ABSTRACT It has taken less than a year for the Zika virus (ZIKV) pandemic to sweep across Latin America and the Caribbean. Over 1,000 cases have been documented in Nicaragua in the past year and active cases continue to be identified. The virus is expected to blanket the country over the next 2-4 years. It is now clear that ZIKV can be transmitted in utero from mother to fetus and that the consequences of congenital infection can be severe. Although not alone among infectious pathogens in its ability to cross the placenta and cause pathology in the developing fetus, ZIKV does present unique diagnostic challenges owing to its cross reactive serology with other flaviviruses. In this application, we propose a series of activities that will contribute substantially to our current understanding of maternal-fetal ZIKV infection. Through a city wide, surveillance of remnant antenatal and delivery blood specimens in León, Nicaragua, we will study ZIKV epidemiology in this mostly ZIKV naïve population, investigating rates of – and risk factors for – vertical transmission at the population level. Our approach makes use of “remnant” specimens collected at delivery and during pregnancy to categorize infants according to their ZIKV exposure and infection status. We will also test new diagnostic protocols under development at the UNC School of Medicine, investigate the fetal/newborn immune response to ZIKV exposure, and follow a cohort of infants for neurodevelopmental outcomes.