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Abstract Objective To systematically evaluate the effectiveness of Skin-to-Skin Contact (SSC) in reducing procedural pain in neonates, compared to standard care and other non-pharmacological interventions. Data Sources A comprehensive search was conducted in major electronic databases and gray literature up to July 2025. The review followed PRISMA and MECIR guidelines and included randomized controlled trials (RCTs) that used validated neonatal pain scales. Risk of bias was assessed using RoB 2.0, and the certainty of evidence was rated using the GRADE approach. Summary of Findings Twenty-nine RCTs involving 2995 neonates were included. SSC significantly reduced procedural pain compared to standard care (SMD = −1.13; 95 % CI: −1.54 to −0.72; p < 0.00001), although heterogeneity was high (I² = 93 %). Subgroup analyses suggested that heterogeneity was partially due to differences in pain assessment timing and study design. Compared to other interventions, SSC showed similar efficacy to carbohydrate solutions (SMD = 0.05; 95 % CI: −0.34 to 0.23), superior efficacy to swaddling (SMD = −0.86; 95 % CI: −1.38 to −0.34), and inferior efficacy to breastfeeding (SMD = 0.44; 95 % CI: 0.21 to 0.66). Conclusion SSC is an effective intervention for reducing procedural pain in neonates, particularly when compared to standard care and swaddling. However, its equivalence to carbohydrate solutions and inferiority to breastfeeding should be interpreted with caution due to methodological limitations and variability across studies. Further high-quality, large-scale RCTs are needed to improve the certainty of the evidence and guide clinical practice.

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Abstract Objective This systematic review aimed to evaluate the efficacy and safety of alternative antibiotics and different standard treatment regimens for bacterial meningitis in children, considering the increasing antimicrobial resistance and the need for adapted therapeutic options. To justify the use of alternative antibiotics, the authors analyzed the specific efficacy of ampicillin, chloramphenicol, cefuroxime and meropenem, which showed potential to overcome cases of antimicrobial resistance. Data sources A search was performed in databases such as PubMed, Scopus, Web of Science and Cochrane Library, without data restrictions, including planned clinical trials that compared alternative antibiotics and different standard treatment regimens, such as ceftriaxone, in children with bacterial meningitis. Inclusion criteria include studies reporting cure rates, complications and safety of treatments. Summary of results An analysis of 14 studies, totaling 2,014 children, indicated that antibiotics such as ampicillin, chloramphenicol, cefuroxime and meropenem had comparable efficacy and safety to standard treatment regimens. The review showed that, in many cases, alternative regimens and shorter treatment durations could be effective, without significantly increasing complications or mortality. Conclusion The results suggest that alternatives to standard treatment, such as ampicillin, chloramphenicol, cefuroxime and meropenem, are viable and safe options for the treatment of bacterial meningitis in children. These results help to adapt clinical practices, especially in settings with high antimicrobial resistance and resource limitations, by providing evidence for shorter and equally effective treatment regimens.

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Abstract Objective To evaluate evidence in the literature on palliative extubation in pediatrics in the context of palliative care, in any healthcare setting, to synthesize knowledge, identify gaps, and highlight future research opportunities. Data sources The PRISMA-ScR recommendations and the JBI Collaboration method were used. Searches were conducted in: Virtual Health Library, PubMed, Scopus, Embase, Cochrane Library and Web of Science. The following strategy was used: Population - children and adolescents (0 to 18 years) undergoing invasive mechanical ventilation; Concept - practices, experiences, or approaches related to palliative extubation; Context - palliative care in a hospital, hospice or home setting. Original articles published up to April 2025 were included; those that didn’t define age or were over 18 years, opinion pieces, editorials, and conference proceedings were excluded. Two independent reviewers extracted the data; discrepancies were resolved by consensus or with a third reviewer. The quality of the studies was assessed using the critical appraisal tools recommended by the JBI. Data synthesis Twelve articles were selected: eight case reports and four cross-sectional studies, totaling 129 patients; 128 were analyzed. In 78.1% of cases, palliative extubation was performed in a hospital setting, mainly in the ICU (72.6%); 93% used an endotracheal tube; 95.3% received analgesia/sedation around the time of extubation; 90.6% died after support withdrawn. Conclusions Knowledge of practices, experiences, and challenges related to palliative extubation in pediatrics is essential to support clinical decision-making and ensure that it is performed in a timely, responsible, and technically appropriate manner, following the principles of palliative care.

