Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

E.W. "Al" Thrasher

Status: Funded - Closed

Developmental Outcome After In Utero ZIKV Exposure in Children Without Congenital Zika Syndrome

Sarah Mulkey, MD, PhD


BACKGROUND: Children exposed to Zika-virus (ZIKV) in utero during the years of 2015-2017 are now in early childhood. Children with severe neurologic injury (congenital Zika syndrome; CZS) have a poor developmental outcome; however the developmental outcome of apparently normal infants following in utero ZIKV-exposure has not been established since these children are only now reaching early childhood. GAP: We will determine if children exposed to ZIKV in utero who are normal appearing at birth have abnormal neurodevelopment in early childhood and the specific domains and degree to which they are impacted. HYPOTHESIS: We hypothesize that ZIKV-exposed normal appearing children will have lower multi-domain developmental assessment scores at 3 and 4 years of age compared to non-ZIKV exposed controls. METHODS: We will perform a prospective neurodevelopmental outcome study of ZIKV-exposed children and of non-exposed controls in the Department of Atlántico, Colombia and at Children’s National Hospital, Washington, DC, USA. In Colombia, eligible controls were born prior to Zika entry into Colombia. In the United States and Colombian children, we will perform multi-domain neurodevelopmental assessments at age 3 and 4 years that include the Behavior Rating Inventory of Executive Function (BRIEF-P), the Pediatric Evaluation of Disability Inventory- Computerized Adaptive Test (PEDI-CAT), and the Movement Assessment Battery for Children (MABC-2). RESULTS: In Colombia, fifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC-2 between groups. In 11% of cases and 1% of controls, parents reported child mood problems. Results of the Colombia children at age 4-5 years and of the U.S. cohort are currently pending. IMPACT: The results of this study will inform the development of national and international guidelines for the long-term neurodevelopmental assessment of children exposed to ZIKV-in utero who do not have CZS. Website Link: Comments The results of this study will be among only a few studies with outcome data past age 2 years and will contribute to the World Health Organization IPD-MA.(Wilder-Smith A, et al. BMJ Open 2019).