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1.
Nat Commun ; 13(1): 16, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013230

RESUMO

Primary microcephaly and megalencephaly are severe brain malformations defined by reduced and increased brain size, respectively. Whether these two pathologies arise from related alterations at the molecular level is unclear. Microcephaly has been largely associated with centrosomal defects, leading to cell death. Here, we investigate the consequences of WDR81 loss of function, which causes severe microcephaly in patients. We show that WDR81 regulates endosomal trafficking of EGFR and that loss of function leads to reduced MAP kinase pathway activation. Mouse radial glial progenitor cells knocked-out for WDR81 exhibit reduced proliferation rate, subsequently leading to reduced brain size. These proliferation defects are rescued in vivo by expressing a megalencephaly-causing mutant form of Cyclin D2. Our results identify the endosomal machinery as an important regulator of proliferation rates and brain growth, demonstrating that microcephaly and megalencephaly can be caused by opposite effects on the proliferation rate of radial glial progenitors.


Assuntos
Proliferação de Células , Microcefalia , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/metabolismo , Vesículas Transportadoras , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Células Cultivadas , Endossomos/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Megalencefalia/etiologia , Megalencefalia/metabolismo , Megalencefalia/patologia , Camundongos , Microcefalia/etiologia , Microcefalia/metabolismo , Microcefalia/patologia , Malformações do Sistema Nervoso/etiologia , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/patologia , Neuroglia/metabolismo , Transporte Proteico/fisiologia , Vesículas Transportadoras/metabolismo , Vesículas Transportadoras/patologia
2.
PLoS One ; 16(9): e0256444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34525107

RESUMO

OBJECTIVE: To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. METHOD: We followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. RESULTS: Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (ß = 0.29; CI 95% = 0.02-0.57) and motor raw scores (ß = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (ß = 1.27; CI 95% = 0.01-2.53) and motor raw scores (ß = 2.03; CI 95% = 0.25-3.81). CONCLUSION: Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.


Assuntos
Deficiências do Desenvolvimento/diagnóstico , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Infecção por Zika virus/diagnóstico , Brasil/epidemiologia , Cefalometria , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/virologia , Exame Neurológico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia
3.
Nat Metab ; 3(8): 1109-1124, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385701

RESUMO

Zika virus (ZIKV) infection during pregnancy can cause microcephaly in newborns, yet the underlying mechanisms remain largely unexplored. Here, we reveal extensive and large-scale metabolic reprogramming events in ZIKV-infected mouse brains by performing a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics and metabolomics approaches. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD+)-related metabolic pathways, including oxidative phosphorylation, TCA cycle and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cyclic GMP-protein kinase G signaling may be associated with ZIKV-induced microcephaly. Notably, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments, which confirm that boosting NAD+ by NAD+ or nicotinamide riboside supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. Nicotinamide riboside supplementation increases the brain and body weight as well as improves the survival in ZIKV-infected mice. Our study provides a comprehensive resource of biological data to support future investigations of ZIKV-induced microcephaly and demonstrates that metabolic alterations can be potentially exploited for developing therapeutic strategies.


Assuntos
Microcefalia/etiologia , Microcefalia/metabolismo , NAD/metabolismo , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Cromatografia Líquida , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Metabolômica , Camundongos , Microcefalia/patologia , Neurônios/metabolismo , Gravidez , Proteômica/métodos , Espectrometria de Massas em Tandem
4.
Pediatr Neonatol ; 62(4): 354-360, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34112604

RESUMO

Microcephaly is defined by an occipital-frontal head circumference (OFD) 2 standard deviations (SD) smaller than the average expected for age, gender and population. Its incidence has been reported between 1.3 and 150 cases per 100,000 births. Currently, new clinical characteristics, causes and pathophysiological mechanisms related to microcephaly continue to be identified. Its etiology is varied and heterogeneous, with genetic and non-genetic factors that produce alterations in differentiation, proliferation, migration, repair of damage to deoxyribonucleic acid and neuronal apoptosis. It requires a multidisciplinary diagnostic approach that includes a medical history, detailed prenatal and postnatal clinical evaluation, cerebral magnetic resonance imaging, neuropsychological evaluation, and in some cases complementary tests such as metabolic screening, tests to rule out infectious processes and genetic testing. There is no specific treatment or intervention to increase cerebral growth; however, timely intervention strategies and programs can be established to improve motor and neurocognitive development, as well as to provide genetic counseling. The objective of this work is to review the available information and reinforce the proposal to carry out an etiopathogenic approach for microcephaly diagnosis and management.