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Abstract Objective To investigate the behavior of weight-for-age z-score (WAZ) and associated factors in preterm newborns (PTNB) with very low birth weight (VLBW) and extremely low birth weight (ELBW), comparing them to low birth weight (LBW) during four weeks (wk.) of hospitalization in a neonatal intensive care unit (NICU). Methods Longitudinal study conducted using data from PTNB records in the southern Brazil NICU, between January 2017 and December 2020. Non-twin PTNB with gestational age of ≥ 24 and < 37 wk. and a birth weight (BW) ≥ 500 g were included. The outcome was WAZ, and the exposure was the PTNB’s BW, categorized as VLBW/ELBW (< 1500 g) and LBW (≥ 1500 g up to 2500 g). Energy (kcal/kg/day) and protein (g/kg/day) intakes were also evaluated. Two-way ANOVA and multiple linear regression were used to assess the association between demographic, clinical, and nutritional factors and the WAZ. Results The majority of PTNB were male (60 %) and had a birth weight ≥1500 g (65 %). A significant interaction was between the BW category and the length of hospitalization on WAZ (F = 4.0; p = 0.003). In the VLBW and ELBW, the WAZ was significantly lower in the first wk. compared to the LBW [−1.05 (−1.34;−0.75) vs −0.34 (−0.49;−0.18)]. Factors such as male sex, sepsis, initiation of enteral nutrition (EN), and protein intake were associated with WAZ behavior. Conclusion The downward trend of the WAZ curve was associated with the interaction between birth weight and length of hospitalization, especially in PTNB with VLBW and ELBW. The study concluded that male sex and sepsis contributed to the observed decline.

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Abstract Objective To develop and validate entrustable professional activities (EPAs) for the training of pediatric residents on topics that interface with pediatric surgical areas in the Brazilian context. Methods The study was conducted in two phases. In the first phase, experts were oriented and contextualized, and they were responsible for developing the initial list of EPAs. In the second phase, the Delphi technique was applied in three rounds: the first for consensus, the second for selection according to relevance and agreement, and the third for validation and detailing of the EPAs. Results In the first phase of the study, 9 experts listed 88 EPAs, which were applied in the Delphi method. In the first round of Delphi, the consensus of these experts defined 31 EPAs, with CVI ≥ 0.80, and ICC of 0.893 (95 % CI 0.823–0.945). In the second round, 25 coordinators of Medical Residency Programs selected 17 EPAs by agreement and relevance (CVI ≥ 0.80, and ICC of 0.851–95 % CI 0.753 to 0.924). In the third round, 50 preceptors from all over Brazil validated 14 EPAs with CVI ≥ 0.965 and ICC 0.866 (95 % CI 0.804–0.915), which were organized and detailed into 7 final EPAs. Conclusion Seven pediatric surgery EPAs were developed, consensualized, selected, and validated by experts for the work of pediatricians in Brazil through the Delphi method. The great participation and interest of medical residency preceptors with a wide geographical coverage in Brazil were strong points of this study, and these EPAs can be applied, reviewed, and updated.

