Postnatal Zika virus infection leads to morphological and cellular alterations within the neurogenic niche.

The Zika virus received significant attention in 2016, following a declaration by the World Health Organization of an epidemic in the Americas, in which infections were associated with microcephaly. Indeed, prenatal Zika virus infection is detrimental to fetal neural stem cells and can cause premature cell loss and neurodevelopmental abnormalities in newborn infants, collectively described as congenital Zika syndrome. Contrastingly, much less is known about how neonatal infection affects the development of the newborn nervous system. Here, we investigated the development of the dentate gyrus of wild-type mice following intracranial injection of the virus at birth (postnatal day 0). Through this approach, we found that Zika virus infection affected the development of neurogenic regions within the dentate gyrus and caused reactive gliosis, cell death and a decrease in cell proliferation. Such infection also altered volumetric features of the postnatal dentate gyrus. Thus, we found that Zika virus exposure to newborn mice is detrimental to the subgranular zone of the dentate gyrus. These observations offer insight into the cellular mechanisms that underlie the neurological features of congenital Zika syndrome in children.

Prenatal and Postnatal Ocular Abnormalities Following Congenital Zika Virus Infections: A Systematic Review.

OBJECTIVE: To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons. METHODS: A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists. RESULTS: Studies reporting ocular abnormalities during the prenatal (n = 5) and postnatal (n = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed. CONCLUSION: This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.

Proteomics and Metabolomics in Congenital Zika Syndrome: A Review of Molecular Insights and Biomarker Discovery.

Zika virus (ZIKV) infection can be transmitted vertically, leading to the development of congenital Zika syndrome (CZS) in infected fetuses. During the early stages of gestation, the fetuses face an elevated risk of developing CZS. However, it is important to note that late-stage infections can also result in adverse outcomes. The differences between CZS and non-CZS phenotypes remain poorly understood. In this review, we provide a summary of the molecular mechanisms underlying ZIKV infection and placental and blood-brain barriers trespassing. Also, we have included molecular alterations that elucidate the progression of CZS by proteomics and metabolomics studies. Lastly, this review comprises investigations into body fluid samples, which have aided to identify potential biomarkers associated with CZS.

Multiomics Approach Reveals Serum Biomarker Candidates for Congenital Zika Syndrome.

The Zika virus (ZIKV) can be vertically transmitted, causing congenital Zika syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances of developing CZS. This syndrome involves several pathologies with a complex diagnosis. In this work, we aim to identify biological processes and molecular pathways related to CZS and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. We analyzed serum samples of healthy pregnant women and ZIKV-infected pregnant women bearing nonmicrocephalic and microcephalic fetuses. A total of 1090 proteins and 512 metabolites were identified by bottom-up proteomics and untargeted metabolomics, respectively. Univariate and multivariate statistical approaches were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as CZS signatures. Five proteins and four metabolites were selected as CZS biomarker candidates. Serum multiomics analysis led us to propose nine putative biomarkers for CZS prognosis with high sensitivity and specificity.

Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development.

PURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression. EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.

Prevalence of urologic sequelae and bladder and bowel dysfunctions in patients with congenital Zika syndrome: A multicenter evaluation of the Zika virus bladder and bowel sequelae assistance network.

INTRODUCTION: Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ. OBJECTIVE: To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states. STUDY DESIGN: Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent. RESULTS: The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder. DISCUSSION: A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population. CONCLUSION: A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests.

Congenital Zika Virus Infection Impairs Corpus Callosum Development.

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in PH3+ cells, intermediate progenitor cells, and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV-infected cultures show a reduction in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis, but also axon guidance and growth across the midline.

Serological investigation of vaccine-induced antibodies for measles, rubella, and yellow fever viruses in children vertically exposed to Zika virus or with down syndrome.

