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Objective To evaluate the validity of the triage system CLARIPED in a pediatric population in the city of São Paulo, Brazil. Methods Prospective, observational study in a secondary-level pediatric emergency service from Sep-2018 to Ago-2019. A convenience sample of all patients aged 0-18 years triaged by the computerized CLARIPED system was selected. Associations between urgency levels and patient outcomes were analyzed to assess construct validity. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) to identify the most urgent patients were estimated, as well as under-triage and over-triage rates. Results The distribution of 24,338 visits was: RED 0.02%, ORANGE 0.9%, YELLOW 23.5%, GREEN 47.9%, and BLUE 27.7% (highest to the lowest level of urgency). The frequency of the following outcomes increased with increasing urgency: hospital admission (0.0%, 0.02%, 0.1%, 7.1% and 20%); stay in ED observation room (1.9%, 2,4%, 4.8%, 24.1%, 60%); use of ≥ 2 diagnostic/therapeutic resources (2.3%, 3.0%, 5.9%, 28.8%, 40%); ED length of stay (12, 12, 15, 99.5, 362 min). The most urgent patients (RED, ORANGE, and YELLOW) exhibited higher chances of using ≥ 2 resources (OR 2.55; 95%CI: 2.23-2.92) or of being hospitalized (OR 23.9; 95%CI: 7.17-79.62), compared to the least urgent (GREEN and BLUE). The sensitivity to identify urgency was 0.88 (95%CI: 0.70-0.98); specificity, 0.76 (95%CI: 0.75-0.76); NPV, 0.99 (95%CI: 0.99-1.00); overtriage rate, 23.0%, and undertriage, 11.5%. Conclusion This study corroborates the validity and safety of CLARIPED, demonstrating significant correlations with clinical outcomes, good sensitivity, and low undertriage rate in a secondary-level Brazilian pediatric emergency service.

Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.

Objective: To assess Brazilian pediatric intensivists’ general knowledge of extracorporeal membrane oxygenation, including evidence for its use, the national funding model, indications, and complications. Methods: This was a multicenter cross-sectional survey including 45 Brazilian pediatric intensive care units. A convenience sample of 654 intensivists was surveyed regarding their knowledge on managing patients on extracorporeal membrane oxygenation, its indications, complications, funding, and literature evidence. Results: The survey addressed questions regarding the knowledge and experience of pediatric intensivists with extracorporeal membrane oxygenation, including two clinical cases and 6 optional questions about the management of patients on extracorporeal membrane oxygenation. Of the 45 invited centers, 42 (91%) participated in the study, and 412 of 654 (63%) pediatric intensivists responded to the survey. Most pediatric intensive care units were from the Southeast region of Brazil (59.5%), and private/for-profit hospitals represented 28.6% of the participating centers. The average age of respondents was 41.4 (standard deviation 9.1) years, and the majority (77%) were women. Only 12.4% of respondents had taken an extracorporeal membrane oxygenation course. Only 19% of surveyed hospitals have an extracorporeal membrane oxygenation program, and only 27% of intensivists reported having already managed patients on extracorporeal membrane oxygenation. Specific extracorporeal membrane oxygenation management questions were responded to by only 64 physicians (15.5%), who had a fair/good correct response rate (median 63.4%; range 32.8% to 91.9%). Conclusion: Most Brazilian pediatric intensivists demonstrated limited knowledge regarding extracorporeal membrane oxygenation, including its indications and complications. Extracorporeal membrane oxygenation is not yet widely available in Brazil, with few intensivists prepared to manage patients on extracorporeal membrane oxygenation and even fewer intensivists recognizing when to refer patients to extracorporeal membrane oxygenation centers. RESUMO Objetivo: Avaliar os conhecimentos gerais dos intensivistas pediátricos brasileiros sobre oxigenação por membrana extracorpórea, incluindo evidências de uso, modelo de custeio nacional, indicações e complicações. Métodos: Este estudo foi um inquérito transversal multicêntrico que incluiu 45 unidades de terapia intensiva pediátrica brasileiras. Realizou-se inquérito de conveniência com 654 intensivistas quanto aos seus conhecimentos sobre manejo de pacientes em oxigenação por membrana extracorpórea, suas indicações, complicações, custeio e evidências bibliográficas. Resultados: O inquérito abordou questões relativas aos conhecimentos e à experiência dos intensivistas pediátricos sobre oxigenação por membrana extracorpórea, incluindo dois casos clínicos e seis questões facultativas sobre o manejo de pacientes em oxigenação por membrana extracorpórea. Dos 45 centros convidados, 42 (91%) participaram do estudo, e 412 (63%) dos 654 intensivistas pediátricos responderam ao inquérito. A maioria das unidades de terapia intensiva pediátrica eram da Região Sudeste do Brasil (59,5%), e os hospitais privados com fins lucrativos representavam 28,6% dos centros participantes. A média de idade dos respondentes era de 41,4 (desvio-padrão de 9,1) anos, e a maioria (77%) era mulher. Apenas 12,4% dos respondentes tinham formação em oxigenação por membrana extracorpórea. Dos hospitais pesquisados, apenas 19% tinham um programa de oxigenação por membrana extracorpórea, e apenas 27% dos intensivistas declararam já ter manejado pacientes em oxigenação por membrana extracorpórea. Apenas 64 médicos (15,5%) responderam a questões específicas sobre o manejo de oxigenação por membrana extracorpórea (mediana 63,4%; oscilando entre 32,8% e 91,9%). Conclusão: A maioria dos intensivistas pediátricos brasileiros demonstrou conhecimentos limitados de oxigenação por membrana extracorpórea, incluindo suas indicações e complicações. A oxigenação por membrana extracorpórea ainda não está amplamente disponível no Brasil, com poucos intensivistas preparados para o manejo de pacientes em oxigenação por membrana extracorpórea e ainda menos intensivistas capazes de reconhecer quando devem encaminhar pacientes para centros de oxigenação por membrana extracorpórea.

