IJE Advance Access originally published online on March 16, 2006
International Journal of Epidemiology 2006 35(5):1220-1230; doi:10.1093/ije/dyl038
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Association between Agent Orange and birth defects: systematic review and meta-analysis
1 School of Public Health, University of Texas Health Science Center, USA
2 School of Population Health, University of Queensland, Australia
3 Center for Prenatal Health Services Research, University of Sydney, Australia
4 Garvan Institute of Medical Research, Sydney, Australia
* Corresponding author. Senior Research Fellow and Associate Professor, Bone and Mineral Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010 Australia. E-mail: t.nguyen{at}garvan.org.au
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to 2002; reviewing the reference list of retrieved articles and conference proceedings; and contacting researchers for unpublished studies.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 (I2) 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.
Keywords Agent Orange, dioxin, birth defects, meta-analysis, Vietnam
Accepted 13 February 2006
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  A. Schecter and J. D Constable Commentary: Agent Orange and birth defects in Vietnam Int. J. Epidemiol., October 1, 2006; 35(5): 1230 - 1232. [Full Text] [PDF]
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