title: Paternal exposure to Agent Orange and spina bifida: a meta-analysis.
abstract: The objective of this study is to conduct a meta-analysis of published and unpublished studies that examine the association between Agent Orange (AO) exposure and the risk of spina bifida.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a review of the reference list of retrieved articles and conference proceedings; and by contacting researchers for unpublished studies.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.
authors.affiliation: School of Population Health, University of Queensland, Brisbane, QLD, Australia. n.anh@sph.uq.edu.au
authors.forename: Anh Duc
authors.initials: AD
authors.lastname: Ngo
authors.forename: Richard
authors.initials: R
authors.lastname: Taylor
authors.forename: Christine L
authors.initials: CL
authors.lastname: Roberts
mesh_terms: D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000014:Abnormalities, Drug-Induced; D000075182:Agent Orange; D000013:Congenital Abnormalities / Q000209:etiology; D003678:Defoliants, Chemical / Q000633:toxicity*; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D018812:Paternal Exposure; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018570:Risk Assessment; D016135:Spinal Dysraphism / Q000139:chemically induced*; D014744:Vietnam
chemical_list: D003678:Defoliants, Chemical; D000072317:Polychlorinated Dibenzodioxins; D015084:2,4-Dichlorophenoxyacetic Acid; D000075182:Agent Orange; D015085:2,4,5-Trichlorophenoxyacetic Acid