Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Research Article
  • Published:

School-age child neurodevelopment following antenatal Zika virus exposure

Pediatric Research volume 98, pages 1856–1863 (2025)Cite this article

Abstract

Background

Children exposed antenatally to Zika virus (ZIKV) during the 2015-2016 epidemic are now in school; little is known about their neurodevelopment at this age. The objective was to evaluate neurodevelopment of ZIKV-exposed Colombian children compared to non-exposed controls at ages 5–6.

Methods

In total, 48 normocephalic children with antenatal ZIKV exposure (Cases) were recruited for a longitudinal cohort study in Atlántico, Colombia. Two age-matched control groups of 118 non-ZIKV-exposed children were recruited from same communities as Cases: 63 born before ZIKV epidemic but experienced COVID-19-related school entry delays, and 55 born post-ZIKV epidemic but started school on time. Multi-domain neurodevelopment was assessed at 5–6 years using standardized measures. Standard regression and proportional odds models were used to compare outcomes. P values were adjusted using the Benjamini-Hochberg false discovery rate (FDR) (p < 0.05).

Results

There were no differences in age at assessment between groups. Case Full-Scale IQ scores were lower than both control groups (p = 0.002), driven by visual reasoning (p < 0.001). Controls with school entry delay had more executive control problems and lower adaptive functioning skills than Cases and Controls without school entry delay.

Conclusions

ZIKV-exposed children have lower cognitive performance compared to controls. Early childhood experiences can affect pediatric outcomes research.

Impact

  • Normocephalic ZIKV-exposed children have lower full-scale IQ than their unexposed peers from the same communities.

  • Normocephalic children with antenatal ZIKV exposure have differences in neurodevelopment that can impact them long-term.

  • There is a need for continued follow-up of children with antenatal ZIKV exposure to determine long-term effects on higher-order areas of cognitive function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Waves of COVID-19 pandemic, school closures, and 5–6-year evaluations of Cases, Control-School Entry Delay (SED) and Control-No School Entry Delay (NSED) children.
Fig. 3: Domains of functioning at age 5–6 years in ZIKV-exposed cases and non-exposed control groups.

Similar content being viewed by others

Data availability

De-identified data are available from the corresponding author upon reasonable request.

References

  1. Walker, C. L. et al. Zika virus and the nonmicrocephalic fetus: Why we should still worry. Am. J. Obstet. Gynecol. 220, 45–56 (2019).

    Article  PubMed  Google Scholar 

  2. Marbán-Castro, E. et al. Neurodevelopment in normocephalic children exposed to Zika virus in utero with no observable defects at birth: A systematic review with meta-analysis. Int. J. Environ. Res. Public Health 19, 7319 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Blackmon, K. et al. Neurodevelopment in normocephalic children with and without prenatal Zika virus exposure. Arch. Dis. Child. 107, 244 (2022).

    Article  PubMed  Google Scholar 

  4. Grant, R. et al. In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study. BMC Med 19, 12 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fernandes, M. et al. Does intra-uterine exposure to the zika virus increase risks of cognitive delay at preschool ages? findings from a Zika-Exposed Cohort from Grenada, West Indies. Viruses 15, 1290 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Alger, J. et al. Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people. Pediatr. Res. 95, 566–572 (2024).

    Article  PubMed  CAS  Google Scholar 

  7. Nielsen-Saines, K. et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat. Med. 25, 1213–1217 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Mulkey, S. B. et al. Preschool neurodevelopment in Zika virus-exposed children without congenital Zika syndrome. Pediatr. Res. 94, 178–184 (2023).

    Article  PubMed  Google Scholar 

  9. Mulkey, S. B. et al. Neurodevelopmental outcomes of normocephalic colombian children with antenatal Zika virus exposure at school entry. Pathogens 13, 170 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Adebanjo, T. et al. Update: Interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection - United States, October 2017. MMWR Morb. Mortal. Wkly. Rep. 66, 1089–1099 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hcini, N. et al. Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life. Nat. Commun. 12, 3270 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Mulkey, S. B. et al. Sequential neuroimaging of the fetus and newborn with in Utero Zika virus exposure. JAMA Pediatr. 173, 52–59 (2019).

    Article  PubMed  Google Scholar 

  13. Mulkey, S. B. et al. Neurodevelopmental abnormalities in children with in Utero Zika virus exposure without congenital Zika Syndrome. JAMA Pediatr. 174, 269–276 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kuehn, L. M. et al. Socioemotional development of infants and toddlers during the COVID-19 Pandemic. JAMA Pediatr. 178, 151–159 (2024).

    Article  PubMed  Google Scholar 

  15. Rouse, H. L. et al. Developmental impacts of the COVID-19 pandemic on young children: A conceptual model for research with integrated administrative data systems. Int. J. Popul. Data Sci. 5, 1651 (2020).

