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Approved in September 26, 2017, at clinical research ethics committee at Instituto de Puericultura e Pediatria Martagão Gesteira, number CAAE 67129617.5.0000.5264.
Early-life nutrition plays a critical role in long-term health. Although complementary feeding has been widely studied, the influence of portion size during this stage on subsequent overweight risk remains unclear. This study aimed to evaluate whether portion size during complementary feeding is associated with overweight risk in childhood and preadolescence. Secondary analysis of the European Childhood Obesity Project, a randomised clinical trial across five European countries. Dietary data was collected at 6, 12, 18 and 24 months using 3-day food records and food portions standardised as internal z-scores; anthropometry was assessed at 2, 8 and 11 years. Associations between early portion size and later overweight were examined using logistic regression (adjusted for feeding type, country, parental education, birth weight, meal frequency and energy intake) and structural equation modelling. Larger portion sizes at 6 months were associated with more than a twofold higher risk of overweight at 2 years (OR 2.36, p = 0.031). Portion size at later complementary feeding stages showed positive trends with overweight at 2, 8 and 11 years and indirect associations with overweight at 8 and 11 years mediated by portion size at 8 years. Larger portion sizes early in life are associated with increased risk of overweight later in childhood. These findings highlight portion size guidance during complementary feeding as a potential early target for obesity prevention.
Few studies have described long-term respiratory sequelae of adolescent (people aged 10-19 years) tuberculosis (TB) survivors. We hypothesized that compared with healthy adolescents with no history of TB, survivors of adolescent pulmonary TB have greater respiratory impairment (reduced lung function) and disability (symptoms and activity limitations). In this prospective cohort study in Lima, Peru, we used spirometry, oscillometry, and the St George's Respiratory Questionnaire (SGRQ) to evaluate, on 2 separate occasions, the lung health of adolescents successfully treated for pulmonary TB and matched healthy controls. TB survivors with abnormal lung function underwent chest computed tomography (CT). Using mixed-effects regression with an interaction term for time since treatment completion and random effects for individual and matched pairs, we modeled changes in lung function and disability over 24 months from treatment completion, comparing findings between TB survivors and controls. Compared with 101 controls (median age 17 years, 56% male), 101 TB survivors (median age 18 years, 56% male) had less favorable forced expiratory volume in 1 second, forced vital capacity, total airway resistance (R5), small airway resistance (R5-20), and reactance area (AX). Over the study period, AX, R5, and R5-20 improved for TB survivors but remained worse than controls. TB survivors had persistently greater respiratory disability (measured by SGRQ). Chest CTs of TB survivors demonstrated architectural distortion, reticular patterns, nodules, and bronchiectasis. Adolescent TB survivors experience persistent, symptomatic chronic lung disease despite bacteriological cure. Our findings highlight the need for respiratory assessments beyond treatment completion.
Glanzmann thrombasthenia (GT) is a rare inherited platelet disorder associated with recurrent and sometimes life-threatening bleeding. Recombinant activated factor VII (rFVIIa) is approved for treatment of bleeding episodes or surgical prophylaxis in patients with GT who are refractory or alloimmunized to platelet transfusions. However, evidence for its use as secondary prophylaxis remains scarce. This study described the efficacy and safety of rFVIIa secondary prophylaxis in patients with GT and recurrent and uncontrolled bleeding despite standard therapy. A multicenter, retrospective study of patients with GT included in the Spanish Registry of Patients with Inherited Platelet Disorders (RETPLAC) was performed. We evaluated bleeding severity using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT) and calculated the annualized bleeding rate (ABR) before and during rFVIIa prophylaxis. Of the 37 patients with GT included in RETPLAC, 4 patients received regular rFVIIa prophylaxis due to recurrent severe bleeding. Median baseline ISTH-BAT score was 13.5 (IQR, 9.5-18), and median preprophylaxis ABR was 3 (IQR, 3-5.25). All patients received rFVIIa of 90 μg/kg, 3 twice weekly and 1 monthly. The median prophylaxis duration was 7.5 months (IQR, 6.75-12). Prophylaxis led to a 57.1% overall reduction in ABR, with resolution of severe bleeding in 2 patients and reduction in frequency in the remaining 2. Three patients achieved transfusion independence. All patients showed improvement in hemoglobin and iron profile. No thrombotic or adverse events occurred. Secondary prophylaxis with rFVIIa may be an effective option in patients with GT and recurrent severe bleeding unresponsive to standard therapy. Prospective studies are necessary to optimize dosing schedules and define its role in secondary prophylaxis.
