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Abstract Objectives To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality. Methods A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. Results Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. Conclusion This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

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Abstract Objective In this systematic review (SR), the authors aimed to identify the possible impact of the social restriction imposed by the Coronavirus Disease-19 (COVID-19) pandemic on children/adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Data sources This SR was registered on PROSPERO CRD42021255569. Eligible articles were selected from PubMed, Embase, and LILACS, according to the following characteristics: ADHD patients < 18 years old, exposed to the COVID-19 pandemic, and the outcomes, medications, relationships, sleep, media use, remote learning, and comorbidities such as depression/sadness, inattention, anxiety, and irritability/aggressiveness. Newcastle-Ottawa Scale (NOS) for cohort, cross-sectional and case-control studies was used to assess methodological quality and the risk of bias. Summary of findings Of the 222 articles identified, 27 were included, with information on 7,235 patients. Most studies (n = 22) were cross-sectional and received a mean NOS 4.63/10 followed by longitudinal (n = 4) with 3.75/8 points and case-control (n = 1), with 3/9 points. The pandemic affected patients’ access to treatment, behavior, and sleep. Difficulties in remote learning and increased use of social media were described, as well as significant and positive changes in relationships with family and peers. Conclusion Although the studies were heterogeneous, they indicated that the pandemic-related issues experienced by patients with ADHD were mostly manifested affecting their behavior and sleep patterns.

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Abstract Objective To evaluate the effect of oropharyngeal colostrum immunotherapy (OCI) on the mortality of preterm newborns (PTNB) with very low birth weight (VLBW). Method Non-randomized clinical trial, carried out with 138 mother-child pairs attended at a public maternity hospital. The treatment group used raw colostrum, dripping 4 drops (0.2 ml) into the oropharyngeal mucosa, totaling 8 administrations in 24 h, up to the 7th complete day of life (OCI). The control group was composed of newborns admitted to the same maternity hospital before the implementation of the OCI. Analyzes were performed: descriptive, bivariate, multiple logistic regression, and survival analysis, with a significance level of 5% and 95% CI. Results The treatment group had an RR of death of 0.26 (95% CI = 0.07-0.67; p= 0.00), adjusted for maternal age, marital status, gestational hypertension, type of delivery, number of prenatal visits, and birth weight. Number Needed to Treat (NNT) demonstrated that for every 5 individuals treated with OCI, one death was prevented NNT = 4.9 (95% CI = 1.84-5.20); however, for PTNB with VLBW who remained hospitalized for 50, 100 and 150 days, the NNT reduces to 4, 4 and 3, respectively. Conclusion The OCI proved to be a beneficial intervention, since it reduced the risk of mortality in PTNB with VLBW when compared to the control group.

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Abstract Objectives To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n= 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

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Abstract Objective Children with spina bifida (SB) are at risk for stunting and overweight. However, height and Body Mass Index (BMI) z-score distribution in children and adolescents with SB are unclear. The aim of this study was to examine height and BMI z-score distribution in Brazilian children and adolescents with and without SB. This study further aimed to examine whether height and BMI z-scores differ between individuals with and without SB. Method This study included 101 participants (SB: n= 18; non-SB: n= 83, aged 7-16 years). The World Health Organization (WHO) AnthroPlus software was used to calculate height and BMI z-scores. AnthroPlus z-score distribution graphs were used to examine individual z-scores based on the 2007 WHO normal distribution curve. Effects of the group (SB vs non-SB) on height and BMI z-scores were examined with sequential regression. Results In the WHO distribution graph analysis, height z-scores of participants with SB were slightly left-shifted compared to the WHO normal distribution curve. In the regression analysis, group (SB vs non-SB) was a significant predictor of height z-scores after controlling for sex and age (ΔR2= 0.064, p= 0.010). BMI z-scores of participants with SB were right-shifted compared to the WHO normal curve. However, there was no contribution of the group to BMI z-scores (ΔR2= 0.011, p= 0.301). Conclusions These findings suggest that Brazilian children and adolescents with SB may be at risk for reduced height and increased BMI.

