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ABSTRACT Objective: The aim of this review was to summarize the most common extrapulmonary manifestations in pediatric patients with COVID-19, as well as to discuss clinical, epidemiological, and pathophysiological aspects of these clinical presentations in children. Source of data: An extensive search of literature was performed in order to identify pediatric cases with extrapulmonary manifestations between January 1, 2020 and June 21, 2020. Generic keywords, such as “Novel coronavirus” or “Novel coronavirus 2019” or “2019 nCoV” or “COVID-19” or “SARS-CoV-2” were searched on PubMed database, associated either with age filters or generic pediatric terms. Summary of findings: A total of 28 articles, including 199 patients, were considered suitable to review and data extraction. The main findings were summarized in tables. The main non-pulmonary manifestations in pediatric patients, in decreasing order of frequency, were gastrointestinal, renal, cardiovascular, neurological, hematological and lymphatic, cutaneous, hepatic, ocular, olfactory, and gustatory. Multisystem impairment and Kawasaki-like disease were also described. Conclusions: Differences in immune response of children and variations of tissue expression of angiotensin converting enzyme 2, the virus receptor, are likely to influence clinical, epidemiological, and pathophysiological patterns of the disease.

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ABSTRACT Objective: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment. The diagnostic criteria involve clinical, laboratory, and complementary tests. This review aims to draw pediatrician attention to this diagnosis, suggesting early treatment strategies, and proposing a pediatric emergency care flowchart. Sources: The PubMed/MEDLINE/WHO COVID-19 databases were reviewed for original and review articles, systematic reviews, meta-analyses, case series, and recommendations from medical societies and health organizations published through July 3, 2020. The reference lists of the selected articles were manually searched to identify any additional articles. Summary of the findings: COVID-19 infection is less severe in children than in adults, but can present as MIS-C, even in patients without comorbidities. There is evidence of an exacerbated inflammatory response with potential systemic injury, and it may present with aspects similar to those of Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. MIS-C can develop weeks after COVID-19 infection, suggesting an immunomediated cause. The most frequent clinical manifestations include fever, gastrointestinal symptoms, rash, mucous membrane changes, and cardiac dysfunction. Elevated inflammatory markers, lymphopenia, and coagulopathy are common laboratory findings. Supportive treatment and early immunomodulation can control the intense inflammatory response and reduce complications and mortality. Conclusions: MIS-C associated with COVID-19 is serious, rare, and potentially fatal. The emergency department pediatrician must recognize and treat it early using immunomodulatory strategies to reduce systemic injury. Further studies are needed to identify the disease pathogenesis and establish the most appropriate treatment.

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ABSTRACT Objective: Infant sleep problems can affect the child's health. Maternal characteristics have been associated with the quality of infant sleep, but few studies have investigated the impact of intrauterine conditions. The aim of the study was to evaluate the association between adverse intrauterine environments (maternal smoking, hypertension, diabetes, and intrauterine growth restriction) and extrauterine factors on infant sleep in the first 6 months of life. Methods: Prospective cohort study, including singleton and at-term infants. Mothers were interviewed after delivery and at 30 days, 3 months, and 6 months of life. Socioeconomic, breastfeeding, and sleep data were self-reported by mothers using semi-structured interviews. Maternal stress (Perceived Stress Scale) and postpartum depression symptoms (Edinburgh Postpartum Depression Scale) were assessed. Results: There was no statistically significant association between intrauterine environments and the sleep of infants of the 359 mother–child dyads investigated. Total infant sleep time decreased from approximately 13–11 h from 30 days to 6 months of age (p < 0.001) and the longest period of uninterrupted sleep increased from approximately 4–6 h during the same period (p < 0.001). Breastfed infants slept longer in 24-h periods in the first month, but they woke up more often throughout the night when compared to infants receiving formula. Mothers with depressive symptoms reported increased sleep latency time. Conclusions: Adverse intrauterine environments did not significantly affect sleep measures in the first 6 months of life. Maternal characteristics and practices, however, were associated with infant sleep, suggesting that environmental factors significantly contribute to sleep quality early in life.