To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders.Multicenter, cross-sectional study using an electronic survey.Twenty-nine public and private Brazilian PICUs.Multidisciplinary PICU workers.None.Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p0.001), and depression symptoms (32.5% vs 15%; p0.001), with superior PCL-5 scores for PTSD (p0.001). Public hospital workers presented more burnout (29% vs 18.6%, p0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out (p0.05 in all three dimensions).The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

ObjectiveTo validate the PIM3 score in Brazilian PICUs and compare its performance with the PIM2.MethodsObservational, retrospective, multicenter study, including patients younger than 16 years old admitted consecutively from October 2013 to September 2019. We assessed the Standardized Mortality Ratio (SMR), the discrimination capability (using the area under the receiver operating characteristic curve – AUROC), and the calibration. To assess the calibration, we used the calibration belt, which is a curve that represents the correlation of predicted and observed values and their 95% Confidence Interval (CI) through all the risk ranges. We also analyzed the performance of both scores in three periods: 2013–2015, 2015–2017, and 2017–2019.Results41,541 patients from 22 PICUs were included. Most patients aged less than 24 months (58.4%) and were admitted for medical conditions (88.6%) (respiratory conditions = 53.8%). Invasive mechanical ventilation was used in 5.8%. The median PICU length of stay was three days (IQR, 2–5), and the observed mortality was 1.8% (763 deaths). The predicted mortality by PIM3 was 1.8% (SMR 1.00; 95% CI 0.94–1.08) and by PIM2 was 2.1% (SMR 0.90; 95% CI 0.83–0.96). Both scores had good discrimination (PIM3 AUROC = 0.88 and PIM2 AUROC = 0.89). In calibration analysis, both scores overestimated mortality in the 0%–3% risk range, PIM3 tended to underestimate mortality in medium-risk patients (9%–46% risk range), and PIM2 also overestimated mortality in high-risk patients (70%–100% mortality risk).ConclusionsBoth scores had a good discrimination ability but poor calibration in different ranges, which deteriorated over time in the population studied.

Objective The proportion of children with complex chronic conditions is increasing in PICUs around the world. We determined the prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic. Methods The authors conducted a point prevalence cross-sectional study among fifteen Brazilian PICUs during the COVID-19 pandemic. The authors enrolled all children admitted to the participating PICUs with complex chronic conditions on three different days, four weeks apart, starting on April 4th, 2020. The authors recorded the patient's characteristics and functional status at admission and discharge days. Results During the 3 study days from March to June 2020, the authors enrolled 248 patients admitted to the 15 PICUs; 148 had CCC (prevalence of 59.7%). Patients had a median of 1 acute diagnosis and 2 chronic diagnoses. The use of resources/devices was extensive. The main mode of respiratory support was conventional mechanical ventilation. Most patients had a peripherally inserted central catheter (63.1%), followed by a central venous line (52.5%), and 33.3% had gastrostomy or/and tracheostomy. The functional status score was significantly better at discharge compared to admission day due to the respiratory status improvement. Conclusions The prevalence of children with CCC admitted to the Brazilian PICUs represented 59.7% of patients during the COVID-19 pandemic. The functional status of these children improved during hospitalization, mainly due to the respiratory component.

Background: The use of realistic simulation in pediatric emergencies is particularly valuable, as it allows the training of technical, attitudinal, and cognitive skills helping to ensure patient safety. This study aims to describe the student's perception of using the High-Fidelity Realistic Simulation in the pediatric emergency modules during the internship. Methods:Observational, descriptive study with a quantitative and qualitative approach. A semi-structured questionnaire was applied to sixth-year medical students at the end of pediatric internship modules, eight weeks long, from August to December 2020. All participated in two types of activities on 14 themes: high fidelity simulation (HFS) and structured discussion of clinical cases (SDCC). Results: Of the 33 participants, 29 answered the questionnaire. The mean age was 24 ± 1.8 years, and 58.6% were female. All agreed that the experience with HFS contributed to safer performance in pediatric emergencies, considered optimal by 76% and good for the rest. Most thought the association of HFS and SDCC was the ideal method (96%). The content analysis of the responses on HFS highlighted thematic units in five categories: significant learning, contribution to professional training, skills, attitude/behavior, and quality of the activity. Conclusions: Students' reaction to using HFS in pediatric emergencies was very positive, and its association with SDCC was considered the ideal teaching method. Knowing students' reactions helps teachers plan their activities to improve the teaching-learning method.

ObjectiveTo estimate the incidence of retinoblastoma in children and adolescents in Brazil based on Population-Based Cancer Registry (PBCR), describing temporal trends and some quality indicators of this registry.MethodsBased on secondary data from the PBCR of the National Institute of Cancer (INCA) (2000–2018), by selecting the morphological code of retinoblastoma, the annual incidences per million (0–19 years of age) in each local PBCR were estimated by sex and age group, global combined and by region, in addition to the percentage of diagnosis only by death certificate (DC) or not informed (NI), and the male/female ratio (M/F). An annual incidence trend in the five Brazilian geographic regions was also analyzed using the inflection point regression technique.Results675 patients were identified in 28 PBCR, 91% between 0 and 4 years of age. The overall combined incidence per million by age group was: 7.02 (0–4 years old), ranging from 5.25 in the Midwest to 11.26 in the Northeast; 0.46 (5–9 years old); 0.05 (10–14 years old) and 0.03 (15–19 years old). The combined incidence per million, adjusted for the world population, was 2.23 (0–14 years old) and 2.24 (0–19 years old). The DC and NI percentages were 13% and 18%, respectively; the M/F ratio was 1.3. The incidence remained stable throughout the study period, except for the city of São Paulo, where there was a significant reduction of 3.4% per year.ConclusionsIn Brazil, except for the Northeast region, the incidences of retinoblastoma were lower than those reported in several countries worldwide, suggesting possible underreporting, and the time series analysis showed a stable trend. Although this pioneering study brings a recent panel of available data on retinoblastoma in Brazil, more precise estimates are needed and welcome for better planning of onco-ophthalmologic care in the country.

