Inflammatory markers in prepubertal children and their associations with abdominal fat.

OBJECTIVE: To evaluate the association between inflammatory markers and abdominal fat assessed by ultrasound in prepubertal children with and without excess weight. METHODS: A cross-sectional study involving 241 prepubertal children, 156 with obesity, 37 with overweight, and 48 with normal weight, aged five to ten years, who were followed at a research unit on Childhood Obesity from a teaching hospital belonging to a public health system. The concentration of interleukin-6, tumor necrosis factor-α and C-reactive protein were assessed and regression analyses, considering outcome variables such as abdominal wall and intra-abdominal fat thickness measured by ultrasound, were performed. RESULTS: The findings highlighted an association between abdominal fat and inflammatory markers, even in children at this young age group. Subcutaneous fat showed a stronger association with inflammatory biomarkers compared to intra-abdominal fat when performing logistic regression, with a positive association between tumor necrosis factor-α and abdominal wall thickness equal to or greater than the 75th percentile in adjusted logistic regression (OR: 18.12; CI 95 %: 1.57: 209.55). CONCLUSIONS: Abdominal wall fat, in contrast to what is often observed in adults, appears to have a greater impact on chronic inflammation related to excessive weight in very young children.

Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review.

Although vitamin D deficiency resulting from insufficient sunlight exposure or inadequate dietary vitamin D intake is the most common cause of rickets, mutations in genes involved in vitamin D metabolism can cause genetic forms of rickets termed Vitamin D-Dependent Rickets (VDDR). In 2018, Roizen et al. described a new type of VDDR, named VDDR3, caused by a recurrent missense mutation in the CYP3A4 gene that leads to accelerated inactivation of vitamin D metabolites. Here, we describe the third case of VDDR3 due to the same CYP3A4 mutation in a 2-year-old boy with bone deformities associated with poor growth. As in the previously reported cases, this patient had no family history of rickets. Serial measurements of vitamin D metabolites after a single 150,000 IU dose of cholecalciferol demonstrated an accelerated inactivation of 25(OH)D and 1,25(OH)2D. Significant improvement in growth velocity and healing of bone deformities were achieved after a short period of treatment with 10.000 IU of cholecalciferol daily, showing the importance of early recognition and prompt precision therapy of this condition.

A Recreational Swimming Intervention during the Whole School Year Improves Fitness and Cardiometabolic Risk in Children and Adolescents with Overweight and Obesity.

The benefits of swimming as a treatment for overweight children are undefined. We investigated the effects of recreational swimming on cardiometabolic risk in children/adolescents with normal and excess weight. Participants (n = 49, 26 girls, 10.3 ± 1.8 y) were grouped as 'eutrophic swimming' (EU-Swim, n = 14); 'excess weight swimming' (EW-Swim, n = 20) with an 'obese swimming' subgroup (OB-Swim, n = 10); and 'excess weight sedentary' (EW-Sed, n = 15) with an 'obese sedentary' subgroup (OB-Sed, n = 11). Swimming (50 min, twice/week, moderate-vigorous intensity) was an extra activity during the school year (6 + 3 months with a 3-month school break). Nutritional status, blood pressure (BP), physical activity, cardiorespiratory fitness, biochemical variables, autonomic modulation, endothelial function, abdominal fat, and carotid thickness were assessed at baseline, 6, and 12 months. Greater improvements (p < 0.05) occurred in EW-Swim vs. EW-Sed in body mass index (z-BMI, -16%, d+ 0.52), waist-to-height ratio (W/H, -8%, d+ 0.59-0.79), physical activity (37-53%, d+ 1.8-2.2), cardiorespiratory fitness (30-40%, d+ 0.94-1.41), systolic BP (SBP, -6-8%, d+ 0.88-1.17), diastolic BP (DBP, -9-10%, d+ 0.70-0.85), leptin (-14-18%, d+ 0.29-0.41), forearm blood flow (FBF, 26-41%, d+ 0.53-0.64), subcutaneous fat (SAT, -6%, d+ 0.18), and intra-abdominal fat (VAT, -16%, d+ 0.63). OB-Swim showed improvements vs. OB-Sed in TNFα (-17%, d+ 1.15) and adiponectin (22%, d+ 0.40). Swimming improved fitness and cardiometabolic risk in children/adolescents with overweight/obesity. (TCTR20220216001).

Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature.

