative risk (RR) of birth defects associated with exposure to Agent Orange was 1.95 [95% confidence interval (95% CI) 1.59-2.39], with substantial heterogeneity across studies. Vietnamese studies showed a higher summary RR (RR = 3.00; 95% CI 2.19-4.12) than non-Vietnamese studies (RR = 1.29; 95% CI 1.04-1.59). Sub-group analyses found that the magnitude of association tended to increase with greater degrees of exposure to Agent Orange, rated on intensity and duration of exposure and dioxin concentrations measured in affected populations. Conclusion Parental exposure to Agent Orange appears to be associated with an increased risk of birth defects.