Title: Assessing Zika virus infection during pregnancy and adverse outcomes: The ZIKV Individual Participant Data Meta-analyses Phase II and surveillance-based IPD analysis (ZIKV-IPD-MA-2S)
Granting agency: CIHR
Period: 2 years
Amount: $
Assessing absolute and relative risk of Zika virus (ZIKV) adverse outcomes, including congenital malformations, fetal demise, neonatal and child mortality, or developmental issues, is challenging. Challenges in estimation include data scarcity, lack of appropriate ZIKV-exposure ascertainment (e.g., diagnosis and timing), and the unbiased attribution of adverse outcomes, especially on neurodevelopmental delays that may or may not have been seen yet. Zika is an arboviral disease transmitted by the bite of infected Aedes mosquitoes, introduced in the Americas region in 2015. The spread and magnitude of severe outcomes in 2016 constituted the declaration of a Public Health Emergency of International Concern. There is no vaccine or medication to treat ZIKV infection. After six years, some may think that ZIKV is no longer a threat, but in 2022 there were over 36,000 ZIKV cases in the Americas region. Still, the short- and especially the long-term effects of ZIKV are not sufficiently assessed.
To address these challenges, we propose a research project that leverages data from 64 studies (22 countries) participating in the ZIKV Individual Participant Data (IPD) Consortium, a World Health Organization (WHO) led collective initiative that assembled longitudinal studies assessing ZIKV exposure during pregnancy or at birth to conduct IPD meta-analyses (MA). The ZIKV-IPD Consortium currently counts on 64 cohorts and surveillance-based studies from 22 countries and territories in the Americas, Asia, Europe, and Africa; totaling 33,061 pregnant individuals from which 11,030 are confirmed ZIKV cases and 18,281 are children. Currently, 33 out of the 64 studies that contributed the data are harmonized.
Our project, the ZIKV-IPD-MA-2S, includes the Phase II of the consortium’s IPD-MA and focuses on addressing epidemiological and statistical challenges identified in preliminary analyses, specifically for surveillance-based studies (e.g., accounting for population at risk, differential reporting, and estimating population level risks); assessing neurodevelopmental delays and addressing measurement error. Therefore, our proposal aims specifically to:
1. Finalize the data contribution and harmonization of the 31 remaining ZIKV-IPD Consortium contributing studies for the IPD-MA Phase II.
2. Assess the short- and long-term adverse effects of ZIKV infection.
- Finalize the assessment of risk among cohort studies (fetal, infant, and child outcomes).
- Assess risk in the subset of surveillance-based studies (fetal, infant, and child outcomes).
- Assess neurodevelopmental delays by study design (infant and child outcomes).
3. Develop methodological approaches to address challenges related to measurement error and over or underreporting in the analysis of adverse outcomes due to ZIKV infection.
Our research has the potential to advance knowledge in the field of epidemiology, infectious diseases, and reproductive health. Our research team at McGill University and University of British Columbia (Canada), Utrecht Medical Center, Utrecht University (Netherlands), the ZIKV-IPD consortium (international partners from 22 countries), and our knowledge user the WHO, aim at leveraging existing data to assess the impact of ZIKV during pregnancy, generate evidence to inform public policy, healthcare providers, and pregnant individuals, improving prevention and vector control measures during imminent future outbreaks.