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Abstract Objective This study aims to analyze the diagnostic yield of aCGH in pediatric patients with suspected rare diseases, focusing on its diagnostic value and effectiveness depending on different clinical symptoms. Methods This observational study analyzed 600 aCGH tests performed in a pediatric unit (2018–2022) for patients with suspected rare diseases. DNA was extracted from peripheral blood; aCGH resolution was adjusted to clinical features. CNVs were classified per international guidelines. Forty sociodemographic, clinical, and genetic variables were analyzed using IBM SPSS v.26. Results Of the 600 patients analyzed, 543 were included in the final study. The median age was 4.7 years (IQR: 6.36 years), and 66.3% were male. Most referrals came from pediatric neurology (84.3%), and the most common clinical manifestations were altered phenotype (38.6%), autism spectrum disorder (ASD) (38.6%), dysmorphia (28.2%), global developmental delay (GDD) (27.1%), and intellectual disability (21.0%). Among 543 patients, 30.4% presented CNVs, with 12.4% identified as pathogenic and 18.1% as variants of uncertain significance. Diagnostic yield was 12.2%, with 66 conclusive results — 90.9% of which were pathogenic. CNVs were most frequently detected on chromosomes 15 and 16. The highest yield was observed in clinical features such as coordination problems (35.7%), learning disorders (28.6%), and microcephaly (22.6%). Conclusion The diagnostic yield of aCGH in this study was 12.2%. The test demonstrated higher diagnostic value in patients with multiple clinical manifestations, highlighting the importance of aCGH as a first-line diagnostic tool for rare diseases. This technique enables earlier diagnosis, improves clinical management, and provides better counseling for affected families.

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Abstract Objective Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, particularly concerning in pediatric populations due to their unique etiologies, clinical outcomes, and long-term complications. This study aims to examine pediatric cases of SJS/TEN reported in the U.S. FDA’s FAERS database, focusing on age-stratified patterns and drug associations. Method A retrospective cross-sectional analysis was conducted using FAERS reports submitted until the end of 2024. Pediatric cases (0–17 years) with a diagnosis of SJS or TEN and a single suspected drug were included. Reports were analyzed by age group (0–11 and 12–17 years), gender, and drug classification using ATC codes. Statistical analyses assessed associations between demographic groups and implicated medications. Results Out of 2673 pediatric reports, 67.4 % involved SJS and 32.6 % TEN. The majority (62.3 %) were in the 0–11 age group. Nervous system agents—especially antiepileptics—were predominantly associated with older children, while systemic antiinfectives such as amoxicillin, azithromycin, and cefaclor were more frequent in younger children. Lamotrigine showed both age groups and female predominance. Conversely, paracetamol and ibuprofen were significantly associated with the TEN phenotypes in younger males. Conclusions The study reveals clear age- and drug-specific patterns in pediatric SJS/TEN. Findings emphasize the importance of age-stratified pharmacovigilance issues and cautious prescribing of high-risk drugs such as lamotrigine and antibiotics. Better awareness of potential biases, such as protopathic misattribution, is crucial for accurate signal detection in pediatric pharmacovigilance.

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Abstract Objectives To investigate the effect of a bolus of saline on extravascular lung water (EVLW), and to analyze correlations of EVLW with outcome. Methods Prospective cohort. Patients received 10 mL/kg of saline (bolus). Central venous blood gas analysis and echocardiography measurements were performed before and after. Lung ultrasound was performed with 12 measurements, repeated after expansion. Statistics included paired t-test and logistic regression models. The magnitude of the effect was assessed using Cohen's test. Results 88 measurements were made on 83 patients. There was a response to volume in 48 measurements (54.5 %). 28 patients (33.7 %) had signs of shock, and 60 were on mechanical ventilation (MV, 72.2 %). In 68 paired measurements, there was an increase in B-lines after expansion (77.2 %). The mean number of B-lines pre- was 1.42 (SD 1.12) per intercostal space, increasing to 1.71 (SD 1.17) post-expansion (p < 0.001, Cohen's d 0.97). The mean pre-expansion cardiac index was 3.43 L/min/m2 (SD 1.05), increasing to 3.87 (SD 1.21, p < 0.001, Cohen's d = 0.8). In a multivariate model, lactate and mean pre-expansion B-lines were independent predictors of death in ICU: pre-B-lines, Odds ratio 1.87, p = 0.012; pre-lactate OR 1.59, p = 0.012. The same was observed with post-volume B-lines, in a model which also included MV: post-volume B-lines, OR 1.87, p = 0.01; post-volume lactate, OR 1.51, p = 0.03; MV, OR 4.32, p = 0.041. Conclusions Most patients showed signs of fluid intolerance, with increased EVLW. EVLW assessed by ultrasound is a predictor of mortality.

