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Pharmacological Research Jun 2023Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations.... (Meta-Analysis)
Meta-Analysis Review
Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Vitamin D deficiency has in turn several consequences especially among children and adolescents. Therefore, a few supplementation strategies of vitamin D for pediatric subjects with an excessive body weight have been proposed, but their efficacy remains controversial. The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation in overweight and obese children and adolescents. Three databases (PubMed, Embase and Web of Science) were searched to collect trials on the effect of vitamin D supplementation in the pediatric overweight or obese population. Twenty-three studies were included in the systematic review. Results on modification of metabolic or cardiovascular outcomes were controversial. On the other hand, the meta-analysis showed a mean difference by 1.6 ng/ml in subjects supplemented with vitamin D as compared to placebo. In conclusion, vitamin D supplementation slightly increases 25(OH)D levels in pediatric subjects with overweight and obesity. However, the effects on metabolic and cardiovascular outcomes remain controversial. New efforts should be devoted to promoting effective interventions to improve the health of children and adolescents with overweight and obesity.
Topics: Humans; Child; Adolescent; Overweight; Pediatric Obesity; Vitamin D; Vitamin D Deficiency; Dietary Supplements; Vitamins; Weight Gain
PubMed: 37178775
DOI: 10.1016/j.phrs.2023.106793 -
British Journal of Sports Medicine Feb 2018To determine if the combination of aerobic and resistance exercise is superior to aerobic exercise alone for the health of obese children and adolescents. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine if the combination of aerobic and resistance exercise is superior to aerobic exercise alone for the health of obese children and adolescents.
DESIGN
Systematic review with meta-analysis.
DATA SOURCES
Computerised search of 3 databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry).
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies that compared the effect of supervised concurrent exercise versus aerobic exercise interventions, with anthropometric and metabolic outcomes in paediatric obesity (6-18 years old). The mean differences (MD) of the parameters from preintervention to postintervention between groups were pooled using a random-effects model.
RESULTS
12 trials with 555 youths were included in the meta-analysis. Compared with aerobic exercise alone, concurrent exercise resulted in greater reductions in body mass (MD=-2.28 kg), fat mass (MD=-3.49%; and MD=-4.34 kg) and low-density lipoprotein cholesterol (MD=-10.20 mg/dL); as well as greater increases in lean body mass (MD=2.20 kg) and adiponectin level (MD=2.59 μg/mL). Differences were larger for longer term programmes (>24 weeks).
SUMMARY
Concurrent aerobic plus resistance exercise improves body composition, metabolic profiles, and inflammatory state in the obese paediatric population.
TRIAL REGISTRATION NUMBER
CRD42016039807.
Topics: Adiponectin; Adiposity; Adolescent; Body Mass Index; Child; Cholesterol, LDL; Exercise; Humans; Pediatric Obesity; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 27986760
DOI: 10.1136/bjsports-2016-096605 -
Public Health Nutrition Jan 2018To review the available literature on the association between consumption of ultra-processed foods and body fat during childhood and adolescence. (Review)
Review
OBJECTIVE
To review the available literature on the association between consumption of ultra-processed foods and body fat during childhood and adolescence.
DESIGN
A systematic review was conducted in the PubMed, Web of Science and LILACS databases. Studies that evaluated the association between consumption of ultra-processed food (exposure) and body fat (outcome) during childhood and adolescence were eligible.
SUBJECTS
Healthy children and adolescents.
RESULTS
Twenty-six studies that evaluated groups of ultra-processed foods (such as snacks, fast foods, junk foods and convenience foods) or specific ultra-processed foods (soft drinks/sweetened beverages, sweets, chocolate and ready-to-eat cereals) were selected. Most of the studies (n 15) had a cohort design. Consumption was generally evaluated by means of FFQ or food records; and body composition, by means of double indirect methods (bioelectrical impedance analysis and skinfolds). Most of the studies that evaluated consumption of groups of ultra-processed foods and soft drinks/sweetened beverages found positive associations with body fat.
CONCLUSIONS
Our review showed that most studies have found positive associations between consumption of ultra-processed food and body fat during childhood and adolescence. There is a need to use a standardized classification that considers the level of food processing to promote comparability between studies.