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ABSTRACT Objective: This study aimed to evaluate gestational weight gain and birth weight in women with gestational diabetes mellitus of two Brazilian cohorts enrolled three decades apart. Methods: The authors compared data of 2362 women from the Lifestyle INtervention for Diabetes Prevention After Pregnancy study (LINDA-Brasil, 2014–2017) to those of 359 women from the Estudo Brasileiro de Diabetes Gestacional study (EBDG, 1991–1995). Gestational weight gain was classified by the 2009 Institute of Medicine criteria; large and small for gestational age newborns, by the Intergrowth-21st chart. Differences in birth weight means between pregestational BMI and gestational weight gain categories were evaluated by ANOVA; the associations of gestational weight gain and birth weight, through multivariable Poisson regression. Results: In LINDA-Brasil, women presented higher pregestational body mass index (30.3 ± 6.5 vs. 24.6 ± 4.4 kg/m2) and were frequently obese (46.4 vs. 11.1%) compared to those of the EBDG. In the EBDG, gestational weight gain was larger (11.3 ± 6.1 vs. 9.2 ± 7.6 kg) and rates of small for gestational age higher (7.5 vs. 4.5%) compared to LINDA-Brasil. In LINDA-Brasil, excessive gestational weight gain was associated to macrosomia (adjusted relative risk [aRR]: 1.59, 95% CI 1.08–2.35) and large for gestational age (aRR: 1.40; 95% CI 1.05–1.86); less gain increased the risk of low birth weight (aRR: 1.66; 95% CI 1.05–2.62) and small for gestational age (aRR: 1.79; 95% CI 1.03–3.11). These associations were similar in the EBDG, although not statistically significant. Conclusions: Improvements in gestational weight gain and rates of small for gestational age occurred over time in gestational diabetes mellitus pregnancies, accompanied by a worsening in maternal weight profile. This highlights the nutritional transition during this period and the importance of avoiding excessive gestational weight gain as well as promoting adequate weight before conception.

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Abstract Objectives: To develop and validate an instrument about nutritional knowledge and feeding practices to be used in children aged 7–11 years, based on the latest Brazilian Food Guide. Methods: Review on the subject; instrument creation; content validity with two groups of judges: first, nutritionists and, after adjustments, a multidisciplinary group (content validity index [CVI]); FACE validity; reproducibility analysis (intraclass correlation coefficient [ICC], level of agreement, and kappa [k]); internal consistency analysis (Cronbach's alpha[α]) and construct validity (Kaiser–Meyer–Olkin and exploratory factorial analysis). The sample was calculated, considering at least ten subjects for each question of the questionnaire. Results: There was a final sample of 453 children (53.6% girls), with a mean age of 9.45 years (SD = 1.44). The content validity showed a CVI ≥ 0.80 for relevance in 62.3% of the items for nutritionists’ group and 100% of the items for the multidisciplinary group, clarity (49.4%, 91.8%), and pertinence (58.8%, 98.4%), respectively. The test-retest showed a level of agreement of 84.3% and k = 0.740 for the Knowledge dimension and ICC = 0.754 for the Food Practices dimension. The internal consistency showed α = 0.589 for the Knowledge dimension and α = 0.618 for the Food Practices dimension. For the construct validity, Kaiser–Meyer–Olkin was 0.724 and exploratory factorial analysis showed a variance of 47.01 with varimax rotation and defined five factors for the Practices Dimension. Conclusion: The Food Knowledge and Practices Questionnaire (Questionário de Conhecimento e Práticas Alimentares [QCPA]) instrument showed validity and reliability to assess nutritional knowledge and food practices in children aged 7–11 years.

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Abstract Objective: Comprehend the profile and prevalence of non-suicidal self-injury (NSSI) in adolescents and its association with impulsiveness and loneliness. Methods: Cross-sectional study carried out in 2017 in Maceió-Alagoas, Northeast Brazil, in the households of 505 adolescents aged 12–17 years, using a sample stratified and randomized by gender and neighborhood. The following instruments were used: a sociodemographic questionnaire, Brazilian version of Functional Assessment of Self-Mutilation (FASM), the Brazilian Barratt Impulsiveness Scale (BIS-11), and the Brazilian Loneliness Scale (UCLA-BR). Results: A prevalence of 6.53% was found for non-suicidal self-injury disorder (DSM-5). Significant differences ( p ≤ 0.05) were observed regarding: the most frequently used forms of NSSI were the items “cut oneself” and “scratch oneself”; engaging in three or more different forms of self-injurious behavior (66.67%) and, reporting as reasons, “to relieve feelings of emptiness or indifference” and “to stop bad feelings/sensations.” Significance was also related to the sociodemographic profile: 72.73% were females and 63.54% had family income below one minimum wage. Individuals with self-injurious behavior also had higher impulsiveness and loneliness scores (p ≤ 0.05). Conclusions: The study identified a direct association between NSSI and impulsiveness and loneliness among adolescents, being more prevalent in females and in young individuals with socioeconomic vulnerability. The data provide support for improving public health policies, aimed at education, prevention, and treatment of adolescents with NSSI.

