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F1000Research 2018The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and...
The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is "sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS". This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 - 18.01.2017, update 1. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.
Topics: Animals; Brain; Female; Fetus; Global Health; Guillain-Barre Syndrome; Humans; Nervous System Malformations; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 30631437
DOI: 10.12688/f1000research.13704.1 -
Molecular Mechanisms of ZIKV-Induced Teratogenesis: A Systematic Review of Studies in Animal Models.Molecular Neurobiology Jan 2023Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted... (Review)
Review
Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated.
Topics: Pregnancy; Humans; Child; Female; Animals; Mice; Guinea Pigs; Zika Virus; Zika Virus Infection; Microcephaly; Teratogenesis; Chickens; Nervous System Malformations; Models, Animal
PubMed: 36215025
DOI: 10.1007/s12035-022-03046-4 -
Developmental Medicine and Child... Dec 2020To describe the standardized neurodevelopmental outcomes after the first year of life in children with congenital Zika syndrome (CZS) and those exposed to Zika virus...
AIM
To describe the standardized neurodevelopmental outcomes after the first year of life in children with congenital Zika syndrome (CZS) and those exposed to Zika virus (ZIKV) during fetal life, but without microcephaly at birth.
METHOD
This scoping review included observational studies about the standardized neurodevelopmental outcome in children with CZS or exposed to ZIKV, but without microcephaly, assessed after 12 months of age. The databases searched were MEDLINE/Pubmed, LILACS, Scielo, Scopus, PsycINFO, CINAHL, and Embase. Risk of bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists.
RESULTS
Seventeen papers were included: 12 focused on children with CZS, four on children born without microcephaly, and one described both. Only one of the studies about CZS reported a child with microcephaly and typical development; the remainder described a severe pattern of global developmental delay and cerebral palsy. The prevalence of epilepsy was 74.6%. In the reports about children born without microcephaly, 6.9% to 8.7% had some domain with a score below -2 SD, and three children developed autism spectrum disorder.
INTERPRETATION
CZS is associated with severe global developmental delay and cerebral palsy after 1 year of age. In children born without microcephaly, although most have typical development, some may be at risk for impairments.
Topics: Humans; Neurodevelopmental Disorders; Zika Virus Infection
PubMed: 32931050
DOI: 10.1111/dmcn.14675 -
Canadian Journal of Public Health =... Oct 2019Zika virus (ZIKV) infection is a vector-borne disease that can be transmitted sexually and vertically. The vertical transmission of the virus may lead to congenital Zika... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Zika virus (ZIKV) infection is a vector-borne disease that can be transmitted sexually and vertically. The vertical transmission of the virus may lead to congenital Zika syndrome in infants. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of congenital Zika-related disorders in infants of mothers infected with ZIKV during pregnancy.
METHODS
We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic and Web of Science databases to identify human studies reporting prevalence of congenital disorders in infants of ZIKV-infected mothers.
RESULTS
We identified 25 reports selected for inclusion in the current study (n = 4683 subjects). The majority of the studies were from South American high-risk countries. Only one third of the identified studies were conducted in the United States. Clinical maternal symptoms included maculopapular rash (76.9%), arthralgia (46.4%), fever (45.5%) and headache (31.8%) with myalgia and conjunctivitis only presented in 25% of the cases. The most prevalent congenital disorder in the newborns was brain calcifications (42.6; 95% CI, 30.8-54.4), followed by ventriculomegaly (21.8; 95% CI, 15.2-28.4), joint abnormalities (13.2; 95% CI, 9.4-18.2), ocular abnormalities (4.2; 95% CI, 1.0-7.5) and microcephaly (3.9; 95% CI, 2.4-5.4).
CONCLUSION
The current study highlights the high prevalence of a range of congenital disorders in newborns of mothers infected with ZIKV. It warrants developing studies to further clarify the mechanisms by which each of these disorders occurs in response to the viral infection during pregnancy and its vertical transmission to the infants.
Topics: Congenital Abnormalities; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Zika Virus Infection
PubMed: 31077071
DOI: 10.17269/s41997-019-00215-2 -
Value in Health : the Journal of the... Jul 2020In this systematic review, we synthesize the current evidence on health-related quality of life (HRQoL) for the two of the most relevant outcomes of Zika virus infection...
OBJECTIVES
In this systematic review, we synthesize the current evidence on health-related quality of life (HRQoL) for the two of the most relevant outcomes of Zika virus infection in humans, microcephaly and Guillain-Barré Syndrome (GBS).
METHODS
We searched the following databases: MEDLINE, Embase, CINAHL, LILACS, WHO's ICTRP clinical trials registries database and PROSPERO. Search terms included quality of life, microcephaly, and Guillain-Barré Syndrome. We included primary studies where HRQoL was quantitatively assessed for microcephaly and GBS using validated instruments. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the risk of bias of individual studies.
