Rounding Up Proof: Zika Virus and Birth Defects

The Zika virus epidemic in the Americas continues to spread, along with the fear that additional geographic areas will become involved; moreover, the full range of clinical complications from this infection may not yet have been fully defined. Certainly, serious birth defects associated with congenital Zika virus infection have now been recognized. Because causal links between Zika infection and disease complications have not been irrefutably determined, however, experts from the CDC reviewed available data and used two established sets of criteria to determine if causality has been established.

Shepard's Criteria for Proof of Teratogenicity in Humans is based on both a “rare exposure, rare defect phenomenon” and epidemiologic features to evaluate causality. Of six applicable criteria, four were met (e.g., proven exposure at a critical prenatal time), one was partially met, and one was not met (this last criterion depends on availability of results of an animal model of infection, which have not been reported). Bradford Hill Criteria for Evidence of Causation include nine conditions, with the understanding that not all must be met to establish causality. Seven criteria were met (e.g., strength of association) and one criterion (“biologic gradient”) was considered nonapplicable to the topic under scrutiny.