Assuntos
Microcefalia , Cefalometria , Feminino , Testes Genéticos , Humanos , Imageamento por Ressonância Magnética , Microcefalia/etiologia , Microcefalia/genética , Gravidez
5.
Acta Paediatr ; 110(8): 2375-2381, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33872416

RESUMO

AIM: Our aim was to analyse 12-month outcomes of children who were prenatally exposed to the Zika virus and asymptomatic at birth. METHODS: This was an observational, exploratory study of infants exposed to the Zika virus during gestation and born between March 2016 and April 2017 without congenital Zika syndrome. They were followed until the age of 22 months. The outcome measure was neurodevelopment at 12 months of life, which was evaluated with the Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III). The scores were adjusted for maternal education and prematurity. RESULTS: A total of 96 infants were included in the study and 35.4% scored below the normal range in at least one Bayley-III domain. The majority (91.2%) of the infants with delayed scores presented with language delay, which was not associated with the gestational age at exposure. Receptive language was more affected by exposure than expressive language (27.0% vs 19.8%). There was a direct, and significant, association between the head circumference Z-score at birth and language delay. CONCLUSION: Language delay was associated with a smaller head circumference at birth in infants prenatally exposed to the Zika virus and born asymptomatic. This may indicate future learning difficulties.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Infecção por Zika virus/diagnóstico
6.
Sci Rep ; 11(1): 8474, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875756

RESUMO

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015-2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017-2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1ß, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1ß, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Mediadores da Inflamação/líquido cefalorraquidiano , Microcefalia/patologia , Complicações Infecciosas na Gravidez/patologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Microcefalia/líquido cefalorraquidiano , Microcefalia/epidemiologia , Microcefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/líquido cefalorraquidiano , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/etiologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Infecção por Zika virus/virologia
7.
Viruses ; 13(4)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924398

RESUMO

The emergence of the Zika virus (ZIKV) mirrors its evolutionary nature and, thus, its ability to grow in diversity or complexity (i.e., related to genome, host response, environment changes, tropism, and pathogenicity), leading to it recently joining the circle of closed congenital pathogens. The causal relation of ZIKV to microcephaly is still a much-debated issue. The identification of outbreak foci being in certain endemic urban areas characterized by a high-density population emphasizes that mixed infections might spearhead the recent appearance of a wide range of diseases that were initially attributed to ZIKV. Globally, such coinfections may have both positive and negative effects on viral replication, tropism, host response, and the viral genome. In other words, the possibility of coinfection may necessitate revisiting what is considered to be known regarding the pathogenesis and epidemiology of ZIKV diseases. ZIKV viral coinfections are already being reported with other arboviruses (e.g., chikungunya virus (CHIKV) and dengue virus (DENV)) as well as congenital pathogens (e.g., human immunodeficiency virus (HIV) and cytomegalovirus (HCMV)). However, descriptions of human latent viruses and their impacts on ZIKV disease outcomes in hosts are currently lacking. This review proposes to select some interesting human latent viruses (i.e., herpes simplex virus 2 (HSV-2), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), human parvovirus B19 (B19V), and human papillomavirus (HPV)), whose virological features and co-exposition with ZIKV may provide evidence of the syndemism process, shedding some light on the emergence of the ZIKV-induced global congenital syndrome in South America.


Assuntos
Coinfecção/complicações , Coinfecção/virologia , Microcefalia/etiologia , Viroses/complicações , Infecção por Zika virus/etiologia , Coevolução Biológica , Reservatórios de Doenças/virologia , Humanos , Microcefalia/virologia , América do Sul , Tropismo Viral , Viroses/classificação , Latência Viral , Replicação Viral , Zika virus/patogenicidade , Infecção por Zika virus/congênito
8.
Sci Rep ; 11(1): 2908, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536524

