744 - Neurodevelopmental outcomes of Colombian children with antenatal Zika virus exposure at school age during the COVID-19 pandemic

Publication Number: 744.5800

Sarah B. Mulkey, Children's National Health System, Washington, DC, United States; Regan Andringa-Seed, Children's National Health System, Washington, DC, United States; Elizabeth Corn, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Meagan Williams, Children's National Health System, Washington, DC, United States; Colleen Peyton, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Margarita Arroyave-Wessel, Children's National Health System, Washington, DC, United States; Robert Podolsky, MedStar Health Research Institute, Rockville, MD, United States; Michael E. Msall, Comer Children's Hospital at University of Chicago Medical Center, Chicago, IL, United States; Madison Berl, Children's National Hospital, Washington, DC, United States; Carlos A. Cure, BIOMELAB SAS, Barranquilla, Atlantico, Colombia

Background: Children with antenatal Zika virus (ZIKV) exposure may be at risk for developmental delays, even in the absence of congenital Zika syndrome (CZS) or microcephaly. Little is known about their neurodevelopment at school age relative to their peers.

Objective: To evaluate multi-domain development of normocephalic children with antenatal ZIKV-exposure compared to non-exposed controls at ages 5-6. Secondarily, to compare two control groups who experienced the COVID-19 pandemic at different ages.

Design/Methods: Our prospective cohort study includes 48 ZIKV-exposed children without CZS (Cases) and two control groups of 118 non-exposed controls from rural and semi-rural communities in Atlántico, Colombia. Case maternal-fetal dyads were recruited during pregnancy following symptomatic, lab-confirmed ZIKV infection and followed serially. Control-1 children (n=63) were born prior to ZIKV entry to Colombia and Control-2 children (n=55) were born after the ZIKV epidemic. Control-2 children were enrolled due to COVID-19-related delays in school entry experienced by Control-1 but not Cases; like Cases, Control-2 experienced no delays in starting school (Figure). Neurodevelopment was assessed in all groups at ages 5-6 years using the Behavior Rating Inventory of Executive Function (BRIEF), Adaptive Behavior Assessment System (ABAS), Movement Assessment Battery for Children (MABC), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Standard regression models were used to compare outcomes with close-to-normal distributions; proportional odds models were used for those without. P-values were adjusted using the Benjamini-Hochberg false discovery rate (FDR) (significance, p< 0.05).

Results: Cases were evaluated at mean±SD age 5.9±0.2 years; Control-1 at 5.9±0.3 years; Control-2 at 5.2±0.2 years. Case WPPSI full-scale IQ scores were lower than both controls (p=0.002), driven by differences in Visual Spatial Index (p < 0.001) (Table). Control-2 MABC scores were lower than Control-1 and Cases (p < 0.001). BRIEF scores were elevated, and ABAS scores were lower, in Control-1 compared to Control-2 and Cases (p < 0.001) (Table).

Conclusion(s): ZIKV-exposed children without CZS have lower cognitive performance at school-age compared to controls, but do not demonstrate impairment in executive function or motor skills. Motor skills, executive function, and adaptive behavior are lower among controls who had COVID-19-related delay in starting school compared to controls born later. Early childhood COVID-19 experiences can affect pediatric outcomes research.

Table 1: Outcomes of child assessment measures
MABC-2= Movement Assessment Battery for Children, WPPSI-IV= Wechsler Preschool and Primary Scale of Intelligence, BRIEF-2= Behavior Rating Inventory of Executive Function, ABAS-3= Adaptive Behavior Assessment System

Figure: COVID-19 cases, school closures, and child evaluations
COVID-19 cases in Department of Atlantico, Colombia between 2020 and 2023 are shown. The gray box indicates the period of school closures in the state. The timing of the child evaluations for ZIKV-exposed children (orange), non-exposed control-1 (blue), and non-exposed control-2 (green) are shown.