Neurodevelopmental Outcomes in ZIKV-Exposed Children

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.

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.

Eligibility Criteria:
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