Topics: Adiposity; Adolescent; Adolescent Behavior; Child; Child Behavior; Fast Foods; Food Handling; Health Behavior; Humans; Observational Studies as Topic; Pediatric Obesity; Prevalence; Snacks
PubMed: 28676132
DOI: 10.1017/S1368980017001331 -
JAMA Network Open Mar 2023Type 2 diabetes (T2D) is increasing globally. Diabetic retinopathy (DR) is a leading cause of blindness in adults with T2D; however, the global burden of DR in pediatric... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Type 2 diabetes (T2D) is increasing globally. Diabetic retinopathy (DR) is a leading cause of blindness in adults with T2D; however, the global burden of DR in pediatric T2D is unknown. This knowledge can inform retinopathy screening and treatments to preserve vision in this population.
OBJECTIVE
To estimate the global prevalence of DR in pediatric T2D.
DATA SOURCES
MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, the Web of Science, and the gray literature (ie, literature containing information that is not available through traditional publishing and distribution channels) were searched for relevant records from the date of database inception to April 4, 2021, with updated searches conducted on May 17, 2022. Searches were limited to human studies. No language restrictions were applied. Search terms included diabetic retinopathy; diabetes mellitus, type 2; prevalence studies; and child, adolescent, teenage, youth, and pediatric.
STUDY SELECTION
Three teams, each with 2 reviewers, independently screened for observational studies with 10 or more participants that reported the prevalence of DR. Among 1989 screened articles, 27 studies met the inclusion criteria for the pooled analysis.
DATA EXTRACTION AND SYNTHESIS
This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines for systematic reviews and meta-analyses. Two independent reviewers performed the risk of bias and level of evidence analyses. The results were pooled using a random-effects model, and heterogeneity was reported using χ2 and I2 statistics.
MAIN OUTCOMES AND MEASURES
The main outcome was the estimated pooled global prevalence of DR in pediatric T2D. Other outcomes included DR severity and current DR assessment methods. The association of diabetes duration, sex, race, age, and obesity with DR prevalence was also assessed.
RESULTS
Among the 27 studies included in the pooled analysis (5924 unique patients; age range at T2D diagnosis, 6.5-21.0 years), the global prevalence of DR in pediatric T2D was 6.99% (95% CI, 3.75%-11.00%; I2 = 95%; 615 patients). Fundoscopy was less sensitive than 7-field stereoscopic fundus photography in detecting retinopathy (0.47% [95% CI, 0%-3.30%; I2 = 0%] vs 13.55% [95% CI, 5.43%-24.29%; I2 = 92%]). The prevalence of DR increased over time and was 1.11% (95% CI, 0.04%-3.06%; I2 = 5%) at less than 2.5 years after T2D diagnosis, 9.04% (95% CI, 2.24%-19.55%; I2 = 88%) at 2.5 to 5.0 years after T2D diagnosis, and 28.14% (95% CI, 12.84%-46.45%; I2 = 96%) at more than 5 years after T2D diagnosis. The prevalence of DR increased with age, and no differences were noted based on sex, race, or obesity. Heterogeneity was high among studies.
CONCLUSIONS AND RELEVANCE
In this study, DR prevalence in pediatric T2D increased significantly at more than 5 years after diagnosis. These findings suggest that retinal microvasculature is an early target of T2D in children and adolescents, and annual screening with fundus photography beginning at diagnosis offers the best assessment method for early detection of DR in pediatric patients.
Topics: Adult; Adolescent; Humans; Child; Child, Preschool; Diabetic Retinopathy; Diabetes Mellitus, Type 2; Prevalence; Retina; Obesity; Observational Studies as Topic
PubMed: 36930156
DOI: 10.1001/jamanetworkopen.2023.1887 -
The Cochrane Database of Systematic... Jan 2018The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions.
OBJECTIVES
To assess whether lifestyle interventions (in the areas of diet, physical activity, sedentary behaviour and behavioural therapy) improve school achievement, cognitive function (e.g. executive functions) and/or future success in children and adolescents with obesity or overweight, compared with standard care, waiting-list control, no treatment, or an attention placebo control group.
SEARCH METHODS
In February 2017, we searched CENTRAL, MEDLINE and 15 other databases. We also searched two trials registries, reference lists, and handsearched one journal from inception. We also contacted researchers in the field to obtain unpublished data.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials (RCTs) of behavioural interventions for weight management in children and adolescents with obesity or overweight. We excluded studies in children and adolescents with medical conditions known to affect weight status, school achievement and cognitive function. We also excluded self- and parent-reported outcomes.