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Abstract Objective To evaluate the lifestyle and quality of life in Brazilian children and adolescents during the COVID-19 social distancing period in 2020. Methods This cross-sectional study evaluated children and adolescents (2-18 years of age) and their parents, who voluntarily participated in an online survey. Snowball sampling was used to recruit participants during the first 6 months of the pandemic. A questionnaire was used to characterize the study population. The PedsQL 4.0 and the EUROHIS-QOL 8-item index were used to assess the quality of life (QoL) in children/adolescents and parents, respectively. Data were analyzed using SPSS 18.0 statistical program through the ANOVA with post hoc Bonferroni analysis, student's t test, and the generalized estimating equation. Results Mean screen time increased from 2h pre-pandemic to 5h during the pandemic (p <0.001), which was associated with a decline in PedSQL4.0 scores (from 75.7 ± 2.6 to 71.3 ± 13.7, p <0.001). Unhealthy eating habits increased from 11% to 34% and were associated with worse QoL scores compared with improved or unchanged eating habits during the pandemic (69.7 ± 13.3 vs 72.80 ± 13.4 vs 76.4 ± 12.6; p <0.001). Poor sleep quality increased from 9% to 31.7% and was associated with worse QoL scores compared to improved or unchanged sleep quality during the pandemic (67.3 ± 13.1 vs 74.5 ± 13.1 vs 76.8 ± 12.2; p <0.05). Physical exercise was associated with better PedSQL4.0 scores (77.5 ± 12.3 vs 72.5 ± 14.4; p <0.001). Children aged 2-4y old had the best QoLscores. Conclusions Pandemic-related social distancing promoted significant lifestyle changes in children and adolescents, increasing screen time, reducing physical activity, and worsening food and sleep quality, which resulted in worse QoL scores.

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Abstract Objective Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI). Methods Patients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour. Results 103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p =0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p =0,025). Thirty patients underwent the YFV desensitization protocol. Conclusion There is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.

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Abstract Objective Kidney shortage for pediatric kidney transplantation (PKT) entails the need to use low-weight and age donors, despite the apprehension. The aim of this study was to analyze the pediatric deceased donor kidney transplantations (pDDKT) outcomes in the first year after the procedure, stratified by donor age. Method Retrospective cohort of pDDKTs carried out between January 2013, and January 2018, at a PKT reference hospital in Southern Brazil. Donors were divided into group 1 (≤ 6 years), and group 2 (> 6 years); the analysis of the outcomes was carried out in the same period. Results There were 143 pDDKTs; 51 (35.66%) in group 1; and 92 (64.34%) in group 2. In both groups there were 17 graft losses (11.8%), with vascular thrombosis as the main cause (group 1: 5; group 2: 4). Among the complications, renal artery stenosis (RAS) with indication for angioplasty and stenting was more frequent in group 1 (7.8%; group 2: 2.2%). The 1-year Renal Transplant Recipients' and graft survival did not show significant differences between the groups, (p= = 0.95). However, the Glomerular Filtration Rate analysis was higher in group 2, reaching, in the 12th month, 79.3 mL/min/1,73m2, compared to 69.7 mL/min/1,73m2 in group 1(p= = 0.033). Conclusions Small donors can be considered for pDDKTs, as long as there is an expert team to perform the transplantation.