RESUMO

Microcephaly and macrocephaly can be considered both cranial growth defects and clinical symptoms. There are two assessment criteria: one applied in dysmorphology and another conventionally used in clinical practice. The determination of which definition or under which paradigm the terminology should be applied can vary on a daily basis and from case to case as necessity dictates, as can defining the relationship between microcephaly or macrocephaly and syndromes or diseases associated with neurodysfunction. Thus, there is a need for standardization of the definition of microcephaly and macrocephaly. This study was designed to investigate associations between abnormal cranial development (head size) and diseases or syndromes linked to neurodysfunction based on essential data collected upon admission of patients to the Neurological Rehabilitation Ward for Children and Adolescents in Poland. The retrospective analysis involved 327 children and adolescents with medical conditions associated with neurodysfunction. Two assessment criteria were applied to identify subgroups of patients with microcephaly, normal head size, and macrocephaly: one system commonly used in clinical practice and another applied in dysmorphology. Based on the results, children and adolescents with syndromes or diseases associated with neurodysfunction present abnormal cranial development (head size), and microcephaly rarely co-occurs with neuromuscular disease. Macrocephaly frequently co-occurs with neural tube defects or neuromuscular diseases and rarely with cerebral palsy (p < 0.05); microcephaly frequently co-occurs with epilepsy and hypothyroidism (p < 0.001). Traditional classification facilitates the identification of a greater number of relationships and is therefore recommended for use in daily practice. There is a need to standardize the definition of microcephaly and macrocephaly and to include them in 'Human Phenotype Ontology' terms.


Assuntos
Cefalometria/normas , Megalencefalia/diagnóstico , Microcefalia/diagnóstico , Doenças do Sistema Nervoso/complicações , Crânio/crescimento & desenvolvimento , Adolescente , Desenvolvimento do Adolescente/fisiologia , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Humanos , Masculino , Megalencefalia/etiologia , Megalencefalia/fisiopatologia , Microcefalia/etiologia , Microcefalia/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Polônia , Estudos Retrospectivos , Síndrome
9.
Congenit Anom (Kyoto) ; 61(1): 9-13, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33405251

RESUMO

We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not-Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not-Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of NDTs and MIC are significantly higher than in not-Polissia. In Polissia, the prevalence rates of NDTs and MIC are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re-ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate, and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken.


Assuntos
Acidente Nuclear de Chernobyl , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/etiologia , Contagem de Células Sanguíneas , Radioisótopos de Césio , Feminino , Geografia Médica , Humanos , Microcefalia/epidemiologia , Microcefalia/etiologia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Gravidez , Prevalência , Vigilância em Saúde Pública , Ucrânia/epidemiologia
10.
Arch Dis Child ; 106(9): 855-861, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33419730

RESUMO

PURPOSE: To estimate the minimum incidence of congenital Zika syndrome (CZS) and severe microcephaly in Canada and describe key clinical, epidemiological, aetiological and outcome features of these conditions. METHODS: Two separate national surveillance studies were conducted on CZS and severe microcephaly using the well-established Canadian Paediatric Surveillance Program from 2016 to 2019. Over 2700 paediatricians across Canada were surveyed monthly and asked to report demographic details, pregnancy and travel history, infant anthropometry, clinical features and laboratory findings of newly identified cases. Reports were reviewed to assign an underlying aetiology of severe microcephaly. Incidence rates were estimated using monthly live birth denominators. RESULTS: Thirty-four infants met the case definition for severe microcephaly and <5 met the case definition for CZS. The associated minimum incidence rates were 4.5 per 100 000 live births for severe microcephaly and 0.1-0.5 per 100 000 live births for CZS. Of severe microcephaly cases, 53% were attributed to genetic causes, 15% to infectious or ischaemic causes and 32% to unknown causes. The median head circumference-for-age Z-score at birth was -3.2 (IQR -3.8 to -2.6), and catch-up growth was often not achieved. Common clinical features included intracranial abnormalities (n=23), dysmorphology (n=19) and developmental delays (n=14). Mothers of infants with non-genetic aetiologies travelled during pregnancy more often (10/16) than mothers of infants with genetic aetiologies (<5/18; p<0.01). CONCLUSION: Severe microcephaly and CZS are both rare in Canada. Minimum incidence rates can be used as a baseline against which novel or re-emergent causes of severe microcephaly or CZS can be compared.


