Importance:The incidence and risk (predictive) factors for early life food allergy development remain uncertain. Objective:To estimate the incidence and quantify risk factors for food allergy development. Data Sources:MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025. Study Selection:Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses. Data Extraction and Synthesis:Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds ratios (ORs). Risk of bias was assessed using the QUIPS tool, and certainty of evidence assessed using GRADE. Main Outcome and Measure:The primary outcome was food allergy to age 6 years. Results:A total of 190 studies involving 2.8 million participants across 40 countries were analyzed. Among studies using food challenge, overall food allergy incidence was likely 4.7% (moderate certainty). Among 176 studies identifying 342 risk factors with varying certainty, the strongest and most certain factors included prior allergic conditions (eg, atopic dermatitis [eczema] within the first year of life [OR, 3.88; risk difference [RD], 12.0%; 95% CI, 8.8%-15.7%], allergic rhinitis [OR, 3.39; RD, 10.1%; 95% CI, 6.7%-14.4%], and wheeze [OR, 2.11; RD, 5.0%; 95% CI, 2.1%-8.8%]), severity of atopic dermatitis (OR, 1.22; RD, 1.0%; 95% CI, 0.6%-1.6%), increased skin transepidermal water loss (OR, 3.36; RD, 10.0%; 95% CI, 6.3%-14.8%), filaggrin gene sequence variations (OR, 1.93; RD, 4.2%; 95% CI, 2.4%-6.4%), delayed solid food introduction (eg, peanut after age 12 months [OR, 2.55; RD, 6.8%; 95% CI, 1.9%-14.6%]), infant antibiotic use (first month [OR, 4.11; RD, 12.8%; 95% CI, 0.4%-40%], first year [OR, 1.39; RD, 1.8%; 95% CI, 0.8%-3.1%], during pregnancy [OR, 1.32; RD, 1.5%; 95% CI, 0.6%-2.5%]), male sex (OR, 1.24; RD, 1.1%; 95% CI, 0.7%-1.6%), firstborn child (OR, 1.13; RD, 0.6%; 95% CI, 0.3%-1.0%), family history of food allergy (eg, mother [OR, 1.98; RD, 4.4%; 95% CI, 2.5%-6.8%], father [OR, 1.69; RD, 3.2%; 95% CI, 1.3%-5.5%], both parents [OR, 2.07; RD, 4.8%; 95% CI, 1.3%-5.5%], siblings [OR, 2.36; RD, 6.0%; 95% CI, 4.4%-8.0%]), parental migration (OR, 3.28; RD, 9.7%; 95% CI, 4.9%-16.3%), self-identification as Black (vs White [OR, 3.93; RD, 12.1%; 95% CI, 5.2%-22.5%], vs non-Hispanic White [OR, 2.23; RD, 5.5%; 95% CI, 3.0%-8.7%]), and cesarean delivery (OR, 1.16; RD, 1.0%; 95% CI, 0.3%-1.2%). Factors like low birth weight, postterm birth, maternal diet, and stress during pregnancy showed no significant risk difference. Conclusions and Relevance:In this meta-analysis, the most credible risk factors associated with development of childhood food allergy are a combination of major and minor risk factors, including early allergic conditions (atopic march/diathesis), delayed allergen introduction, genetics, antibiotic exposure, demographic factors, and birth-related variables.

OBJECTIVE:Examine associations between neighbourhood characteristics and health behaviours (physical activity, screen time, sleep duration) in boys and girls initiating obesity management care across Canada. METHODS:We analysed cross-sectional data from the CANadian Paediatric Weight management Registry (2013-2017) for 803 participants (with overweight or obesity; 5-17 years old). Questionnaire-assessed health behaviours included total physical activity (PA), organised PA outside of school, screen time, and sleep duration. Total PA was classified as high vs. low based on current recommendations, organised PA as high vs. low based on average attained levels for Canadian children, and screen time and sleep duration as meeting vs. not meeting recommendations. Neighbourhood characteristics (walkability, greenness, material and social deprivation) were computed for the first three digits of residential postal codes. Covariate-adjusted associations were examined using generalised estimating equations stratified by sex. RESULTS:Participants (50% boys; mean ± SD: age, 11.9 ± 3.1 years; BMI z-score, 3.28 ± 1.06) living in low (vs. high) social deprivation neighbourhoods were more likely to engage in high total PA, particularly among boys (PR = 1.32, 95% CI: 1.01, 1.73). Boys living in neighbourhoods with high (vs. low) walkability (PR = 3.56, 95% CI: 1.97, 6.44) and higher greenness (PR = 1.72, 95% CI: 1.17, 2.64) were more likely to engage in high organised PA. Girls living in neighbourhoods with very low (vs. high) material deprivation were more likely to engage in high organised PA (PR = 4.17, 95% CI: 1.52, 11.45). No associations were found for screen time or sleep duration. CONCLUSIONS:This study adds to the evidence linking neighbourhood environments to health behaviours in children and adolescents living with obesity and who are initiating obesity management care. Specifically, less social deprivation and greater walkability and greenness were associated with higher PA among boys, while less material deprivation was linked to higher PA among girls.

