Table 1.

Examples of Studies Used to Examine Effects of West Nile and Zika Viruses during Pregnancy on the Fetus by Types of Study Designs

Types of study designs	West Nile virus	Zika virus
Case reports/case series	• Initial case report of infant with abnormal brain and eye findings born to mother infected with West Nile virus at 27 weeks gestation (Alpert et al., 2003; Centers for Disease Control and Prevention, 2002a). • Additional reports of four infants born to West Nile virus‐infected mothers without abnormalities (Chapa et al., 2003; O'Leary et al., 2006).	• Case series of infants in Brazil assessed because of microcephaly demonstrated a consistent phenotype, now known as congenital Zika syndrome (Franca et al., 2016; Schuler‐Faccini et al., 2016).
Birth defects surveillance systems	• Not used	• CDC has funded 45 jurisdictions to conduct birth defects surveillance defects believed to be associated with congenital Zika infection – in progress (see Gilboa et al., this issue).
Pregnancy registries	• West Nile Virus Pregnancy Registry, developed by CDC in collaboration with state and local health departments showed that most infants born to West Nile‐infected mothers had no abnormalities evident at birth or during the first year of life (O'Leary et al., 2006). • Follow‐up of eleven of these infants age focused on growth, ophthalmologic, and developmental outcomes up until 3 years of age show no evidence of adverse outcomes (Sirois et al., 2014).	• United States Zika Pregnancy Registry (in the 50 US states and District of Columbia, American Samoa, and US Virgin Islands) and the ZAPSS (Puerto Rico) (Simeone et al., 2016) were set up to better understand the effects of Zika virus during pregnancy. • United States Zika Pregnancy Registry data have been used to study the phenomenon of prolonged Zika viremia among pregnant women (Meaney‐Delman et al., 2016) and to estimate the risk of Zika‐associated defects among fetuses and infants born to women possibly infected with Zika during pregnancy (Honein et al., 2016).
Cohort studies	• A prospective cohort study was used to study the effects of West Nile virus during pregnancy, including the potential effects on developmental outcomes at age 24 months (Pridjian et al., 2016).	• A prospective cohort study was conducted of women with a rash illness during pregnancy who tested positive (Zika‐affected) and negative (Zika unaffected) for Zika virus infection during pregnancy. No differences were noted in rates of fetal deaths, but adverse outcomes were noted in 46% of Zika‐affected and 11% of Zika‐unaffected pregnancies (p < 0.001). Adverse outcomes were noted in all three trimesters (Brasil et al., 2016a, 2016b).
Case–control studies	• Not used	• A case–control study conducted in Brazil demonstrated a substantial association between congenital Zika infection and microcephaly (crude odds ratio 55·5; 95% CI 8.6–∞) (de Araujo et al., 2016).