Objective: Most children with short stature remain without an etiologic diagnosis after extensive clinical and laboratory evaluation and are classified as idiopathic short stature (ISS). This study aimed to determine the diagnostic yield of a multigene analysis in children classified as ISS. Design and methods: We selected 102 children with ISS and performed the genetic analysis as part of the initial investigation. We developed customized targeted panel sequencing, including all genes already implicated in the isolated short-stature phenotype. Rare and deleterious single nucleotide or copy number variants were assessed by bioinformatic tools. Results: We identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%). Three patients had more than one P/LP genetic alteration. Most of the findings were in genes associated with the growth plate differentiation: IHH (n = 4), SHOX (n = 3), FGFR3 (n = 2), NPR2 (n = 2), ACAN (n = 2), and COL2A1 (n = 1) or involved in the RAS/MAPK pathway: NF1 (n = 2), PTPN11 (n = 1), CBL (n = 1), and BRAF (n = 1). None of these patients had clinical findings to guide a candidate gene approach. The diagnostic yield was higher among children with severe short stature (35% vs 12.2% for height SDS ≤ or > -3; P = 0.034). The genetic diagnosis had an impact on clinical management for four children. Conclusion: A multigene sequencing approach can determine the genetic etiology of short stature in up to one in six children with ISS, removing the term idiopathic from their clinical classification.

Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients.

BACKGROUND: Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries. METHODS: Latin American experts (from Argentina, Brazil, Chile and Colombia) particiáted of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia. RESULTS: Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included. CONCLUSIONS: This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.

Growth hormone deficiency and the transition from pediatric to adult care

Abstract Objective: To discuss the approach to patients diagnosed with growth hormone deficiency (GHD) in childhood during the transition period from puberty to adulthood, focusing on the following: (1) physiology; (2) effects of recombinant human GH (rhGH) interruption/reinstitution after adult height achievement; (3) re-evaluation of somatrotropic axis; (4) management of rhGH reinstitution, when necessary. Source of data: Narrative review of the literature published at PubMed/MEDLINE until September 2020 including original and review articles, systematic reviews and meta-analyses. Synthesis of data: Growth hormone is crucial for the attainment of normal growth and for adequate somatic development, which does not end concomitantly with linear growth. Retesting adolescents who already meet the criteria that predict adult GHD with high specificity is not necessary. Patients with isolated GHD have a high likelihood of normal response to GH testing after puberty. Adolescents with confirmed GHD upon retesting should restart rhGH replacement and be monitored according to IGF-I levels, clinical parameters, and complementary exams. Conclusion: Patients with isolated idiopathic GHD in childhood are a special group who must be reevaluated for GHD as many of them have normal GH provocative tests upon retesting after puberty. Patients who confirm the persistence of GHD in the transition period should maintain rhGH replacement in order to reach an ideal peak bone mass, satisfactory body composition, lipid and glucose profiles, and quality of life.

Daily physical activity, cardiorespiratory fitness, nutritional status, endothelial function, and autonomic modulation in school-age adolescents: A principal component analysis.

PURPOSE: This study evaluated the association between cardiorespiratory fitness, abdominal obesity, blood pressure, endothelial function, and autonomic modulation in school-age adolescents exhibiting different levels of habitual physical activity and nutritional status, through a multivariate statistical approach. METHODS: 101 adolescents aged 15-18 years (54 females) underwent assessments of daily physical activity, body mass index, cardiorespiratory fitness, reactive hyperemia, and heart rate variability. Based on BMI adjusted for age and sex (z-BMI), 21 adolescents were classified as 'overweight' (9 girls), and 9 as 'obese' (4 girls). The common variation between those variables was assessed through Principal Component Analysis (PCA). RESULTS: Main axis of common variation of outcomes analyzed defined four principal components (PCs) accounting for 69.7% of overall variance, related to 'abdominal obesity and blood pressure' (PC1; eigenvalue=2.76), 'cardiorespiratory fitness, endothelial function, and autonomic modulation' (PC2, eigenvalue=1.98), 'cardiorespiratory fitness' (PC3, eigenvalue=1.21), and 'sedentary behavior' (PC4, eigenvalue=1.02). Girls reported longer screen time and sedentary behavior than boys. Notwithstanding, in both sexes poorer cardiorespiratory fitness corresponded to lower reactive hyperemia and vagal modulation, irrespective of the nutritional status. Overall, adolescents classified as 'obese' and 'sedentary' exhibited poorer CRF concomitantly to autonomic and endothelial dysfunctions. CONCLUSION: In school-age adolescents, endothelial and autonomic dysfunctions related to poor cardiorespiratory fitness, irrespective of the nutritional status and physical activity level. However, endothelial and autonomic dysfunctions were more prevalent among adolescents combining poor cardiorespiratory fitness, reduced levels of daily physical activity, and overweight/obesity.

Growth hormone deficiency and the transition from pediatric to adult care.

