Neurodevelopmental Outcomes of Children Following In Utero Exposure to Zika in Nicaragua

• Type of Material: Article
• Authors: Elizabeth M Stringer, University of North Carolina Chapel Hill; Evelin Martinez, National Autonomous University of Nicaragua at León; Bryan Blette, University of North Carolina Chapel Hill; Christain Eduardo Toval Ruiz, National Autonomous University of Nicaragua at León; Michael Boivin, Michigan State University; Omar Zepeda, Natl Autonomous Univ Nicaragua Leon; Jeffrey SA Stringer, University of North Carolina Chapel Hill; Marlen Morales, Natl Autonomous Univ Nicaragua Leon; Shiara Ortiz-Pujols, New York Presbyterian Hosp; Itziar Familiar, Michigan State University; Matthew Collins, Emory University; Meylin Chavarria, National Autonomous University of Nicaragua at León; Barbara Goldman, University of North Carolina Chapel Hill; Natalie Bowman, University of North Carolina Chapel Hill; Aravinda de Silva, University of North Carolina Chapel Hill; Daniel Westreich, University of North Carolina Chapel Hill; Michael Hudgens, University of North Carolina Chapel Hill; Sylvia Becker-Dreps, University of North Carolina Chapel Hill; Filemon Bucardo, National Autonomous University of Nicaragua at León
• Language: English
• Date: 2021-03-01
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciaa1833
• Title of Journal or Parent Work: CLINICAL INFECTIOUS DISEASES
• Volume: 72
• Issue: 5
• Start Page: E146
• End Page: E153
• Grant/Funding Information: This work was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number R01 HD094009 to E. M. S.) and the National Institute for Allergy and Infectious Diseases (grant numbers R21AI137902 and K24AI141744 to S. B.-D.) and R21 AI137902 to N. B.). S. B. -D. and O. Z. are also supported through the Fogarty Global Health Training Program D43-TW010923. This work was also supported by an internal grant Emerging Challenges in Biomedical Research pilot award from the University of North Carolina School of Medicine.
• Keywords: Infectious Diseases; children; Science & Technology; Life Sciences & Biomedicine; neurodevelopmental outcome; Zika; Nicaragua; VIRUS; Microbiology; Immunology
• Research Categories: Health Sciences, Public Health; Health Sciences, Epidemiology; Biology, Microbiology; Biology, Biostatistics

Abstract

Background: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. Methods: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. Results: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P =. 01) and low-birthweight infants (<2500 g) (P =. 006) had lower composite ECL scores. Conclusions: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.