Background: Vaccination schedules, as well as their effectiveness and contraindications, need to be evaluated regularly, especially in specific situations. Congenital Zika Syndrome (CZS) is a severe condition that results in extensive functional and neurological impairment of fetuses and newborns due to Zika virus tropism for fetal neural progenitor cells. Down Syndrome (DS) is the leading genetic cause of intellectual disability. The immune impairment in DS has already been described, but little is known about the immune response of CZS children. Thus, CZS and DS are specific conditions that can be considered for a reassessment of the available immunizations. Here, we carried out serological analyses of attenuated vaccines-induced antibodies for measles, rubella, and yellow fever viruses in children aged 2-7, grouped into asymptomatic controls, DS children, and CZS children. Methods: Plasma samples were taken, and vaccination records were compiled during clinical follow-up. Enzymatic immunoassays for quantifying anti-measles and anti-rubella IgG were performed to assess the response to the Measles, Mumps, and Rubella (MMR) vaccine. Plaque Reduction Neutralization Test (PRNT) was performed to investigate neutralizing antibodies in response to the Brazilian vaccine strain of yellow fever (YF-17DD). Results: We highlight similar levels of anti-measles IgG and neutralizing antibodies for YF-17DD among CZS, DS, and asymptomatic children, although low positivity of measles data was seen in the three groups. In DS children, the 2-4-year-old group had an increased level of anti-measles IgG compared to the older group of children aged five to seven years. Lower anti-rubella IgG levels were observed in CZS and DS children compared to asymptomatic children. For anti-rubella IgG, the good performance of vaccination in asymptomatic children is due to younger ones rather than older ones. Conclusions: There were no reports of adverse events after the use of the MMR and YF-17DD indicating that CZS and DS could continue to receive these vaccines, but our data draws attention to the necessity of monitoring the vaccination response in CZS and DS children over time and the possible need to adhere to national measles vaccination campaigns. Scientific research needs to continue to help develop appropriate CZS and DS health guidelines.

Prevalence of sleep disorders in children with Congenital Zika Syndrome.

Studies have reported that children with Congenital Zika Syndrome (CZS) experience changes in their sleep patterns, which can result in mood disturbances, behavioral issues and delays in growth and development. This systematic review synthesized the available evidence on the prevalence of sleep disorders in children with CZS. Eligible studies were those with an observational design that reported sleep disorders in children with CZS using validated questionnaires, polysomnography/electroencephalographic recording or parent/caregiver reports. Searches were conducted in PubMed, Web of Science, SCOPUS and Embase, as well as a gray literature search using Google Scholar. The Freeman-Tukey double-arcsine transformation with a random-effects model was used to estimate the pooled prevalence of sleep disorders with a 95% confidence interval (CI). Five studies were included and data from 340 Brazilian children with CZS were analyzed. The overall prevalence of sleep disorders was 27.4% (95% CI 16.7-39.4), without differences among studies using validated questionnaires (29.4%, 95% CI 21.4-37.8) or report from parents and caregivers (27.4%, 95% CI 11.5-47.0). Sleep disorders are prevalent in children with CZS, impacting their development and quality of life. It is critical to examine the quality of sleep in these children to develop appropriate interventions that can mitigate these issues.

The article discusses a systematic review of studies that have explored the prevalence of sleep disorders in children with Congenital Zika Syndrome (CZS), a condition caused by the Zika virus. The study found that children with CZS often experience changes in their sleep patterns, which can lead to mood disturbances, behavioral issues and delays in growth and development. The review included five studies with a total of 340 Brazilian children with CZS, and the overall prevalence of sleep disorders was found to be 27.4%. This indicates that sleep disorders are prevalent in children with CZS and can significantly impact their development and quality of life. The authors suggest that further research is needed to develop appropriate interventions to mitigate these issues.

Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model.

Introduction: Zika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes. Methods: Here, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized. Results: Dams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection. Discussion: Thus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further.

Evaluation and monitoring of eye findings in children exposed to Zika virus during gestation: 3 years of follow-up.