Assuntos
Microcefalia/epidemiologia , Vigilância da População/métodos , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/congênito , Adulto , Antropometria/métodos , Peso ao Nascer/fisiologia , Canadá/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Lactente , Recém-Nascido , Nascido Vivo/epidemiologia , Masculino , Microcefalia/etiologia , Microcefalia/genética , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologia
11.
PLoS Negl Trop Dis ; 15(1): e0008984, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395432

RESUMO

Zika virus (ZIKV) emerged in Brazil during 2013-2014 causing an epidemic of previously unknown congenital abnormalities. The frequency of severe congenital abnormalities after maternal ZIKV infection revealed an unexplained geographic variability, especially between the Northeast and the rest of Brazil. Several reasons for this variability have been discussed. Prior immunity against Dengue virus (DENV) affecting ZIKV seems to be the most likely explanation. Here we summarise the current evidence regarding this prominent co-factor to potentially explain the geographic variability. This systematic review followed the PRISMA guidelines. The search was conducted up to May 15th, 2020, focussing on immunological interactions from Zika virus with previous Dengue virus infections as potential teratogenic effect for the foetus. Eight out of 339 screened studies reported on the association between ZIKV, prior DENV infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. Prior DENV infection was associated with enhancement for ZIKV infection and increased neurovirulence in one included in vitro study only. Interestingly, the seven in vivo studies exhibited a heterogeneous picture with three studies showing a protective effect of prior DENV infections and others no effect at all. According to several studies, socio-economic factors are associated with increased risk for microcephaly. Very few studies addressed the question of unexplained variability of infection-related microcephaly. Many studies focussed on ADE as mechanism without measuring microcephaly as endpoint. Interestingly, three of the included studies reported a protective effect of prior DENV infection against microcephaly. This systematic review strengthens the hypothesis that immune priming after recent DENV infection is the crucial factor for determining protection or enhancement activity. It is of high importance that the currently ongoing prospective studies include a harmonised assessment of the potential candidate co-factors.


Assuntos
Anormalidades Congênitas/etiologia , Dengue/complicações , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Dengue/imunologia , Feminino , Humanos , Microcefalia/etiologia , Gravidez , Infecção por Zika virus/imunologia
12.
Hum Mol Genet ; 29(21): 3516-3531, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33105479

RESUMO

Neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G > A (p.Arg128Gln), c.520G > T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.


Assuntos
Hidrolases Anidrido Ácido/deficiência , Deficiência Intelectual/patologia , Microcefalia/patologia , Hipotonia Muscular/patologia , Mutação , Transtornos do Neurodesenvolvimento/patologia , Monoéster Fosfórico Hidrolases/genética , Alelos , Animais , Pré-Escolar , Feminino , Humanos , Lactente , Deficiência Intelectual/etiologia , Deficiência Intelectual/metabolismo , Masculino , Camundongos , Microcefalia/etiologia , Microcefalia/metabolismo , Hipotonia Muscular/etiologia , Hipotonia Muscular/metabolismo , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/metabolismo , Linhagem , Fenótipo
13.
Neuropediatrics ; 52(1): 34-43, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33111304

RESUMO

BACKGROUND: Little information on gross motor function of congenital Zika syndrome (CZS) children is available. OBJECTIVES: To evaluate gross motor function in CZS children aged up to 3 years, and its associated factors and changes in a minimum interval of 6 months. METHODS: One hundred children with CZS and cerebral palsy (36 with confirmed and 64 with presumed CZS) were evaluated with the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88/GMFM-66). Forty-six were reevaluated. Wilcoxon tests, Wilcoxon tests for paired samples, percentile scores, and score changes were performed. RESULTS: Clinical and socioeconomic characteristics (except maternal age), GMFM scores and GMFCS classification of confirmed and probable cases, which were analyzed together, were similar. The mean age was 25.6 months (±5.5); the median GMFM-88 score was 8.0 (5.4-10.8); and the median GMFM-66 score was 20.5 (14.8-23.1); 89% were classified as GMFCS level V. Low economic class, microcephaly at birth, epilepsy, and brain parenchymal volume loss were associated with low GMFM-66 scores. The median GMFM-66 percentile score was 40 (20-55). On the second assessment, the GMFM-66 scores in two GMFCS level I children and one GMFCS level IV child improved significantly. In one GMFCS level III child, one GMFCS level IV child, and the group of GMFCS level V children, no significant changes were observed. CONCLUSIONS: Almost all CZS children had severe cerebral palsy; in the third year of life, most presented no improvement in gross motor function and were likely approaching their maximal gross motor function potential.


