Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)

NCT03255369 | Unknown DMC

• 1 other identifier: 52675616.0.0000.5269
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The recent increase in the number of cases of congenital microcephaly observed in Brazil is a reason of great concern. This increase occurred a few months after Zika virus (ZIKV) was introduced in the country, which was associated with reports of pregnant women presenting fever and rash illness during pregnancy. Thus, the hypothesis of a relationship between ZIKV infection and microcephaly became plausible. However, studies on the pathophysiology of maternal ZIKV infection, its consequences for the fetus, and the development of severe encephalopathy are still needed. Knowledge about the natural history of vertical transmission and its association with changes in fetal development in early life is still scarce. Studies on factors which determine the severity and clinical evolution, such as inflammatory response mechanisms, viral evolution, and development of serological tests to identify ZIKV infection, are still needed. The Aedes aegypti is responsible for the transmission of various types of viruses of interest to human health. Currently, it is primarily responsible for the transmission of the dengue, chikungunya, and ZIKV in epidemic proportions. In addition, it is not yet known whether there is an interaction between these viruses and whether the interaction can determine the severity of the disease. The aim of this study is to evaluate the natural history of ZIKV disease in two cohorts( pregnant women and children) starting with pregnant women or newborns or evennursing mothers, identifying risk biomarkers, mapping the anti-viral inflammatory response, evaluating the molecular evolution of the virus,which areimportant to determine the mechanisms of vertical viral infection and verify children neurodevelopment from birth to the end of 3rd year of life.

Conditions

ZIKA VIRUS INFECTION; Child Development; Microcephaly

Keywords

Zika virus; Microcephaly; Child; pregnancy

Outcome Measures

Primary Outcomes (1)

• Microcephaly and/or delay in development

  Microcephaly at birth or delay in development in Bayley test 3rd edition at 12, 18 and between 24-36 months of age

  36 months of age

Secondary Outcomes (2)

• ocular injury and cognitive disorder in Bayley Test 3rd edition

  36 months of age

• Hearing injury and language delay in Bayley Test 3rd edition

  36 monthsof age

Study Arms (3)

Child exposed Zika virus proved

child born to mothers with proved zika virus in pregnancy by RT-PCR

Other: Child exposed Zika virus proved

Child exposed to zika virus suspected

Child born with symptoms similar to babies proved exposed to zika virus but mothers without symptoms or positive RT-PCR

Other: Child exposed Zika virus proved

Normal Child

Normal child from mothers without Zika (IgG and IgM negative)

Other: Child exposed Zika virus proved

Interventions

Child exposed Zika virus proved OTHER

There will be applied Bayley Teste 3rd edition

Also known as: Child exposed Zika virus suspected

Child exposed Zika virus proved; Child exposed to zika virus suspected; Normal Child

Eligibility Criteria

• Age: 2 Days - 3 Years
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The exposure will be confirmed by the positivity in diagnostic tests (PCR or serological tests). Women with and without symptoms will have theirblood sampled for serological tests in the three trimesters of pregnancy and at birth. The pregnant women in the cohort presenting positive results for specifictests (PCR in the acute phase and serological tests later) will be considered exposed to infection whereas pregnant women with negative results will be considered not exposed.

You may qualify if:

• The study population will be composed of pregnant women who present symptoms compatible with ZIKAV infection, with skin rash, arthralgia-associated fever, myalgia, non-purulent conjunctivitis, or headache and asymptomatic pregnant women identified at the same time of possibility of exposure. We will include patients with RT- PCR positive.
• All pregnant women who are in the prenatal follow up at IFF and CSGSF, irrespective of the gestational age, are elegible as a not exposed in the beginning.
• Children born during the outbreak by mothers with confirmed infection, suspected infection and normal pregnancy

You may not qualify if:

• Pregnant women with chromosomal abnormalities detected during fetal life or birth will be excluded.