Childhood and adolescent obesity is a major global health concern that contributes to early atherosclerotic changes and increased cardiometabolic risk. High-intensity interval training (HIIT) has emerged as a time-efficient intervention that can improve cardiometabolic outcomes. However, its effectiveness on cardiometabolic risk markers, including atherosclerotic indicators in children and adolescents with overweight/obesity, remains inconclusive. This systematic review and meta-analysis aimed to analyze the impact of HIIT on cardiometabolic markers in this population. A systematic literature search was conducted across PubMed, Web of Science, ScienceDirect, SportDiscus, Cochrane, Embase, and Scopus through June 2025. Randomized and nonrandomized controlled trials examining HIIT interventions lasting ≥2 weeks in apparently healthy children and adolescents (aged 8-19 y) with overweight/obesity (body mass index ≥ 85th percentile) were included. Data were synthesized using Hedges' g to calculate effect sizes, with subgroup analyses comparing HIIT versus moderate-intensity interval training, moderate-intensity continuous training, school-based exercise, and pre-post intervention values. Subgroup meta-analyses for specific comparators were performed when data from more than one study were available. Twenty studies involving 889 participants (M and F) were included. HIIT significantly improved (P ≤ .04) anthropometric indicators (body mass: g = -0.51; body mass index: g = -0.61; body fat percentage: g = -0.69; waist circumference: g = -0.38), blood pressure (systolic: g = -0.63; diastolic: g = -0.42), lipid profile (total cholesterol: g = -0.72; triglycerides: g = -0.63; lipoprotein cholesterol: g = -0.63; high-density lipoprotein cholesterol: g = +0.57), and glycemic markers (glucose: g = -0.27; insulin: g = -0.70; homeostatic model assessment for insulin resistance: g = -0.57), as well as enhancing cardiorespiratory fitness (VO2peak: g = +1.52). Subgroup analyses showed a higher superiority of HIIT on most outcomes compared with moderate-intensity continuous training, but not versus moderate-intensity interval training or school-based exercise. However, comparisons with moderate-intensity interval training and school-based exercise were based on a limited number of studies. Moderate heterogeneity (I2 = 48%-73%) was observed across outcomes. Our data show that HIIT is an effective strategy for improving cardiometabolic health in children and adolescents with overweight/obesity as it significantly reduces blood lipids and improves body composition, glycemic control, and cardiorespiratory fitness, with this effect often surpassing that of traditional moderate-intensity continuous training protocols. Further studies should identify optimal HIIT protocols and explore long-term benefits to develop clinical guidelines.
Epigenetic alterations, including aberrant DNA hypermethylation and histone modifications, contribute to oncogenesis by disrupting normal gene expression programs. Unlike genetic mutations, these changes are potentially reversible, providing a strong biological rationale for the development of histone deacetylase inhibitors (HDACi) for therapy. Several HDACi are currently under investigation, either as monotherapy or in combination with other anticancer agents. A comprehensive understanding of toxicity is essential to appropriately balance risks and benefits, particularly because HDACi are most frequently evaluated within combination regimens. To date, no epigenetic agents have received regulatory approval for pediatric malignancies, and clinical development in this population remains at an early stage. The aim of this study was to systematically characterize the toxicity profiles associated with HDACi administration in pediatric patients with cancer, including both solid tumors and hematologic malignancies. To this end, we conducted a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Toxicity profiles were extracted from twelve studies investigating six HDACi: panobinostat, vorinostat, entinostat, pracinostat, valproic acid, and depsipeptide. Eleven studies were Phase I or Phase I/II clinical trials, and one was a retrospective study. Patients with solid central nervous system tumors represented the most frequently studied population. Overall, treatment-related toxicities were predominantly mild, with few severe (grade 4) adverse events, mainly within the hematologic category. According to the Common Terminology Criteria for Adverse Events grading system, hematologic toxicities were the most common adverse events across all HDACi, particularly thrombocytopenia, followed by mild gastrointestinal and metabolic toxicities. Cardiac, neurological, respiratory, and systemic toxicities were generally mild, less frequent, and considered treatment-related. Dose and route of administration influenced both the frequency and severity of toxicities. Pan-HDAC inhibitors were associated with the highest rates of toxicity. HDACi-related toxicities were moderate and manageable in pediatric patients. Differences in toxicity were observed among treatments, with higher doses linked to increased toxicity. These findings support further clinical trial development of HDACi in pediatric malignancies. However, Phase I design, small patient numbers, and heterogeneity in age, weight, and disease characteristics are major limitations in accurately assessing HDACi-induced toxicity.
