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.

Cerebrospinal fluid analysis of pregnant women at early stages of COVID-19.

OBJECTIVE: To determine the presence or absence of SARS-CoV-2 in the cerebrospinal fluid of pregnant women at early stages of COVID-19. MATERIALS AND METHODS: We conducted a prospective observational study with pregnant women undergoing cesarean section and real-time polymerase chain reaction to SARS-CoV-2 was performed in the cerebrospinal fluid in the early stages of COVID-19. RESULTS: Fourteen pregnant women, whose COVID-19 symptoms started between four to 18 days prior to delivery, were included. Eleven of the women reported anosmia, dysgeusia, and headaches and there were two fatal cases. SARS-Cov-2 was not present in the cerebrospinal fluid of these COVID-19 patients with early neurological symptoms, even in severe cases. CONCLUSION: Our study suggests that peripheric cell damage and parainfectious phenomena may predominate over direct central nervous system injury in the pathophysiology of COVID-19 related early neurological symptoms on pregnant women.

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.

Influence of growth hormone replacement on neurological and psychomotor development. Case report.

The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score -6.89), low growth rate, and low weight (z-score -7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children - for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.

Influence of growth hormone replacement on neurological and psychomotor development. Case report / Influência da reposição do hormônio do crescimento no desenvolvimento neuropsicomotor. Relato de caso

ABSTRACT The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score −6.89), low growth rate, and low weight (z-score −7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children — for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.

RESUMO A resposta estatural ao uso de hormônio do crescimento na baixa estatura já está comprovada na literatura. A influência dos componentes do eixo fator de crescimento semelhante à insulina tipo 1 (GH-IGF1) sobre desenvolvimento, função, regeneração, neuroproteção, cognição e funções motoras tem sido avaliada em estudos experimentais e em adultos com lesão de sistema nervoso central. No entanto, ainda são poucas as pesquisas sobre o impacto clínico da reposição hormonal no desenvolvimento neuropsicomotor. Este relato apresenta o caso de um paciente com excelente recuperação pôndero-estatural e, de forma ainda mais surpreendente, de desenvolvimento neuropsicomotor, em resposta ao uso de hormônio do crescimento. O resultado observado fortalece a correlação entre achados experimentais e clínicos, no que diz respeito à resposta da plasticidade cerebral ao hormônio do crescimento em crianças. Paciente do sexo masculino nasceu pré-termo com múltiplos agravos no período neonatal e de lactente jovem, e que, por 6 anos, apresentou deficit relevante do crescimento, na maturação óssea e do desenvolvimento neuropsicomotor. Aos 6 anos de idade, apresentava baixa estatura (escore Z de −6,89), baixa velocidade de crescimento e baixo peso (escore Z de −7,91). Era incapaz de sustentar o peso axial, não tinha desenvolvido habilidade motora fina e nem controle esfincteriano, e apresentava também disfunção na deglutição e na linguagem. Exames complementares mostraram IGF1 baixo, sem alterações na imagem da região hipotálamo-hipofisária e idade óssea compatível com 3 anos — para a idade cronológica de 6 anos e 1 mês. A terapia de reposição com hormônio do crescimento promoveu forte impacto na recuperação pôndero-estatural e também do desenvolvimento neuropsicomotor desta criança.

Progresso, calamidade e trabalho: pobreza e urbanidade incipiente na cidade em fins do oitocento / Progress, calamity and work: poverty and initial urbanity in the city in late XIX century

Trata da confrontaçäo ocorrida durante a Grande Seca de 1877 no Ceará. Utilizando as palavras progresso, calamidade e trabalho como janelas para o entendimento das várias sensibilidades geradas em torno da problemática da seca, procura compreender os sentidos atribuídos a elas, historicamente, pelos vários grupos estudados. (AU)