Clinical trial NCT03393286: ZIKAlliance Children Cohort (ZIKAllianceCH)
Official title: Children (CH) Cohort for the Evaluation of Developmental and Neurological Abnormalities in Infants Born to Mothers Residing in Areas With Zika Virus Transmission During Pregnancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Zika Virus
Lead sponsor: University of Heidelberg Medical Center
Sponsor class: OTHER
First posted: 2018-01-08
Enrollment: 1554
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: New born children

Brief summary: The aim of this proposal is to evaluate the causal relationship between Zika virus (ZIKV) infections in pregnancy and congenital malformations. The study 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. The study 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.

The study 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.

The study 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.

Eligibility criteria: Inclusion Criteria:

* Born within the Pregnant Woman cohort
* Born to mothers with confirmed ZIKA

Exclusion Criteria:

-

Primary outcomes:
measure: Congenital Abnormalities detected after birth as defined by the evolving definition of the congenital zika syndrome
timeFrame: Birth
measure: Hearing abnormalities measured after birth
timeFrame: Between birth and 2 years
measure: Visual abnormalities measured after birth
timeFrame: Between birth and 2 years
measure: Developmental / cognitive abnormalities measured by the Ages and Stages 3rd Edition (ASQ3)
timeFrame: Between birth and 2 years
measure: Developmental / cognitive abnormalities measured by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Guaqui
country: Bolivia
facility: Sosecali Ltd. (SOSE)
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:
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.