OBJECTIVE: To discuss the approach to patients diagnosed with growth hormone deficiency (GHD) in childhood during the transition period from puberty to adulthood, focusing on the following: (1) physiology; (2) effects of recombinant human GH (rhGH) interruption/reinstitution after adult height achievement; (3) re-evaluation of somatrotropic axis; (4) management of rhGH reinstitution, when necessary. SOURCE OF DATA: Narrative review of the literature published at PubMed/MEDLINE until September 2020 including original and review articles, systematic reviews and meta-analyses. SYNTHESIS OF DATA: Growth hormone is crucial for the attainment of normal growth and for adequate somatic development, which does not end concomitantly with linear growth. Retesting adolescents who already meet the criteria that predict adult GHD with high specificity is not necessary. Patients with isolated GHD have a high likelihood of normal response to GH testing after puberty. Adolescents with confirmed GHD upon retesting should restart rhGH replacement and be monitored according to IGF-I levels, clinical parameters, and complementary exams. CONCLUSION: Patients with isolated idiopathic GHD in childhood are a special group who must be reevaluated for GHD as many of them have normal GH provocative tests upon retesting after puberty. Patients who confirm the persistence of GHD in the transition period should maintain rhGH replacement in order to reach an ideal peak bone mass, satisfactory body composition, lipid and glucose profiles, and quality of life.

Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing.

OBJECTIVE: To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. STUDY DESIGN: For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. RESULTS: Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. CONCLUSIONS: The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children / Aptidão e atividade física, perfil metabólico, adipocinas e função endotelial em crianças

Abstract Objectives: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Method: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). Results: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p < 0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p < 0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p < 0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho = −0.41; p = 0.01), and this association remained after adjusting for body mass index z-score (rho = 0.28; p = 0.03). Conclusion: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Resumo: Objetivos: A prevalência da obesidade está aumentando. O objetivo deste estudo foi investigar se há disfunção endotelial nas crianças com peso normal ou excesso de peso e se o perfil metabólico, as adipocinas e a disfunção endotelial seriam mais fortemente associados à aptidão física ou aos níveis de atividade física. Método: Estudo transversal que envolve crianças de 5-12 anos. A avaliação incluiu pletismografia de oclusão venosa, níveis séricos de adiponectina, leptina, insulina e lipidograma, escore de atividade física (questionário PAQ-C) e avaliação da aptidão física (teste Yo-yo). Resultados: Um total de 62 crianças participou deste estudo. Com base no índice de massa corporal, 27 eram eutróficos, 10 estavam acima do peso e 25 estavam obesos. Os níveis de triglicerídeos, colesterol LDL, HOMA-RI e leptina estavam mais elevados nas crianças obesas e com excesso de peso que o grupo de eutróficos (p < 0,01). Os níveis de colesterol HDL e adiponectina estavam mais elevados no grupo de eutróficos em comparação ao grupo de obesos e com excesso de peso (p < 0,01). A vasodilatação mediada pelo fluxo após hiperemia foi maior no grupo de eutróficos em comparação aos indivíduos obesos e com excesso de peso (p < 0,05). Não houve nenhuma diferença nos níveis de atividade física entre os grupos medidos pelo PAQ-C. O teste de ida e volta foi significativamente associado ao colesterol HDL (ró = −0,41; p = 0,01) e essa associação continuou após ajustar o escore z do índice de massa corporal (ró = 0,28; p = 0,03). Conclusão: Este estudo mostrou que a disfunção endotelial já está presente nas crianças obesas, sugeriu uma predisposição à doença aterosclerótica. Além disso, os níveis de colesterol HDL foram correlacionados à aptidão física, independentemente do índice de massa corporal.

Growth hormone therapy in children; research and practice - A review.

Short stature remains the most common reason for referral to a pediatric Endocrinologist and its management remains a challenge. One of the main controversies is the diagnosis of idiopathic short stature and the role of new technologies for genetic investigation of children with inadequate growth. Complexities in management of children with short stature includes selection of who should receive interventions such as recombinant human growth hormone, and how should this agent dose be adjusted during treatment. Should anthropometrical data be the primary determinant or should biochemical and genetic data be used to improve growth response and safety? Furthermore, what is considered a suboptimal response to growth hormone therapy and how should this be managed? Treatment of children with short stature remains a "hot" topic and more data is needed in several areas. These issues are reviewed in this paper.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

OBJECTIVES: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. METHOD: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). RESULTS: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p<0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p<0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p<0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). CONCLUSION: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults.

OBJECTIVE: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. PARTICIPANTS: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. EVIDENCE: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. CONSENSUS PROCESS: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. CONCLUSIONS: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.

Leptin as a predictor of metabolic syndrome in prepubertal children

ABSTRACT Objective Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). Subjects and methods This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. Results A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). Conclusions Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.

Long-term response to growth hormone therapy in a patient with short stature caused by a novel heterozygous mutation in NPR2.

