Neurodevelopmental Outcomes in ZIKV-Exposed Children

Children's National

Status: Invitation-only

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

Treatments: Other: Neurodevelopmental assessments

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04398901

1R01HD102445-01 (U.S. NIH Grant/Contract)

Pro00012759

Details and patient eligibility

About

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.

Full 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.

Enrollment: 204 estimated patients

Sex: All

Ages: 3 to 7 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

204 participants in 4 patient groups

Colombia ZIKV-exposed

Description:

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.

Treatment:

Other: Neurodevelopmental assessments

Colombia Non-ZIKV exposed control

Description:

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.

Treatment:

Other: Neurodevelopmental assessments

United States ZIKV-exposed

Description:

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.

Treatment:

Other: Neurodevelopmental assessments

United States Non-ZIKV exposed control

Description:

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

Treatment:

Other: Neurodevelopmental assessments