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

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 (1^st, 2^nd and 3^rd 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 2^nd and 3^rd 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 2^nd (3x increase) and the 3^rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3^rd 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 3^rd 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.

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.

Introduction: Little is known about the effects of intrauterine exposure to SARS-CoV-2, especially on growth and neurodevelopment in children. Objective: We wished to verify the effect of intrauterine exposure to SARS-CoV-2 on neurological development in children. Methods: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy were enrolled in a prospective descriptive–analytical study involving outpatient appointments performed 6 and 12 months after birth. Their neurological development was assessed using the Bayley-III Scale, using a score of >85 as the cutoff threshold for identifying developmental delay. Differences between groups were assessed through an ANOVA, using Bonferroni correction for multiple comparisons. Regression models were employed to examine the associations between the Bayley-III scores and maternal features. Results: Two hundred and sixty-nine infants were evaluated, most of whom were born full-term and with birth weights appropriate for gestational age at delivery. Developmental delays were observed in 26% of the infants in at least one of the Bayley-III domains. The language domain was particularly affected, with impairments observed in children exposed to SARS-CoV-2 closer to the time of delivery. These findings were statistically significant (p < 0.05). Conclusions: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy presented developmental delays at 6 and 12 months, particularly in the language domain. These findings reinforce the relevance of long-term clinical follow-ups of newborns exposed to SARS-CoV-2 infection during pregnancy.

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.