Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

DOI
Publisher DOI
PubMed ID
31217315
Abstract
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).
Date Issued
2019-06-18
Publication Type
Article
Subject(s)
Subjects
Microcephaly Zika Virus congenital Zika syndrome individual participant data meta-analysisis prognosis risk prediction model
Language(s)
en
Author(s)
Wilder-Smith, Annelies
Wei, Yinghui
Araújo, Thalia Velho Barreto de
VanKerkhove, Maria
Turchi Martelli, Celina Maria
Turchi, Marília Dalva
Teixeira, Mauro
Tami, Adriana
Souza, João
Sousa, Patricia
Soriano-Arandes, Antoni
Soria-Segarra, Carmen
Sanchez Clemente, Nuria
Rosenberger, Kerstin Daniela
Reveiz, Ludovic
Prata-Barbosa, Arnaldo
Pomar, Léo
Pelá Rosado, Luiza Emylce
Perez, Freddy
Passos, Saulo D
Nogueira, Mauricio
Noel, Trevor P
Moura da Silva, Antônio
Moreira, Maria Elisabeth
Morales, Ivonne
Miranda Montoya, Maria Consuelo
Miranda-Filho, Demócrito de Barros
Maxwell, Lauren
Macpherson, Calum N L
Lan, Zhiyi
LaBeaud, Angelle Desiree
Koopmans, Marion
Kim, Caron
João, Esaú
Jaenisch, Thomas
Hofer, Cristina Barroso
Gustafson, Paul
Gérardin, Patrick
Ganz, Jucelia S
Dias, Ana Carolina Fialho
Elias, Vanessa
Duarte, Geraldo
Debray, Thomas Paul Alfons
Cafferata, María Luisa
Buekens, Pierre
Broutet, Nathalie
Brickley, Elizabeth B
Brasil, Patrícia
Brant, Fátima
Bethencourt, Sarah
Benedetti, Andrea
Avelino-Silva, Vivian Lida
Ximenes, Ricardo Arraes de Alencar
Alves da Cunha, Antonio
Alger, Jackeline
Additional Credits
Journal
BMJ open
Publisher
BMJ Publishing Group
ISSN
2044-6055
Access(Rights)
open.access
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