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Purpose: To assess associations between sedentary time (ST), physical activity (PA), and cardiovascular health in early childhood. Method: Cross-sectional study including 160 children (age 6.1 y [SD 0.5], 86 boys, 93 maternal body mass index ≥ 30 kg/m2, and 73 gestational diabetes) assessed for pulse wave velocity, echocardiography, ultra-high frequency 48–70 MHz vascular ultrasound, and accelerometery. Results: Boys had 385 (SD 53) minutes per day ST, 305 (SD 44) minutes per day light PA, and 81 (SD 22) minutes per day moderate to vigorous PA (MVPA). Girls had 415 (SD 50) minutes per day ST, 283 (SD 40) minutes per day light PA, and 66 (SD 19) minutes per day MVPA. In adjusted analyses, MVPA was inversely associated with resting heart rate (β = −6.6; 95% confidence interval, −12.5 to −0.7) and positively associated with left ventricular mass (β = 6.8; 1.4–12.3), radial intima-media thickness (β = 11.4; 5.4–17.5), brachial intima-media thickness (β = 8.0; 2.0–14.0), and femoral intima-media thickness (β = 1.3; 0.2–2.3). MVPA was inversely associated with body fat percentage (β = −3.4; −6.6 to −0.2), diastolic blood pressure (β = −0.05; −0.8 to −0.1), and femoral (β = −18.1; −32.4 to −0.8) and radial (β = −13.4; −24.0 to −2.9) circumferential wall stress in boys only. ST and pulse wave velocity showed no significant associations. Conclusions: In young at-risk children, MVPA is associated with cardiovascular remodeling, partly in a sex-dependant way, likely representing physiological adaptation, but ST shows no association with cardiovascular health in early childhood. [ABSTRACT FROM AUTHOR]

Purpose: Previous literature has demonstrated the mediating role of adiposity in the association between cardiorespiratory fitness (CRF) and cardiometabolic risk as well as the potential role of CRF in attenuating the adverse consequences associated with excess weight. This study aimed to evaluate the mediating role of CRF and adiposity in the possible association with cardiometabolic risk. Method: Observational 3-year longitudinal study that included 420 children and adolescents (10.50 [2.05] y of age at baseline; 56.2% girls). Body mass index (BMI) was calculated, and CRF was evaluated using field assessments. A clustered cardiometabolic risk score (cMetS) was calculated from glucose, systolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, and triglycerides z scores. Analyses evaluated the mediating role of BMI in the association between CRF and cMetS as well as whether CRF mediated the association between BMI and cMetS. Results: BMI at baseline was directly associated with the cMetS at follow-up (0.102; 95% confidence interval, 0.020 to 0.181), independently of CRF, whereas CRF was only indirectly associated with cMetS at follow-up through BMI (−0.036; 95% confidence interval, −0.070 to −0.009), meaning that the association between CRF and cMetS was explained via the mediation role of BMI. Conclusions: BMI presented direct association with cMetS, whereas CRF exhibited indirect association with cMetS mediated via BMI. [ABSTRACT FROM AUTHOR]

Childhood obesity is a major problem worldwide and a key contributor to adult obesity. This research explores caregivers' lay beliefs and food parenting practices, and their long-term, intergenerational effects on their children's food consumption and physiology. First, a cross-cultural survey reveals the link between parents' belief that tasty food is unhealthy and the use of extrinsic rewards to encourage their children to eat healthily, with adverse downstream consequences for the children's body mass indices. Next, two studies demonstrate the mechanism by which this strategy backfires, as providing extrinsic rewards ironically increases children's unhealthy food consumption, which in turn leads to an increase in their body mass indices. The final two studies demonstrate potential solutions for public policy and health practitioners, either by manipulating "unhealthy = tasty" beliefs directly or by breaking the association between these food beliefs and the use of extrinsic rewards through an intervention. [ABSTRACT FROM AUTHOR]

Family-based behavioral treatment (FBT) is one of the most effective treatments for childhood obesity. These programs include behavior change strategies and basic parenting training to help parents make healthy diet and physical activity changes for their children. While effective, not all families respond to this program. Additional training on how to effectively deliver these behavior change strategies may improve outcomes. The authoritative parenting style is associated with many positive academic and socio-emotional outcomes in children, and is characterized by displays of warmth and support while also being consistent with setting limits and boundaries. This parenting style has also been associated with normal weight status. Furthermore, parenting training programs that promote this parenting style for children with behavioral issues have shown unintended effects on decreasing child weight status. Therefore, our goal was to examine the effect of adding more intensive parenting training to FBT on child weight status. We randomized 140 children and their parent to either FBT or FBT + Parenting Training (FBT + PT). Assessments were conducted at baseline, mid-treatment (month 3), post-treatment (month 6), 6-month follow-up (month 12), and 12-month follow-up (month 18). Primary outcome was change in child weight status. Secondary outcomes were rates of drop-out, treatment adherence, and acceptability. If effective, this program may provide another alternative for families to help improve outcomes in childhood obesity management.