    PubMed  Google Scholar 

  16. de Laia Almeida, I. L., Rego, J. F., Teixeira, A. C. G. & Moreira, M. R. Social isolation and its impact on child and adolescent development: a systematic review. Rev. Paul. Pediatr. 40, e2020385 (2022).

  17. Chaabane, S., Doraiswamy, S., Chaabna, K., Mamtani, R. & Cheema, S. The impact of COVID-19 school closure on child and adolescent health: A rapid systematic review. Child Basel 8, 415 (2021).

    Article  Google Scholar 

  18. Pan American Health Organization/World Health Organization. Zika Epidemiological Report - Colombia. 7 https://www.paho.org/en/documents/zika-epidemiological-report-colombia (2017).

  19. Ministerio de Salud y Protección Social. Colombia, primer país del continente que cierra epidemia de zika. Ministerio de Salud y Protección Social. https://www.minsalud.gov.co/Paginas/Colombia-primer-pais-del-continente-que-cierra-epidemia-de-zika.aspx (2016).

  20. Mulkey, S. B. et al. Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure. Pediatr. Res. 96, 654–662 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gioia, G. A., Isquith, P. K., Guy, S. C. & Kenworthy, L. Behavior Rating Inventory of Executive Function® Second Edition. (PAR, 2015).

  22. Harrison, P. L. & Oakland, T. ABAS-3: Adaptive Behavior Assessment System. (Western Psychological Services, Los Angeles, CA, 2015).

  23. Achenbach, T. M. & Rescorla, L. A. Manual for the ASEBA School-Age Forms & Profiles. (University of Vermont Research Center for Children, Youth, & Families, 2001).

  24. Dunn, L., Lugo, D., Padilla, E. & Dunn, L. Test de Vocabulario en Imágenes Peabody. (American Guidance Service, Circle Pines, MN, 1986).

  25. Henderson, S. E., Sugden, D. & Barnett, A. L. Movement Assessment Battery for Children-2. (Pearson, 2007).

  26. Wechsler, D. Wechsler preschool and primary scale of intelligence—fourth edition. (Psychol. Corp., San Antonio, TX, 2012).

  27. Weintraub, S. et al. I. NIH Toolbox Cognition Battery (CB): introduction and pediatric data. Monogr. Soc. Res. Child Dev. 78, 1–15 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mulkey, S. B. et al. Harnessing the power of telemedicine to accomplish international pediatric outcome research during the COVID-19 pandemic. J. Telemed. Telecare. 30, 388–392 (2024).

    Article  PubMed  Google Scholar 

  29. Harris, P. A. et al. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inf. 42, 377–381 (2009).

    Article  Google Scholar 

  30. R. Core Team. _R: A Language and Environment for Statistical Computing_. https://www.R-project.org/ (2023).

  31. Chica-Olmo, J., Sánchez, A. & Sepúlveda-Murillo, F. H. Assessing Colombia’s policy of socio-economic stratification: An intra-city study of self-reported quality of life. Cities 97, 102560 (2020).

    Article  Google Scholar 

  32. Krasileva, K. E., Sanders, S. J. & Bal, V. H. Peabody picture vocabulary test: Proxy for verbal IQ in genetic studies of autism spectrum disorder. J. Autism Dev. Disord. 47, 1073–1085 (2017).

    Article  PubMed  Google Scholar 

  33. Yates, E. F. & Mulkey, S. B. Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned. Pediatr. Res. 96, 64–72 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Roth, N. M. et al. Notes from the field: Autism spectrum disorder among children with laboratory evidence of prenatal Zika virus exposure - Puerto Rico, 2023. MMWR Morb. Mortal. Wkly. Rep. 72, 802–804 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Anderson, P. Assessment and development of executive function (EF) during childhood. Child Neuropsychol. 8, 71–82 (2002).

    Article  PubMed  Google Scholar 

  36. Williams, M. E. et al. Neurodevelopmental assessments used to measure preschoolers’ cognitive development in Latin America: a systematic review. J. Pediatr. Psychol. 49, 321–339 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Peçanha, P. M. et al. Neurodevelopment of children exposed intra-uterus by Zika virus: A case series. PLOS ONE 15, e0229434 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Anderson, V. et al. Children’s executive functions: Are they poorer after very early brain insult. Neuropsychologia 48, 2041–2050 (2010).

    Article  PubMed  Google Scholar 

  39. Mulkey, S. B. et al. Neurodevelopmental outcomes of preschoolers with antenatal Zika virus exposure born in the United States. Pathogens 13, 542 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chichinina, E. A. & Gavrilova, M. N. Growth of executive functions in preschool-age children during the COVID-19 lockdown: Empirical evidence. Psychol. Russ. 15, 124–136 (2022).

    PubMed  PubMed Central  Google Scholar 

  41. Günindi, Y. The effect of online education on children’s social skills during the COVID-19 pandemic. Int. Electron. J. Elem. Educ. 14, 657–665 (2023).

