TY - JOUR
T1 - 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
AU - Wilder-Smith, Annelies
AU - Wei, Yinghui
AU - Araújo, Thalia Velho Barreto De
AU - Vankerkhove, Maria
AU - Turchi, Marília Dalva
AU - Turchi, Marília Dalva
AU - Teixeira, Mauro
AU - Tami, Adriana
AU - Souza, João
AU - Sousa, Patricia
AU - Soriano-Arandes, Antoni
AU - Soria-Segarra, Carmen
AU - Sanchez, Clemente N
AU - Rosenberger, Kerstin Daniela
AU - Reveiz, Ludovic
AU - Prata-Barbosa, Arnaldo
AU - Pomar, Léo
AU - Pelá, Rosado LE
AU - Perez, Freddy
AU - Passos, Saulo D.
AU - Nogueira, Mauricio
AU - Noel, Trevor P.
AU - Moura, da Silva A
AU - Moreira, Maria Elisabeth
AU - Morales, Ivonne
AU - Miranda, Montoya MC
AU - Miranda-Filho, Demócrito De Barros
AU - Maxwell, Lauren
AU - Macpherson, Calum N.L.
AU - Low, Nicola
AU - Lan, Zhiyi
AU - Labeaud, Angelle Desiree
AU - Koopmans, Marion
AU - Kim, Caron
AU - João, Esaú
AU - Jaenisch, Thomas
AU - Hofer, Cristina Barroso
AU - Gustafson, Paul
AU - Gérardin, Patrick
AU - Ganz, Jucelia S.
AU - Dias, Ana Carolina Fialho
AU - Elias, Vanessa
AU - Duarte, Geraldo
AU - Debray, Thomas Paul Alfons
AU - Cafferata, María Luisa
AU - Buekens, Pierre
AU - Broutet, Nathalie
AU - Brickley, Elizabeth B.
AU - Brasil, Patrícia
AU - Brant, Fátima
AU - Bethencourt, Sarah
AU - Benedetti, Andrea
AU - Avelino-Silva, Vivian Lida
AU - Ximenes, Ricardo Arraes De Alencar
AU - Alves, da Cunha A
AU - Alger, Jackeline
PY - 2019/6
Y1 - 2019/6
N2 - IntroductionZika 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 analysisWe 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 disseminationThe 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 numberPROSPERO International prospective register of systematic reviews (CRD42017068915).
AB - IntroductionZika 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 analysisWe 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 disseminationThe 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 numberPROSPERO International prospective register of systematic reviews (CRD42017068915).
U2 - 10.1136/bmjopen-2018-026092
DO - 10.1136/bmjopen-2018-026092
M3 - Article
SN - 2044-6055
VL - 9
SP - e026092-e026092
JO - BMJ Open
JF - BMJ Open
IS - 6
ER -
