Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Avaliação audiológica em bebês nascidos de mães que tiveram covid-19 no período gestacional / Audiological assessment in babies born to mothers who had covid-19 during gestation / Evaluación audiológica en bebés nacidos de madres que tenían covid-19 durante la gestación

Introdução: No final de dezembro de 2019, um grupo de casos inexplicáveis de pneumonia foi relatado em Wuhan, China. Alguns dias depois, o agente causador dessa misteriosa doença foi identificado como um novo coronavírus que se disseminou de forma rápida. As infecções maternas, contraídas antes ou durante a gravidez, podem ser transmitidas ao feto, durante a gestação (infecção congênita), durante o parto (infecção perinatal) e pela amamentação (infecção pós-natal) e podem causar danos ao feto ou ao recém-nascido. Objetivo: descrever a avaliação audiológica realizada em uma série de crianças cujas mães tiveram COVID-19, em sua forma leve, no período gestacional. Metodologia: Para a avaliação audiológica foram realizadas a anamnese e os exames de emissões otoacústicas por produto de distorção, nas frequências de 1,5 a 12KHz e pontencial auditivo de tronco encefálico por click. Resultados: A amostra foi composta por 47 recém-nascidos recém-nascidos. Os resultados dos testes das emissões otoacústicas evocadas por produto de distorção indicaram funcionalidade das estruturas avaliadas apontando normalidade da função coclear com nível de resposta adequado para a média de resultados obtidos até a frequência de 11kHz para a amplitude de resposta e para a relação sinal-ruído. Foi possível encontrar em toda a amostra a presença das ondas I, III e V na intensidade de 80dBHL e presença da onda V nas intensidades de 50 e 35dBHL bilateralmente. Conclusão: Não foi estabelecida uma correlação direta da infecção materna pelo vírus da covid-19 com os achados audiológicos nos recém- nascidos. Cabe mencionar que esse foi um estudo preliminar e que essas crianças precisam continuar em acompanhamento para investigação de futuros desfechos tardios no aparelho auditivo.

Introduction: In late December 2019, a cluster of unexplained pneumonia cases was reported in Wuhan, China. A few days later, the causative agent of this mysterious disease was identified as a new coronavirus that spread rapidly. Maternal infections, contracted before or during pregnancy, can be transmitted to the fetus during pregnancy (congenital infection), during childbirth (perinatal infection) and through breastfeeding (postnatal infection) and can cause harm to the fetus or newborn. -born. Objective: to describe the audiological evaluation carried out in a series of children whose mothers had COVID-19, in its mild form, during the gestational period. Methodology: For the audiological evaluation, anamnesis and distortion product otoacoustic emissions tests were carried out, at frequencies from 1.5 to 12KHz and brainstem auditory potential by click. Results: The sample consisted of 47 newborns. The results of the distortion product evoked otoacoustic emissions tests indicated functionality of the evaluated structures, pointing to normal cochlear function with an adequate response level for the average of results obtained up to a frequency of 11kHz for the response amplitude and the signal-to-noise ratio. . It was possible to find in the entire sample the presence of waves I, III and V at an intensity of 80dBHL and the presence of wave V at intensities of 50 and 35dBHL bilaterally. Conclusion: A direct correlation between maternal infection by the Covid-19 virus and audiological findings in newborns was not established. It is worth mentioning that this was a preliminary study and that these children need to continue being monitored to investigate future late outcomes with the hearing aid.

Introducción: A finales de diciembre de 2019, se informó un grupo de casos de neumonía inexplicable en Wuhan, China. Unos días después, el agente causante de esta misteriosa enfermedad fue identificado como un nuevo coronavirus que se propagó rápidamente. Las infecciones maternas, contraídas antes o durante el embarazo, pueden transmitirse al feto durante el embarazo (infección congénita), durante el parto (infección perinatal) y a través de la lactancia (infección posnatal) y pueden causar daños al feto o al recién nacido. Objetivo: describir la evaluación audiológica realizada a una serie de niños cuyas madres tuvieron COVID-19, en su forma leve, durante el período gestacional. Metodología: Para la evaluación audiológica se realizaron pruebas de anamnesis y otoemisiones acústicas de productos de distorsión, en frecuencias de 1,5 a 12KHz y potencial auditivo de tronco encefálico mediante click. Resultados: La muestra estuvo compuesta por 47 recién nacidos. Los resultados de las pruebas de distorsión producto de emisiones otoacústicas evocadas indicaron funcionalidad de las estructuras evaluadas, apuntando a una función coclear normal con un nivel de respuesta adecuado para los resultados promedio obtenidos hasta una frecuencia de 11kHz para la amplitud de respuesta y la relación señal-ruido. . Se pudo encontrar en toda la muestra la presencia de ondas I, III y V con una intensidad de 80dBHL y la presencia de la onda V con intensidades de 50 y 35dBHL de forma bilateral. Conclusión: No se estableció una correlación directa entre la infección materna por el virus Covid-19 y los hallazgos audiológicos en los recién nacidos. Cabe mencionar que este fue un estudio preliminar y que estos niños necesitan seguir siendo monitoreados para investigar futuros resultados tardíos con el audífono.