DATA COLLECTION AND ANALYSIS
Four review authors independently selected studies for inclusion. Two review authors extracted data, assessed quality and risks of bias, and evaluated the quality of the evidence using the GRADE approach. We contacted study authors to obtain additional information. We used standard methodological procedures expected by Cochrane. Where the same outcome was assessed across different intervention types, we reported standardised effect sizes for findings from single-study and multiple-study analyses to allow comparison of intervention effects across intervention types. To ease interpretation of the effect size, we also reported the mean difference of effect sizes for single-study outcomes.
MAIN RESULTS
We included 18 studies (59 records) of 2384 children and adolescents with obesity or overweight. Eight studies delivered physical activity interventions, seven studies combined physical activity programmes with healthy lifestyle education, and three studies delivered dietary interventions. We included five RCTs and 13 cluster-RCTs. The studies took place in 10 different countries. Two were carried out in children attending preschool, 11 were conducted in primary/elementary school-aged children, four studies were aimed at adolescents attending secondary/high school and one study included primary/elementary and secondary/high school-aged children. The number of studies included for each outcome was low, with up to only three studies per outcome. The quality of evidence ranged from high to very low and 17 studies had a high risk of bias for at least one item. None of the studies reported data on additional educational support needs and adverse events.Compared to standard practice, analyses of physical activity-only interventions suggested high-quality evidence for improved mean cognitive executive function scores. The mean difference (MD) was 5.00 scale points higher in an after-school exercise group compared to standard practice (95% confidence interval (CI) 0.68 to 9.32; scale mean 100, standard deviation 15; 116 children, 1 study). There was no statistically significant beneficial effect in favour of the intervention for mathematics, reading, or inhibition control. The standardised mean difference (SMD) for mathematics was 0.49 (95% CI -0.04 to 1.01; 2 studies, 255 children, moderate-quality evidence) and for reading was 0.10 (95% CI -0.30 to 0.49; 2 studies, 308 children, moderate-quality evidence). The MD for inhibition control was -1.55 scale points (95% CI -5.85 to 2.75; scale range 0 to 100; SMD -0.15, 95% CI -0.58 to 0.28; 1 study, 84 children, very low-quality evidence). No data were available for average achievement across subjects taught at school.There was no evidence of a beneficial effect of physical activity interventions combined with healthy lifestyle education on average achievement across subjects taught at school, mathematics achievement, reading achievement or inhibition control. The MD for average achievement across subjects taught at school was 6.37 points lower in the intervention group compared to standard practice (95% CI -36.83 to 24.09; scale mean 500, scale SD 70; SMD -0.18, 95% CI -0.93 to 0.58; 1 study, 31 children, low-quality evidence). The effect estimate for mathematics achievement was SMD 0.02 (95% CI -0.19 to 0.22; 3 studies, 384 children, very low-quality evidence), for reading achievement SMD 0.00 (95% CI -0.24 to 0.24; 2 studies, 284 children, low-quality evidence), and for inhibition control SMD -0.67 (95% CI -1.50 to 0.16; 2 studies, 110 children, very low-quality evidence). No data were available for the effect of combined physical activity and healthy lifestyle education on cognitive executive functions.There was a moderate difference in the average achievement across subjects taught at school favouring interventions targeting the improvement of the school food environment compared to standard practice in adolescents with obesity (SMD 0.46, 95% CI 0.25 to 0.66; 2 studies, 382 adolescents, low-quality evidence), but not with overweight. Replacing packed school lunch with a nutrient-rich diet in addition to nutrition education did not improve mathematics (MD -2.18, 95% CI -5.83 to 1.47; scale range 0 to 69; SMD -0.26, 95% CI -0.72 to 0.20; 1 study, 76 children, low-quality evidence) and reading achievement (MD 1.17, 95% CI -4.40 to 6.73; scale range 0 to 108; SMD 0.13, 95% CI -0.35 to 0.61; 1 study, 67 children, low-quality evidence).
AUTHORS' CONCLUSIONS
Despite the large number of childhood and adolescent obesity treatment trials, we were only able to partially assess the impact of obesity treatment interventions on school achievement and cognitive abilities. School and community-based physical activity interventions as part of an obesity prevention or treatment programme can benefit executive functions of children with obesity or overweight specifically. Similarly, school-based dietary interventions may benefit general school achievement in children with obesity. These findings might assist health and education practitioners to make decisions related to promoting physical activity and healthy eating in schools. Future obesity treatment and prevention studies in clinical, school and community settings should consider assessing academic and cognitive as well as physical outcomes.
