Heterogeneity of Zika virus exposure and outcome ascertainment across cohorts of pregnant women, their infants and their children: a metadata survey

BMJ Open. 2022 Nov 22;12(11):e064362. doi: 10.1136/bmjopen-2022-064362.


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.

Keywords: Epidemiology; INFECTIOUS DISEASES; Public health.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Child
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Meta-Analysis as Topic
  • Metadata
  • Parturition
  • Pregnancy
  • Pregnancy Complications, Infectious* / epidemiology
  • Pregnant Women
  • Prospective Studies
  • Zika Virus Infection* / complications
  • Zika Virus Infection* / epidemiology
  • Zika Virus*