Síndrome Inflamatória Multissistêmica e Covid-19 em crianças e adolescentes: aspectos epidemiológicos, Brasil, 2020-2021 / Multisystem Inflammatory Syndrome and COVID-19 in children and adolescents: epidemiological aspects, Brazil, 2020-20211

RESUMO Este estudo descreve aspectos epidemiológicos da Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P) associada à Covid-19 e óbitos por Covid-19 em crianças (0-9 anos de idade) e adolescentes (10-19 anos de idade). As fontes de dados, de 2020-2021, foram os Sistemas de Vigilância Epidemiológica para SIM-P e de Informação sobre Mortalidade para Covid-19, gerenciados pelo Ministério da Saúde. Foram notificados 1.503 casos, mais frequentes em crianças (77%) do que em adolescentes (23%); e 93 óbitos por SIM-P em 26 das 27 Unidades da Federação. O maior número de casos em crianças foi notificado em São Paulo (268), contudo, a maior incidência ocorreu no Distrito Federal (7,8/100 mil habitantes). A proporção de óbitos por SIM-P foi 5,4% em crianças e 8,7% em adolescentes. No período avaliado, houve 2.329 óbitos por Covid-19 em menores de 20 anos de idade, com maior taxa em adolescentes (4,4/100 mil habitantes) do que em crianças (2,7/100 mil habitantes), com maiores taxas em Roraima. Recomenda-se intensificação da imunização contra Covid-19 nessa população, aumentando a proteção contra os efeitos negativos dessa doença e da SIM-P, que podem apresentar consequências em curto, médio e/ou longo prazo, de modo a não comprometer a inserção plena destes cidadãos na sociedade.

ABSTRACT This study describes epidemiological aspects of the Multisystemic Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 and mortality by COVID-19 in children (0-9 years old) and adolescents (10-19 years old). The data sources, for 2020-2021, were the Epidemiological Surveillance System for MIS-C and Mortality Information System for COVID-19, both managed by the Ministry of Health. There were 1,503 cases, more frequent in children (77%) than in adolescents (23%), and 93 reported deaths due to MIS-C in 26 of the 27 States of the Country. The highest number of cases in children was reported in São Paulo (268), but the highest incidence took place in the Federal District (7.8 per 100,000 inhabitants). The rate of deaths due to MIS-C was 5.4% in children and 8.7% in adolescents. There were 2,329 deaths due to COVID-19 in the population under 20 years old, with a higher rate in adolescents (4.4 per 100,000 inhabitants) than in children (2.7); the highest rate occurred in Roraima. We recommend intensifying immunization against COVID-19 in such population, increasing protection against the negative effects of COVID-19 and MIS-C, which may have short, medium and/or long-term consequences, so as not to compromise the full integration of these citizens into society.

Olfactory sensory and perceptual evaluation in newborn infants: A systematic review.

Fetuses are able to process olfactory stimuli present in the womb and continue to show a preference for these odors for months after birth. Despite the accumulated knowledge about their early ability to perceive odors, there is a lack of validated scales for odor response in newborns. The evaluation of reactions of the olfactory system to environmental stimuli in infants has been defined by methodological theoretical approaches of experimental and clinical assessment tools. These approaches are mainly based on psychophysical approaches and predominantly use behavioral and physiological measures. Examples can be found in studies describing early abilities of newborn babies for behaviors or heart rate variability showing memory of maternal food preferences or mother's breast milk. This systematic review aimed to determine whether validated odor assessment tools can be feasibly used in studies. Particularly in light of the current COVID-19 pandemic and evidence of associated olfactory impairment resulting from SARS-COV-2 infection, the study is also motivated by the need for tools to assess olfactory function in neonates.

