Introduction Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.
Methods and analysis We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.
Ethics and dissemination The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.
Trial registration number PROSPERO International prospective register of systematic reviews (CRD42017068915).
- individual participant data meta-analysisis
- congenital Zika syndrome
- Zika Virus
- risk prediction model
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Contributors NB, CBH, TJ, NL, LM, JS and LR contributed to the initial conception of the study. AB, TD, PG, NL, LM and YW made substantial contributions to the statistical methodology proposed for the IPD-MA. LM wrote the first draft of the protocol. AW-S, YW, TVBA, MV, CMTM, MDT, MT, AT, PS, JPS, AS-A, CSS, AMS, NSC, KDR, LR, APB, LP, LEPR, FP, SP, MN, TN, MEM, IM, MCMM, DBMF, LM, CM, NL, ZL, ADL, MK, CK, EJ, TJ, CH, PG, PG, JG, ACFD, VE, GD, TPAD, MLC, PB, NB, EB, PB, FB, SB, AB, VAS, RAAX, AAC and JA provided substantial revisions to the protocol. All authors approved the final version of the protocol.
Funding The development of the IPD-MA protocol was supported by a Wellcome Trust grant to the WHO Department of Reproductive Health and Research Human Reproduction Programme, grant number 206532/Z/17/Z.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators Liège Maria Abreu de Carvalho; Rosangela Batista; Ana Paula Bertozzi; Gabriel Carles; Denise Cotrim; Luana Damasceno; Lady Dimitrakis; María Manoela Duarte Rodrigues; Cassia F. Estofolete; Maria Isabel Fragoso da Silveira Gouvêa; Vicky Fumadó-Pérez; Rosa Estela Gazeta; Neely Kaydos-Daniels; Suzanne Gilboa; Amy Krystosik; Véronique Lambert; Milagros García López-Hortelano; Marisa Marcia Mussi-Pinhata; Christina Nelson; Karin Nielsen; Denise M. Oliani; Renata Rabello; Marizelia Ribeiro; Barry Rockx; Laura C. Rodrigues; Silvia Salgado; Katia Silveira; Elena Sulleiro; Van Tong; Diana Valencia; Wayner Vieira de Souza; Luis Angel Villar Centeno; Andrea Zin.
Patient consent for publication Not required.
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