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Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure

Pediatric Research (2024)Cite this article

Abstract

Since 2016, international research groups have focused on assessing outcomes of children with in utero Zika virus (ZIKV) exposure. While the more severe outcomes of congenital Zika syndrome (CZS) occur in up to 10% of children with antenatal exposure, early findings among ZIKV-exposed children without CZS ages 0–5 years suggest that they may also have differences in multiple domains of neurodevelopment. Thus, longitudinal follow-up of all children with antenatal ZIKV exposure has been recommended. This review presents a summary of neurodevelopmental phenotypes of infants and children following antenatal ZIKV exposure. We present a multidimensional framework to understand child neurodevelopment from an interdisciplinary and whole-child perspective (International Classification of Functioning, Disability and Health model) and multi-domain ZIKV Outcome Toolboxes. The toolboxes are for clinicians, researchers, child educators, and others to implement longitudinal multi-domain neurodevelopmental assessments between ages 0–12 years. Recent innovations in telehealth and neuroimaging can help evaluate outcomes in ZIKV exposed children. The objective is to describe the multiple facets of neurodevelopmental focused care that can support the health, function, and well-being of children with antenatal ZIKV exposure. The research and clinical follow-up strategies are applicable to ZIKV and other congenital infectious or environmental exposures that can impact child neurodevelopment.

Impact

  • International longitudinal cohort studies have revealed a range of differences in neurodevelopment among children with antenatal Zika virus (ZIKV) exposure.

  • A multidimensional and whole-child framework is necessary to understand the neurodevelopment of children with antenatal ZIKV exposure in relation to family life, community participation, and environment.

  • Multi-domain toolboxes that utilize parent questionnaires and child evaluations are presented. These toolboxes can be used internationally alongside telehealth, brain imaging, and other innovations to improve understanding of child outcomes.

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Fig. 1: Interdisciplinary collaboration and multiple facets of care in promoting long-term child health, function, and well-being of children with antenatal ZIKV exposure.
Fig. 2: International Classification of Functioning (ICF) Disability and Health framework.
Fig. 3: International Classification of Functioning (ICF) Disability and Health framework.

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Acknowledgements

We appreciate the families and their children who have participated in our research studies in the United States and in Colombia and experienced Zika virus firsthand or in their community. The ICF model was created in Spanish during a virtual interactive Zoom session with members of the Biomelab research team in Barranquilla, Colombia: Ana Cecilia Perez, Lorenzo Cervantes, Javier Restrepo, Ramiro Galindo, Jose Ospino, and Miguel Castillo. The ICF models were created in Spanish and translated by Regan Andringa-Seed, BA, a clinical research coordinator at Children’s National Hospital, Washington, DC.

Funding

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (grant number R01HD102445 [to S.B.M.]), the Thrasher Research Fund (to S.B.M.), the National Center for Advancing Translational Sciences (grant KL2TR001424 [to C.P.]), and the DC Intellectual and Developmental Disabilities Research Center (NICHD P50HD105328-01 [to M.M.B.]). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.B.M. has an additional contract with the US Centers for Disease Control and Prevention for work on Zika virus separate from this study and M.E.M. received additional funding from the Health Resources and Services Administration of the US Department of Health and Human Services under award UA6MC32492, the Life Course Intervention Research Network.

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Authors and Affiliations

  1. Children’s National Hospital, Washington, DC, USA

    Sarah B. Mulkey, Meagan E. Williams, Margarita Arroyave-Wessel & Madison M. Berl

  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

  4. Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, USA

    Colleen Peyton

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

    Madison M. Berl

  6. BIOMELab, Barranquilla, Colombia

    Carlos Cure

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

    Michael E. Msall

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Contributions

Sarah B. Mulkey—conceptualization, obtained funding, literature review, writing initial draft, participated in development of ICF models, review of manuscript and editing, review and approval of final draft. Meagan E. Williams—literature review, writing initial draft, developed figures and tables, participated in development of ICF models, review of manuscript and editing, review and approval of final draft. Colleen Peyton—conceptualization, literature review, writing initial draft, participated in development of ICF models, review of manuscript and editing, review and approval of final draft. Margarita Arroyave-Wessel—writing initial draft, participated in development of ICF models, review of manuscript and editing, review and approval of final draft. Madison M. Berl—conceptualization, writing initial draft, review of manuscript and editing, review and approval of final draft. Carlos Cure—conceptualization, participated in development of ICF models, review of manuscript and editing, review and approval of final draft. Michael E. Msall—conceptualization, literature review, writing initial draft, participated in development of ICF models, review of manuscript and editing, review and approval of final draft.

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Correspondence to Sarah B. Mulkey.

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Mulkey, S.B., Williams, M.E., Peyton, C. et al. Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03056-z

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