Olfactory sensory evaluation in newborn children of women infected with COVID-19 during pregnancy / Avaliação sensorial olfativa em crianças recémnascidas de mulheres infectadas com COVID-19 durante a gravidez

INTRODUCTION: In adults, olfactory loss is one of the earliest and most frequent acute clinical manifestations of SARS-CoV-2 infection. The number of children infected with SARS-CoV-2 is relatively small, perhaps due to the lower expression of Angiotensin Converting Enzyme 2 (ACE2) in children compared to adults. Little is known about foetal impairment in mothers infected with SARS-CoV-2. This paper describes an ongoing scientific project on smell perception in infantsOBJECTIVE: The goal of the study is to develop and validate a behavioural evaluative scale of olfactory perception in healthy newborns and to apply this scale to newborn children of women infected with COVID-19 during pregnancy comparing to newborn children of women without COVID-19 infection history, in order to compare these groupsMETHODS: This is a retrospective comparative analytical cohort study of 300 newborns exposed and unexposed to COVID-19 during pregnancy. The data collection will follow the experimental procedure in a previous study that explored odours of the maternal breastmilk, vanilla (sweet) and distilled water (neutral). A coffee smell was implemented as an addition to this previous study in order to include acid/bitterness category to the categories of stimuliDISCUSSION: It is feasible to argue the hypothesis of the involvement of the foetus' olfactory bulb as one of the indelible pathophysiological manifestations to the clinical diagnosis of COVID-19 with neurosensory olfactory deficit in foetuses and newborns affected by intrauterine infection. This study aims to investigate if newborn children of women infected with COVID-19 during pregnancy have olfactory sensory changes. The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC- RBR-65qxs2

INTRODUÇÃO: Em adultos, a perda olfativa é uma das manifestações clínicas agudas mais precoces e frequentes da infecção por SARS-CoV-2. O número de crianças infectadas com SARS-CoV-2 é pequeno, talvez devido à menor expressão da Enzima Conversora da Angiotensina 2 (ACE2) em crianças em comparação com adultos. Pouco se sabe sobre o comprometimento fetal em mães infectadas com SARS-CoV-2. Este artigo descreve um projeto em andamento sobre a percepção olfativa em bebês recém-nascidosOBJETIVO: o objetivo do presente estudo é desenvolver e validar uma escala de avaliação comportamental da percepção olfativa em recém-nascidos saudáveis e aplicá-la a recém-nascidos de mulheres infectadas com COVID-19 durante a gravidez e comparar a recém-nascidos de mulheres sem histórico de infecção por COVID-19MÉTODO: Este é um estudo de coorte analítico comparativo retrospectivo de 300 recém-nascidos expostos e não expostos ao COVID-19 durante a gravidez. A coleta de dados seguirá o procedimento experimental de estudo anterior que explorou odores do leite materno, baunilha (doce) e água destilada (neutro). Um cheiro de café foi implementado como um complemento a este estudo anterior, a fim de incluir a categoria ácido / amargo nas categorias de estímulosDISCUSSÃO: É possível argumentar a hipótese do envolvimento do bulbo olfatório do feto durante a vida intrauterina como uma das manifestações fisiopatológicas indeléveis para o diagnóstico clínico de COVID-19 com déficit olfatório neurossensorial em fetos e recém-nascidos afetados por infecção intrauterina. Este estudo tem como objetivo investigar se filhos recém-nascidos de mulheres infectadas com COVID-19 durante a gravidez apresentam alterações sensoriais olfativas. O ensaio clínico foi registrado no Registro Brasileiro de Ensaios Clínicos (ReBEC- RBR-65qxs2

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children. OBJECTIVE: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. METHODS: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. RESULTS: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. CONCLUSIONS: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies. TRIAL REGISTRATION: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26477.

Comparison of conventional, amplitude-integrated and geodesic sensor net EEG used in premature neonates: a systematic review.

