[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
BMJ Open. 2019 Jun 18;9(6):e026092. doi: 10.1136/bmjopen-2018-026092.
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.
Wilder-Smith A1, Wei Y2, Araújo TVB3, VanKerkhove M4, Turchi Martelli CM5, Turchi MD6, Teixeira M7, Tami A8, Souza J9, Sousa P10, Soriano-Arandes A11, Soria-Segarra C12, Sanchez Clemente N13, Rosenberger KD14, Reveiz L15, Prata-Barbosa A16, Pomar L17, Pelá Rosado LE18, Perez F19, Passos SD20, Nogueira M21, Noel TP22, Moura da Silva A23, Moreira ME24, Morales I14, Miranda Montoya MC25, Miranda-Filho DB26, Maxwell L27,28, Macpherson CNL22, Low N29, Lan Z30, LaBeaud AD31, Koopmans M32, Kim C33, João E34, Jaenisch T14, Hofer CB35, Gustafson P36, Gérardin P37,38, Ganz JS39, Dias ACF7, Elias V40, Duarte G41, Debray TPA42, Cafferata ML43, Buekens P44, Broutet N33, Brickley EB45, Brasil P46, Brant F7, Bethencourt S47, Benedetti A48, Avelino-Silva VL49, Ximenes RAA50, Alves da Cunha A51, Alger J52; Zika Virus Individual Participant Data Consortium.
Collaborators (33): Abreu de Carvalho LM, Batista R, Bertozzi AP, Carles G, Cotrim D, Damasceno L, Dimitrakis L, Duarte Rodrigues MM, Estofolete CF, Fragoso da Silveira Gouvêa MI, Fumadó-Pérez V, Gazeta RE, Kaydos-Daniels N, Gilboa S, Krystosik A, Lambert V, López-Hortelano MG, Mussi-Pinhata MM, Nelson C, Nielsen K, Oliani DM, Rabello R, Ribeiro M, Rockx B, Rodrigues LC, Salgado S, Silveira K, Sulleiro E, Tong V, Valencia D, De Souza WV, Villar Centeno LA, Zin A.
Author information: 1 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. 2 Centre for Mathematical Sciences, University of Plymouth, Plymouth, UK. 3 Department of Social Medicine, Universidade Federal de Pernambuco, Recife, Brazil. 4 Health Emergencies Programme, Organisation mondiale de la Sante, Geneve, Switzerland. 5 Department of Collective Health, Institute Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation, Recife, Brazil. 6 Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia, Brazil. 7 Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 8 Department of Medical Microbiology, University Medical Center Groningen, Groningen, The Netherlands. 9 Department of Social Medicine, University of São Paulo, São Paulo, Brazil. 10 Reference Center for Neurodevelopment, Assistance, and Rehabilitation of Children, State Department of Health of Maranhão, Sao Luís, Brazil. 11 Department of Pediatrics, University Hospital Vall d’Hebron, Barcelona, Spain. 12 SOSECALI C. Ltda, Guayaquil, Ecuador. 13 Department of Epidemiology, University of São Paulo, São Paulo, Brazil. 14 Department of Infectious Diseases, Section Clinical Tropical Medicine, UniversitatsKlinikum Heidelberg, Heidelberg, Germany. 15 Evidence and Intelligence for Action in Health, Pan American Health Organization, Washington, District of Columbia, USA. 16 Department of Pediatrics, D’Or Institute for Research & Education, Rio de Janeiro, Brazil. 17 Department of Obstetrics and Gynecology, Centre Hospitalier de l’Ouest Guyanais, Saint-Laurent du Maroni, French Guiana. 18 Hospital Materno Infantil de Goiânia, Goiânia State Health Secretary, Goiás, Brazil. 19 Communicable Diseases and Environmental Determinants of Health Department, Pan American Health Organization, Washington, District of Columbia, USA. 20 Department of Pediatrics, FMJ, São Paulo, Brazil. 21 Faculdade de Medicina de Sao Jose do Rio Preto, Department of Dermatologic Diseases, São José do Rio Preto, Brazil. 22 Windward Islands Research and Education Foundation, St. George’s University, True Blue Point, Grenada. 23 Department of Public Health, Universidade Federal do Maranhão – São Luís, São Luís, Brazil. 24 Department of Neonatology, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. 25 Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. 26 Faculty of Medical Sciences, University of Pernambuco, Recife, Brazil. 27 Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 28 Hubert Department of Global Health, Emory University, Atlanta, Georgia, USA. 29 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 30 McGill University Health Centre, McGill University, Montréal, Canada. 31 Pediatric Infectious Diseases, Stanford Hospital, Palo Alto, California, USA. 32 Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands. 33 Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 34 Department of Infectious Diseases, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. 35 Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 36 Statistics, University of British Columbia, British Columbia, Vancouver, Canada. 37 INSERM CIC1410 Clinical Epidemiology, CHU La Réunion, Saint Pierre, Réunion. 38 UM 134 PIMIT (CNRS 9192, INSERM U1187, IRD 249, Université de la Réunion), Universite de la Reunion, Sainte Clotilde, Réunion. 39 Children’s Hospital Juvencio Matos, São Luís, Brazil. 40 Sustainable Development and Environmental Health, Pan American Health Organization, Washington, District of Columbia, USA. 41 Department of Gynecology and Obstetrics, University of São Paulo, São Paulo, Brazil. 42 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 43 Mother and Children Health Research Department, Instituto de Efectividad Clinica y Sanitaria, Buenos Aires, Argentina. 44 School of Public Health and Tropical Medicine, Tulane University, New Orleans, USA. 45 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. 46 Instituto de pesquisa Clínica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. 47 Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Carabobo, Bolivarian Republic of Venezuela. 48 Departments of Medicine and of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Quebec, Canada. 49 Department of Infectious and Parasitic Diseases, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil. 50 Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil. 51 Department of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 52 Facultad de Ciencias Médicas, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras.
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).
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
KEYWORDS: Microcephaly; Zika Virus; congenital Zika syndrome; individual participant data meta-analysisis; prognosis; risk prediction model
PMID: 31217315 DOI: 10.1136/bmjopen-2018-026092
Keywords: Zika Virus; Microcephaly; Pregnancy; Zika Congenital Infection; Zika Congenital Syndrome.