Venous thromboembolism (VTE) in children is a rare condition. It encompasses different clinical scenarios that require an individualized and multidisciplinary approach. The aim of this document is to provide a practical guideline for the management of pediatric VTE based on the best available evidence. An exhaustive literature review was performed, gathering information from current clinical guidelines and recent studies. This document compiles the recommendations on the diagnosis and treatment of VTE in infants, children, and adolescents endorsed by the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Thrombosis and Hemostasis (SETH), and the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Neonatal VTE, arterial thrombosis, and superficial venous thrombosis are beyond the scope of this work. This document includes a list of definitions aimed at standardizing terminology and another two distinct sections: (1) particularities of treatment, including recommendations regarding dosing, monitoring and cautions in the pediatric population, and (2) particularities in management, including specific recommendations for the most frequent scenarios in children.
Imipenem/cilastatin/relebactam (IMI/REL), a fixed-dose combination of imipenem/cilastatin with the β-lactamase inhibitor relebactam, has broad gram-negative coverage. Prospectively obtained safety and efficacy data in neonates and children are needed. Children (birth to <18 years old) with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI), including pyelonephritis, were enrolled in an open-label, randomized, active-controlled, multinational phase 2/3 trial (ClinicalTrials.gov: NCT03969901). Participants were randomized 3:1 to IMI/REL or active-control, standard-of-care antibacterial therapy for 7-14 days (HABP/VABP; intravenous [IV] only) or 5-14 days (cIAI, cUTI; with oral step-down permitted after 3 days of IV). The primary endpoint was safety, assessed through 14 days after the end of therapy (EOT) as adverse events (AEs) and AE-related discontinuations of IV therapy. Clinical and microbiologic responses were also assessed at EOT and follow-up visits. This was an estimation study without hypothesis testing. Eighty-six children were randomized to IMI/REL and 29 to active control. AEs were reported in 67.1% of IMI/REL versus 50.0% of active control arm participants (treatment difference: 17.1% [95% confidence interval: -3.5, 37.2]), leading to 3 versus 0 discontinuations of IV therapy, respectively. Treatment outcomes were generally comparable at all time points; at EOT, clinical response was 78.8% versus 75.0% and microbiologic response 95.6% versus 90.9% with IMI/REL and active control, respectively, with no mortality in either arm. IMI/REL was generally well tolerated in neonates and older pediatric patients with HABP/VABP, cIAI, or cUTI, with safety and efficacy profiles comparable to standard-of-care antibacterial therapy.
To describe the redesign and implementation of an electronic alert management system aimed at supporting the identification and management of patients requiring transmission-based precautions in a high-complexity hospital. An organizational and technological intervention was carried out focusing on the revision of the alert workflow for patients at risk of transmitting microorganisms within the electronic health record system (HCIS). Standardized icons were designed for each type of precaution and integrated into bed maps and patient locator tools. A digital workflow was established allowing provisional alert activation by clinical or admission staff and subsequent validation by the Preventive Medicine Department. Alerts were automatically linked to a non-pharmacological prescription specifying the required precautionary measures, and a real-time locator system was developed. The evaluation was conducted through a descriptive before-after analysis across two six-month periods (2023-2024 and 2024-2025). A total of 1205 alerts were generated during both periods. Changes were described in the validation rates of provisional alerts and in the mean validation times, particularly for contact alerts. The intervention allowed the reorganization and standardization of electronic alert management for transmission-based precautions, providing an organizational and technological framework that may be useful for other hospitals.
This review article summarizes the pathophysiology, clinical presentation, diagnostic approach, and management principles of unrepaired congenital shunt lesions in adulthood, with emphasis on individualized decision-making and indications and contraindications for defect closure.
Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization.