IntroductionMeta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.ObjectiveThe objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.MethodsWe used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure.ResultsOnly 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P  100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

Background: Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. Methods: To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Results: Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals' metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Conclusions: Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background. High numbers of young people are living with obesity in England, with associated negative impacts on their mental and physical health. Social prescribing involves professionals referring individuals to community‐based services to provide additional health and well‐being support. Social prescribing may be a helpful way to provide holistic support to young people living with obesity alongside weight management services. However, there is a need to better understand the availability of community‐based services that could provide this support. Aims. This study aimed to explore the process for mapping community‐based services to be part of a social prescribing offer within children's specialist weight management services in one region of England and to provide an understanding of the availability of community‐based services in this region that are accessible for this population. Method. Community‐based services providing physical activity opportunities to young people in an area local to a specialist weight management service (South Yorkshire) were mapped using a mixed methods approach, including scoping of online resources and meetings with relevant contacts. Services were identified and reviewed against criteria developed through stakeholder engagement to assess suitability for young people living with obesity. Results. A total of 933 community‐based services were identified across South Yorkshire between January and June 2023. Scoping and suitability assessment of these services took 6 months. There was often limited information provided about services, particularly relating to costs. Nineteen services met all suitability criteria. Conclusion. It requires time and capacity to identify relevant community‐based services as part of a social prescribing offering. Although a high number of services were identified, few of these were suitable for young people living with obesity. Consideration should be given to how young people can be supported to access services, as well as how services can be supported to meet the needs of young people living with severe obesity. [ABSTRACT FROM AUTHOR]

Summary Objective Methods Results Conclusion To summarize the literature on pharmacotherapy for managing paediatric obesity.A systematic review and meta‐analysis were conducted of randomized controlled trials (RCTs) with <18‐year‐olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy‐reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs).Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon‐like peptide‐1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3−24 months). Metformin had little to no benefit on PROMs (e.g., health‐related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z‐score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA‐IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL‐cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions.Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long‐term effectiveness and safety of GLP1RAs remain to be evaluated. [ABSTRACT FROM AUTHOR]

The proopiomelanocortin (Pomc)‐derived peptides, including adrenocorticotropic hormone and α‐melanocyte stimulating hormone (α‐Msh), play both a central and a peripheral role in modulating the stress response. The central role is predominantly associated with nutrient homeostasis, while peripherally they play an important role in the synthesis of glucocorticoids (GCs) in response to stress. Pomc mutations are a major risk factor in the development of early‐onset childhood obesity in humans. This is attributed primarily to their central effects on melanocortin receptor dysfunction leading to hyperphagia and reduced energy expenditure, while the peripheral mechanism contributing to obesity has largely been unexplored. Here, we tested the hypothesis that Pomc mutation‐mediated adrenal insufficiency and the associated changes in GC signaling contribute to postnatal adiposity using zebrafish as a model. We generated a ubiquitous Pomc knockout zebrafish that mimicked the mammalian mutant phenotype of adrenal insufficiency and enhanced adiposity. The loss of Pomc inhibited stress‐induced cortisol production and reprogrammed GC signaling by reducing glucocorticoid receptor responsiveness, whereas the mineralocorticoid receptor (Mr) signaling was enhanced. Larval feeding led to enhanced growth and adipogenesis in the Pomc mutants, and this was inhibited by eplerenone, an Mr antagonist. Altogether, our results underscore a key role for Mr signaling in early developmental adipogenesis and a possible target for therapeutic intervention for early‐onset childhood obesity due to Pomc dysfunction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to develop a systems thinking framework to describe the common complexities of childhood obesity in the Caribbean region and identify potential areas of intervention. Methods: Group model building (GMB) is a form of systems science. Trained GMB facilitators in Puerto Rico, the US Virgin Islands, Barbados, and Trinidad and Tobago convened a group of multi-disciplinary stakeholders in a series of virtual meetings in 2021 to elaborate a hypothesis of the system driving childhood obesity represented by causal loop diagrams (CLD). Commonalities and differences between the CLDs from each island were identified and reconciled to create a synthesized CLD. Results: A single explanatory CLD across the islands was developed and includes nine reinforcing loops. These loops addressed the interconnected role of schools, policy, commercial determinants, community and the personal experience of the child in rising childhood obesity rates. Conclusions: Despite differences across settings, there is a core system driving childhood obesity in the Caribbean, as described by stakeholders in GMB workshops. Policy solutions to the problem must be multi-faceted and multi-level to address the interlinked reinforcing loops of the complex system and reduce rates of childhood obesity. [ABSTRACT FROM AUTHOR]

