Clinical trial NCT03188731: ZIKAlliance Pregnant Women Cohort
Official title: Pregnant Women (PW) Cohort for Evaluation of Risks of Congenital Malformations and Other Adverse Pregnancy Outcomes After Zika Virus Infection (Part of ZIKAlliance)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Zika Virus
Pregnancy Related
Keywords: ZIKA
Dengue
Chikungunya
Pregnant Women
Pregnant Woman
ZIKV
Lead sponsor: University of Heidelberg Medical Center
Sponsor class: OTHER
Collaborators: name: European Union
name: ZIKAlliance
name: Oswaldo Cruz Foundation
name: University of Sao Paulo
name: London School of Hygiene and Tropical Medicine
name: Federal University of Bahia
name: Universidade Federal de Goias
name: University Medical Center Groningen
name: University of Carabobo
name: Universidad Industrial de Santander
name: Sosecali Hospital, Guyaquil
name: Instituto de Medicina Tropical "Pedro Kourí (IPK), Cuba
name: Mexican National Institute of Public Health
name: Instituto Mexicano del Seguro Social
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Erasmus Medical Center
First posted: 2017-06-15
Enrollment: 3852
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pregnant Women

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Congenital Abnormalities
timeFrame: At birth
Secondary outcomes:
Other outcomes:
Locations:
city: Guaqui
country: Bolivia
facility: Sosecali Ltd. (SOSE)
city: Santa Cruz
country: Bolivia
facility: INSERM
city: Bahia
country: Brazil
facility: Federal University of Bahia (UFB)
city: Belo Horizonte
country: Brazil
facility: Universidade Federal de Minas Gerais
city: Goiás
country: Brazil
facility: Federal University of Goias
city: Recife
country: Brazil
facility: Fundacao Oswaldo Cruz (FIOCRUZ)
city: Rio de Janeiro
country: Brazil
facility: Fundacao Oswaldo Cruz (FIOCRUZ)
city: São Paulo
country: Brazil
facility: University of Sao Paulo
city: Bucaramanga
country: Colombia
facility: Industrial University of Santander (UIS)
city: Havana
country: Cuba
facility: Pedro Kouri Institute (IPK)
city: Pointe-à-Pitre
country: Guadeloupe
facility: INSERM
city: Guadalajara
country: Mexico
facility: IMSS Mexico (IMSS)
city: Mérida
country: Mexico
facility: National Institute of Public Health (INSP)
city: Valencia
country: Venezuela
facility: Universidad de Carabobo / UMC Groningen (UMCG)
Study officials:
affiliation: University Hospital Heidelberg
name: Thomas Jänisch
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.