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Abstract Objective: To indicate neck circumference (NC) cutoff points to identify excess weight at different stages of somatic maturation and evaluate the association between NC and body mass index (BMI). Methods: Cross-sectional study with 1715 adolescents. BMI was classified according to the World Health Organization (WHO) criteria. Somatic maturation was obtained through the peak growth velocity (PGV). To define the cutoff points, curves of the receiver operating characteristic (ROC) model were constructed. The agreement between the anthropometric evaluation instruments was analyzed. The association between the variables was verified. Results: Of the girls, 93 were in the pre-PGV stage, 266 in the PGV stage, and 481 in the post-PGV stage. Of the boys, 264 were in the pre-PGV stage, 334 in the PGV stage, and 277 in the post-PGV stage. For the pre-PGV group, the cutoff point was 28 cm for females and 29 cm for males; for the group during PGV, the cutoff points were 30 cm for females and 33 cm for males; in the post-PGV group the cutoff values were 32 cm in females and 35 cm in males. The prevalence of excess weight was higher in the pre-PGV stage in males and in the PGV stage in females. The correlation coefficients were higher in the pre-PGV and PGV stages. Conclusion: The cutoff points for NC found in this study showed good sensitivity and specificity to identify excess weight in Brazilian adolescents and can be used as a reference in epidemiological studies.

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Abstract Objective: Irritable bowel syndrome is a frequent functional gastrointestinal disorder. The aims of this study were to investigate its epidemiology, focusing on the role of intestinal mucosal integrity and to evaluate the impact on the quality of life. Methods: A community-based survey applying a comparative cross sectional approach was conducted in six high schools in Palembang. Subjects were recruited using multistage random sampling divided in two groups. Rome III criteria were used to establish a diagnosis of IBS in combination with a questionnaire to determine risk factors. Determination of fecal alpha-1-antitrypsin and calprotectin levels was performed to determine impaired intestinal mucosal integrity. A questionnaire was used to evaluate how quality of life was affected by irritable bowel syndrome. Results: The survey was performed in 454 14−18 years old adolescents, of whom 30.2% fulfilled the Rome III criteria for IBS, with the following subtypes: 36.5% diarrhea, 18.9% constipation, 21.9% mixed, and 22.6% unclassified. Major risk factors were female gender, bullying, age 14–16 years, history of constipation and diarrhea, eating nuts, and drinking coffee, tea, and soft drinks. There was a significant association with intestinal inflammation (p = 0.013). A significantly impaired quality of life was found (p = 0.001). Conclusions: The prevalence of irritable bowel syndrome in adolescents was high, with bullying, female gender, age 14–16 years, constipation and diarrhea, and dietary consumption of soft drinks, coffee, and tea as risk factors. A significant association with intestinal inflammation was found.

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Abstract Objective: This study aims to describe the epidemiological characteristics and survival rates of children with acute myeloid leukemia treated in hospitals in southern Brazil and compare them with international data. Methods: A multicenter cohort study was conducted with retrospective data collection of all new patients with acute myeloid leukemia under 18 treated at five referral centers in pediatric hematology-oncology in southern Brazil between January 2005 and December 2015. Results: Of the 149 patients with acute myeloid leukemia, 63.0% (n = 94) were male. The median age at diagnosis was 10.5 years (range 0–18 years) and 40.3% (n = 60) had a white blood cell count below 50,000/mm2. The most common Franco-American-British (FAB) subtype was M3 (n = 43, 28.9%). Nine (6.0%) patients had central nervous system disease. In M3 patients, overall survival (OS) was 69.2% and 3-year event-free survival was 67.7%; in non-M3 patients, these rates were 45.3% and 36.7%, respectively. In non-M3 patients, OS was significantly different between transplanted (61.8%) and non-transplanted (38.2%) patients (p = 0.031). Conclusions: These results show a higher prevalence of the Franco-American-British M3 subtype than that reported in the international literature, as well as a decreased OS compared with that of developed countries. Further multicenter Brazilian studies with a larger sample size are encouraged to better understand the characteristics of acute myeloid leukemia, and to improve the treatment and prognosis in this population.

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Abstract Objective: The aim of this study was to identify the pattern of pediatric dermatoses of patients evaluated at a dermatologic clinic of a reference center in Brazil and to compare these results to similar surveys conducted in other countries. Methods: A retrospective study was performed of patients up to 18 years old, evaluated at a dermatologic clinic between January 1, 2017 and December 31, 2017. Variables collected for analysis included age, gender, dermatological diagnosis, multidisciplinary follow-up, hospitalization, and complementary exams. Results: A total of 2330 patients were included for analysis, with a mean age of 9.7 years. 295 patients were diagnosed with more than one skin disease, leading to a total of 2668 diagnoses. Skin diseases were organized into categories and inflammatory dermatoses corresponded to the largest group (31.2%), mostly due to atopic dermatitis (18.3%). The other main categories were: genodermatoses (14.2%), infectious diseases (12.6%), adnexal disorders (12.5%), cysts and neoplasms (10.7%), and vascular disorders (7.0%). Fifty-six patients needed to be admitted to the dermatology ward; 25 of them (44.6%) for management of worsening of the skin disease, mainly atopic dermatitis, psoriasis, and drug reactions. There were 885 biopsies performed in 38.0% of the subjects and 751 patients (32.2%) required multidisciplinary care; most of them had some genodermatoses. Conclusions: Dermatologic disorders are very common in the pediatric age group and differ from those in adults, suffering influence from cultural, ethnic, socioeconomic, and environmental factors. Knowing the magnitude and distribution of these dermatoses is important to better plan healthcare policies.

