Neurodevelopmental Outcomes in ZIKV-Exposed Children

NCT04398901 | Enrolling By Invitation

• 2 other identifiers: Pro000127591R01HD102445-01
• Study Type: observational
• Target: 204
• Locations: 2 countries
• Sites: 2

Brief Summary

In this study the investigators will follow the neurodevelopmental outcome of children with in utero ZIKV exposure who do not have microcephaly or severe abnormalities consistent with Congenital Zika Syndrome. The ZIKV-exposed children will be compared to non-ZIKV exposed controls. Children will be assessed at age 3 and 4 years using standardized neurodevelopmental assessments. Children will also have neurodevelopmental assessment at age 5 and 7 years along with a brain MRI at age 7 years.

Conditions

Zika Virus; Congenital Zika Syndrome; Congenital Infection; Child Development

Keywords

ZIKV

Outcome Measures

Primary Outcomes (4)

• Neurodevelopmental assessment at age 4 years

  PEDI-CAT score

  4 years of age

• Executive function

  BRIEF-2 score

  5 and 7 years of age

• Motor function assessment

  MABC-2 score

  5 and 7 years of age

• Brain maturation

  Quantitative brain MRI volumetric measurement

  7 years of age

Secondary Outcomes (2)

• Motor function assessment

  4 years of age

• Intellectual ability

  5 and 7 years of age

Study Arms (4)

Colombia ZIKV-exposed

Seventy children in Colombia were previously enrolled as part of a fetal-neonatal neuroimaging study in 2016-2017 and were from Department of Atlantico, Colombia on the Caribbean coast. Eligible children had prior normal fetal MRI and fetal US, normal birth head circumference, normal clinical exam, no more than mild non-specific postnatal imaging findings, and are thus without findings of CZS.

Other: Neurodevelopmental assessments

Colombia Non-ZIKV exposed control

The investigators will enroll 70 non-ZIKV exposed children, age 4 to 5 years, in Department of Atlántico, Colombia with birth dates prior to March 31, 2016. Based on the arrival of ZIKV to Colombia in November 2015, this date would ensure a control cohort without congenital ZIKV exposure in the first half of gestation and unlikely during any of the pregnancy.

Other: Neurodevelopmental assessments

United States ZIKV-exposed

The US cohort either presented during pregnancy or after birth and sought clinical care with the Children's National Congenital Zika Program in Washington, DC and were ZIKV-exposed.

Other: Neurodevelopmental assessments

United States Non-ZIKV exposed control

The investigators will enroll 32 non-ZIKV exposed children, age 4 years, in Washington, DC.

Other: Neurodevelopmental assessments

Interventions

Neurodevelopmental assessments OTHER

The investigators will evaluate multiple domains of neurodevelopment at age 3, 4, 5 and 7 years using parental questionnaires and child exams. At age 7 years, the children will have a non-sedated quantitative brain MRI.

Colombia Non-ZIKV exposed control; Colombia ZIKV-exposed; United States Non-ZIKV exposed control; United States ZIKV-exposed

Eligibility Criteria

• Age: 3 Years - 7 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Zika-exposed children at 3-4 years of age (will be enrolled and studied up to age 8 years) Non-exposed controls at 4 to 5 years of age

You may qualify if:

• Zika-exposed cohort:
• born to mothers with Zika lab confirmation by PCR, IgM, and/or PRNT, or mother was symptomatic for Zika but infection could not be excluded due to late testing and evaluated at Children's National, Washington, DC (USA) or at BIOMELAB, Barranquilla (Colombia)
• normal fetal neuroimaging
• normal birth head circumference
• normal birth clinical exam
• no more than mild non-specific postnatal cranial ultrasound or brain MRI findings during infancy (if performed)
• able to be contacted for follow-up
• Non-ZIKV exposed Controls:
• healthy
• no chronic medical conditions
• no developmental concerns
• born at term (\>= 37 weeks)
• birth date prior to March 31, 2016 (Colombian controls)

You may not qualify if:

• Zika-exposed cohort:
• another diagnosis that would impact neurodevelopment
• Non-ZIKV exposed controls:
• chronic medical condition with in-patient hospitalization since birth
• under care of a medical specialty provider for a chronic medical condition
• history of seizure
• abnormal vision (children wearing corrective lenses are eligible)
• abnormal hearing affecting language development
• developmental concerns expressed by caregiver
• receiving physical, occupational, speech or developmental therapy
• receiving special education services in school
• behavioral or psychological condition
• birth date March 31, 2016 or later (Colombian controls)
• preterm birth (≤36 weeks)
• planned relocation of child within 5 years and likely inability to complete study

Sponsors & Collaborators

• Children's National Research Institute: lead
• Thrasher Research Fund: collaborator
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Biomelab

Barranquilla, Atlántico, Colombia

Location

Related Publications (12)

• Mulkey SB, Peyton C, Ansusinha E, Corn E, Arroyave-Wessel M, Zhang A, Biddle C, Gutierrez C, Sorkar A, Cure A, Cure D, du Plessis AJ, DeBiasi RL, Msall ME, Cure C. Preschool neurodevelopment in Zika virus-exposed children without congenital Zika syndrome. Pediatr Res. 2023 Jul;94(1):178-184. doi: 10.1038/s41390-022-02373-5. Epub 2022 Nov 30.