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Abstract Objective Evaluate autonomic function and low-grade inflammation and characterize the correlation between these variables in schoolchildren with obesity living in the Brazilian northeast region. Methods 84 children with obesity and 41 with normal weight were included in this cross-sectional study. Anthropometry, body composition, blood pressure (BP), inflammatory biomarkers, and heart rate variability (HRV) indexes were analyzed in children aged 7 to 11 years. Results children with obesity had increased systolic (p= 0.0017) and diastolic (p= 0.0131) BP and heart rate (p= 0.0022). The children with obesity displayed significantly lower SDNN, RMSSD, NN50, HF (ms), HF (nu), SD1, SD2, and higher LF (ms), LF (nu), LF/HF, SD1/SD2, DFA-α1, and DFA-α2, compared to normal weight. A lower and higher capacity for producing IL-10 (p= 0.039) and IL-2 (p= 0.009), respectively, were found in children with obesity compared to children with normal weight. Although IL-2, IL-4 and IL17A did not correlate with HRV parameters, IL-6 was positively correlated with SDNN, LF (ms) and SD2, TNF-α was positively correlated with LF/HF and SD1/SD2 ratio, and IFN-γ was positively correlated with SDNN, RMMSSD, NN50, LF (ms), HF (ms), SD1, and SD2. Conclusions The findings suggest that children with obesity have impaired autonomic function and systemic low-grade inflammation compared to children within the normal weight range, the inflammatory biomarkers were correlated with HRV parameters in schoolchildren living in the northeastern region of Brazil.

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Abstract Objective To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. Conclusion Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

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Abstract Objective To analyze access to surgical care for congenital heart diseases in public specialized centers in the state of São Paulo before and during the COVID-19 pandemic and availability of surgical care in specialized hospitals, to identify bottlenecks in the care path for neonatal cardiac surgery. Methods This study included 1,437 children, under one year old, with congenital heart disease and formal referral to heart surgery between February 1, 2019, and February 28, 2021. Quantitative data analysis was performed using t-tests or the Mann-Whitney test. Results Approximately 30 % of children with urgent congenital heart disease could not access recommended care, mainly those needing complex surgeries (categories RACHS 4 to 6). The main diagnoses of neonates accessing care were patency of the ductus arteriosus (10.5 %) and coarctation of the aorta (10.1 %). Referral time for children in RACHS 1 to 3 was 4 days (median), while for those in categories 4 to 6, it was 7 days (p< 0.001). Longer referral time (20 days) was associated with court orders. During the pandemic, referral time decreased to 3 days, compared to 5 days (median) in the pre-pandemic period (p< 0.001). Conclusion The emergency surgical treatment supply for congenital heart diseases is insufficient compared to the current demand. Future research should evaluate if access to care in publicly funded hospitals could be improved by better access to prenatal care for pregnant women, increased diagnostic and therapeutic capacity in pediatric cardiology, and financial incentives for complex cardiac surgeries.

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Abstract Objectives To assess the prevalence and pattern of behavioral problems in children and adolescents with atopic dermatitis (AD) and to study their associations with clinical data and severity. Methods This was a single-center, cross-sectional study of patients (6-17 years) with AD. Assessment of competencies and syndrome scale scores of behavioral problems was performed by applying the Child Behavior Checklist 6-18 (CBCL 6-18) and AD severity using the Eczema Area Severity Index (EASI) score. Results Of the 100 patients with AD, 56% were male, with a mean age of 11±3 years, and 43% had moderate/severe AD. Borderline or abnormal values were found in 75% of the patients for total social competence, 57% for internalization, 27% for externalization, and 18% for aggressive behavior. A higher prevalence of aggressive behavior (27.9% vs. 10.5%; p= 0.02) and sleep disorders (32.6% vs. 15.8%; p= 0.04) was observed in patients with moderate/severe AD than in those with mild AD. Children with current or previous use of immunosuppressants/immunobiological tests had a lower frequency of normal social competence (53% vs. 83%, p= 0.012). Regarding the critical questions, 8% responded affirmatively to suicidal ideation. Conclusion A high prevalence of behavioral problems was observed among children and adolescents with AD, with a predominance of internalizing profiles, mainly anxiety and depression. Children with moderate/severe AD have a higher prevalence of aggressive behaviors and sleep disorders. These findings highlight the importance of multidisciplinary teams, including mental health professionals, in caring for patients with AD.

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Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

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Abstract Objective This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. Methods Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. Results Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. Conclusion Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.