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      Zika Virus Infection in Pregnant Women and Microcephaly* Translated title: Infecção do vírus Zika em gestantes e microcefalia*

      review-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 2 , 10 , 11 , 1 , 12 , 13 , 14 , 13 , 2 , 15
      RBGO Gynecology & Obstetrics
      Thieme Revinter Publicações Ltda
      pregnancy complications, Zika virus, arbovirus infections, microcephaly/ultrasonography, real-time polymerase chain reaction, deafness/ etiology, blindness/ etiology, complicações na gravidez, vírus da Zika, infecções por arbovírus, microcefalia/ultrassonografia, reação em cadeia da polimerase em tempo real, surdez/ etiologia, cegueira/ etiologia

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          Abstract

          From the discovery of the Zika virus (ZIKV) in 1947 in Uganda (Africa), until its arrival in South America, it was not known that it would affect human reproductive life so severely. Today, damage to the central nervous system is known to be multiple, and microcephaly is considered the tip of the iceberg. Microcephaly actually represents the epilogue of this infection's devastating process on the central nervous system of embryos and fetuses. As a result of central nervous system aggression by the ZIKV, this infection brings the possibility of arthrogryposis, dysphagia, deafness and visual impairment. All of these changes of varying severity directly or indirectly compromise the future life of these children, and are already considered a congenital syndrome linked to the ZIKV. Diagnosis is one of the main difficulties in the approach of this infection. Considering the clinical part, it has manifestations common to infections by the dengue virus and the chikungunya fever, varying only in subjective intensities. The most frequent clinical variables are rash, febrile state, non-purulent conjunctivitis and arthralgia, among others. In terms of laboratory resources, there are also limitations to the subsidiary diagnosis. Molecular biology tests are based on polymerase chain reaction (PCR) with reverse transcriptase (RT) action, since the ZIKV is a ribonucleic acid (RNA) virus. The RT-PCR shows serum or plasma positivity for a short period of time, no more than five days after the onset of the signs and symptoms. The ZIKV urine test is positive for a longer period, up to 14 days. There are still no reliable techniques for the serological diagnosis of this infection. If there are no complications (meningoencephalitis or Guillain-Barré syndrome), further examination is unnecessary to assess systemic impairment. However, evidence is needed to rule out other infections that also cause rashes, such as dengue, chikungunya, syphilis, toxoplasmosis, cytomegalovirus, rubella, and herpes. There is no specific antiviral therapy against ZIKV, and the therapeutic approach to infected pregnant women is limited to the use of antipyretics and analgesics. Anti-inflammatory drugs should be avoided until the diagnosis of dengue is discarded. There is no need to modify the schedule of prenatal visits for pregnant women infected by ZIKV, but it is necessary to guarantee three ultrasound examinations during pregnancy for low-risk pregnancies, and monthly for pregnant women with confirmed ZIKV infection. Vaginal delivery and natural breastfeeding are advised.