RESULTS
From a total of 1,657 abstracts screened and 66 full texts reviewed, 21 studies met the eligibility criteria; one study for microcephaly and 20 for GBS. Adjusted disutilities for microcephaly compared to a normative childhood utility ranged from -0.745 to -0.820. For GBS, time traded-off the expected lifetime ranged from 16 days to 3 years. HRQoL follows the clinical course of GBS, with lower scores in the first months, recovery within the first year post onset, and stabilization after one year.
CONCLUSIONS
Included studies reported a wide range of HRQoL for GBS, due in part to a high level of heterogeneity in methods, inclusion criteria, follow-up and reporting of results. Opportunities exist for primary studies assessing the longitudinal HRQoL over the entire course of the diseases to inform clinical practice, economic evaluations and health policy.
Topics: Child; Guillain-Barre Syndrome; Humans; Microcephaly; Quality of Life; Time Factors; Zika Virus Infection
PubMed: 32762999
DOI: 10.1016/j.jval.2020.03.004 -
Frontiers in Medicine 2022The aim of this study was to assess the accuracy of prenatal imaging for the diagnosis of congenital Zika syndrome.
OBJECTIVE
The aim of this study was to assess the accuracy of prenatal imaging for the diagnosis of congenital Zika syndrome.
DATA SOURCES
Medline (via Pubmed), PubMed, Scopus, Web of Science, and Google Scholar from inception to March 2022. Two researchers independently screened study titles and abstracts for eligibility.
STUDY ELIGIBILITY CRITERIA
Observational studies with Zika virus-infected pregnant women were included. The index tests included ultrasound and/or magnetic resonance imaging. The reference standard included (1) Zika infection-related perinatal death, stillbirth, and neonatal death within the first 48 h of birth, (2) neonatal intensive care unit admission, and (3) clinically defined adverse perinatal outcomes.
SYNTHESIS METHODS
We extracted 2 × 2 contingency tables. Pooled sensitivity and specificity were estimated using the random-effects bivariate model and assessed the summary receiver operating characteristic (ROC) curve. Risk of bias was assessed using QUADAS 2 tool. The certainty of the evidence was evaluated with grading of recommendations.
RESULTS
We screened 1,459 references and included 18 studies (2359 pregnant women, 347 fetuses with confirmed Zika virus infection). Twelve studies (67%) were prospective cohorts/case series, and six (37%) were retrospective cohort/case series investigations. Fourteen studies (78%) were performed in endemic regions. Ten studies (56%) used prenatal ultrasound only, six (33%) employed ultrasound and fetal MRI, and two studies (11%) used prenatal ultrasound and postnatal fetal MRI. A total of six studies (ultrasound only) encompassing 780 pregnant women (122 fetuses with confirmed Zika virus infection) reported relevant data for meta-analysis (gestation age at which ultrasound imagining was captured ranged from 16 to 34 weeks). There was large heterogeneity across studies regarding sensitivity (range: 12 to 100%) and specificity (range: 50 to 100%). Under a random-effects model, the summary sensitivity of ultrasound was 82% (95% CI, 19 to 99%), and the summary specificity was 97% (71 to 100%). The area under the ROC curve was 97% (95% CI, 72 to 100%), and the summary diagnostic odds ratio was 140 (95% CI, 3 to 7564, < 0.001). The overall certainty of the evidence was "very low".
CONCLUSION
Ultrasound may be useful in improving the diagnostic accuracy of Zika virus infection in pregnancy. However, the evidence is still substantially uncertain due to the methodological limitations of the available studies. Larger, properly conducted diagnostic accuracy studies of prenatal imaging for the diagnosis of congenital Zika syndrome are warranted.
SYSTEMATIC REVIEW REGISTRATION
Identifier [CRD42020162914].
PubMed: 36250095
DOI: 10.3389/fmed.2022.962765 -
Obstetrics and Gynecology May 2020To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome...
OBJECTIVE
To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome abnormalities.
DATA SOURCES
Systematic searches were performed in 27 databases, including ClinicalTrials.gov, from inception to July 1, 2019, for articles with the keywords "Zika," "prenatal," "ultrasound," and "amniocentesis."
METHODS OF STUDY SELECTION
A total of 3,049 unique records were identified. Two reviewers independently assessed titles, abstracts, and full texts for relevance; 84 articles met the inclusion criteria. These articles describe 402 mother-fetus or mother-neonate dyads; 385 were included in the review of prenatal ultrasound examination, and 56 in the review of amniocentesis (39 in both).
TABULATION, INTEGRATION, AND RESULTS
Among 195 fetuses with congenital Zika syndrome findings on prenatal ultrasound examination, postnatal congenital Zika syndrome abnormalities were reported for 153 (78%; 95% CI 7-84%). High proportions of microcephaly (76%; 95% CI 69-82%) and brain abnormalities (78%; 95% CI 69-86%) were confirmed postnatally. Among 190 fetuses without congenital Zika syndrome findings on prenatal ultrasound examination, 17% (95% CI 12-24%) had congenital Zika syndrome abnormalities identified postnatally. Structural congenital Zika syndrome abnormalities were identified postnatally in approximately equal proportions among dyads with and without Zika virus RNA detected in an amniotic fluid specimen (68% and 67%; 95% CI 52-82% and 95% CI 38-88%). In six pregnancies, Zika virus RNA was detected in amniotic fluid but not in a subsequent amniocentesis specimen.
