ZIKAlliance Pregnant Women Cohort (ZIKAlliancePW)

Pregnant Women (PW) Cohort for Evaluation of Risks of Congenital Malformations and Other Adverse Pregnancy Outcomes After Zika Virus Infection (Part of ZIKAlliance)

The aim of this proposal is to evaluate the causal relationship between Zika virus (ZIKV) infections in pregnancy and congenital malformations. We will estimate the absolute and relative risks of congenital malformations and other adverse outcomes of pregnancy among women who become infected with ZIKV during pregnancy compared to uninfected pregnant women, also leading to further validation of the Congenital Zika Syndrome.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Zika Virus

Detailed Description

The aim of this proposal is to evaluate the causal relationship between Zika virus (ZIKV) infections in pregnancy and congenital malformations. We will estimate the absolute and relative risks of congenital malformations and other adverse outcomes of pregnancy among women who become infected with ZIKV during pregnancy compared to uninfected pregnant women, also leading to further validation of the Congenital Zika Syndrome.

We will also determine the ZIKV maternal to child transmission rate and evaluate co-factors or effect modifiers that account for the large variability seen in the preliminary absolute risk estimates derived from population figures and reporting of microcephaly in different states in Brazil and across Latin America.

We will carry out a pregnant women (PW) multicentre cohort study in areas across Latin America and the Caribbean. Women will be enrolled early in pregnancy and followed every 4 weeks, in connection with their routine antenatal care visits. At each visit, urine and blood samples will be collected, tested and stored.

Among PW reporting recent or current undifferentiated fever/rash syndrome at any point in time, the acute illness episode will be characterized in greater detail. PW with suspected ZIKV infection (i.e. meeting the Pan American Health Organization (PAHO) clinical case definition) during pregnancy will be managed according to national protocols. Irrespective of symptoms, pregnant women will be followed prospectively and revisited at birth (or after abortion) for a detailed documentation of the outcome of their pregnancy.

Live newborns will receive a detailed neonatal examination. In the course of examination of the newborns, biological samples will be collected and stored. Other potential causes of congenital abnormalities (TORCHS infections in the mother, toxic substances, chromosomal abnormalities), and potential effect modifiers (for example past flavivirus infections/vaccinations, socio-economic status) will also be assessed.

With appropriate counselling and consent, biological samples of newborns with severe abnormalities, deceased newborns, stillborn babies, and aborted foetuses from ZIKV-infected mothers will be collected to help elucidate the aetiological contribution of ZIKV in neurological and other congenital malformations.

Children of women infected with ZIKV during pregnancy - and a subset of the children born to uninfected women - will be followed prospectively after birth for the assessment of neuro-developmental milestones (separate protocol).

• Study Type: Observational
• Enrollment (Actual): 3852

Contacts and Locations

Study Locations

• Bolivia
  • Guaqui, Bolivia
    • Sosecali Ltd. (SOSE)
  • Santa Cruz, Bolivia
    • Inserm
• Brazil
  • Bahia, Brazil
    • Federal University of Bahia (UFB)
  • Belo Horizonte, Brazil
    • Universidade Federal de Minas Gerais
  • Goiás, Brazil
    • Federal University of Goiás
  • Recife, Brazil
    • Fundacao Oswaldo Cruz (FIOCRUZ)
  • Rio de Janeiro, Brazil
    • Fundacao Oswaldo Cruz (FIOCRUZ)
  • São Paulo, Brazil
    • University of Sao Paulo
• Colombia
  • Bucaramanga, Colombia
    • Industrial University of Santander (UIS)
• Cuba
  • Havana, Cuba
    • Pedro Kouri Institute (IPK)
• Guadeloupe
  • Pointe-à-Pitre, Guadeloupe
    • Inserm
• Mexico
  • Guadalajara, Mexico
    • IMSS Mexico (IMSS)
  • Mérida, Mexico
    • National Institute of Public Health (INSP)
• Venezuela
  • Valencia, Venezuela
    • Universidad de Carabobo / UMC Groningen (UMCG)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Pregnant Women

Description

Inclusion Criteria:

• at least 16 years old
• Pregnancy status confirmed
• Within first or second trimester or first month of marked transmission season

Exclusion Criteria:

• Planing to leave area
• Unable to attend follow-up visits
• Unable to undergo venipuncture
• Participates in another pregnant women study for ZIKA
• Unable to consent without legal guardian

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pregnant Women

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Congenital Abnormalities	At birth

Collaborators and Investigators

• Sponsor: University of Heidelberg Medical Center
• Collaborators: London School of Hygiene and Tropical Medicine; Institut National de la Santé Et de la Recherche Médicale, France; University Medical Center Groningen; Erasmus Medical Center; University of Sao Paulo; Oswaldo Cruz Foundation; Instituto Mexicano del Seguro Social; European Union; Universidade Federal de Goias; Federal University of Bahia; Universidad Industrial de Santander; Mexican National Institute of Public Health; ZIKAlliance; University of Carabobo; Sosecali Hospital, Guyaquil; Instituto de Medicina Tropical "Pedro Kourí (IPK), Cuba
• Investigators: Principal Investigator: Thomas Jänisch, University Hospital Heidelberg

Publications and helpful links

General Publications

• Avelino-Silva VI, Mayaud P, Tami A, Miranda MC, Rosenberger KD, Alexander N, Nacul L, Segurado A, Pohl M, Bethencourt S, Villar LA, Viana IFT, Rabello R, Soria C, Salgado SP, Gotuzzo E, Guzman MG, Martinez PA, Lopez-Gatell H, Hegewisch-Taylor J, Borja-Aburto VH, Gonzalez C, Netto EM, Saba Villarroel PM, Hoen B, Brasil P, Marques ETA, Rockx B, Koopmans M, de Lamballerie X, Jaenisch T; ZIKAlliance Clinical Study Group. Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium. BMC Infect Dis. 2019 Dec 26;19(1):1081. doi: 10.1186/s12879-019-4685-9.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Dengue; Pregnant Women; Chikungunya; ZIKA; Pregnant Woman; ZIKV
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Zika Virus Infection
• Other Study ID Numbers: 734548PW (EC | H2020 | RIA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The ZIKAlliance birth cohort is part of the 3 EC-funded Zika consortia. The data are intended to be shared after the individual cohort data is analyzed and published.; The ZIKAlliance birth cohort is part of the WHO-moderated IPD meta-analysis Consortium. The data are intended to be shared after the individual cohort data is analyzed and published.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No