Topics: Achievement; Adolescent; Child; Educational Status; Executive Function; Exercise; Humans; Life Style; Mathematics; Overweight; Pediatric Obesity; Randomized Controlled Trials as Topic; Reading; Sensitivity and Specificity
PubMed: 29376563
DOI: 10.1002/14651858.CD009728.pub3 -
Nutrients Oct 2020An effective behavior change program is the first line of prevention for youth obesity. However, effectiveness in prevention of adolescent obesity requires several...
An effective behavior change program is the first line of prevention for youth obesity. However, effectiveness in prevention of adolescent obesity requires several approaches, with special attention paid to disordered eating behaviors and psychological support, among other environmental factors. The aim of this systematic review is to compare the impact of two types of obesity prevention programs, inclusive of behavior change components, on weight outcomes. "Energy-balance" studies are aimed at reducing calories from high-energy sources and increasing physical activity (PA) levels, while "shared risk factors for obesity and eating disorders" focus on reducing disordered eating behaviors to promote a positive food and eating relationship. A systematic search of ProQuest, PubMed, PsycInfo, SciELO, and Web of Science identified 8825 articles. Thirty-five studies were included in the review, of which 20 regarded "energy-balance" and 15 "shared risk factors for obesity and eating disorders". "Energy-balance" studies were unable to support maintenance weight status, diet, and PA. "Shared risk factors for obesity and eating disorders" programs also did not result in significant differences in weight status over time. However, the majority of "shared risk factors for obesity and eating disorders" studies demonstrated reduced body dissatisfaction, dieting, and weight-control behaviors. Research is needed to examine how a shared risk factor approach can address both obesity and eating disorders.
Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Body Weight Maintenance; Energy Metabolism; Exercise; Feeding Behavior; Feeding and Eating Disorders; Female; Humans; Male; Pediatric Obesity; Preventive Health Services; Program Evaluation; Psychology, Adolescent; Risk Factors
PubMed: 33066501
DOI: 10.3390/nu12103134 -
The International Journal of Behavioral... Sep 2021Excessive screen time ([Formula: see text] 2 h per day) is associated with childhood overweight and obesity, physical inactivity, increased sedentary time, unfavorable... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Excessive screen time ([Formula: see text] 2 h per day) is associated with childhood overweight and obesity, physical inactivity, increased sedentary time, unfavorable dietary behaviors, and disrupted sleep. Previous reviews suggest intervening on screen time is associated with reductions in screen time and improvements in other obesogenic behaviors. However, it is unclear what study characteristics and behavior change techniques are potential mechanisms underlying the effectiveness of behavioral interventions. The purpose of this meta-analysis was to identify the behavior change techniques and study characteristics associated with effectiveness in behavioral interventions to reduce children's (0-18 years) screen time.
METHODS
A literature search of four databases (Ebscohost, Web of Science, EMBASE, and PubMed) was executed between January and February 2020 and updated during July 2021. Behavioral interventions targeting reductions in children's (0-18 years) screen time were included. Information on study characteristics (e.g., sample size, duration) and behavior change techniques (e.g., information, goal-setting) were extracted. Data on randomization, allocation concealment, and blinding was extracted and used to assess risk of bias. Meta-regressions were used to explore whether intervention effectiveness was associated with the presence of behavior change techniques and study characteristics.
RESULTS
The search identified 15,529 articles, of which 10,714 were screened for relevancy and 680 were retained for full-text screening. Of these, 204 studies provided quantitative data in the meta-analysis. The overall summary of random effects showed a small, beneficial impact of screen time interventions compared to controls (SDM = 0.116, 95CI 0.08 to 0.15). Inclusion of the Goals, Feedback, and Planning behavioral techniques were associated with a positive impact on intervention effectiveness (SDM = 0.145, 95CI 0.11 to 0.18). Interventions with smaller sample sizes (n < 95) delivered over short durations (< 52 weeks) were associated with larger effects compared to studies with larger sample sizes delivered over longer durations. In the presence of the Goals, Feedback, and Planning behavioral techniques, intervention effectiveness diminished as sample size increased.
CONCLUSIONS
Both intervention content and context are important to consider when designing interventions to reduce children's screen time. As interventions are scaled, determining the active ingredients to optimize interventions along the translational continuum will be crucial to maximize reductions in children's screen time.
