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

Author:

Stringer Elizabeth M1,Martinez Evelin2,Blette Bryan3,Toval Ruiz Christian Eduardo2,Boivin Michael4,Zepeda Omar2,Stringer Jeffrey S A1,Morales Marlen2,Ortiz-Pujols Shiara5,Familiar Itziar4,Collins Matthew6,Chavarria Meylin2,Goldman Barbara7,Bowman Natalie8,de Silva Aravinda9,Westreich Daniel10,Hudgens Michael3,Becker-Dreps Sylvia11,Bucardo Filemon2ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

2. Department of Microbiology, Faculty of Medical Science, National Autonomous University of Nicaragua at León, Managua, Nicaragua

3. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

4. Department of Psychiatry, Michigan State University, East Lansing, Michigan, USA

5. Division of Endocrinology, New York–Presbyterian Hospital and Weill Cornell Medical Center, New York, New York, USA

6. Department of Medicine, Emory University, Atlanta, Georgia, USA

7. Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

8. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

9. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

10. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

11. Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Abstract

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.

Funder

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute of Allergy and Infectious Diseases

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference38 articles.

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4. Zika virus associated with microcephaly;Mlakar;N Engl J Med,2016

5. Vector-borne transmission and evolution of Zika virus;Gutiérrez-Bugallo;Nat Ecol Evol,2019

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