Neurodevelopmental Outcomes in ZIKV-Exposed Children

Child Development Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04398901
• Other study ID #: Pro00012759
• Secondary ID: 1R01HD102445-01
• Status: Enrolling by invitation
• Start date: November 23, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: August 2022
• Source: Children's National Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 204
• Est. completion date: June 30, 2025
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 6 Years

Eligibility

Inclusion Criteria:

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)

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Child Development
• Congenital Infection
• Congenital Zika Syndrome
• Syndrome
• Zika Virus
• Zika Virus Infection

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Colombia	Biomelab	Barranquilla	Atlantico
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
Children's National Research Institute	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Thrasher Research Fund

Countries where clinical trial is conducted

United States,  Colombia, 

References & Publications (4)

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. — View Citation

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. Erratum in: JAMA Pediatr. 2020 Mar 1;174(3):305. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurodevelopmental assessment at age 4 years	PEDI-CAT score	4 years of age
Primary	Executive function	BRIEF-2 score	5 and 7 years of age
Primary	Motor function assessment	MABC-2 score	5 and 7 years of age
Primary	Brain maturation	Quantitative brain MRI volumetric measurement	7 years of age
Secondary	Motor function assessment	MABC-2 score	4 years of age
Secondary	Intellectual ability	Age-appropriate Wechsler	5 and 7 years of age