Topics: Child; Humans; Pediatric Obesity; Screen Time; Sedentary Behavior; Time Factors
PubMed: 34530867
DOI: 10.1186/s12966-021-01189-6 -
The Journal of Pediatrics Sep 2021To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity.
STUDY DESIGN
Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events.
RESULTS
Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m, I 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I 0%), without significant increases in other gastrointestinal symptoms.
CONCLUSIONS
This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea.
PROSPERO ID
CRD42020195869.
Topics: Adolescent; Blood Glucose; Blood Pressure; Body Mass Index; Child; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Pediatric Obesity
PubMed: 33984333
DOI: 10.1016/j.jpeds.2021.05.009 -
Obesity Reviews : An Official Journal... Sep 2019This review aimed to investigate the impact of obesity treatment, with a dietary component, on eating disorder (ED) prevalence, ED risk, and related symptoms in children... (Meta-Analysis)
Meta-Analysis
This review aimed to investigate the impact of obesity treatment, with a dietary component, on eating disorder (ED) prevalence, ED risk, and related symptoms in children and adolescents with overweight or obesity. Four databases were searched to identify pediatric obesity treatment interventions, with a dietary component, and validated pre-post intervention assessment of related outcomes. Of 3078 articles screened, 36 met inclusion criteria, with a combined sample of 2589 participants aged 7.8 to 16.9 years. Intervention duration ranged from 1 week to 13 months, with follow-up of 6 months to 6 years from baseline. Prevalence of ED was reported in five studies and was reduced post-intervention. Meta-analyses showed a reduction in bulimic symptoms (eight studies, standardized mean difference [SE], -0.326 [0.09], P < 0.001), emotional eating (six studies, -0.149 [0.06], P = 0.008), binge eating (three studies, -0.588 [0.10], P < 0.001), and drive for thinness (three studies, -0.167 [0.06], P = 0.005) post-intervention. At follow-up, a reduction in ED risk (six studies, -0.313 [0.13], P = 0.012), emotional eating (five studies, -0.259 [0.05], P < 0.001), eating concern (three studies, -0.501 [0.06], P < 0.001), and drive for thinness (two studies, -0.375 [0.07], P < 0.001) was found. Structured and professionally run obesity treatment was associated with reduced ED prevalence, ED risk, and symptoms.
Topics: Adolescent; Adolescent Behavior; Behavior Therapy; Child; Child Behavior; Feeding and Eating Disorders; Female; Guidelines as Topic; Humans; Male; Obesity Management; Pediatric Obesity; Prevalence; Risk Factors
PubMed: 31131531
DOI: 10.1111/obr.12866 -
Obesity Facts 2018Current guidelines for prevention of obesity in childhood and adolescence are discussed.
OBJECTIVE
Current guidelines for prevention of obesity in childhood and adolescence are discussed.
METHODS
A literature search was performed in Medline via PubMed, and appropriate studies were analyzed.
RESULTS
Programs to prevent childhood obesity have so far remained mainly school-based and effects have been limited. Analyses by age group show that prevention programs have the best results in younger children (<12 years). Evidence-based recommendations for pre-school- and early school-aged children indicate the need for interventions that address parents and teachers alike. During adolescence, school-based interventions proved most effective when adolescents were addressed directly. To date, obesity prevention programs have mainly focused on behavior-oriented prevention. Recommendations for community- or environment-based prevention have been suggested by the German Alliance of Noncommunicable Diseases and include a minimum of 1 h of physical activity at school, promotion of healthy food choices by taxing unhealthy foods, mandatory standards for meals at kindergartens and schools as well as a ban on unhealthy food advertisement aimed at children.
CONCLUSION
Behavior-oriented prevention programs showed only limited long-term effects. Certain groups at risk for the development of obesity are not reached effectively by current programs. Although universally valid conclusions cannot be drawn given the heterogeneity of available studies, clearly combining behavior-based programs with community-based prevention to counteract an 'obesogenic environment' is crucial for sustainable success of future obesity prevention programs.
Topics: Adolescent; Behavior Therapy; Child; Child, Preschool; Female; Humans; Infant; Internationality; Male; Pediatric Obesity; Practice Guidelines as Topic; Preventive Medicine; School Health Services
PubMed: 29969778
DOI: 10.1159/000486512