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Abstract Objectives: To summarize and differentiate abdominal ultrasound findings of necrotizing enterocolitis and food protein-induced enterocolitis syndrome. Methods: From January 2017 to December 2018, the abdominal ultrasound results of 304 cases diagnosed necrotizing enterocolitis or food protein-induced enterocolitis syndrome were retrospectively analyzed. The presence of pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility, focal fluid collections and hypoechoic change of gallbladder wall were calculated, and the results were compared and analyzed. Results: Pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility weakened/absent, focal fluid collections and hypoechoic change of gallbladder wall can be found in both necrotizing enterocolitis and food protein-induced enterocolitis syndrome infants. However, in infants with necrotizing enterocolitis, intestinal motility was weakened/absent in whole abdomen, and in food protein-induced enterocolitis syndrome, it only involved isolated segment of bowel. The positive rates of above signs in necrotizing enterocolitis infants were significantly higher than those in food protein-induced enterocolitis syndrome (p < 0.01). Moreover, it was observed that the rate of weakened intestinal motility besides the lesion segment of bowel in necrotizing enterocolitis infants was 100%, and in food protein-induced enterocolitis syndrome infants, it was 0%, which is supposed to be a main sign for identification. Conclusion: In the early stage, abdominal ultrasound can be used to differentiate necrotizing enterocolitis and food protein-induced enterocolitis syndrome.

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Abstract Objective: To investigate association between parental locus of control (belief of individuals about what or who has control of the events of their lives) and bottle feeding habits among children from 3 to 5 years of age. Methodology: Parental locus of control validated in Brazil, and semi-structured questionnaire to obtain sociodemographic, health, and oral habit behaviors was applied to mothers of 992 preschool children. Outcome variable “use of feeding bottle” was studied according to the time of its use (≤36 months and >36 months). Simple logistic regression models were adjusted and raw odds ratios were estimated for variables of distal blocks, which contemplated parental locus of control, socioeconomic characteristics of family, and maternal habits. In the intermediate block, the variables for conditions of the child's birth and place of health care attendance during the prenatal period and early childhood were included. In the proximal block, the time of breastfeeding and pacifier use were reported. Variables were analyzed from the distal to the proximal block, and the individual analyses that presented p ≤ 0.20 remained in each model; included in the subsequent block were the variables with p ≤ 0.10, because this was a study of prevention. Results: Longer time of feeding bottle use was associated with the internal parental locus of control, mothers older than 31 years of age, white race, premature children, who used pacifiers and are treated in the private health system. Conclusions: Children who maintained the habit of feeding bottle use for a longer time were those whose mother presented an internal locus of control.

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Abstract Objective: To investigate the extent to which sexual orientation-based bullying relates to self-reported feelings of loneliness and sleeping difficulty among Brazilian middle school students. Method: This is a cross-sectional study using data from the 2015 PeNSE (Pesquisa Nacional de Saúde do Escolar), a survey designed to monitor the health of children and adolescents enrolled in the ninth grade in public and private Brazilian schools. Multiple linear regressions stratified by sex were used on a sample of 101,646 students, considering as reference students who had not experienced bullying, as well as students who had experienced other causes of bullying; a significance level of p < 0.05 was accepted. Results: When the reference group was composed of students who had not experienced bullying, the associations between sexual orientation-based bullying and feelings of loneliness and between sexual orientation-based bullying and sleeping difficulty were positive (p < 0.05) for both male and female students, with magnitudes about twice as large as those found among those who reported having experienced other cause s of bullying. However, when the reference group was composed of students who had experienced other causes of bullying, only the association between sexual orientation-based bullying and feelings of loneliness was positive (p < 0.05) for both male and female students. Conclusion: This study highlights that sexual orientation-based bullying is a predictor of feelings of loneliness.

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Abstract Objective: Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. Method: The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <−2 and osteopenia as a Z-score of between −1.0 and −2. Results: A total of 37 patients were included in this analysis, with a mean age of 13.4 ± 3.9 years and a mean duration of illness of 2.1 ± 2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B = 2.02; p = 0.0001), and negatively associated with the presence of extraintestinal manifestations (B = −1.51, p = 0.009) and the use of biologics (B = −1.33, p = 0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B = 0.26, p = 0.004) and duration of illness in years (B = 0.35, p = 0.003). Conclusions: Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.