ImportanceTargeted analgosedation is a challenge in critically ill children, and this challenge becomes even more significant with drug shortages.ObservationsPublished guidelines inform the provision of analgosedation in critically ill children. This review provides insights into general approaches using these guidelines during drug shortages in Pediatric Intensive Care Units as well as strategies to optimize both pharmacological and non-pharmacological approaches in these situations.Conclusions and relevanceConsidering that drug shortages are a recurrent worldwide problem, this review may guide managing these drugs in critically ill children in situations of scarcity, such as in pandemics or disasters.

Objectives To study the impact of the implementation of the Pediatric Surviving Sepsis Campaign protocol on early recognition of sepsis, 1 -h treatment bundle and mortality. Methods Retrospective, single-center study, before and after the implementation of the sepsis protocol. Outcomes: sepsis recognition, compliance with the 1 -h bundle (fluid resuscitation, blood culture, antibiotics), time interval to fluid resuscitation and antibiotics administration, and mortality. Patients with febrile neutropenia were excluded. The comparisons between the periods were performed using non-parametric tests and odds ratios or relative risk were calculated. Results We studied 84 patients before and 103 after the protocol implementation. There was an increase in sepsis recognition (OR 21.5 [95% CI: 10.1-45.7]), in the compliance with the 1 -h bundle as a whole (62% x 0%), and with its three components: fluid resuscitation (OR 31.1 [95% CI: 3.9−247.2]), blood culture (OR 15.9 [95% CI: 3.9−65.2]), and antibiotics (OR 35.6 [95% CI: 8.9−143.2]). Significant reduction between sepsis recognition to fluid resuscitation (152min × 12min, p < 0.001) and to antibiotics administration (137min × 30min) also occurred. The risk of death before protocol implementation was four times greater (RR 4.1 [95% CI: 1.2-14.4]), and the absolute death risk reduction was 9%. Conclusion Even if we considered the low precision of some estimates, the lower limits of the Confidence Intervals show that the implementation of the Pediatric Surviving Sepsis Campaign guidelines alongside a qualitive assurance initiative has led to improvements in sepsis recognition, compliance with the 1 -h treatment bundle, reduction in the time interval to fluid resuscitation and antibiotics, and reduction in sepsis mortality.

Objective To evaluate the validity of the computerized version of the pediatric triage system CLARIPED. Methods Prospective, observational study in a tertiary emergency department (ED) from Jan-2018 to Jan-2019. A convenience sample of patients aged 0-18 years who had computerized triage and outcome variables registered. Construct validity was assessed through the association between urgency levels and patient outcomes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), undertriage, and overtriage rates were assessed. Results 19,122 of 38,321 visits were analyzed. The urgency levels were: RED (emergency) 0.02%, ORANGE (high urgency) 3.21%, YELLOW (urgency) 35.69%, GREEN (low urgency) 58.46%, and BLUE (no urgency) 2.62%. The following outcomes increased according to the increase in the level of urgency: hospital admission (0.4%, 0.6%, 3.1%, 11.9% and 25%), stay in the ED observation room (2.8%, 4.7%, 15.9%, 40.4%, 50%), ≥ 2 diagnostic or therapeutic resources (7.8%, 16.5%, 33.7%, 60.6%, 75%), and ED length of stay in minutes (18, 24, 67, 120, 260). The odds of using ≥ 2 resources or being hospitalized were significantly greater in the most urgent patients (Red, Orange, and Yellow) compared to the least urgent (Green and Blue): OR 7.88 (95%CI: 5.35-11.6) and OR 2.85 (95%CI: 2.63-3.09), respectively. The sensitivity to identify urgency was 0.82 (95%CI: 0.77-0.85); specificity, 0.62 (95%CI: 0.61-0.6; NPV, 0.99 (95%CI: 0.99-1.00); overtriage rate, 4.28% and undertriage, 18.41%. Conclusion The computerized version of CLARIPED is a valid and safe pediatric triage system, with a significant correlation with clinical outcomes, good sensitivity, and low undertriage rate.

To date, no specific diagnostic criteria for sepsis-associated encephalopathy (SAE) have been established. We studied 33 pediatric patients with sepsis prospectively and evaluated the level of consciousness, the presence of delirium, electroencephalographic (EEG) findings, and plasma levels of neuron-specific enolase and S100-calcium-binding protein-B. A presumptive diagnosis of SAE was primarily considered in the presence of a decreased level of consciousness and/or delirium (clinical criteria), but specific EEG abnormalities were also considered (EEG criteria). The time course of the biomarkers was compared between groups with and without clinical or EEG criteria. The Functional Status Scale (FSS) was assessed at admission, discharge, and 3–6 months post-discharge. Clinical criteria were identified in 75.8% of patients, EEG criteria in 26.9%, both in 23.1%, and none in 23.1%. Biomarkers did not differ between groups. Three patients had an abnormal FSS at discharge, but no one on follow-up. A definitive diagnostic pattern for SAE remained unclear. Clinical criteria should be the basis for diagnosis, but sedation may be a significant confounder, also affecting EEG interpretation. The role of biomarkers requires a better definition. The diagnosis of SAE in pediatric patients remains a major challenge. New consensual diagnostic definitions and mainly prognostic studies are needed.

The PIPA project is the first birth cohort study in Brazil focusing on the investigation of environmental pollutant exposure effects on child health. This program was developed in Rio de Janeiro, a highly urbanized city that encompasses a diversity of environmental and socioeconomic factors potentially harmful to human health. A pilot study was carried out between September 2017 and August 2018. This paper describes the socioeconomic environment and exposure pollutant profile of the PIPA pilot study population. The PIPA pilot study enrolled 139 pregnant women with a total of 135 (97%) births. Maternal blood (n = 139) and urine (n = 139) samples were collected between the 32nd and 38th weeks of pregnancy. Newborn umbilical cord blood (n = 125) and urine (n = 34) samples were collected at birth and during the 1st, 3rd, and 6th months of life (n = 132). Up to 75% of the study population reported a per capita income lower than US$200, 19% received governmental financial aid, and 21% were single mothers. At least 20% lived in low-income communities. Metals were observed above the limits of detection in 100% of the mother and newborn samples, while 48% and 23.5% showed detectable pyrethroid metabolite levels. Perfluoroalkyl acids were detected in approximately 80% of mother blood and urine samples and 70% of cord blood samples. At least one organochlorine compound was detected in approximately 30% of the newborn and mother samples. Pregnant women from poor communities in Rio de Janeiro and their children are exposed to several harmful pollutants.

Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric immunosuppressed patients is unknown. Emerging data describe a milder or asymptomatic course in children compared with adults in this scenario. We present the seroprevalence and clinical features of coronavirus disease 2019 in a prospective cohort of 114 immunosuppressed children and adolescents from three groups: kidney transplantation, liver transplantation, and cancer patients. Among the thirty-five (30.7%) patients who had a positive serological test for SARS-CoV-2, 77% did not report previous symptoms and none of them developed any complications of coronavirus disease 2019 (COVID-19) after 30 or more days of follow-up. Among those who were symptomatic, diarrhea, fever, and cough were the most common findings.Conclusion: Seroprevalence of SARS-CoV-2 infection is high among immunosuppressed children and adolescents. COVID-19 has a mild or asymptomatic course in most of these patients. What is Known: • The number of immunosuppressed patients with coronavirus disease 2019 is increasing. • Viral infections have the potential for greater severity in immunocompromised children. What is New: • Seroprevalence for severe acute respiratory syndrome coronavirus 2 in immunocompromised pediatric patients was 31%. • A quarter of the serology-positive patients reported mild symptoms and none of them developed multisystem inflammatory syndrome in children associated with coronavirus disease 2019.

Objectives To review, analyze, and present the available evidence on the usefulness of point-of-care pulmonary ultrasound in the diagnosis and monitoring of community-acquired pneumonia (CAP), aiming to facilitate its potential inclusion into pediatric clinical reference guidelines. Source of data A non-systematic research was carried out in the MEDLINE (PubMed), LILACS, and SciELO databases, from January 1985 to September 2019. The articles that were considered the most relevant were selected. Synthesis of data CAP is a relevant cause of morbidity and mortality in pediatrics and its clinical management remains a major challenge. The systematic use of chest X-ray for its diagnosis is controversial because it exposes the child to ionizing radiation and there are interobserver differences in its interpretation. Recently, the use of point-of-care pulmonary ultrasound by the pediatrician has been presented as an alternative for the diagnosis and monitoring of CAP. A great deal of evidence has disclosed its high sensitivity and diagnostic specificity, with the advantages of no ionizing radiation, relatively low cost, immediate results, portability, and the possibility of repetition according to the requirements of disease evolution. Moreover, its use can help rule out possible bacterial etiology and thus prevent inappropriate antibiotic treatments that favor bacterial resistance. Conclusions Point-of-care ultrasonography represents an opportunity to improve the diagnosis and monitoring of CAP. However, as an operator-dependent technique, training is required for adequate image acquisition, correct interpretation, and integration with clinical data for correct decision-making.

The PIPA Project is a prospective birth cohort study based in Rio de Janeiro, Brazil, whose pilot study was carried out between October 2017 and August 2018. Arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) concentrations were determined in maternal (n = 49) and umbilical cord blood (n = 46). The Denver Developmental Screening Test II (DDST-II) was applied in 50 six-month-old infants. Metals were detected in 100% of the mother and newborn samples above the limits of detection. Maternal blood lead concentrations were higher in premature newborns (GM: 5.72 µg/dL; p = 0.05). One-third of the infants (n = 17–35.4%) exhibited at least one fail in the neurodevelopment evaluation (fail group). Maternal blood arsenic concentrations were significantly (p = 0.03) higher in the “fail group” (GM: 11.85 µg/L) compared to infants who did not fail (not fail group) (GM: 8.47 µg/L). Maternal and umbilical cord blood arsenic concentrations were higher in all Denver Test’s domains in the “fail group”, albeit non-statistically significant, showing a tendency for the gross motor domain and maternal blood (p = 0.07). These findings indicate the need to further investigate the toxic effects of prenatal exposure to metals on infant neurodevelopment.

Sepsis continues to be one of the leading causes of admission to the Pediatric Intensive Care Unit, representing a great challenge for researchers and healthcare staff. This mini review aims to assess research on pediatric sepsis over the years. Of the 2,698 articles retrieved from the Scopus database, the 100 most cited were selected (50 published since 2000 and 50 published since 2016). The most cited studies, published in the 21st century, are highlighted, with their main findings and perspectives.

Objectives: To study the impact of the coronavirus disease 2019 pandemic, considering the physical distancing and schools closing, on the characteristics of admission and epidemiology on Brazilian PICUs. Design: Observational, multicenter, time series analysis, of electronic medical records from 15 PICU in Brazil. Data consisted of all March, April, and May PICU admissions from 2017 to 2020. Setting: Fifteen private PICUs in Brazil. Patients: Pediatric patients admitted to the PICU from March to May since 2017. Interventions: None. Measurements and Main Results: The period from March 11, 2020, to March 17, 2020, was considered the “intervention point” studied, corresponding to the suspension of school activities and the beginning of physical distancing in Brazil. During the pandemic period studied, there were 28 cases of coronavirus disease 2019 (one death). The mean age was higher (p = 0.000), the length of stay was shorter (p = 0.000), but mortality rates were similar among the periods (p = 0.36). The model estimated a reduction of 1,483 PICU admissions from March 2020 to May 2020. At the end of May, there was an estimated drop of –146.6 bronchiolitis admissions (95% CI, –242.8 to –50.3; p = 0.016); –71 asthma admissions (95% CI, –93.6 to –48.63; p = 0.000); and –59 community-acquired pneumonia admissions (95% CI, –74.7 to –43.3; p = 0.000) per period. The model showed no effect of the “intervention” (physical distancing) on hospitalization rates for epilepsy, diarrhea, sepsis, bacterial meningitis, or surgery when analyzed individually. When assessed together, the model estimated a reduction of 73.6 admissions (95% IC, –132 to –15.2; p = 0.43). Conclusions: The coronavirus disease 2019 pandemic strongly affected Brazilian PICUs, reducing admissions, length of stay, and the epidemiological profile. The measures to oppose the coronavirus disease 2019 pandemic may have prevented thousands of PICU hospitalizations across the country.

