Clinical progression and predictors of outcomes in congenital Zika syndrome - PROJECT SUMMARY/ABSTRACT Although rates of congenital Zika virus syndrome (CZS) have declined since the 2015–2016 Zika virus (ZIKV) outbreak in Brazil, transmission of the virus still occurs, with nearly 9,000 cases reported already in 2023. Without global eradication, the threat of another large outbreak exists. Longitudinal research is necessary to better understand the long-term impact of CZS and factors associated with various health outcomes. For this application, we will extend our successful collaboration between RTI International and Altino Ventura Foundation (FAV), to include the University of North Carolina and Purdue University to bring new, expanded expertise in imaging, EEG, and heart rate sustained attention. We will continue to evaluate the impact of severe CZS on the medical and developmental outcomes for 187 children who have been followed since birth. Our cohort, now entering middle childhood, is the largest sample of children with well- documented CZS to be followed longitudinally since infancy. We will examine the evolution of the primary clinical signs of CZS (brain, ocular, orthopedic) and assess the long-term medical, developmental, and mental health outcomes for children with CZS and their families using innovative approaches, such as a novel heart-rate variability paradigm, that address specific challenges in accurately assessing the development of children with severe disabilities. Lastly, we will examine malleable predictors of outcomes for children and their families. This study has the potential to contribute to global knowledge that could lead to improved outcomes for children and families living with CZS and for children impacted by other conditions with similar clinical findings.