Zika virus in Pregnancy in a Honduran cohort: neurodevelopmental assessment of normocephalic children born to Zika virus exposed and non-exposed pregnant people
Authors: Alger Jackeline , Cafferata María Luisa , López Raquel , Wiggins Lisa D. , Callejas Allison , Castillo Mario , Fúnes Jenny , Rico Fátima , Valencia Diana , Varela Douglas , Alvarez Zulma , Berrueta Mabel , Bock Harry , Bustillo Carolina , Calderón Alejandra , Ciganda Alvaro , García Jorge , García Kimberly , Gibbons Luz , Gilboa Suzanne M. , Harville Emily W. , Hernández Gustavo , López Wendy , Lorenzana Ivette , Luque Marco T. , Maldonado Carlos , Moore Cynthia , Ochoa Carlos , Parham Leda , Pastrana Karla , Paternina-Caicedo Angel , Rodríguez Heriberto , Stella Candela , Tannis Ayzsa F. , Wesson Dawn , Zúniga Concepción , Tong Van T. , Buekens Pierre 
Published: March 2023

Abstract
Background
Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results limited by the absence of a comparison group. The present study aimed to assess the neurodevelopmental outcomes among a cohort of children born with normal head circumference from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study between July and December 2016.
Methods
Enrollment of pregnant people was voluntary and occurred during their first prenatal visit at a health center in Tegucigalpa, with collection of venous blood. Children with the following characteristics were selected for the longitudinal follow-up study: normal birth head circumference, > 6 months of age, born at one of two hospitals in Tegucigalpa, and known in utero ZIKV exposure status. In utero exposure to ZIKV was defined as a positive prenatal ZIKV IgM and/or positive ZIKV RNA result at enrollment. The developmental evaluation included Spanish language versions of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional, Second Edition (ASQ:SE-2).
Results
One hundred fifty-two children were assessed between May 2018 and March 2020. The mean age was 2.0 years, and > 93% had adequate anthropometric growth. Sixty children were exposed to ZIKV during pregnancy. BSID-III and ASQ:SE-2 were performed in 151 and 152 children, respectively. Forty-one children had a delay (< 85 composite score) in any of the BSID-III domains. There were no statistically significant differences between exposed and unexposed groups; however, children with in utero exposure to ZIKV had lower cognitive and language scores that persisted after adjusting for maternal age and education and after excluding children born preterm and low birth weight from the analysis. Assessment of socioemotional development showed that 92% of children had adequate development with a score equal to or below the cutoff point; there were no statistically significant differences between exposed and non-exposed children.
Conclusions
The exploration of cognitive and language differences in ZIKV exposed vs. non-exposed children could be informed by additional research in larger samples. Children with prenatal ZIKV exposure can be monitored for cognitive and language delays and referred for interventions as needed.