Background: Incorporating principles of family-centered care into pediatric weight management interventions can improve the effectiveness and quality of treatment and reduce attrition rates. To assess the family-centeredness of interventions, reliable, valid, and easy-to-administer scales are needed. The purpose of the study was to develop a shortened version of the modified Family Centered Care Assessment (mFCCA) and assess its psychometric properties. Methods: The mFCCA, a scale to assess the family-centeredness of interventions for childhood obesity, was administered to families following the Connect for Health randomized control trial evaluating the effectiveness of a primary care-based pediatric weight management intervention. We iteratively removed items from the mFCCA and used Rasch modeling to examine the reliability and validity of the shortened scale. Results: We included data from 318 parents and the exploratory factor analysis showed the presence of a single factor. The results of the Rasch modeling demonstrated acceptable internal consistency of the scale (0.7) and strong validity as evidenced by the overall model fit and range of item difficulty. Following the psychometric analyses, we reduced the number of items from 24 to 8 items. Conclusion: The mFCCA short version demonstrates good psychometrics and can be used to evaluate the family-centeredness of childhood obesity interventions with reduced participant burden, thereby improving outcomes for children with obesity. Trial registration: Clinicaltrials.gov NCT02124460 registered on April 24, 2014. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Childhood obesity is associated with maternal obesity, but the link to gestational weight gain (GWG) is not fully elucidated. We examined the relationship between early pregnancy maternal body mass index (BMI) and GWG on early childhood growth.Data from 30 197 mother–child pairs from Uppsala County Mother and Child Cohort were divided into 15 groups according to maternal BMI and GWG, based on World Health Organization classification and Institute of Medicine guidelines, respectively. Postnatal growth patterns were analyzed with linear mixed regression models within maternal BMI groups. Odds ratios of overweight and obesity at 4 years of age were assessed with logistic regression analyses. We treated children of mothers with normal weight and adequate GWG as the reference group, and all analyses were adjusted for potential confounders.GWG was associated with infant BMI z‐score at birth, independent of potential confounding factors. Independent of GWG, we observed an overall decrease in BMI z‐score from 18 months to 5 years in children of mothers who were underweight, while an increase in BMI z‐score was seen in children of mothers who were overweight or obese. In children of normal‐ and overweight mothers, the risk of childhood overweight and obesity was associated with excessive compared to adequate GWG (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 1.01–1.36 for normal‐weight mothers, and aOR 1.25, 95% CI 1.04–1.51 for overweight mothers, respectively). Children of mothers with obesity and excessive GWG had the highest risk of being overweight or obese at 4 years (aOR 2.88, 95% CI 2.40–3.44, and 4.38, 95% CI 3.37–5.67, respectively). Associations did not differ between children of mothers with obesity class 1 and 2–3 when comparing excessive and adequate GWG (aOR 1.33, 95% CI 0.96–1.85, and 1.12, 95% CI 0.74–1.70, respectively).Maternal GWG affects infant birth size and growth until 18 months, although maternal BMI is more crucial for childhood growth beyond 18 months. Further, children of mothers who are normal‐ or overweight and experience excessive GWG have an increased risk of obesity at 4 years. [ABSTRACT FROM AUTHOR]

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity. [ABSTRACT FROM AUTHOR]

Consistent evidence increasingly highlights the significance of integrating sex and gender medicine to ensure a precision approach according to individual patient needs. Gender discrepancies emerge across various areas, even from pediatric age. The importance of recognizing these differences in pediatric nutrition is critical for the development of targeted nutritional strategies and interventions, particularly in cases of associated pathologies, including obesity, metabolic-associated fatty liver disease, eating disorders, and inflammatory bowel disease. The review highlights the biological and sociocultural factors that contribute to different nutritional needs and health outcomes in male and female children. By examining current evidence, we underscore the necessity for precision medicine approaches in pediatric care that consider these sex- and gender-based differences. Moreover, differences in dietary requirements and dietary patterns between males and females are evident, underscoring the need for precise nutrition strategies for a more accurate management of children and adolescents. This approach is essential for improving clinical outcomes and promoting equitable healthcare practices. This review aims to provide an overview of nutrition-related medical conditions exhibiting sex- and gender-specific discrepancies, which might lead to distinct outcomes requiring unique management and prevention strategies. Future research and public health initiatives should address these differences in designing effective lifestyle education programs and nutrition interventions targeting both children and adolescents. [ABSTRACT FROM AUTHOR]