CONCLUSION
Prenatal ultrasound examination frequently detects structural findings associated with Zika virus infection; however, not all abnormalities are detected, and some may represent transient findings. As with other congenital infections, prenatal detection may vary with timing of infection, timing of ultrasound examination, technical expertise, and severity of abnormalities. The detection of Zika virus RNA in amniotic fluid in the included studies did not predict the risk for congenital Zika syndrome abnormalities in these cases, and clearance of Zika virus RNA from amniotic fluid appears possible after maternal infection. Diagnostic testing for Zika virus infection remains a shared decision between patients and clinicians, and more data are needed to define clinical predictors that will inform these decisions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42018080959.
Topics: Adult; Amniocentesis; Female; Fetal Diseases; Humans; Pregnancy; Ultrasonography, Prenatal; Young Adult; Zika Virus; Zika Virus Infection
PubMed: 32282593
DOI: 10.1097/AOG.0000000000003829 -
Scientific Reports May 2017To assess the accuracy of ultrasound measurements of fetal biometric parameters for prenatal diagnosis of microcephaly in the context of Zika virus (ZIKV) infection, we... (Meta-Analysis)
Meta-Analysis
To assess the accuracy of ultrasound measurements of fetal biometric parameters for prenatal diagnosis of microcephaly in the context of Zika virus (ZIKV) infection, we searched bibliographic databases for studies published until March 3rd, 2016. We extracted the numbers of true positives, false positives, true negatives, and false negatives and performed a meta-analysis to estimate group sensitivity and specificity. Predictive values for ZIKV-infected pregnancies were extrapolated from those obtained for pregnancies unrelated to ZIKV. Of 111 eligible full texts, nine studies met our inclusion criteria. Pooled estimates from two studies showed that at 3, 4 and 5 standard deviations (SDs)
microcephaly than its presence. Topics: Fetal Diseases; Humans; Microcephaly; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography, Prenatal; Zika Virus; Zika Virus Infection
PubMed: 28536443
DOI: 10.1038/s41598-017-01991-y -
Ciencia & Saude Coletiva Feb 2020The scope of this article is to analyze the concept of the Zika Virus Congenital Syndrome. It is a conceptual analysis, based on Walker and Avant. In order to...
The scope of this article is to analyze the concept of the Zika Virus Congenital Syndrome. It is a conceptual analysis, based on Walker and Avant. In order to operationalize the search, a systematic review was conducted. The essence of the concept of the Zika Virus Congenital Syndrome is determined by the following attributes: intracranial calcification, ventriculomegaly, and diminished brain volume. For this syndrome to occur, it is necessary to have the following antecedents: transplacental transmission of a mother infected by the bite of the Aedes SSP mosquito or by sexual contact. Accordingly, this entails a set of signs and symptoms that go beyond fetal or postnatal microcephaly, such as, for example, delayed neuropsychomotor development, auditory and visual abnormalities, craniofacial disproportion, overlapping cranial sutures, prominent occipital bone, excess nuchal skin, epilepsy, irritability, dyskinesia, hypertonia, hypotonia, hemiplegia, hemiparesis, spasticity and hyperreflexia. The concept of the Zika Virus Congenital Syndrome is newly acknowledged. The presence of the set of signs and symptoms by the Zika Virus Congenital Syndrome is determined by intracranial calcification and decreased brain volume, and the baby may present microcephaly at birth or subsequently.
Topics: Calcinosis; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Zika Virus Infection
PubMed: 32022196
DOI: 10.1590/1413-81232020252.30002017 -
Revista Da Escola de Enfermagem Da U S P 2021To review the literature on sleep changes and brain function in children with microcephaly due to Zika virus.
OBJECTIVE
To review the literature on sleep changes and brain function in children with microcephaly due to Zika virus.
METHOD
Systematic review conducted in the databases MEDLINE (PubMed), Scopus, Web of Science, CINAHL, EMBASE, LILACS, and SciELO and the grey databases Google Scholar and OpenGrey.
RESULTS
Ten Brazilian primary studies with observational research design were included. These were published between 2017 and 2020 with 516 children with microcephaly due to Zika virus infection aged 4 months to 4 years. Out of these, 4 investigated qualitative aspects of sleep using the questionnaires Brief Infant Sleep Questionnaire or Infant Sleep Questionnaire and 6 investigated changes in brain activities during sleep using the Electroencephalogram or Video-Electroencephalogram exams. The children's quality of sleep was not compromised in most studies. Changes in brain activity during sleep were frequent, with epileptogenic activity being a common finding among the studies.
CONCLUSION
The quality of sleep of children with microcephaly due to Zika virus has shown to be similar to that of children with typical development and the presented behavioral changes may be related to changes in electric brain activity.
Topics: Brazil; Child; Female; Humans; Infant; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Sleep; Zika Virus; Zika Virus Infection
PubMed: 34479309
DOI: 10.1590/1980-220X-REEUSP-2020-0507