Cow's milk allergy (CMA) is among the most common food allergies in early childhood, affecting approximately 2-3% of children under 3 years of age. Management requires strict elimination of cow's milk and dairy products, typically replaced with hypoallergenic formulas. Although essential, this dietary restriction may predispose infants-particularly during the first 2 years of life-to nutritional imbalances. This mini review synthesizes current evidence on micronutrient status and growth outcomes in children with CMA, with emphasis on the impact of dietary management. Across observational studies, vitamin D inadequacy is the most consistently reported abnormality, with insufficiency affecting approximately 30-55% of children and deficiency around 20-25%. Iron deficiency is also frequent, including both overt anemia and subclinical depletion. Lower levels of calcium, vitamin B12, and iodine have been described, generally within reference ranges but suggestive of suboptimal intake. Growth impairment is commonly observed at diagnosis, particularly affecting weight more than linear growth. Appropriate nutritional management, including the use of hypoallergenic formulas (HF) and dietary counselling, is associated with significant catch-up growth. However, an increased risk of being overweight has been reported during follow-up, highlighting the need for balanced nutritional strategies. Key risk factors for nutritional compromise include multiple food allergies, prolonged dietary restriction without adequate substitution, poor adherence to supplementation, and restrictive maternal diets during breastfeeding. Overall, CMA management should extend beyond allergen avoidance to include proactive nutritional surveillance, targeted supplementation, and individualized dietary planning to support optimal growth and long-term health.
We aimed to characterize encephalitis, myositis, and myocarditis, in hospitalized children during the 2023 - 2024 dengue epidemic in Argentina. This case series included patients younger than 16 years with laboratory-confirmed dengue hospitalized for atypical manifestations across ten centers from Argentina between July 2023 and July 2024. Data was collected via a REDCap form version 12.4.1 (Vanderbilt University). Statistical analysis was performed by RStudio. We enrolled 47 patients; median age was 7 years [IQR 2 - 11], 64% were male, and 62% had no underlying conditions. Encephalitis was the most frequent clinical manifestation (60%), followed by myositis (38%) and myocarditis (4%). One patient had concurrent myositis and myocarditis. DENV-2 and DENV-1 were the identified serotypes. The 32% of patients required PICU admission, primarily those with encephalitis (n = 13) and myocarditis (n = 2). Thirteen patients required inotropic support and mechanical ventilation. Empirical antibiotics were administered in 32% of cases; no bacterial co-infections were identified. Median hospital stay was 5 days [IQR 3 - 8]. In 4 patients residual sequelae at discharge (persistent muscle weakness, myocardial fibrosis, and seizures) were detected. No deaths occurred. Encephalitis, myositis, and myocarditis are uncommon but clinically significant dengue complications in children.  Encephalitis and myositis were the most frequent atypical manifestations of dengue in this multicenter registry. Encephalitis and myocarditis were associated with a higher rate of PICU admission. • Atypical dengue manifestations in children such as encephalitis, myocarditis, and myositis, affect males predominantly, and may be associated with greater severity. • These clinical pictures are frequent in endemic countries, with a high burden of cases annually. • Argentina has become an endemic country with a cyclic epidemic pattern. • This was the largest epidemic in the country with a high burden of cases of dengue. • The cases had mild evolution in this new endemic scenario, with adequate clinical support.
Background: Children with autism spectrum disorder (ASD) commonly exhibit impairments in executive functioning, which can affect their cognitive and adaptive functioning. Play-based neurohabilitation approaches have been proposed as complementary strategies to stimulate frontal-executive processes. Objectives: The primary objective of this study was to assess the effectiveness of LEGO®-Based Neurotherapy (LBN) in enhancing executive functioning in children with autism spectrum disorder (ASD). Methods: A pilot quasi-experimental pre-post intervention study was conducted in children with ASD. Children voluntarily enrolled either in a LBN program or in a non-intervention comparison group being control (CTRL) group. Executive functions were assessed at baseline and follow-up using the BANFE-3 battery. Results: Children participating in the LBN program showed greater improvements in dorsolateral executive-function scores and total executive-function indices compared with CTRL group. These findings suggest a potential association between participation in LBN and executive-function improvement. Conclusions: LBN may represent a promising complementary neurohabilitation approach for supporting executive functions in children with ASD.
