title: Does Zika Virus Cause Microcephaly - Applying the Bradford Hill Viewpoints.
abstract: BACKGROUND
  Zika virus has been documented since 1952, but been associated with mild, self-limiting disease. Zika virus is classified as an arbovirus from a family of Flaviviridae and primarily spread by Aedes Aegypti mosquitos. However, in a large outbreak in Brazil in 2015, Zika virus has been associated with microcephaly.
  
  
  METHODS
  In this review we applied the Bradford-Hill viewpoints  to investigate the association between Zika virus and microcephaly. We examined historical studies, available data and also compared historical rates of microcephaly prior to the Zika virus outbreak. The available evidence was reviewed against the Bradford Hill viewpoints.
  
  
  RESULTS
  All  the nine criteria were met to varying degrees: strength of association, consistency of the association, specificity, temporality, plausibility, coherence, experimental evidence, biological gradient and analogy. Conclusion: Using the Bradford Hill Viewpoints as an evaluation framework for causation is highly suggestive that the association between Zika virus and microcephaly is causal. Further studies using animal models on the viewpoints which were not as strongly fulfilled would be helpful.
authors.affiliation: University Of New South Wales University Of New South Wales.
authors.forename: Asma
authors.initials: A
authors.lastname: Awadh
authors.affiliation: University of New South Wales.
authors.forename: Abrar Ahmad
authors.initials: AA
authors.lastname: Chughtai
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Amalie
authors.initials: A
authors.lastname: Dyda
authors.affiliation: Faculty of Medicine The University of New South Wales.
authors.forename: Mohamud
authors.initials: M
authors.lastname: Sheikh
authors.forename: David J
authors.initials: DJ
authors.lastname: Heslop
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Chandini Raina
authors.initials: CR
authors.lastname: MacIntyre