INTRODUCTION: Congenital Zika syndrome (CZS) is a recently described disease. Our main objective was to evaluate and monitor, over 3 years, the ophthalmoscopic findings in children exposed to zika virus (ZIKV) during gestation. METHODS: This prospective observational study was conducted in Rio de Janeiro, Brazil, between April 2016 and May 2019. We evaluated two groups with exanthema serving as a proxy for viremia: (i) children whose mothers had exanthema during pregnancy and (ii) children who had microcephaly without maternal exanthema during pregnancy. We performed indirect ophthalmoscopy at recruitment and every 6 months thereafter. We also tested the association between ocular findings with maternal exanthema, microcephaly, CZS and maternal infection confirmed by reverse transcriptase quantitative polymerase chain reaction and gender. RESULTS: Of the 72 children included, 16 (22.2%) had optic nerve and/or retinal lesions. All 16 had CZS and 15 (93.7%) had microcephaly (14 at birth and 1 postnatally). The child with postnatally acquired microcephaly was born to a mother without exanthema during pregnancy. Fifty-six (77.8%) of the 72 children were followed for a median time of 24 months and none exhibited differences between admission and follow-up examinations. After logistic regression, only microcephaly at birth was associated with eye abnormalities (odds ratio, 77.015; 95% confidence interval, 8.85-670.38; p < 0.001). CONCLUSION: We observed that there was no progression of the lesions over the follow-up period. We also showed that the eye findings were associated only with microcephaly at birth. Attention should be paid to all children born during a ZIKV epidemic, regardless of maternal exanthema and/or microcephaly at birth.

Low CCL2 and CXCL8 Production and High Prevalence of Allergies in Children with Microcephaly Due to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFNγ and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols.

A Birth Cohort Follow-Up Study on Congenital Zika Virus Infection in Vietnam.

We assessed the development, sensory status, and brain structure of children with congenital Zika virus (ZIKV) infection (CZI) at two years and preschool age. CZI was defined as either ZIKV RNA detection or positive ZIKV IgM and neutralization test in the cord or neonatal blood. Twelve children with CZI born in 2017-2018 in Vietnam, including one with Down syndrome, were assessed at 23-25.5 months of age, using Ages and Stages Questionnaire (ASQ-3), ASQ:Social-Emotional (ASQ:SE-2), Modified Checklist for Autism in Toddlers, automated auditory brainstem response (AABR), and Spot Vision Screener (SVS). They underwent brain CT and MRI. They had detailed ophthalmological examinations, ASQ-3, and ASQ:SE-2 at 51-62 months of age. None had birthweight or head circumference z-score < -3 except for the one with Down syndrome. All tests passed AABR (n = 10). No ophthalmological problems were detected by SVS (n = 10) and detailed examinations (n = 6), except for a girl's astigmatism. Communication and problem-solving domains in a boy at 24 months, gross-motor area in a boy, and gross-motor and fine-motor areas in another boy at 59-61 months were in the referral zone. Brain CT (n = 8) and MRI (n = 6) revealed no abnormalities in the cerebrum, cerebellum, or brainstem other than cerebellar hypoplasia with Down syndrome. The CZI children were almost age-appropriately developed with no brain or eye abnormalities. Careful and longer follow-up is necessary for children with CZI.

The burden of global outbreaks: Photos of the daily lives of children with congenital Zika syndrome during the COVID-19 pandemic.

INTRODUCTION: In Brazil, more than 3500 children with congenital Zika syndrome (CZS) face difficulties participating in activities of daily living, which may be aggravated by health emergencies, such as the COVID-19 pandemic. Participation could be defined as the individual's involvement in daily life situations, and participation restrictions are problems that may arise in involvement in everyday situations. AIM: To explore the daily lives of children with CZS during the COVID-19 pandemic using photographic narratives captured by mothers and discuss possible strategies to improve participation results. METHODS: In this participatory action research, seven young Brazilian mothers acted as co-researchers using photovoice to describe the experiences of their children with CZS (from 2 to 5 years old). Also, mothers contributed to validate the contents. The research was conducted online and included the following steps: pilot study, recruitment, individualized training, sociodemographic interview, photovoice training, photo taking, focus group for contextualization, data transcription and analysis and validation of analyses by the mothers. RESULTS: Content analysis revealed five categories that influenced the participation of the children: participation preferences, family relationships, access to healthcare, access to education and social isolation. Regarding participation preferences, mothers reported their children's desire to play with peers and family members and have autonomy. Mothers described the family environment as a happy, peaceful and safe place for the children. Lack of therapy was perceived to negatively impact the health of children; thus, treatments were considered essential for child development. Access to education included accessibility of remote education and a perceived lack of infrastructure and pedagogical preparation. Last, social isolation due to COVID-19 directly affected the daily lives and behaviour of the children, interrupting therapies and medical appointments. CONCLUSION: The photos and narratives captured several aspects of the daily lives of children with CZS impacted by the COVID-19 pandemic, reinforcing the importance of considering the negative effects of social isolation and offering education and social assistance to promote participation and integral health. PATIENT/PUBLIC CONTRIBUTION: Consistent with a participatory action research framework, Mothers acted as co-researchers and participated in all stages of the research, especially in validating the data analysed by the researchers.

Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography.

STUDY OBJECTIVES: We performed this study to describe the characteristics of sleep in children with congenital Zika syndrome through polysomnographic assessment. METHODS: Polysomnography with neurological setup and capnography was performed. Respiratory events were scored according to American Academy of Sleep Medicine criteria. Children were classified based on neuroclinical examination as having corticospinal plus neuromuscular abnormalities or exclusively corticospinal abnormalities. Neuroradiological classification was based on imaging exams, with children classed as having supratentorial plus infratentorial abnormalities or exclusively supratentorial abnormalities. RESULTS: Of 65 children diagnosed with congenital Zika syndrome, sleep apnea was present in 23 children (35.4%), desaturation in 26 (40%), and snoring in 13 (20%). The most prevalent apnea type was central in 15 children (65.2%), followed by obstructive apnea in 5 (21.7%) and mixed type in 3 (13%). The average of the lowest saturation recorded was slightly below normal (89.1 ± 4.9%) and the mean partial pressure of end-tidal carbon dioxide value was normal. Periodic leg movements were present in 48 of 65 children. Lower ferritin levels were observed in 84.6% of children. Palatine and pharyngeal tonsils (adenoids) were small in most children and not associated with the presence of obstructive apnea. Ventriculomegaly and subcortical and nucleus calcification were the most frequent neuroimaging findings. Supratentorial and infratentorial anomalies were present in 26.7% (16 of 60) and exclusively supratentorial changes in 73.3% (44 of 60). In the neuroclinical classification, isolated corticospinal changes were more frequent and the mean peak in capnography was lower in this group. There was no difference regarding the presence of apnea for children in the neuroclinical and neuroradiological classification groups. CONCLUSIONS: Sleep disorders were frequent in children with congenital Zika syndrome, with central sleep apnea being the main finding. CITATION: Brandão Marquis V, de Oliveira Melo A, Pradella-Hallinan M, et al. Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography. J Clin Sleep Med. 2023;19(10):1759-1767.

Síndrome congênita do zika e impactos para as famílias: uma revisão integrativa / Congenital zika syndrome and family impacts: an integrative review

Resumo Em 2015, um espectro de anomalias congênitas, incluindo microcefalia, acometeu recém-nascidos como resultado da transmissão vertical pelo vírus zika, posteriormente denominada síndrome congênita do zika (SCZ). Desde então, cerca de 4 mil crianças foram afetadas em 27 países, sendo o Brasil o mais atingido. Cuidadores familiares também têm sido impactados. Esse estudo analisa publicações científicas que investigam as maneiras como a doença afetou as dinâmicas de vida de cuidadores familiares de crianças com SCZ. Realizou-se uma revisão integrativa de literatura consultando as bases de dados PubMed, Biblioteca Virtual em Saúde e Embase. Após as etapas de triagem, foram identificados 31 artigos. Os principais resultados foram agrupados em quatro categorias: a) impactos sociais que evidenciaram mudanças nas relações familiares, nos projetos de vida e no convívio social; b) impactos subjetivos - sentimentos de resiliência, solidão, luto, sobrecarga, medo, incerteza e relação com a espiritualidade; c) impactos econômicos e materiais - perda de renda, aumento de despesas, mudança de moradia e desemprego e d) impactos na saúde - despreparo dos serviços, renúncia do cuidado de si, modificações dos padrões nutricionais e de sono, repercussão para a saúde mental e níveis de estresse, ansiedade e depressão.

