Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero (ZENI)

Risk Evaluation of Fetal Nervous System and Neurodevelopment Disorders in Infants of Women Exposed to Zika Virus Infection During Pregnancy

This prospective cohort study will determine the natural history of fetal exposure to Zika virus (ZIKV) and its effects on the fetus and newborn with emphasis on neurodevelopment outcome. Exposure of the fetus will be determined by maternal symptomatology, RT-PCR ZIKV (blood and urine) and serologic test specific for ZIKV. Neonates will be classified according to trimester of infection and as exposed and unexposed to ZIKV.

Study Overview

• Status: Completed
• Conditions: Microcephaly; Mental Retardation
• Intervention / Treatment: Other: Symptomatic pregnant women with positive RT-PCR ZIKV in serum or urine, or a positive serologic test specific for ZIKV

Detailed Description

Infection with Zika Virus (ZIKV) is an emerging disease in South America and a serious public health problem due to a high prevalence of one of the vectors that transmit the virus, Aedes Aegypti, and the severe and sometimes fatal complications that can be generated in the fetus of women infected by the virus during their pregnancy. Retrospective studies have shown an association with microcephaly, cerebral calcifications, dysgenesis of the corpus callosum, and other anomalies of the central nervous system (CNS). The high risk of neurodevelopmental impairment in the exposed newborn is a major concern.

The epidemiologic and neurobiological evidence supporting the link between infection of pregnant women, trimester of infection, and the development of such anomalies in the fetus is growing to the extent that the Center for Disease Control has officially made a statement supporting this association. Although the dimension of the public health impact is still unknown, limited prospective data makes counseling of pregnant women difficult, especially when they are considering termination of pregnancy.

Given that evidence supporting the neurotropic quality of ZIKV and the potential variations of the effect the virus may have on the developing fetal brain according to the gestational age of infection, we have designed a prospective cohort study to determine whether exposure of the fetus to ZIKV in symptomatic mothers results in fetal CNS anomalies and/or impaired neurodevelopmental outcome of the newborn. As a secondary aim we will determine the effect gestational age has on severity of CNS anomalies and neurodevelopmental outcome.

• Study Type: Observational
• Enrollment (Actual): 284

Contacts and Locations

• Study Contact: Name: Mario A Rojas, MD, MPH; Phone Number: 3301 577634000; Email: mario.augusto.rojas@gmail.com
• Study Contact Backup: Name: Luis A Diaz, MD, MSc; Phone Number: 3301 577634000; Email: ladimar@uis.edu.co

Study Locations

• Colombia
  • Santander
    • Bucaramanga, Santander, Colombia, 68001
      • Hospital Universitario de Santander

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

ZIKV symptomatic and asymptomatic pregnant women in hyper endemic areas of ZIKV in Colombia

Description

Inclusion Criteria:

1. Pregnant women who on their first prenatal visit (independent of gestational age) confirm through a pre-designed questionnaire that they have had any symptom(s) compatible with ZIKV infection (rash [exanthema or sprout], conjunctivitis, arthralgia or myalgia, fever). Pregnant women with an affirmative response will be categorized in two groups:

   • Acute Infection: symptoms of ZIKV infection that occurred within the previous 14 days of the day the pregnant women attended her prenatal visit.
   • Late Infection: symptoms of ZIKV infection that occurred more then 14 days from her prenatal visit. Gestational age of onset of symptomatology will be documented at this time.
2. Pregnant women without symptoms of ZIKV infection who have a negative RT-PCR for ZIKV and a negative specific serologic test for ZIKV at initial prenatal visit with normal prenatal evaluation. These pregnant women will be selected from non high-risk delivery services.

Exclusion Criteria:

1. Eligible pregnant women that refuse to sign consent for participation in the ZEN Initiative.
2. Enrolled pregnant women that withdraw their consent to participate at any time in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed; Symptomatic pregnant women with positive RT-PCR ZIKV in serum or urine, or a positive serologic test specific for ZIKV	Other: Symptomatic pregnant women with positive RT-PCR ZIKV in serum or urine, or a positive serologic test specific for ZIKV
Unexposed; Asymptomatic pregnant women with a negative RT-PCR ZIKV in serum and urine, and a negative specific serology for ZIKV at enrollment into the study and at the time of delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental Outcome	Bayley Scales of Infant and Toddler Development Third Edition	24 months corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal CNS Impairment	Prenatal Level III Ultrasound Identification of Fetal CNS Abnormalities	Until Birth

Collaborators and Investigators

• Sponsor: Universidad Industrial de Santander
• Collaborators: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Mario A Rojas, MD, MPH, Professor of Pediatrics; Study Director: Luz A Gutierrez, MD, Universidad Industrial de Santander; Study Chair: Luis A Diaz, MD, MSc, Universidad Industrial de Santander

Publications and helpful links

General Publications

• Diaz-Martinez LA, Rojas MA, Pinilla-Garcia LS, Becerra-Mojica CH, Perez-Vera LA, Gutierrez-Sanchez LA, Contreras-Garcia GA, Rueda-Ordonez CG, Villar L. Neurodevelopmental outcome of infants without central nervous system anomalies born to symptomatic RT-PCR ZIKV positive women. PLoS Negl Trop Dis. 2022 Mar 7;16(3):e0009854. doi: 10.1371/journal.pntd.0009854. eCollection 2022 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): December 15, 2020
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Child Development; Pregnancy; Developmental Disabilities; Fetal Development; Zika Virus Infection
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Neurologic Manifestations; Neurobehavioral Manifestations; Congenital Abnormalities; Musculoskeletal Diseases; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Neurodevelopmental Disorders; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Microcephaly; Intellectual Disability; Zika Virus Infection
• Other Study ID Numbers: 4110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No