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Abstract Objective To evaluate the impact of a quality improvement project (QI) on reducing proven late-onset sepsis (LOS) in centers of the Brazilian Network Neonatal Research (BNNR). Method An interventional study conducted in 12 BNNR centers from 2021 to 2023. Included preterm infants (PT) born at 22–36 weeks' gestational age, weighing 400–1499 grams, without malformations, and admitted to the NICU for > 72 h. QI tools were used and four process indicators were defined: central catheter complication (≤ 20 %); antibiotic discontinuation ≤48 h in non-infected infants (≥ 80 %); breast milk expression within the first 48 h and enteral feeding within the first 24 h of life (≥ 80 %); full enteral feeding without parenteral nutrition by day 11 (≥ 70 %). The outcome was the proportional reduction of LOS according to each center’s baseline (2020). Indicators were analyzed descriptively across three periods. Results A total of 1993 PT < 1500 grams were included. Half of the centers achieved the target for umbilical catheter complications, and 92 % for percutaneous catheters. Antibiotics were discontinued within 48 h in 67 % of non-infected infants. Early breast milk expression and enteral feeding were achieved in 44 % and 75 % of cases, respectively. 58 % achieved full enteral nutrition without parenteral support by day 11. LOS incidence declined in 67 % of centers, and half met their targets, with an overall 18.5 % reduction. Conclusions The project reduced LOS in most centers, although some clinical practices still need improvement. It demonstrates a reproducible, low-cost strategy with the potential to guide other neonatal units facing high sepsis incidence.

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Abstract Objective This study aimed to translate and cross-culturally adapt the Dubowitz Neurological Examination (DNE) instrument into Brazilian Portuguese for the neurological assessment of preterm newborns (PTNBs), as well as to evaluate its psychometric properties. Method This is a methodological study of translation and cross-cultural adaptation. The methodological process consisted of two forward translations from the original to the target language, a synthesis of the translations, two back-translations, an evaluation by an expert committee, pre-testing, and the development and application of the final version in 40 PTNBs followed at a high-risk outpatient clinic. Results Concordance among experts was 98.03 %, the intraclass correlation was 0.81, the content validity index (CVI) was 0.96 and the Kappa coefficient value was 0.76, indicating substantial agreement. Furthermore, the internal consistency indices were considered acceptable (α = 0.75). The comprehension of the 34 instrument items during the pre-test phase ranged from 82 % to 100 %. Conclusions DNE was adequately translated and adapted for Brazilian culture, showing evidence of semantic, idiomatic, and conceptual equivalence. The results demonstrate satisfactory internal consistency and high inter-rater agreement.

