Studying the effects of emerging infections on the fetus: Experience with West Nile and Zika viruses.

Emerging infections have the potential to produce adverse effects on the pregnant woman or her fetus; however, studying these effects is often challenging. We review our experiences with investigating the prenatal effects of two mosquito-borne infections that emerged in the past 2 decades, West Nile virus (WNV) and Zika virus. Concerns regarding teratogenicity were raised about both viruses; Zika virus has been confirmed to be teratogenic, while WNV appears not to increase the risk for adverse outcomes, although teratogenicity has not been excluded. Study designs used to examine the effects of both viruses include case reports and series, pregnancy registries, and cohort studies. Case-control studies and birth defects surveillance systems are being used to study the effects during pregnancy of Zika virus, but not the effects of WNV, because a specific phenotype was observed among infants with congenital Zika infection, but not among infants with congenital WNV infection. Experimental data that demonstrated that Zika virus was neurotropic have also been useful because they provided biologic plausibility for Zika virus's teratogenic effects: these findings were consistent with observations in congenitally infected infants. Challenges encountered with studies to evaluate the effects of these infections include the broad range of possible adverse outcomes, the inability to include all infected pregnant women in studies because many infections are asymptomatic, and the difficulty with interpretation of diagnostic testing of infants (WNV and Zika) and pregnant women (Zika). This review might be helpful to guide future studies of the effects of emerging infections during pregnancy. Birth Defects Research 109:363-371, 2017. © 2017 Wiley Periodicals, Inc.