Rounding Up Proof: Zika Virus and Birth Defects

April 20, 2016

Rounding Up Proof: Zika Virus and Birth Defects

  1. Larry M. Baddour, MD

Evidence strongly supports a causal relation between congenital Zika virus infection and fetal brain anomalies.

  1. Larry M. Baddour, MD

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.


Although these two sets of criteria show some overlap, the authors' structured approach to detailing specific evidence supporting a causal relation between Zika viral infection and its complications is key as we consider global directives for combating this infection. Sufficient funding to support these efforts will probably be an issue.

Editor Disclosures at Time of Publication

  • Disclosures for Larry M. Baddour, MD at time of publication Royalties UpToDate, Inc. (Authorship duties)


Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.