BACKGROUND: Heterozygous loss-of-function mutations in the natriuretic peptide receptor B gene (NPR2) are responsible for short stature in patients without a distinct phenotype. Some of these patients have been treated with recombinant human growth hormone (rhGH) therapy with a variable response. CASE PRESENTATION: The proband was a healthy boy who presented at the age of 5.1 years with familial short stature (height SDS of -3.1). He had a prominent forehead, a depressed nasal bridge, centripetal fat distribution and a high-pitched voice resembling that of children with GH deficiency. His hormonal evaluation showed low insulin-like growth factor-1 (IGF-1) but a normal GH peak at a stimulation test. During the first year of rhGH treatment, his growth velocity increased from 3.4 to 10.4 cm/year (height SDS change of +1.1). At the last visit, he was 8.8 years old and still on treatment, his growth velocity was 6.4 cm/year and height SDS was -1.8. RESULTS: We identified through exome sequencing a novel heterozygous loss-of-function NPR2 mutation (c.2905G>C; p.Val969Leu). Cells cotransfected with the p.Val969Leu mutant showed a significant decrease in cyclic guanosine monophosphate (cGMP) production compared to the wild type (WT), suggesting a dominant negative effect. CONCLUSIONS: This case reveals a novel heterozygous loss-of-function NPR2 mutation responsible for familial short stature and the good response of rhGH therapy in this patient.

Leptin as a predictor of metabolic syndrome in prepubertal children.

OBJECTIVE: Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). SUBJECTS AND METHODS: This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. RESULTS: A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). CONCLUSIONS: Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.

Health markers in obese adolescents improved by a 12-week recreational soccer program: a randomised controlled trial.

The effects of a recreational soccer program (RSP) upon body composition, heart rate variability (HRV), biochemical markers, cardio-respiratory fitness, and endothelial function in obese adolescents were investigated. A randomised controlled clinical trial was conducted with 30 adolescents aged 12-17 years and body mass index (BMI) >2 standard deviations of WHO reference values, which were assigned to RSP (n = 10, 2 girls) and obese control (n = 10, 4 girls) groups. The 12-week RSP included 60-min sessions performed 3 times/week. BMI, waist circumference, blood pressure, blood glucose, lipid profile, insulin, C-reactive protein, HRV, and maximal oxygen consumption (VO2peak) were evaluated following standardised procedures. Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography. After intervention, RSP exhibited significant reductions in BMI (-0.7 ± 0.2 kg · m(-2)), waist circumference (-8.2 ± 1.4 cm), %body fat (-2.2 ± 0.4%), systolic blood pressure (-5.0 ± 2.3 mmHg), total cholesterol (-16.2 ± 5.8 mg · dL(-1)), triglycerides (-20.5 ± 12.9 mg · dL(-1)), C-reactive protein (-0.06 ± 0.01 mg · dL(-1)), insulin resistance (HOMA-IR, -1.4 ± 0.6), and sympathetic activity (LF, -13.9 ± 6.6 un) vs. controls (P < 0.05). Significant increase was observed in parasympathetic activity (HF, 13.9 ± 6.6 un), VO2peak (7.9 ± 2.8 ml · kg(-1) · min(-1)), and high-density lipoprotein cholesterol (11.0 ± 6.3 mg · dL(-1)) (P < 0.05). Vascular conductance (19.5 ± 8.1 ml · min(-1) · 100 ml, P = 0.005) increased and vascular resistance (-5.9 ± 2.4 ml · min(-1) · 100 ml, P = 0.041) decreased in RSP, but not in controls. A 12-week recreational soccer intervention was effective to improve biochemical, cardiovascular, and fitness health markers in obese adolescents.

Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children.

BACKGROUND: Early exposure to cardiovascular risk factors creates a chronic inflammatory state that could damage the endothelium followed by thickening of the carotid intima-media. OBJECTIVE: To investigate the association of cardiovascular risk factors and thickening of the carotid intima. SUBJECTS/METHODS: Media in prepubertal children. In this cross-sectional study, carotid intima-media thickness (cIMT) and cardiovascular risk factors were assessed in 129 prepubertal children aged from 5 to 10 year. Association was assessed by simple and multivariate logistic regression analyses. RESULTS: In simple logistic regression analyses, body mass index (BMI) z-score, waist circumference, and systolic blood pressure (SBP) were positively associated with increased left, right, and average cIMT, whereas diastolic blood pressure was positively associated only with increased left and average cIMT (p<0.05). In multivariate logistic regression analyses increased left cIMT was positively associated to BMI z-score and SBP, and increased average cIMT was only positively associated to SBP (p<0.05). CONCLUSIONS: BMI z-score and SBP were the strongest risk factors for increased cIMT.

Evaluation of sublingual microcirculation in children with dengue shock.

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target.