Arboviruses are emerging infectious diseases with the ability to expand geographically and rapidly affect large populations. Arbovirus infections can be more severe in pregnant women than in the general population, facing vertical transmission reported for many arboviruses that severely affect pregnancy outcome. The recent epidemic caused by the Zika virus in the Americas and congenital Zika syndrome associated with maternal infection has called out attention to the importance of studying arboviruses during pregnancy. Some issues that should be focused on are the improvement of diagnostic tests, including specific and sensitive molecular tests, associated with ultrasound screening; more accurate estimates of maternal, fetal, and neonatal risks; and the development of preventive vaccines, among other therapeutic options.

Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene (NR3C1) and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 (F) region of the NR3C1 gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 (F). Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 (F) region of the NR3C1 gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.

Objective To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. Method Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. Results Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. -Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5–6.5). The median length of PICU stay was six days (IQR 5–11), and one death occurred (1.8%). Conclusions Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Introduction: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas. Objective: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection. Methods: Bibliographic research conducted in March/2018–April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included. Results: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy. Conclusion: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy. Resumo: Introdução: Possíveis associações entre a infecção pelo Zika vírus e perda auditiva foram observadas durante a epidemia nas Américas. Objetivo: Descrever as alterações auditivas, a patogênese e as recomendações de seguimento em indivíduos com infecção por Zika vírus pré-natal ou adquirida. Método: Uma pesquisa bibliográfica foi realizada em março/2018 a abril/2019 nas principais bases de dados disponíveis. A seleção dos artigos, extração de dados e avaliação de qualidade foram realizadas por dois revisores independentes. Estudos com avaliação auditiva de pacientes com infecção por Zika vírus congênita ou adquirida; e/ou hipóteses ou evidências sobre a fisiopatologia do comprometimento auditivo associado ao Zika vírus; e/ou recomendações sobre triagem e seguimento de pacientes com comprometimento auditivo pelo Zika vírus foram incluídos na pesquisa. Resultados: Um total de 27 artigos foram selecionados. Perdas auditivas neurossensorial e transitória foram relatadas em seis adultos com infecção pelo Zika vírus adquirida. Das 962 crianças estudadas, 482 apresentavam microcefalia e 145 tinham confirmação diagnóstica do Zika vírus; 515 das 624 crianças com avaliação auditiva haviam realizado apenas testes de triagem com teste de emissões otoacústicas e/ou teste de potencial evocado auditivo de tronco encefálico automático com estímulo clique. Estudos em crianças expostas no período pré-natal foram muito heterogêneos e grandes variações na frequência de emissões otoacústicas e potencial evocado auditivo de tronco encefálico automático alterados ocorreram ao longo dos estudos; alterações nas emissões otoacústicas variaram de 0% a 75%, enquanto as alterações no potencial evocado auditivo de tronco encefálico automático variaram de 0% a 29,2%. Não foi possível descartar comprometimento neurossensorial, retrococlear ou de origem central. Um estudo com camundongos infectados não encontrou dano microscópico nas células ciliadas da cóclea. Estudos sobre a patogênese das alterações auditivas em humanos estão limitados a hipóteses e recomendações ainda apresentam pontos de controvérsia. Conclusão: Os dados disponíveis ainda são insuficientes para compreender todo o espectro do envolvimento dos órgãos auditivos pelo Zika vírus, a patogênese desse envolvimento ou até mesmo para confirmar a associação causal entre o envolvimento auditivo e a infecção pelo vírus. As recomendações de triagem e seguimento ainda apresentam pontos de controvérsia. Keywords: Zika virus infection, Hearing disorders, Hearing loss, Palavras-chave: Infecção pelo Zika vírus, Distúrbios auditivos, Perda de audição

Objectives: To present the currently available evidence of the effects of congenital Zika virus infection on infant growth, to discuss possible intervening factors, and to describe preliminary data on this growth in a cohort of exposed children. Source of data: Non‐systematic review in PubMed, BVS, CAPES, Scopus, Web of Science, Cochrane and Google Scholar databases in the last 5 years, using the terms infection/disease by Zika virus and growth/nutrition/nutritional status/infant nutrition and nutritional needs. Additionally, the anthropometric data of the first 2.5 years of a cohort of children exposed to the Zika virus during pregnancy were reviewed. Synthesis of data: Both intrauterine growth restriction and low birth weight were reported in series of cases of children with congenital Zika syndrome. The postnatal growth deficit of these children appears to be directly proportional to the degree of neurological impairment. The etiology is multifactorial, and nutritional and non‐nutritional factors are probably involved. The data from the present cohort show that the head circumference evolution depends on this measurement at birth and that weight‐height growth has a trend toward lower weight and length in children with congenital microcephaly and normocephalic at birth who develop some neurological abnormality. Conclusions: The few existing data suggest that, in children with congenital Zika, the greater the degree of neurological impairment, the greater the impact on growth, whether or not associated with microcephaly at birth. Resumo: Objetivos: Apresentar as evidências atualmente disponíveis das repercussões da infecção congênita pelo vírus Zika no crescimento infantil, discutir possíveis fatores intervenientes e descrever dados preliminares desse crescimento em uma coorte de crianças expostas. Fonte dos dados: Revisão não sistemática nos portais de banco de dados PubMed, BVS, Capes, Scopus, Web of Science, Cochrane e Google Scholar nos últimos cinco anos, com o uso dos termos infecção/doença pelo vírus Zika e crescimento/nutrição/status nutricional/nutrição infantil e necessidades nutricionais. Além disso, foram revistos os dados antropométricos dos primeiros dois anos e meio de uma coorte de crianças expostas ao vírus Zika durante a gestação. Síntese dos dados: Tanto a restrição do crescimento intrauterino como o baixo peso ao nascer têm sido relatados em séries de casos de crianças com síndrome de Zika congênita. O déficit de crescimento pós‐natal dessas crianças parece ser diretamente proporcional ao grau de comprometimento neurológico. A etiologia é multifatorial, com fatores nutricionais e não nutricionais provavelmente envolvidos. Os dados de nossa coorte mostram que a evolução do perímetro cefálico é dependente do valor dessa medida ao nascimento e que o crescimento pondero‐estatural apresenta uma tendência de menor peso e comprimento em crianças com microcefalia congênita e normocefálicas ao nascimento, mas com alguma anormalidade neurológica evolutiva. Conclusões: Os poucos dados existentes sugerem que em crianças com Zika congênita, o impacto sobre o crescimento será tanto maior quanto maior for o grau de comprometimento neurológico, associado ou não à microcefalia ao nascimento. Keywords: Zika virus infection, Growth, Microcephaly, Palavras‐chave: Infecção pelo Zika vírus, Crescimento, Microcefalia

