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      Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv)


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          Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health.


          The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal ( n = 90), and postpubertal adolescents ( n = 90). Each group will include three subgroups ( n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers.


          The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers’ responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity.

          Clinical Trial Registration

          ClinicalTrials.gov, Identifier NCT05907785.

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          Most cited references67

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          Development of a WHO growth reference for school-aged children and adolescents

          OBJECTIVE: To construct growth curves for school-aged children and adolescents that accord with the WHO Child Growth Standards for preschool children and the body mass index (BMI) cut-offs for adults. METHODS: Data from the 1977 National Center for Health Statistics (NCHS)/WHO growth reference (1-24 years) were merged with data from the under-fives growth standards' cross-sectional sample (18-71 months) to smooth the transition between the two samples. State-of-the-art statistical methods used to construct the WHO Child Growth Standards (0-5 years), i.e. the Box-Cox power exponential (BCPE) method with appropriate diagnostic tools for the selection of best models, were applied to this combined sample. FINDINGS: The merged data sets resulted in a smooth transition at 5 years for height-for-age, weight-for-age and BMI-for-age. For BMI-for-age across all centiles the magnitude of the difference between the two curves at age 5 years is mostly 0.0 kg/m² to 0.1 kg/m². At 19 years, the new BMI values at +1 standard deviation (SD) are 25.4 kg/m² for boys and 25.0 kg/m² for girls. These values are equivalent to the overweight cut-off for adults (> 25.0 kg/m²). Similarly, the +2 SD value (29.7 kg/m² for both sexes) compares closely with the cut-off for obesity (> 30.0 kg/m²). CONCLUSION: The new curves are closely aligned with the WHO Child Growth Standards at 5 years, and the recommended adult cut-offs for overweight and obesity at 19 years. They fill the gap in growth curves and provide an appropriate reference for the 5 to 19 years age group.
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            Physical fitness in childhood and adolescence: a powerful marker of health.

            This review aims to summarize the latest developments with regard to physical fitness and several health outcomes in young people. The literature reviewed suggests that (1) cardiorespiratory fitness levels are associated with total and abdominal adiposity; (2) both cardiorespiratory and muscular fitness are shown to be associated with established and emerging cardiovascular disease risk factors; (3) improvements in muscular fitness and speed/agility, rather than cardiorespiratory fitness, seem to have a positive effect on skeletal health; (4) both cardiorespiratory and muscular fitness enhancements are recommended in pediatric cancer patients/survivors in order to attenuate fatigue and improve their quality of life; and (5) improvements in cardiorespiratory fitness have positive effects on depression, anxiety, mood status and self-esteem, and seem also to be associated with a higher academic performance. In conclusion, health promotion policies and physical activity programs should be designed to improve cardiorespiratory fitness, but also two other physical fitness components such us muscular fitness and speed/agility. Schools may play an important role by identifying children with low physical fitness and by promoting positive health behaviors such as encouraging children to be active, with special emphasis on the intensity of the activity.
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              Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association

              Circulation, 134(24)

                Author and article information

                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                12 September 2023
                : 11
                : 1250731
                [ 1 ]Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation), University of the Balearic Islands (UIB) , Palma, Spain
                [ 2 ]Health Research Institute of the Balearic Islands (IdISBa) , Palma, Spain
                [ 3 ]CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) , Madrid, Spain
                [ 4 ]Department of Pediatrics (Innovation in Paediatrics and Technologies-iPEDITEC- research group), Fundación de Investigación, Consorcio Hospital General, University of Valencia , Valencia, Spain
                [ 5 ]Human and Animal Physiology, Wageningen University , Wageningen, Netherlands
                [ 6 ]Laboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences , Prague, Czech Republic
                [ 7 ]C2VN, INSERM, INRAE, Aix-Marseille University , Marseille, France
                Author notes

                Edited by: Alessandro Leone, University of Milan, Italy

                Reviewed by: Tiago Jeronimo Dos Santos, University of Almeria, Spain Irene Rutigliano, IRCCS Casa Sollievo della Sofferenza Hospital, Italy

                [* ] Correspondence: Paula Oliver paula.oliver@ 123456uib.es
                © 2023 Picó, Lurbe, Keijer, Kopecky, Landrier, Álvarez-Pitti, Martin, Oliver, Palou, Palou, Zouhar, Ribot, Rodríguez, Sánchez, Serra and Bonet.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 30 June 2023
                : 30 August 2023
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 67, Pages: 0, Words: 0
                Funded by: Instituto de Salud Carlos III (ISCIII)
                Award ID:  
                Funded by: Next Generation EU, Mecanismo para la Recuperación y la Resiliencia (MRR)
                Award ID:  
                Funded by: Ministry of Education, Youth and Sports of the Czech Republic
                Award ID:  
                Funded by: French National Research Agency
                Award ID:  
                The study is supported by the project AC21_2/00033, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by Next Generation EU, Mecanismo para la Recuperación y la Resiliencia (MRR); the Ministry of Education, Youth and Sports of the Czech Republic; and the French National Research Agency in the joint funding activity HDHL-INTIMIC: Standardised measurement, monitoring and/or biomarkers to study food intake, physical activity and health (STAMIFY 2021).
                Study Protocol
                Custom metadata
                Pediatric Obesity

                integration analysis,cardiorespiratory fitness,metabolomics,transcriptomics,mirnome,adipokines,cytokines


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