Abstract
OBJECTIVES: To support the Zika virus (ZIKV) Individual Participant Data (IPD) Consortium's efforts to harmonise and analyse IPD from ZIKV-related prospective cohort studies and surveillance-based studies of pregnant women and their infants and children; we developed and disseminated a metadata survey among ZIKV-IPD Meta-Analysis (MA) study participants to identify and provide a comprehensive overview of study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions. SETTING: Cohort and surveillance studies that measured ZIKV infection during pregnancy or at birth and measured fetal, infant, or child outcomes were identified through a systematic search and consultations with ZIKV researchers and Ministries of Health from 20 countries or territories. PARTICIPANTS: Fifty-four cohort or active surveillance studies shared deidentified data for the IPD-MA and completed the metadata survey, representing 33 061 women (11 020 with ZIKV) and 18 281 children. PRIMARY AND SECONDARY OUTCOME MEASURES: Study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions. RESULTS: Median study sample size was 268 (IQR=100, 698). Inclusion criteria, follow-up procedures and exposure and outcome ascertainment were highly heterogenous, differing meaningfully across regions and multisite studies. Enrolment duration and follow-up for children after birth varied before and after the declaration of the Public Health Emergency of International Concern (PHEIC) and according to the type of funding received. CONCLUSION: This work highlights the logistic and statistical challenges that must be addressed to account for the multiple sources of within-study and between-study heterogeneity when conducting IPD-MAs of data collected in the research response to emergent pathogens like ZIKV.