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Despite the worldwide spread of SARS-CoV-2 infection (COVID-19), knowledge of the different clinical presentations, ways of transmission, severity and prognosis in children and adolescents is limited. An increasing number of reports describe some of these characteristics in this age range. A non-systematic review was undertaken using MEDLINE (PubMed), LILACS (VHL), Scopus, Web of Science, Cochrane and CAPES Portal databases from 1 January until 30 September 2020 [103] with the search terms SARS-CoV-2, COVID-19, child, children, youth, adolescent and newborn to identify the more recent clinical aspects of SARS-CoV-2 infection in children. In general, SARS-CoV-2 infection in children tends to be asymptomatic or to have mild or moderate signs, and most young ones are infected by family members. Recent reports offer new insights into the disease. Current evidence on SARS-CoV-2 infection in children and adolescents is presented, especially concerning the clinical presentation, imaging and uncommon severe forms of the disease, particularly the COVID-19-associated multisystem inflammatory syndrome. The impact of COVID-19 infection in the perinatal period is described in detail. Knowledge of the various clinical presentations of SARS-CoV-2 in children and adolescents allows the paediatrician to diagnose earlier, monitor warnings signs, implement treatment and, especially, establish preventive measures.Abbreviations : ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; ARF, acute rheumatic fever; CAA, coronary artery aneurysms; CK-MB, creatine kinase-MB; COVID-19, coronavirus disease-2019; HLA, specific human leucocyte antigen; IPC, infection prevention and control; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, COVID-19-associated multisystem inflammatory syndrome; RNA, ribonucleic acid; RT-PCR, reserve transcription-polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TCT, thoracic computed tomography; TSS, toxic shock syndrome; WHO, World Health Organization.

Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene (NR3C1) and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 F region of the NR3C1 gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 F. Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 F region of the NR3C1 gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.

Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults.

Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults. RESUMO Objetivo: Apresentar as atuais evidências sobre as características clínicas e laboratoriais da infecção pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) durante a infância e a adolescência. Fonte de dados: Revisão narrativa realizada nas bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde na Biblioteca Virtual em Saúde (LILACS/BVS), Scopus, Web of Science, Cochrane Library, portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect e Cumulative Index to Nursing and Allied Health Literature (CINAHL), com o uso dos termos SARS-CoV-2, COVID-19 e novo coronavírus e criança, recém-nascido e adolescente. Síntese dos dados: Diferentemente dos adultos, as crianças infectadas pelo SARS-CoV-2 apresentam formas clínicas leves ou assintomáticas na maior parte dos casos. As crianças sintomáticas apresentam predominantemente febre baixa e tosse, com alguns sintomas gastrointestinais associados. Casos graves são a minoria e ocorrem especialmente abaixo de um ano de idade. A detecção de partículas virais em fezes parece ser mais persistente em crianças, podendo servir como ferramenta diagnóstica e de controle do tempo de quarentena. Diferentemente dos adultos, as crianças podem apresentar respostas inflamatórias distintas, como tem ocorrido nos novos casos de síndrome de Kawasaki-like associada à infecção pelo SARS-CoV-2. Conclusões: Crianças, na sua maioria, apresentam quadros assintomáticos ou leves, com predomínio de febre, tosse e sintomas gastrointestinais. Novos relatos de diferentes reações sistêmicas inflamatórias em crianças têm sido notados, com manifestações clínicas distintas daquelas tipicamente observadas em adultos.

Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity. Resumo Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID-19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico-epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilação mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilação mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID-19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

OBJECTIVES To estimate the frequency of delirium detected by pediatric intensivists, based only on their clinical experience, without a valid and reliable tool. DESIGN Multicenter, prospective, descriptive, observational study. SETTINGS Three PICUs in Rio de Janeiro, Brazil. PATIENTS Twenty-nine days to 18 years old. INTERVENTIONS Electronic forms were sent weekly to the pediatric intensivists responsible for the daily care of patients from March to September 2015, to fill in information about the presence of risk factors and diagnosis of delirium in all patients who remained in the PICU in the last week. Demographics and other clinical data were extracted from an electronic system. MEASUREMENTS AND MAIN RESULTS A total of 504 admissions in the three PICUs (477 patients) were included. The pediatric intensivists reported only two episodes of delirium in two different patients, based on insufficient criteria. Considering all PICUs admissions, the reported frequency of delirium was only 0.4% (2/504). CONCLUSIONS The low frequency of delirium detection and the insufficient criteria used for the diagnosis in these units suggest flaws in the recognition of delirium and probably the occurrence of underdiagnosis/misdiagnosis when it is based only on clinical experience, without the use of a valid and reliable tool.

Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID‐19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March–May 2020) were included. Demographic, clinical‐epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy‐nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length‐of‐stay was five days; there were two deaths (3%) in the non‐ multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43–21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID‐19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity. Resumo: Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID‐19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico‐epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilac¸ão mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilac¸ão mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID‐19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Introduction The association between prenatal Zika virus infection and hearing alterations in offspring has been the object of some studies, although few have assessed children without microcephaly. However, a current trend to include prenatal Zika virus exposure in the group of risk indicators for hearing loss is noted. Objective To present a series of 27 children prenatally exposed to the Zika virus submitted to multiple hearing assessments over time. Methods A cohort of children born to symptomatic mothers with laboratorial Zika virus infection confirmation during pregnancy was submitted to an otoacoustic emission test, auditory brainstem response test (automated, neurodiagnostic and frequency-specific), audiometry, and imitanciometry over a period of 36 months since birth. The hearing assessment was performed independently of the presence of microcephaly or other apparent signs of congenital Zika syndrome. Results The hearing tests presented predominantly normal results. Some children had signs of middle ear pathology. The only microcephalic child had normal electrophysiological tests, as well as preserved audiometric thresholds, but presented altered motor responses to sound. Conclusion Prenatal exposure to Zika virus does not always determine hearing impairment. This risk seems to be more associated to the severity of the central nervous system damage. Hearing screening and follow-ups of the affected children are important, as well as further research in this area.

Objectives: To present the currently available evidence on transmission, clinical, diagnostic methods, treatment, and prevention methods of major arboviruses that occur in childhood. Source of data: Non‐systematic review carried out in MEDLINE (PubMed), LILACS (VHL), Scopus, Web of Science, Cochrane, CAPES Portal, and Google Scholar databases for the past five years using the search terms arboviruses, dengue, chikungunya, Zika, Mayaro, and West Nile fever, as well as child, newborn, and adolescent. Synthesis of data: The main characteristic of arboviruses is the fact that part of their replication cycle occurs inside insect vectors, thus being classically transmitted to humans through the bite of mosquitoes (hematophagous arthropods), although non‐vector transmission of these viruses is also possible in specific situations. These diseases remain a major public health challenge, due to the lack of specific antiviral treatment, the co‐circulation of different arboviruses in endemic/epidemic regions, the lack of effective and safe immunizations for the vast majority of these viruses, and the great difficulty in vector control, especially in large urban centers. Conclusions: Children are especially vulnerable to this group of diseases due to characteristics that facilitate the development of the most severe forms. More detailed knowledge of this group of diseases allows the pediatrician to diagnose them earlier, implement the correct treatment, monitor warning signs for the most severe forms, and establish effective preventive measures. Resumo: Objetivos: Apresentar as evidências atualmente disponíveis sobre transmissão, quadro clínico, métodos diagnósticos, tratamento e métodos de prevenção das principais arboviroses que ocorrem na infância. Fonte de dados: Revisão não sistemática feita nas bases de dados Medline (Pubmed), Lilacs (BVS), Scopus, Web of Science, Cochrane, portal Capes e Google Scholar nos últimos cinco anos, com o uso dos termos arboviroses, dengue, chikungunya, zika, mayaro, febre do oeste do Nilo e criança, recém‐nascido, adolescente. Síntese de dados: Os arbovírus têm como característica principal o fato de parte de seu ciclo de replicação ocorrer em insetos vetores. Assim, são classicamente transmitidos aos seres humanos pela picada de mosquitos (artrópodes hematófagos), embora seja também possível a transmissão não vetorial desses vírus em situações específicas. Essas doenças ainda constituem um grande desafio na saúde pública, devido à inexistência de tratamento antiviral específico, à cocirculação de diferentes arbovírus em regiões endêmicas/epidêmicas, à falta de imunizações efetivas e seguras para a grande maioria desses vírus e à grande dificuldade do controle vetorial, em especial nos grandes centros urbanos. Conclusões: As crianças constituem um grupo especialmente vulnerável a esse grupo de doenças, pois têm características que facilitam o desenvolvimento das formas mais graves. O conhecimento mais detalhado desse grupo de doenças permite ao pediatra diagnosticar mais precocemente, instituir o tratamento correto, vigiar os sinais de alarme para as formas mais graves e colocar em prática efetivas medidas de prevenção. Keywords: Arboviruses, Child, Newborn, Dengue, Chikungunya, Zika, Palavras‐chave: Arboviroses, Crianças, Recém‐nascidos, Dengue, Chikungunya, Zika

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms., Author summary The uncontrolled spreading of cyanobacteria in drinking water reservoirs has been the cause of serious public health problems worldwide. Toxin-producing cyanobacterial blooms commonly occur during drought periods in the northeast (NE) region of Brazil. During Zika Virus (ZIKV) outbreak in 2015–16, Brazilian NE showed disproportionately higher microcephaly incidence. Here, we test the hypothesis that the cyanotoxin saxitoxin (STX) may act as a co-insult for ZIKV. Water quality surveillance data showed increased cyanobacteria population and higher STX amount in NE region during 2014–2018. In vitro, we observed that neural progenitor cell death was doubled after STX exposure to ZIKV-infected brain organoids. In vivo, chronic ingestion of STX during gestational period potentiated ZIKV-derived brain abnormalities in newborn mice. Our study provides new insights that may explain the discrepancies among Brazilian regions regarding CZS severity. Moreover, the data highlight the importance of cyanobacteria and cyanotoxin freshwater monitoring for future arbovirus outbreaks.