  PMID: 36446920 BACKGROUND

• Mulkey SB, Corn E, Williams ME, Peyton C, Andringa-Seed R, Arroyave-Wessel M, Vezina G, Bulas DI, Podolsky RH, Msall ME, Cure C. Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry. Pathogens. 2024 Feb 13;13(2):170. doi: 10.3390/pathogens13020170.

  PMID: 38392908 BACKGROUND

• Corn E, Andringa-Seed R, Williams ME, Arroyave-Wessel M, Tarud R, Vezina G, Podolsky RH, Kapse K, Limperopoulos C, Berl MM, Cure C, Mulkey SB. Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia. Pediatr Radiol. 2024 Aug;54(9):1513-1522. doi: 10.1007/s00247-024-05964-y. Epub 2024 Jul 6.

  PMID: 38970708 BACKGROUND

• Mulkey SB, Corn E, Williams ME, Ansusinha E, Podolsky RH, Arroyave-Wessel M, Vezina G, Peyton C, Msall ME, DeBiasi RL. Neurodevelopmental Outcomes of Preschoolers with Antenatal Zika Virus Exposure Born in the United States. Pathogens. 2024 Jun 27;13(7):542. doi: 10.3390/pathogens13070542.

  PMID: 39057769 BACKGROUND

• Mulkey SB, Arroyave-Wessel M, Peyton C, Ansusinha E, Gutierrez C, Sorkar A, Cure A, Samper Y, Cure D, Msall ME, Cure C. Harnessing the power of telemedicine to accomplish international pediatric outcome research during the COVID-19 pandemic. J Telemed Telecare. 2024 Feb;30(2):388-392. doi: 10.1177/1357633X211063166. Epub 2021 Dec 28.

  PMID: 34962177 BACKGROUND

• Mulkey SB, Williams ME, Peyton C, Arroyave-Wessel M, Berl MM, Cure C, Msall ME. Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure. Pediatr Res. 2024 Aug;96(3):654-662. doi: 10.1038/s41390-024-03056-z. Epub 2024 Mar 4.

  PMID: 38438554 BACKGROUND

• Williams ME, Corn EA, Martinez Ransanz S, Berl MM, Andringa-Seed R, Mulkey SB. Neurodevelopmental assessments used to measure preschoolers' cognitive development in Latin America: a systematic review. J Pediatr Psychol. 2024 May 16;49(5):321-339. doi: 10.1093/jpepsy/jsad089.

  PMID: 38244996 BACKGROUND

• Mulkey SB, Andringa-Seed R, Corn E, Williams ME, Arroyave-Wessel M, Podolsky RH, Peyton C, Msall ME, Cure C, Berl MM. School-age child neurodevelopment following antenatal Zika virus exposure. Pediatr Res. 2025 Nov;98(5):1856-1863. doi: 10.1038/s41390-025-03981-7. Epub 2025 Mar 19.

  PMID: 40108430 BACKGROUND

• Mulkey SB, DeBiasi RL. Do Not Judge a Book by Its Cover: Critical Need for Longitudinal Neurodevelopmental Assessment of In Utero Zika-Exposed Children. Am J Trop Med Hyg. 2020 May;102(5):913-914. doi: 10.4269/ajtmh.20-0197. No abstract available.

  PMID: 32274991 BACKGROUND

• Mulkey SB, Bulas DI, Vezina G, Fourzali Y, Morales A, Arroyave-Wessel M, Swisher CB, Cristante C, Russo SM, Encinales L, Pacheco N, Kousa YA, Lanciotti RS, Cure C, DeBiasi RL, du Plessis AJ. Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure. JAMA Pediatr. 2019 Jan 1;173(1):52-59. doi: 10.1001/jamapediatrics.2018.4138.

  PMID: 30476967 BACKGROUND

• Mulkey SB, Arroyave-Wessel M, Peyton C, Bulas DI, Fourzali Y, Jiang J, Russo S, McCarter R, Msall ME, du Plessis AJ, DeBiasi RL, Cure C. Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome. JAMA Pediatr. 2020 Mar 1;174(3):269-276. doi: 10.1001/jamapediatrics.2019.5204.

  PMID: 31904798 BACKGROUND

• Mulkey SB, Ansusinha E, Cristante C, Russo SM, Biddle C, Kousa YA, Pesacreta L, Jantausch B, Hanisch B, Harik N, Hamdy RF, Hahn A, Chang T, Jaafar M, Ambrose T, Vezina G, Bulas DI, Wessel D, du Plessis AJ, DeBiasi RL. Complexities of Zika Diagnosis and Evaluation in a U.S. Congenital Zika Program. Am J Trop Med Hyg. 2021 Apr 19;104(6):2210-2219. doi: 10.4269/ajtmh.20-1256.

  PMID: 33872214 BACKGROUND

MeSH Terms

Conditions

Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Study Officials

• Sarah B Mulkey, MD, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professsor Pediatrics and Neurology

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 21, 2020
• Study Start: November 23, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 3, 2025

Record last verified: 2025-06

Locations

US (1); CO (1)