Abstract In 2015, a range of congenital anomalies resulting from mother-to-child transmission of the zika virus emerged. Later called congenital zika syndrome (CZS), the condition includes microcephaly. Since then, around 4,000 children have been affected in 27 countries, with Brazil accounting for the largest proportion of cases. Family caregivers have also been affected. This study analyzes the literature on caregivers of children with CZS and how the disease has affected their everyday lives. We conducted an integrative review using the PubMed, Virtual Health Library, and Embase databases. Thirty-one articles were identified for analysis after screening. The findings were grouped into four categories: a) social impacts - changes in family relationships, life projects, and social life; b) subjective impacts - feelings of resilience, loneliness, grief, overburdening, fear, uncertainty, and spirituality and religion; c) economic and material impacts - loss of income, increased household expenses, change of residence, and unemployment; and d) health impacts - service unpreparedness, selflessness, self-care, changes in nutritional and sleep patterns, and mental health problems, including stress, anxiety and depression.

Congenital Zika Syndrome and Disabilities of Feeding and Breastfeeding in Early Childhood: A Systematic Review.

BACKGROUND: The Zika virus outbreak has affected pregnant women and their infants. Affected infants develop microcephaly and other congenital malformations referred to as congenital Zika syndrome. The neurological manifestations of congenital Zika syndrome may result in some feeding disorders, including dysphagia, swallowing dysfunction and choking while feeding. The aim of this study was to assess the prevalence of feeding and breastfeeding difficulties in children with congenital Zika syndrome and to estimate the risk of developing feeding disabilities. METHODS: We searched PubMed, Google Scholar and Scopus for studies published from 2017 to 2021. From the total of 360 papers, reviews, systematic reviews, meta-analyses and publications in languages other than English were excluded. Therefore, the final sample of our study consisted of 11 articles about the feeding/breastfeeding difficulties of infants and children with congenital Zika syndrome. RESULTS: Infants and children with congenital Zika syndrome were likely to suffer from feeding difficulties at various levels, including breastfeeding. Dysphagia problems ranged from 17.9% to 70%, and nutritional and non-nutritive suckling of infants was also affected. CONCLUSIONS: In addition to continuing to investigate the neurodevelopment of affected children, future research should also focus on the severity of factors influencing the degree of dysphagia, as well as the impact of breastfeeding on the child's overall development.

Congenital Zika syndrome.

In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.

En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.

Translation and preliminary validation of the Brazilian family resources scale in a sample of parents of children with congenital Zika virus syndrome.

PURPOSE: Family-centered rehabilitative care optimizes outcomes for children with significant developmental disabilities. Family-centered services involve assessing family resources that promote positive developmental outcomes for children. Little is known regarding family resources in the context of caring for a child with developmental disabilities in Brazil due to an absence of validated measures. This study describes the translation and cultural adaptation of the Family Resource Scale and explored the measurement quality of the resulting measure (the Brazilian-Family Resource Scale, or B-FRS). METHODS: A rigorous serial translation process that emphasized linguistic accuracy as well as cultural adaptation was utilized. The resulting 27-item B-FRS was theoretically related and reflected the contextual intent of the original measure. RESULTS: A four-factor scoring approach yielded acceptable internal consistency estimates for the subscales and total scale score. Overall, low levels of family resources were reported by caregivers of children with Congenital Zika Syndrome. Low family resources were associated with parental depressive and stress-related symptoms. CONCLUSION: Confirmatory factor analysis of the B-FRS in a larger sample is recommended. Practitioners in Brazil should broadly consider family needs and resources to provide family-centered care that is effective for the child and engages the family in a way that highlights their strengths and promotes positive developmental trajectories.

Congenital Zika syndrome / Síndrome congénito por virus Zika

Abstract In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.

Resumen En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.