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Abstract Objectives To describe clinical and cardiologic findings in patients with multisystem inflammatory syndrome in children (MIS-C) in a follow-up of up to 3 years. Materials and methods A retrospective-prospective, observational, longitudinal study was conducted, including children and adolescents up to 18 years diagnosed with MIS-C (WHO criteria), at a university center between March 2020 and December 2024. Demographic, clinical, and laboratory data, electrocardiograms, and transthoracic echocardiograms were analyzed at admission and at 12 months and left ventricular global longitudinal strain (LV-GLS) three years after diagnosis. Statistical analysis used frequencies for categorical variables, and means with standard deviations or medians with interquartile ranges for continuous variables. Differences in proportions between patients with and without cardiovascular abnormalities were assessed using Fisher's exact test, Chi-squared, or Wilcoxon rank-sum test (significant p-value < 0.05). T-test was used to compare left ventricular ejection fraction (LVEF) and coronary artery Z scores. Results Thirty-six patients were included (males 69.4%), with a median age at diagnosis of 2.15 years (IQR 3.3). At admission, 41.7% presented with clinical or echocardiographic abnormalities, which were absent at 1-year follow-up. However, three years after diagnosis, among the 11 patients evaluated with LV-GLS, 10 showed changes indicating subclinical dysfunction not detected by conventional electrocardiogram or echocardiography. Conclusion Clinical and echocardiographic cardiovascular abnormalities are common in the acute phase of MIS-C. Although most patients showed clinical and echocardiographic resolution, LV-GLS proved valuable for detecting subclinical myocardial dysfunction not identified by conventional evaluation, highlighting its potential as a screening tool in short- and long-term follow-up.

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Abstract Objective Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm in which the inflammatory microenvironment plays a crucial role in the development and progression of disease. The prognostic value of circulating lymphocyte subsets and cytokines remains uncertain. Methods The authors retrospectively analyzed baseline peripheral lymphocyte subsets and serum cytokines in 330 consecutive pediatric patients. Immune profiles were compared across disease extent, clinical events, and biological features. Prognostic associations with progression-free survival (PFS) were tested using univariable and multivariable models. Results Peripheral immune profiles varied with disease extent. Patients with multisystem risk-organ involvement (MS RO+) had fewer total T and Th1 cells, more CD4⁺ T and B cells, and higher IL-6, IL-10, and IFN-γ. Patients who progressed or relapsed showed a similar pattern, and non-survivors had particularly high IL-10. In the first-line cohort, the proportions of T, B, CD4⁺ T, CD8⁺ T, and Th1 cells, ratios of CD4/CD8 and Th1/Th2, and levels of IL-6, IL-10 predicted progression/relapse, and Youden-derived cut-offs dichotomized with distinct PFS. On multivariable Cox, IL-6, IL-10, Th1/Th2 ratio, RO status, and week-6 responses were independent predictors, and a nomogram model with good predictive capability was formed. IL-10 remained independently prognostic in multisystem LCH; the immune indices were not prognostic in single-system LCH. External validation in 103 patients confirmed risk stratification and model performance with well-calibrated PFS estimates. Conclusion Baseline peripheral lymphocyte subsets and cytokines carried prognostic information in pediatric LCH. The IL-6, IL-10, and Th1/Th2 profile supported risk stratification and may inform treatment planning.

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Abstract Objectives To evaluate the patterns of pubertal development, growth, and adult height in untreated male patients with CDGP. Methods A retrospective study was conducted at a tertiary care center from 1984 to 2019. Medical records of 46 boys diagnosed with CDGP (after excluding those with hypogonadism) were included for further analysis. Results Most patients were born at term (78%) and appropriate for gestational age (85%). A family history of delayed puberty was noted in 50%. The median age at initial evaluation was 14.3 years (range: 4.8–16.2 years). Short stature before puberty was the main reason for seeking medical attention (48%). Short stature was common at the first evaluation (93%) but improved over time; at the final assessment, only 17% of the patients remained short. For those who reached adult height, the height Z-scores were comparable to target height. Predictions using the Bayley-Pinneau method often overestimated adult height. Delayed bone age was present in 82% of patients at initial evaluation. The median age of spontaneous pubertal onset was 15 years, with a median duration of 2.1 years (range: 1.2–4.8 years, n = 33). None of the patients received pharmacological treatment. The median age at Tanner stage G5 was 17.1 years. Conclusions In boys with CDGP, transient short stature improved spontaneously during puberty. Most achieved their target height without growth-promoting therapy. However, adult height predictions based on the Bayley-Pinneau method were often overestimated. Spontaneous puberty initiation and completion occurred at approximately 15 and 17 years of age, respectively.

