Neurodevelopmental Outcomes in ZIKV-Exposed Children

Официальное название

Developmental Outcome After In Utero ZIKV Exposure in Children Without Congenital Zika Syndrome

Обзор

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.

Подробное описание

Zika-virus (ZIKV) infection in pregnancy can result in severe brain damage in 4-12% of cases. Children exposed to ZIKV in utero during the years of 2015-2017 are now in early childhood. Children with severe neurologic injury (Congenital Zika Syndrome; CZS) have a poor developmental outcome, however the developmental outcome of apparently normal infants following in utero ZIKV-exposure is not well known. The incidence of abnormal neurodevelopmental outcome in apparently normal children with in utero ZIKV-exposure is not known.

The investigators will determine if neurodevelopmental assessment scores in children exposed to ZIKV in utero who are normal appearing differ from norms. The investigators hypothesize that ZIKV-exposed normal appearing children will have lower multi-domain developmental assessment scores compared to normative samples. The investigators hypothesize that the presence of mild postnatal non-specific cranial US findings is associated with persistent lower developmental assessment scores compared to ZIKV-exposed children who had normal cranial US and quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls..

The investigators will perform a prospective developmental outcome study at 2 sites: 1) Department of Atlántico, Colombia through collaboration with BIOMELAB, the research center of Dr. Carlos Cure, and 2) Children's National, Washington, DC.

The objective of the study is to determine whether children who were exposed to ZIKV in utero and who do not have CZS have abnormalities in neurodevelopment during early childhood and at school age.

The primary outcome at early childhood will be neurodevelopmental assessment scores at age 3 and 4 years. Scores will be compared between Zika-exposed children and controls. The primary outcome at school age will be neurodevelopmental assessment scores at age 5 and 7 years and quantitative brain MRI at 7 years.

Вмешательства

• Другое Neurodevelopmental assessments
  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.

Первичные конечные точки

• Neurodevelopmental assessment at age 4 years [Срок оценки: 4 years of age]
• Executive function [Срок оценки: 5 and 7 years of age]
• Motor function assessment [Срок оценки: 5 and 7 years of age]
• Brain maturation [Срок оценки: 7 years of age]

Вторичные конечные точки (2)

• Motor function assessment [Срок оценки: 4 years of age]
• Intellectual ability [Срок оценки: 5 and 7 years of age]

Критерии участия

Критерии включения

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)

Критерии исключения

Zika-exposed cohort:

• another diagnosis that would impact neurodevelopment
• abnormal brain MRI (non-specific mild findings are not an exclusion criteria)

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
• surgery with general anesthesia since birth (brief anesthesia for ear tubes, tonsillectomy, or other minor pediatric procedure is not an exclusion criteria)
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Children's National Hospital — Washington D.C.

Колумбия · 1 центр

• Biomelab — Barranquilla

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT04398901 · Pro00012759 · 1R01HD102445-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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