    Google Scholar 

  42. Cheng, S. Y., Tai, H. L. & Wang, T. T. Impact of COVID-19 pandemic on children’s fundamental motor skills: A study for the taiwanese preschoolers teachers. Int. J. Environ. Res. Public Health 20, 6764 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kılıç, M. & Koçak, Ş. Examination of psycho-motor development of children who were 6–36 months in the COVID-19 stay-at-home period. Sci. Rep. 13, 20801 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the children and families in this study for their continued engagement and participation across years of research and evaluation. We thank Liliana Villegas Echeverri, Daniela Rodriguez, Julieth Cajar, and Lida Utria for conducting the neuropsychological evaluations of the participants. We are also thankful for Ana Cecilia Perez, Ramiro Galindo, Javier Restrepo, Miguel Castillo, Lorenzo Cervantes, and Jose Ospino, the research study coordinators and assistants from BIOMELab in Barranquilla, Colombia, for their long-standing collaboration and dedication to this research. Finally, the authors thank Drs. Adre du Plessis, Roberta DeBiasi, and David Wessel for their support of this research and of the Congenital Infection Program at Children’s National Hospital.

Funding

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Numbers R01HD102445 and 3R01HD102445-04S1 (PI: Mulkey), and P50HD105328-01 (PI: Gaillard). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Zickler Family Prenatal Pediatrics Institute, Children’s National Hospital, Washington, DC, USA

    Sarah B. Mulkey, Regan Andringa-Seed, Elizabeth Corn, Meagan E. Williams & Margarita Arroyave-Wessel

  2. Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Sarah B. Mulkey

  3. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Sarah B. Mulkey & Madison M. Berl

  4. Division of Biostatistics and Study Methodology, Children’s National Hospital, Washington, DC, USA

    Robert H. Podolsky

  5. Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Colleen Peyton

  6. Kennedy Research Center on Intellectual and Neurodevelopmental Disabilities, University of Chicago Medicine, Chicago, IL, USA

    Michael E. Msall

  7. BIOMELab, Barranquilla, Atlántico, Colombia

    Carlos Cure

  8. Division of Pediatric Neuropsychology, Children’s National Hospital, Washington, DC, USA

    Madison M. Berl

  9. Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Madison M. Berl

Authors
  1. Sarah B. Mulkey
    View author publications

    Search author on:PubMed Google Scholar

  2. Regan Andringa-Seed
    View author publications

    Search author on:PubMed Google Scholar

  3. Elizabeth Corn
    View author publications

    Search author on:PubMed Google Scholar

  4. Meagan E. Williams
    View author publications

    Search author on:PubMed Google Scholar

  5. Margarita Arroyave-Wessel
    View author publications

    Search author on:PubMed Google Scholar

  6. Robert H. Podolsky
    View author publications

    Search author on:PubMed Google Scholar

  7. Colleen Peyton
    View author publications

    Search author on:PubMed Google Scholar

  8. Michael E. Msall
    View author publications

    Search author on:PubMed Google Scholar

  9. Carlos Cure
    View author publications

    Search author on:PubMed Google Scholar

  10. Madison M. Berl
    View author publications

    Search author on:PubMed Google Scholar

Contributions

S.B.M. conceptualized and designed the study, obtained funding for the study, developed data collection instruments, trained the study team, reviewed study data, interpreted study data and results of data analyses, drafted the initial manuscript, and reviewed and revised the manuscript. R.A.-S. trained the study team, collected study data, reviewed study data, interpreted study data and data analyses, drafted the initial manuscript, and reviewed and revised the manuscript. E.C. trained the study team, collected study data, reviewed study data, interpreted study data, and reviewed and revised the manuscript. M.E.W. reviewed study data, interpreted study data, developed figures for the manuscript, and reviewed and revised the manuscript. M.A.-W. conceptualized and designed the study, translated data collection instruments, trained the study team, oversaw the use of telehealth for study activities, and reviewed and revised the manuscript. R.H.P. analyzed and interpreted study data, drafted initial tables for the manuscript, and reviewed and revised the manuscript. C.P. conceptualized and designed the study, trained the study team, reviewed study data, and reviewed and revised the manuscript. M.E.M. conceptualized and designed the study, provided additional insight into data interpretation, and reviewed and revised the manuscript. C.C. conceptualized and designed the study, recruited study participants, oversaw data collection, reviewed study data, and reviewed and revised the manuscript. M.M.B. conceptualized and designed the study, trained the study team, reviewed and interpreted data and data analyses, drafted the initial manuscript, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sarah B. Mulkey.

Ethics declarations

Competing interests

The authors declare no competing interests.

Consent statement

Parents or legal guardians provided written informed consent for their child’s participation.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mulkey, S.B., Andringa-Seed, R., Corn, E. et al. School-age child neurodevelopment following antenatal Zika virus exposure. Pediatr Res 98, 1856–1863 (2025). https://doi.org/10.1038/s41390-025-03981-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41390-025-03981-7

This article is cited by

Search

Advanced search

Quick links