To perform a cross-cultural adaptation of the Richmond Agitation-Sedation Scale (RASS) to Brazilian Portuguese for the evaluation of sedation in pediatric intensive care.Cross-cultural adaptation process including the conceptual, item, semantic and operational equivalence stages according to current recommendations.Pretests, divided into two stages, included 30 professionals from the pediatric intensive care unit of a university hospital, who administered the translated RASS to patients aged 29 days to 18 years. The pretests showed a content validity index above 0.90 for all items: 0.97 in the first stage of pretests and 0.99 in the second.The cross-cultural adaptation of RASS to Brazilian Portuguese resulted in a version with excellent comprehensibility and acceptability in a pediatric intensive care setting. Reliability and validity studies should be performed to evaluate the psychometric properties of the Brazilian Portuguese version of the RASS.Realizar adaptação transcultural para o Brasil da Richmond Agitation-Sedation Scale (RASS) para avaliação da sedação em terapia intensiva pediátrica.Processo de adaptação transcultural incluindo as etapas de equivalência conceitual, de itens, semântica e operacional, de acordo com recomendações atuais.Pré-testes, divididos em duas etapas, incluíram 30 profissionais da unidade de terapia intensiva pediátrica de um hospital universitário, que aplicaram a RASS traduzida em pacientes de 29 dias a 18 anos. Os pré-testes mostraram Índice de Validade de Conteúdo acima de 0,90 para todos os itens: 0,97 na primeira etapa de pré-testes e 0,99 na segunda.A adaptação transcultural da RASS para o português do Brasil resultou em versão com excelente compreensão e aceitabilidade em cenário de terapia intensiva pediátrica. Estudos de confiabilidade e de validade devem ser realizados para avaliar as propriedades psicométricas da versão adaptada para o português do Brasil da RASS.

Background/Objective: As a developing country, Brazil presents a wide range of environmental risks that can constitute hazards to child health. The country also presents different socio-economic-cultural conditions that could be responsible for determining different vulnerability and susceptibility levels for the population, which can potentiate the effects of the environmental pollutants. The Rio Birth Cohort Study (PIPA project) is a prospective maternal-infant health study, hosted in the city of Rio de Janeiro (Southeastern Brazil), designed to investigate separate and combined effects of environmental chemical pollutants, as well as the interactions between these exposures and sociocultural environment and epigenetic patterns. This paper presents the learned lessons and strategies to address the shortcomings detected from this pilot study. Methods: The study population will be all children born at the Federal University of Rio de Janeiro Maternity Hospital from July 1st, 2020 to June 30th, 2021. The estimated population is of 2,500 children. The study will collect social, demographic, and health information from pregnant women and their children up to four years of age. Biological samples from both mothers and newborns will be collected to assess metal, pesticide and plasticizer exposure. All newborns will have their landmarks of physical, neurological, psychological, and cognitive development recorded at specific ages. Findings: A pilot study was carried out between September 2017 and August 2018, totaling 142 enrolled pregnant women, leading to 135 (95%) births and the collection of umbilical cord (126–93%,) and mother (139–98%) blood samples, as well as both mother (142–100%) and newborn (54–40%) urine samples and newborn meconium samples (117–86.7%). Conclusions: The study proposes a comprehensive assessment of pre- and postnatal exposure to environmental chemicals at multiple time points in a population living in a highly urbanized developing country. As far as we know, this is the only birth cohort in Brazil specifically designed for this purpose.

Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0–18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions: Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated. Keywords: Pandemic H1N1 Influenza, Co-detection, Pediatric intensive care unit, Severe acute respiratory infection (SARI), Child

To describe the prevalence of microcephaly in infants admitted to the neonatal intensive care units (NICUs) in eight private hospitals in south-eastern and midwestern Brazil, from 2011 to 2015.Observational, cross-sectional study in a cohort of neonates.Eight private NICUs situated in the cities of Rio de Janeiro (RJ), São Paulo (SP) and Federal District of Brasilia (FDB).Neonates up to 7 days of age and23 weeks of gestational age.Primary outcomes were the annual prevalence of microcephaly and severe microcephaly, both overall and in subgroups according to gestational age, type of microcephaly (proportional or disproportional) and the NICU's location in RJ, SP or FDB.In this cohort of 8275 neonates admitted to eight private NICUs, the overall prevalence of microcephaly was 5.6% (95% CI 5.1% to 6.1%) and severe microcephaly, 1.5% (95% CI 1.2% to 1.7%). There was no annual variation in these overall estimates (p=0.48 and p=0.99, respectively), nor in the studied subgroups. Microcephaly prevalence was higher in extremely premature and term newborns (7.7% and 7.2%; p0.001, respectively). Disproportional microcephaly was much more common than proportional microcephaly (prevalence 5.0% vs 0.6%; p0.001).The prevalence of microcephaly showed little variation from 2011 to 2015 in these south-eastern and midwestern Brazilian NICUs, suggesting that the impact of the Zika epidemic in neonates that occurred mainly in the north-eastern region in 2015 did not yet affect the infants of those regions during the studied period. These prevalence results can serve as a reference for comparisons with any future Zika outbreaks in the same or similar populations from these regions.

We describe a case of fetal death associated with a recent infection by Chikungunya virus (CHIKV) in a Brazilian pregnant woman (positive RT-PCR in blood and placenta). Zika virus (ZIKV) infection during pregnancy was also identified, based on a positive RT-PCR in a fetal kidney specimen. The maternal infection caused by the ZIKV was asymptomatic and the CHIKV infection had a classical clinical presentation. The fetus had no apparent anomalies, but her weight was between the 3rd and 10th percentile for the gestational age. This is the second case report of congenital arboviral co-infection and the first followed by antepartum fetal death. Keywords: Zika virus, Chikungunya, Dengue, Stillbirth, Arbovirus

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak was described in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the amount of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Author summaryThe uncontrolled spreading of cyanobacteria in drinking water reservoirs has been the cause of serious public health problems worldwide. Toxin-producing cyanobacterial blooms commonly occur during drought periods in the northeast (NE) region of Brazil. During Zika Virus (ZIKV) outbreak in 2015-16, Brazilian NE showed disproportionately higher microcephaly incidence. Here, we test the hypothesis that the cyanotoxin saxitoxin (STX) may act as a co-insult for ZIKV. Water quality surveillance data showed increased cyanobacteria population and higher STX amount in NE region during 2014-2018. In vitro, we observed that neural progenitor cell death was doubled after STX exposure to ZIKV-infected brain organoids. In vivo, chronic ingestion of STX during gestational period potentiated ZIKV-derived brain abnormalities in newborn mice. Our study provides new insights that may explain the discrepancies among Brazilian regions regarding CZS severity. Moreover, the data highlight the importance of cyanobacteria and cyanotoxin freshwater monitoring for future arbovirus outbreaks.

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).