Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barre syndrome: a living systematic review
Open accessAbstract
Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I 2 =19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I 2 =0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I 2 =0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I 2 =0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I 2 =74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.
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Viral infections such as Zika and SARS-CoV-2 have been associated with neurologic syndromes that include dysautonomia and GI complaints in some patients.
“Viral infections such as Zika and SARS-CoV-2 have also been associated with neurologic syndromes that include dysautonomia and GI complaints in some patients (Counotte et al., 2019; Ghannam et al., 2020).”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Counotte et al., 2019
The Results > GBS section reports a consistent association between Zika virus infection and Guillain-Barré syndrome, supporting the Zika-related neurologic-syndrome portion of the claim. Our copy does not report dysautonomia or GI complaints as features of that syndrome; searches for autonomic dysfunction and gastrointestinal symptoms did not establish those details. The separate SARS-CoV-2 citation is not assessed here. (LLM, conf=0.87)
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141st Annual Meeting of the American Neurological Association
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The Role of Amniocentesis in the Diagnosis of Congenital Zika Syndrome
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- Authors
- Counotte, M. J., Meili, K. W., Taghavi, K., Calvet, G., Sejvar, J., & Low, N.
- Affiliations
- University of Bern (CH)
- Instituto Nacional de Infectologia Evandro Chagas (BR)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Counotte, Michel Jacques
- Low, Nicola
- ORCID
- Venue
- F1000Research
- Publisher
- F1000 Research Ltd
- Published
- 2019-08-14
- Volume
- 8
- Pages
- 1433
- ISSN
- 2046-1402 (ISSN-L)
- PMC
- PMC6852328
- OpenAlex
- W3033655606
- Cited by
- 29
- References
- 284
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 7 · 2019: 1 · 2015: 1
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- F1000Research (publishedVersion, cc-by)
- Americanae (AECID Library) (publishedVersion, other-oa)
- Arca - Repositório Institucional da Fiocruz (publishedVersion, other-oa)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_170069)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- Zika virus infection, congenital brain malformation, Guillain-Barré syndrome, microcephaly, causal inference, Bradford Hill criteria, associative strength, dose-response relationship, specificity, consistency, maternal infection, fetal infection, control selection bias
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