Figure 2. Directed Acyclic Graphs for the Association Between Congenital Cytomegalovirus (CMV) and Microcephaly.

Newborns with microcephaly are more likely to be tested for congenital CMV than newborns without microcephaly, as are newborns with sensorineural hearing loss (SNHL) who fail the newborn hearing screen (or have other congenital CMV–related symptoms). Thus, there are more newborns tested, and more with a positive CMV test result, among those with microcephaly, resulting in upwardly biased estimates of the association of congenital CMV with microcephaly. To avoid this surveillance bias, we restricted to newborns with CMV testing, as represented by the box around CMV testing in the second directed acyclic graph. However, among tested newborns, both individuals with and without microcephaly may be more likely to have congenital CMV–related symptoms such as SNHL that triggered the test. Thus, among tested newborns, there would be an overrepresentation of CMV-positive infants in both the case and referent groups, resulting in biased estimates of the association of congenital CMV with microcephaly.