INTRODUCTION: The use of methods to evaluate cortical activity in neonates has great importance in modern medicine, as it allows the observation and evaluation of several clinical aspects, which guarantees that the health team has knowledge about possible intervention measures that may be necessary in the treatment of newborns. OBJECTIVE: This systematic review aimed to compare the main technologies available for the evaluation of brain functions in neonates, among them: the conventional electroencephalogram (EEG), the amplitude-integrated electroencephalogram (aEEG) and the geodesic sensor net EEG. METHODS: A search was conducted forarticles from national and international periodicals included in the Web of Science, LILACS, SciELO and Medline electronic databases. RESULTS: The search found 39 among 155 articles of interest and the analyses indicated that, in the clinical environment, the use of both conventional EEG and aEEG is highly recommended, as the combination of their functions allows, for example, a greater number of subclinical seizures to be detected. Conversely, the use of a geodesic sensor net EEG could be of great value, as it allows a large amount of data to be analyzed. CONCLUSION: This analysis may be useful in studies and research related to diseases and symptoms, such as seizures, a current challenge for neonatal neuromonitoring, as well as aspects of neurological development and functional studies. However, despite many advances in technology, electroencephalography in preterm neonates remains a challenge worldwide and still requires more robust research and efforts towards the best clinical assistance in this extremely early stage of life.

Comparison of conventional, amplitude-integrated and geodesic sensor net EEG used in premature neonates: a systematic review / Comparação do uso do EEG convencional, EEG de amplitude integrada e EEG geodésico em neonatos prematuros: uma revisão sistemática

ABSTRACT The use of methods to evaluate cortical activity in neonates has great importance in modern medicine, as it allows the observation and evaluation of several clinical aspects, which guarantees that the health team has knowledge about possible intervention measures that may be necessary in the treatment of newborns. Objective: This systematic review aimed to compare the main technologies available for the evaluation of brain functions in neonates, among them: the conventional electroencephalogram (EEG), the amplitude-integrated electroencephalogram (aEEG) and the geodesic sensor net EEG. Methods: A search was conducted forarticles from national and international periodicals included in the Web of Science, LILACS, SciELO and Medline electronic databases. Results: The search found 39 among 155 articles of interest and the analyses indicated that, in the clinical environment, the use of both conventional EEG and aEEG is highly recommended, as the combination of their functions allows, for example, a greater number of subclinical seizures to be detected. Conversely, the use of a geodesic sensor net EEG could be of great value, as it allows a large amount of data to be analyzed. Conclusion: This analysis may be useful in studies and research related to diseases and symptoms, such as seizures, a current challenge for neonatal neuromonitoring, as well as aspects of neurological development and functional studies. However, despite many advances in technology, electroencephalography in preterm neonates remains a challenge worldwide and still requires more robust research and efforts towards the best clinical assistance in this extremely early stage of life.

RESUMO Métodos para avaliar a atividade cortical em neonatos têm grande importância na Medicina moderna, pois permitem a observação e avaliação de diversos aspectos clínicos, garantindo que a equipe de saúde tenha conhecimento sobre possíveis medidas de intervenção que possam ser necessárias no tratamento de recém-nascidos. Objetivo: Esta revisão sistemática tem como objetivo comparar as principais tecnologias disponíveis para a avaliação das funções cerebrais em neonatos: eletroencefalograma convencional (EEG), eletroencefalograma de amplitude integrada (aEEG) e eletroencefalograma da rede do sensor geodésico. Métodos: Os artigos foram selecionados em periódicos nacionais e internacionais, incluídos nas bases de dados eletrônicas Web of Science, LILACS, SciELO e Medline. Resultados: Foram encontrados 39 artigos de interesse entre 155 artigos. As análises indicaram que, em relação ao ambiente clínico, o uso associativo de EEG convencional e aEEG é altamente recomendado, pois permite a combinação de funções, facilitando, por exemplo, que um maior número de convulsões sub-clínicas seja detectado. Por outro lado, o uso do eletroencefalograma da rede do sensor geodésico seria de grande valor, uma vez que permite que uma grande quantidade de dados seja analisada. Conclusão: Essa análise pode ser útil em estudos e pesquisas relacionados a doenças e sintomas, como convulsões, um desafio atual para a neuromonitorização neonatal, bem como aspectos de desenvolvimento neurológico e estudos funcionais. No entanto, apesar de muitos avanços tecnológicos, a eletroencefalografia em recém-nascidos prematuros ainda é um desafio em todo o mundo e requer pesquisas e esforços mais robustos para a melhor assistência clínica neste estágio extremamente precoce da vida.