Necrotizing enterocolitis (NEC) is a multifactorial disease associated with prematurity, intestinal hypoperfusion, dysbiosis, and oxidative stress. Interindividual variability in disease occurrence suggests a role for genetic susceptibility. Null genotypes of the GSTM1 and GSTT1 genes result in absent glutathione S-transferase activity and may impair antioxidant defenses. This study investigated whether GSTM1 and GSTT1 null genotypes are associated with NEC development and severity in preterm newborns. This single-center case-control pilot study included 100 preterm newborns (50 NEC and 50 controls). Genotyping was performed by multiplex polymerase chain reaction. Baseline characteristics were comparable between groups (p > 0.05). Stages II-A and II-B accounted for 82% of NEC cases. A significant inverse correlation was observed between gestational age and postnatal age at NEC diagnosis (r = -0.5994; p < 0.0001). The GSTM1-null genotype was more frequent in the NEC group (60% vs. 36%) and was associated with increased disease risk in both unadjusted (OR = 2.667; 95%CI: 1.188-5.986; p = 0.027) and adjusted analyses (aOR = 3.09; 95%CI: 1.29-7.40; p = 0.011). No significant associations were observed for GSTT1, combined genotypes, or disease severity. These findings provide preliminary evidence of an association between the GSTM1-null genotype and NEC susceptibility. Given the exploratory pilot design, these results should be considered hypothesis-generating and require confirmation in larger prospective studies.
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Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder resulting from pathogenic variants in the TSC1 or TSC2 genes, leading to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and subsequent development of benign neoplasms in multiple organs. Kidney involvement is frequent, being angiomyolipoma the most common lesion. Angiomyolipoma can occur since childhood and progress throughout life, potentially leading to complications such as hemorrhage and chronic kidney disease (CKD). This study aims to characterize the kidney phenotype in a Brazilian cohort of TSC patients and identify potential risk factors associated with kidney complications. This real-world retrospective observational study analyzed data from TSC patients recorded on their first nephrology consultation at two Brazilian university hospitals between September 2019 and August 2024. Clinical, laboratory and imaging data were collected from medical records. Comparative analyses were conducted based on sex, history of kidney hemorrhage, kidney invasive interventions and CKD G3-G5D. 172 patients were included (28 ± 14.2 years, 62.2% female, 22.7% pediatric). Angiomyolipoma was the most frequent renal lesion (91.7%) with increasing prevalence with age, followed by cysts (45.2%). 41.9% of the patients meeting renal indications were receiving mTOR inhibitor. The prevalence of CKD G3-G5, kidney hemorrhage and interventions was 9.9%, 16.6%, and 27.9%, respectively. Comparative analysis matched by age showed that female patients have slightly lower eGFR (117 [94-127] vs. 126 [97-149] mL/min/1.73m2; p = 0.02) and a trend toward higher prevalence angiomyolipomata ≥ 30 mm, kidney invasive interventions and larger angiomyolipomata size. Logistic regression identified age as the only factor independently associated with a history of kidney hemorrhage [OR 1.06 (1.01-1.11)]. CKD G3-G5D was associated with older age, larger angiomyolipoma, previous kidney hemorrhage and invasive interventions. This Brazilian cohort study demonstrated that TSC-related kidney involvement may occur early in life, displays a progressive profile and leads to severe kidney outcomes. The high rates of kidney complications and the suboptimal utilization of mTOR inhibitors underscore the need to increase awareness, early referral to nephrologist and timely therapeutic intervention.
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Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (n = 40) and those diagnosed after clinical presentation (n = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs.
i. To describe clinical, laboratory, and follow-up characteristics of neonates with confirmed dengue infection. ii. Observational, descriptive, retrospective, and multicenter study including neonates with confirmed congenital dengue hospitalized at 6 centers from Argentina, between July 2023 and July 2024. Confirmation required virological or serological testing in both mother and neonate. Data were collected anonymously via REDCap and analyzed with RStudio. iii. 58 neonates were included. Most pregnant individuals presented with fever, myalgia, and headache. Maternal diagnosis was confirmed mainly by NS1 antigen (59%) and PCR (43%); 9% were serotyped, with 4/5 serotypes corresponding to DENV1. Fifty-two pregnant individuals were hospitalized. Median gestational age at birth was 38 weeks; and 21% of neonates were preterm. Most deliveries were cesarean. At admission, 74% of neonates were asymptomatic; 26% showed respiratory distress or temperature instability. Diagnosis was confirmed by PCR in 59% of neonates. Two preterm neonates required mechanical ventilation. Median hospital stay was 9 days. 57% of neonates developed thrombocytopenia within the first week of life. No deaths or sequelae were recorded in neonates. One mother died because of severe dengue with shock. iv. In this multicenter registry, 74% of neonates were asymptomatic and 21% preterm, with no deaths or sequelae at discharge and 30 days of follow-up.