Assuntos
Paralisia Cerebral/fisiopatologia , Epilepsia/fisiopatologia , Destreza Motora/fisiologia , Malformações do Sistema Nervoso/fisiopatologia , Infecção por Zika virus/congênito , Infecção por Zika virus/fisiopatologia , Paralisia Cerebral/etiologia , Pré-Escolar , Epilepsia/etiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Microcefalia/etiologia , Microcefalia/fisiopatologia , Malformações do Sistema Nervoso/etiologia , Índice de Gravidade de Doença , Classe Social , Infecção por Zika virus/complicações
14.
Rev Paul Pediatr ; 39: e2019231, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32844897

RESUMO

OBJECTIVE: To investigate how mothers of children with congenital syndrome (microcephaly) associated with Zika virus perceive their quality of life. METHODS: This is a qualitative study carried out in two stages: at the Maternal and Child University Hospital and at Casa de Apoio Ninar through semi-structured interviews with mothers of children with congenital syndrome associated with Zika virus. Ten women comprised the sample. RESULTS: In line with the critical discourse analysis, four categories emerged based on Fairclough's 2008 assumptions: Quality of Life and Health - quality of life perception associated with the broad meaning of the term health; Quality of Life and Health Care Systems - characterized by care instability and fragmentation; Quality of Life and Free Time - lack of free time for activities of daily living and leisure; Quality of Life and Future Perspectives - lack of future perspective, considering that most participants had to stop working and studying to take care of their children. CONCLUSIONS: Mothers of children with congenital syndrome associated with Zika virus are devoted to their children's care. Their lack of prospects was considered a consequence of the lack of time for activities of daily living and leisure.


Assuntos
Microcefalia/psicologia , Mães/psicologia , Qualidade de Vida , Infecção por Zika virus/complicações , Adulto , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Pesquisa Qualitativa , Síndrome , Adulto Jovem
15.
Arch Dis Child ; 106(9): 849-854, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33229416

RESUMO

OBJECTIVE: To describe infants aged <12 months reported with microcephaly to the Australian Paediatric Surveillance Unit (APSU) following emergence of Zika virus infection internationally. DESIGN, SETTING AND PATIENTS: National, active, monthly surveillance for microcephaly using the APSU. Microcephaly was defined as occipitofrontal circumference (OFC) of more than 2 SDs below the mean for age, gender and gestation. MAIN OUTCOME MEASURES: Clinical spectrum, aetiology and birth prevalence of microcephaly reported by paediatricians. RESULTS: Between June 2016 and July 2018, 106 notifications were received, with clinical details provided for 96 (91%). After excluding ineligible notifications, 70 cases were confirmed, giving an annual birth prevalence of 1.12 (95% CI 0.88 to 1.42) per 10 000 live births. Of the total number of cases, 47 (67%) had primary microcephaly (at birth); and 25 (36%) had severe microcephaly (OFC >3 SDs). Birth defects were reported in 42 (60%). Of 49 infants with developmental assessment details available, 25 (51%) had failed to reach all milestones. Vision impairment was reported in 14 (26%). The cause of microcephaly was unknown in 60%: 13 (19%) had been diagnosed with genetic disorders; 22 (39%) had anomalies on neuroimaging. No congenital or probable Zika infection was identified. Severe microcephaly was more often associated with hearing impairment than microcephaly of >2 SDs but ≤3 SDs below the mean (p<0.007). Indigenous children and children with socioeconomic advantage were over-represented among children with microcephaly. CONCLUSION: Novel national data on microcephaly highlight the high proportion of idiopathic cases. This has implications for prevention and management and suggests the need for a standardised diagnostic approach and ongoing surveillance mechanism in Australia.


Assuntos
Microcefalia/diagnóstico , Microcefalia/epidemiologia , Vigilância em Saúde Pública/métodos , Infecção por Zika virus/epidemiologia , Adulto , Austrália/epidemiologia , Anormalidades Congênitas/epidemiologia , Deficiências do Desenvolvimento/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/genética , Neuroimagem/métodos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , Índice de Gravidade de Doença , Transtornos da Visão/epidemiologia , Zika virus/isolamento & purificação , Infecção por Zika virus/virologia
16.
Eur J Orthod ; 43(3): 346-352, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32524144