          Resumo

          Desde a descoberta do vírus Zika (VZIK) em 1947 em Uganda, na África, até sua chegada na América do Sul, não se tinha notícia de que ele seria capaz de comprometer a vida reprodutiva em humanos de forma tão severa. Hoje, sabe-se que os danos sobre o sistema nervoso central são múltiplos, e a microcefalia é considerada a ponta do iceberg, visto que na realidade ela representa o epílogo de um processo devastador desta infecção sobre o sistema nervoso central do embrião e do feto. Em decorrência da agressão do sistema nervoso central pelo VZIK, esta infecção pode provocar artrogripose, disfagia, surdez e comprometimento visual. Todas estas alterações, de gravidade variável, direta ou indiretamente comprometem a vida futura dessas crianças, já sendo considerada uma síndrome congênita ligada ao VZIK. Uma das principais dificuldades na abordagem dessa infecção é relativa ao diagnóstico. Considerando a parte clínica, observa-se que ela apresenta manifestações comuns às infecções pelos vírus da dengue e da febre chikungunya, variando apenas em suas intensidades subjetivas. As variáveis clínicas mais frequentes são o exantema, febrícula, conjuntivite não purulenta e artralgia. No tocante aos recursos laboratoriais, também existem limitações ao diagnóstico subsidiário. As provas de biologia molecular se fundamentam na reação em cadeia da polimerase (RCP) com ação da transcriptase reversa (TT), visto que o VZIK é um vírus ácido ribonucleico (ARN). A TR-RCP apresenta positividade sérica ou plasmática por um período curto de tempo, não ultrapassando cinco dias após início dos sinais e sintomas. Esta pesquisa do VZIK na urina fica positiva por período mais prolongado, chegando a 14 dias. Ainda não existem técnicas seguras para diagnóstico sorológico dessa infecção. Não havendo complicações (meningoencefalite ou síndrome de Guillain-Barré), dificilmente são necessários mais exames complementares para avaliar o comprometimento sistêmico. No entanto, são necessárias provas para descartar as outras infecções que causam exantema, como dengue, chikungunya, sífilis, toxoplasmose, citomegalovírus, rubéola e herpes. Sabe-se que não existe terapia antiviral específica contra o VZIK, e a abordagem terapêutica de gestantes portadoras da infecção limita-se ao uso de antitérmicos e analgésicos. Orienta-se evitar anti-inflamatórios até que o diagnóstico de dengue seja descartado. Sobre a condução do pré-natal, não há necessidade de modificar o cronograma de consultas pré-natais para gestantes que foram infectadas pelo VZIK, mas é necessária a garantia de três exames ecográficos durante a gravidez para gestantes de baixo risco, e mensais para a gestante com infecção confirmada pelo VZIK. A via de parto é vaginal, e está liberado o aleitamento natural.

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          Most cited references92

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          Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.

          Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our brain-region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.
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            A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants

            Background The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. Methods Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. Results Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. Conclusions The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts.
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              Zika virus outbreak on Yap Island, Federated States of Micronesia.

              In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission. 2009 Massachusetts Medical Society
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                Author and article information

                Journal
                Rev Bras Ginecol Obstet
                Rev Bras Ginecol Obstet
                10.1055/s-00030576
                RBGO Gynecology & Obstetrics
                Thieme Revinter Publicações Ltda (Rio de Janeiro, Brazil )
                0100-7203
                1806-9339
                May 2017
                1 May 2017
                : 39
                : 5
                : 235-248
                Affiliations
                [1 ]Universidade de São Paulo, Ribeirão Preto, SP, Brazil
                [2 ]Universidade Federal de São Paulo, São Paulo, SP, Brazil
                [3 ]Hospital Professor Edmundo Vasconcelos, São Paulo, SP, Brazil
                [4 ]Faculdade de Medicina do ABC, Santo André, SP, Brazil
                [5 ]Hospital Maternidade Leonor Mendes de Barros, São Paulo, SP, Brazil
                [6 ]Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
                [7 ]Alta Excelência Diagnóstica, Rio de Janeiro, RJ, Brazil
                [8 ]Universidade Federal do Amazonas, Manaus, AM, Brazil
                [9 ]Pontifícia Universidade Católica, Porto Alegre, RS, Brazil
                [10 ]Consultório Médico Juvenal Barreto Borriello de Andrade, São Paulo, SP, Brazil
                [11 ]Clínica Marcelo Burlá, Rio de Janeiro, RJ Brazil
                [12 ]Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil
                [13 ]Universidade Estadual de Campinas, Campinas, SP, Brazil
                [14 ]Universidade Federal Fluminense, Niterói, RJ, Brazil
                [15 ]Universidade de São Paulo, São Paulo, SP, Brazil
                Author notes
                Address for correspondence Geraldo Duarte Avenida Bandeirantes, 3900, 14049-900Ribeirão Preto, SPBrazil gduarte@ 123456fmrp.usp.br
                Article
                1703cne
                10.1055/s-0037-1603450
                10316959
                28575919
                0f427782-60dd-4124-8592-a56b60875eae

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.

                History
                : 22 January 2017
                : 21 February 2017
                Categories
                Systematic Review

                pregnancy complications,zika virus,arbovirus infections,microcephaly/ultrasonography,real-time polymerase chain reaction,deafness/ etiology,blindness/ etiology,complicações na gravidez,vírus da zika,infecções por arbovírus,microcefalia/ultrassonografia,reação em cadeia da polimerase em tempo real,surdez/ etiologia,cegueira/ etiologia

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