European Journal of Epidemiology

, Volume 25, Issue 1, pp 37–44 | Cite as

Paternal exposure to Agent Orange and spina bifida: a meta-analysis

  • Anh Duc NgoEmail author
  • Richard Taylor
  • Christine L. Roberts


The objective of this study is to conduct a meta-analysis of published and unpublished studies that examine the association between Agent Orange (AO) exposure and the risk of spina bifida. Relevant studies were identified through a computerized literature search of Medline and Embase from 1966 to 2008; a review of the reference list of retrieved articles and conference proceedings; and by contacting researchers for unpublished studies. Both fixed-effects and random-effects models were used to pool 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. Seven studies, including two Vietnamese and five non-Vietnamese studies, involving 330 cases and 134,884 non-cases were included in the meta-analysis. The overall relative risk (RR) for spina bifida associated with paternal exposure to AO was 2.02 (95% confidence interval [CI]: 1.48–2.74), with no statistical evidence of heterogeneity across studies. Non-Vietnamese studies showed a slightly higher summary RR (RR = 2.22; 95% CI: 1.38–3.56) than Vietnamese studies (RR = 1.92 95% CI: 1.29–2.86). When analyzed separately, the overall association was statistically significant for the three case–control studies (Summary Odds Ratio = 2.25, 95% CI: 1.31–3.86) and the cross sectional study (RR = 1.97, 95% CI: 1.31–2.96), but not for the three cohort studies (RR: 2.11; 95% CI: 0.78–5.73). Paternal exposure to AO appears to be associated with a statistically increased risk of spina bifida.


Agent Orange Dioxin Birth defects Spina bifida Meta-analysis 



Agent Orange


Centers for disease control and prevention


Confidence interval


Exposure opportunity index


Odds ratio


Relative risk


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Anh Duc Ngo
    • 1
    • 4
    Email author
  • Richard Taylor
    • 2
  • Christine L. Roberts
    • 3
  1. 1.School of Population HealthUniversity of QueenslandBrisbaneAustralia
  2. 2.School of Public Health and Community MedicineUniversity of New South WalesSydneyAustralia
  3. 3.Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
  4. 4.VINE ProjectHealth Strategy and Policy InstituteHanoiVietnam

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