RESUMO

INTRODUCTION: The objective of this study is to assess the oral and maxillofacial characteristics of microcephalic children associated with congenital Zika syndrome (CZS). METHODS: A cross-sectional, observational study was carried out with 61 patients with microcephaly/CZS born between June 2015 and September 2017 (29 boys and 32 girls, average age of 22.8 months) and a control group with 58 non-CZS children born in the same period (25 boys and 33 girls, average age of 23.8 months). The functional clinical analysis considered the labial and lingual frena, tongue anterior projection, oral escape, palate form, and first tooth eruption. For the craniofacial analysis, facial anthropometric points and the cephalic perimeter at the time were measured. Demographic data were collected from medical records, and a clinical exam was performed in order to register the intrabuccal characteristics and craniofacial measures. The chi-square test and Student's t-test were used with a significance level of 0.05. RESULTS: The narrow palate form, tongue anterior projection, oral escape, and late first tooth eruption were significantly more present in the group with microcephaly/CZS. As for the craniofacial analysis, face width (Bi-Zi), mandible width (Go-Go), height of face upper third (Tr-G), and monthly growth of cephalic perimeter were significantly smaller, whereas height of face lower third (Sn-Gn) was significantly bigger in the group with microcephaly/CZS (P < 0.05). CONCLUSION: Children with microcephaly resulting from a congenital Zika infection showed functional, oral, and maxillofacial changes and smaller facial development in comparison with non-CZS children in the same age group.


Assuntos
Microcefalia , Infecção por Zika virus , Zika virus , Antropometria , Brasil , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Microcefalia/etiologia , Infecção por Zika virus/complicações
17.
Viruses ; 13(1)2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33374895

RESUMO

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.


Assuntos
Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Microcefalia/epidemiologia , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Zika virus , Biomarcadores , Brasil/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Microcefalia/diagnóstico , Microcefalia/metabolismo , Gravidez , Vigilância em Saúde Pública , Avaliação de Sintomas , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
18.
Viruses ; 12(12)2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302536

RESUMO

The congenital Zika syndrome (CZS) epidemic in Brazil turned the spotlight on many other factors beyond illness, such as poverty, gender, and inequalities in health care. Women were the emblematic subjects in this study, not only because Zika virus is a vertical transmission disease, but also because women-in Brazil and elsewhere-typically represent the primary carers of children. This is a qualitative analytic study using semi-structured interviews with 23 female family carers of children with CZS in Brazil. Through the concept of biographical disruption, we analysed some of the social impacts experienced by women involved in caring for affected children. We identified that the arrival of a child with disabilities resulted in biographical disruption similar to that experienced by people with chronic illnesses. Social support networks were configured through an alliance between women from different generations, revealing solidarity networks, but also highlighting the absence of the state in tackling these social vulnerabilities. Tracing the pathways of these biographical narratives enables us to understand how women have acted to defend the value of their disabled children in a society structured on the model of body normativity and inequality. These results may provide clues to a more inclusive society, which confronts systems of gender oppression and the sexual division of labour focused on women.


Assuntos
Cuidadores , Cuidado da Criança , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/epidemiologia , Zika virus , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Microcefalia/epidemiologia , Microcefalia/etiologia , Mutação , Gravidez , Vigilância em Saúde Pública , Saúde da Mulher , Zika virus/genética , Infecção por Zika virus/complicações , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
19.
Rev Bras Enferm ; 73(suppl 4): e20190883, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33206852

RESUMO

OBJECTIVE: To know the evidence available in the literature on the effects of the zika virus in children development after fetal exposure. METHODS: This is an integrative literature review with 16 scientific articles found in five databases (PubMed, LILACS, CINAHL, Web of Science and Scopus), based on the guiding question: "What are the effects in the development of children aged 0 to 6 years exposed to the zika virus in the fetal period? The STROBE statement was used for data extraction and evaluation of primary studies. RESULTS: Exposure to the zika virus in the fetal period resulted in several congenital anomalies and/or changes in the central nervous system: microcephaly, ocular problems, neurosensorial problems, ventriculomegaly, intracranial calcification, cardiopathy, arthrogryposis, among others. CONCLUSION: The zika virus is neurotropic; its effect in the fetal nervous system causes irreparable damage to the child, so health professionals, especially nurses, must intensify maternal and also childcare.


Assuntos
Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Criança , Feminino , Feto , Humanos , Microcefalia/etiologia , Gravidez , Infecção por Zika virus/complicações
20.
BMC Pediatr ; 20(1): 472, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038931

RESUMO

BACKGROUND: The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly. METHODS: We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10-45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC. RESULTS: Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were 'at risk of development delay' according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were 'at risk of development delay'. For children without microcephaly, the percentages found to be 'at risk of developmental delay' were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N = 94), 13.8%; Group 4 (N = 46), 21.7%. CONCLUSIONS: Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.


Assuntos
Epidemias , Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Microcefalia/epidemiologia , Microcefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
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