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Abstract Objective To determine the frequency of adverse childhood experiences (ACE) among a cohort of pregnant women (primary outcome) and explore their association with prematurity, pre-eclampsia, and fetal growth restriction (secondary outcomes). Methods The Adverse Childhood Experiences International Questionnaire - ACE-IQ was applied to patients during prenatal visits. Information on perinatal outcomes was collected from medical records. The proportion of total ACE and its different domains was estimated. Multiple logistic regressions were performed to assess the association between ACE and outcomes, after adjusting for possible confounding factors. Results A cohort of 307 pregnant women completed the ACE-IQ. The results in the binary and frequency versions were, respectively: mean (SD) scores of 5.84 (2.87) and 3.55 (2.73); the proportion of ACE 4 of 75% and 44%; the most prevalent ACE domains were home dysfunction (89.6 and 86.6%) and exposure to community violence (76.5 and 50%). For fetal growth restriction, pregnant women with ACE ≥ 4 had 2.32 times (95% CI: 1.04–5.37; p = 0.042) higher chance of this outcome. For preterm birth, the odds ratio was 1.1 (95% CI: 0.5–2.6; p = 0.886), indicating no statistically significant association. There was no significant association between the total ACE score, or its domains, and the other perinatal outcomes studied. Conclusions The frequency of ACE was high in this cohort of pregnant women, and exposure to community violence was associated with fetal growth restriction. The investigation of the association with other perinatal outcomes should be extended to a general population of pregnant women.

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Abstract Objective to develop a reference curve for SPL in Brazilian preterm newborns, assessing their postnatal growth adjusted for corrected gestational age (cGA). Materials and Methods This is a prospective cohort study conducted in southern Brazil. Newborns who were born below 37 weeks of gestational age were selected at tertiary care hospital during the first 3 days of life were selected over a one-year period. SPL was measured weekly until the participants reached 37 weeks of cGA or were discharged from the hospital. Statistical analysis included the Lambda Mu Sigma (LMS) method for growth curve construction and the Bland-Altman test to assess measurement agreement. Results A total of 290 SPL measurements were collected from 140 participants. Reference curves were developed for cGA between 26 and 37 weeks. Bland-Altman analysis suggested agreement between measurements taken immediately after birth and those taken during follow-up, inferring that preterm newborns may exhibit penile growth patterns similar to those exhibited during the intrauterine period. Conclusion hypothalamic-pituitary-gonadal axis integrity appears to be the primary determinant of post-natal penile growth. The proposed reference curves aid in the early diagnosis of hormonal and genetic alterations, allowing for timely medical interventions.

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Abstract Objective One of the possible causes of skin microbiome imbalance is the use of dermocosmetics with inadequate pH. This study aims to critically evaluate several children's moisturizers regarding their characteristics so that we can verify the tendency of the products available on the market and whether they are slightly acidic. The importance of dermocosmetics formulated without ingredients with allergenic potential is also discussed in this work. Method Observational, analytical, cross-sectional and quantitative study. Several brands of children's moisturizers were selected and divided into two groups: group 1 (G1), with moisturizers focused on the care of children with normal skin; and group 2 (G2), with moisturizers with a therapeutic focus on atopic children. We analyzed the pH of each one of the moisturizers, as well as cost, presence of potentially allergenic components and other data contained in the packaging. Results The members of G1 had an average pH of 5.81 ± 0.35, while the members of G2 had an average pH of 5.42 ± 0.28, with this difference being considered statistically significant (p ≤ 0.001). G1 differed in terms of cost, which was more affordable for the user, when compared to G2 (p ≤ 0.001), but with a predominance of potential allergens in its composition (p = 0.018). Conclusion This study demonstrates that all moisturizers analyzed in this study respected the acidic pH; however, the group of moisturizers with a therapeutic focus on atopic children had an even lower pH and lower allergenic potential in their composition compared to the group of moisturizers focused on care of children with normal skin.