Sponsors & Collaborators

• Oswaldo Cruz Foundation: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Rio de Janeiro State Research Supporting Foundation (FAPERJ): collaborator

Study Sites (1)

Instituto Fernandes Figueira/Fiocruz

Rio de Janeiro, Rio de Janeiro, 22250020, Brazil

RECRUITING

Related Publications (5)

• Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, Zin AA, Horovitz D, Daltro P, Boechat M, Raja Gabaglia C, Carvalho de Sequeira P, Pilotto JH, Medialdea-Carrera R, Cotrim da Cunha D, Abreu de Carvalho LM, Pone M, Machado Siqueira A, Calvet GA, Rodrigues Baiao AE, Neves ES, Nassar de Carvalho PR, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, Bispo de Filippis AM, Nielsen-Saines K. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016 Dec 15;375(24):2321-2334. doi: 10.1056/NEJMoa1602412. Epub 2016 Mar 4.

  PMID: 26943629 BACKGROUND

• Chimelli L, Melo ASO, Avvad-Portari E, Wiley CA, Camacho AHS, Lopes VS, Machado HN, Andrade CV, Dock DCA, Moreira ME, Tovar-Moll F, Oliveira-Szejnfeld PS, Carvalho ACG, Ugarte ON, Batista AGM, Amorim MMR, Melo FO, Ferreira TA, Marinho JRL, Azevedo GS, Leal JIBF, da Costa RFM, Rehen S, Arruda MB, Brindeiro RM, Delvechio R, Aguiar RS, Tanuri A. The spectrum of neuropathological changes associated with congenital Zika virus infection. Acta Neuropathol. 2017 Jun;133(6):983-999. doi: 10.1007/s00401-017-1699-5. Epub 2017 Mar 22.

  PMID: 28332092 BACKGROUND

• Halai UA, Nielsen-Saines K, Moreira ML, de Sequeira PC, Junior JPP, de Araujo Zin A, Cherry J, Gabaglia CR, Gaw SL, Adachi K, Tsui I, Pilotto JH, Nogueira RR, de Filippis AMB, Brasil P. Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes. Clin Infect Dis. 2017 Sep 15;65(6):877-883. doi: 10.1093/cid/cix472.

  PMID: 28535184 BACKGROUND

• Zin AA, Tsui I, Rossetto J, Vasconcelos Z, Adachi K, Valderramos S, Halai UA, Pone MVDS, Pone SM, Silveira Filho JCB, Aibe MS, da Costa ACC, Zin OA, Belfort R Jr, Brasil P, Nielsen-Saines K, Moreira MEL. Screening Criteria for Ophthalmic Manifestations of Congenital Zika Virus Infection. JAMA Pediatr. 2017 Sep 1;171(9):847-854. doi: 10.1001/jamapediatrics.2017.1474.

  PMID: 28715527 RESULT

• Tiene SF, Cranston JS, Nielsen-Saines K, Kerin T, Fuller T, Vasconcelos Z, Marschik PB, Zhang D, Pone M, Pone S, Zin A, Brickley E, Orofino D, Brasil P, Adachi K, da Costa ACC, Lopes Moreira ME. Early Predictors of Poor Neurologic Outcomes in a Prospective Cohort of Infants With Antenatal Exposure to Zika Virus. Pediatr Infect Dis J. 2022 Mar 1;41(3):255-262. doi: 10.1097/INF.0000000000003379.

  PMID: 35144270 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Urine and blood for RT-PCR Blood for IgG and IgM Saliva for RT-PCR placenta oral swab for genetic studies fetal tissues stillborn for necropsy CSF and amniotic fluid if affected babies breastmilk

MeSH Terms

Conditions

Zika Virus Infection; Microcephaly

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Maria E Moreira, MD

  Fundação Oswaldo Cruz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria E Moreira, MD

CONTACT

552125541918; bebeth@iff.fiocruz.br

Zilton Vasconcelos, PhD

CONTACT

552125541919; zvasconcelos@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 21, 2017
• Study Start: January 2, 2016
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2019
• Last Updated: May 3, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR, ANALYTIC CODE
• Time Frame: 3 years
• Access Criteria: only the principal investigator

Locations

BR (1)