QuestionWhat are the risk factors associated with the development of food allergy in children?FindingsThis systematic review and meta-analysis of 2.8 million participants in 190 studies identified the following largest and most certain risk factors associated with the development of food allergies in children: prior allergic conditions (atopic march/diathesis), atopic dermatitis, increased skin transepidermal water loss, filaggrin gene sequence variations, delayed solid food introduction, infant and intrapartum antibiotic exposure, male sex, being first born, family history of allergy, parental migration, self-identification as Black, and cesarean delivery.MeaningThis systematic review and meta-analysis clarifies the major and minor risk factors associated with developing early-onset food allergy to inform optimal prevention clinical practice, policy, and research. ImportanceThe incidence and risk (predictive) factors for early life food allergy development remain uncertain.ObjectiveTo estimate the incidence and quantify risk factors for food allergy development.Data SourcesMEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.Study SelectionIncidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.Data Extraction and SynthesisPaired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds ratios (ORs). Risk of bias was assessed using the QUIPS tool, and certainty of evidence assessed using GRADE.Main Outcome and MeasureThe primary outcome was food allergy to age 6 years.ResultsA total of 190 studies involving 2.8 million participants across 40 countries were analyzed. Among studies using food challenge, overall food allergy incidence was likely 4.7% (moderate certainty). Among 176 studies identifying 342 risk factors with varying certainty, the strongest and most certain factors included prior allergic conditions (eg, atopic dermatitis [eczema] within the first year of life [OR, 3.88; risk difference [RD], 12.0%; 95% CI, 8.8%-15.7%], allergic rhinitis [OR, 3.39; RD, 10.1%; 95% CI, 6.7%-14.4%], and wheeze [OR, 2.11; RD, 5.0%; 95% CI, 2.1%-8.8%]), severity of atopic dermatitis (OR, 1.22; RD, 1.0%; 95% CI, 0.6%-1.6%), increased skin transepidermal water loss (OR, 3.36; RD, 10.0%; 95% CI, 6.3%-14.8%), filaggrin gene sequence variations (OR, 1.93; RD, 4.2%; 95% CI, 2.4%-6.4%), delayed solid food introduction (eg, peanut after age 12 months [OR, 2.55; RD, 6.8%; 95% CI, 1.9%-14.6%]), infant antibiotic use (first month [OR, 4.11; RD, 12.8%; 95% CI, 0.4%-40%], first year [OR, 1.39; RD, 1.8%; 95% CI, 0.8%-3.1%], during pregnancy [OR, 1.32; RD, 1.5%; 95% CI, 0.6%-2.5%]), male sex (OR, 1.24; RD, 1.1%; 95% CI, 0.7%-1.6%), firstborn child (OR, 1.13; RD, 0.6%; 95% CI, 0.3%-1.0%), family history of food allergy (eg, mother [OR, 1.98; RD, 4.4%; 95% CI, 2.5%-6.8%], father [OR, 1.69; RD, 3.2%; 95% CI, 1.3%-5.5%], both parents [OR, 2.07; RD, 4.8%; 95% CI, 1.3%-5.5%], siblings [OR, 2.36; RD, 6.0%; 95% CI, 4.4%-8.0%]), parental migration (OR, 3.28; RD, 9.7%; 95% CI, 4.9%-16.3%), self-identification as Black (vs White [OR, 3.93; RD, 12.1%; 95% CI, 5.2%-22.5%], vs non-Hispanic White [OR, 2.23; RD, 5.5%; 95% CI, 3.0%-8.7%]), and cesarean delivery (OR, 1.16; RD, 1.0%; 95% CI, 0.3%-1.2%). Factors like low birth weight, postterm birth, maternal diet, and stress during pregnancy showed no significant risk difference.Conclusions and RelevanceIn this meta-analysis, the most credible risk factors associated with development of childhood food allergy are a combination of major and minor risk factors, including early allergic conditions (atopic march/diathesis), delayed allergen introduction, genetics, antibiotic exposure, demographic factors, and birth-related variables. This systematic review and meta-analysis estimates the incidence of and quantifies risk factors for food allergy development in children.

INTRODUCTION:For adolescents living with higher body weight, changing lifestyle behaviours can be met with challenges due to psychosocial factors, such as mental health and emotional challenges. Few behavioural interventions have included skill development to manage these mental health and emotional challenges. METHODS AND ANALYSIS:The feasibility of a dialectical behavioural therapy (DBT)-enhanced lifestyle intervention will be evaluated through a pilot randomised controlled trial. We will recruit 90 adolescents aged 14-17 years with a body mass index Z-score >1.4 and mild-to-moderate depressive symptoms to participate with a caregiver in the trial. Adolescents will be randomised 2:2:1 to one of the three study arms: (A) behavioural lifestyle intervention with DBT skills training, (B) behavioural lifestyle intervention alone (ie, without DBT skills training) or (C) control. The interventions will include two sessions weekly for 16 weeks that include (1) one modified DBT skills training with two facilitators, supervised by a clinical psychologist, combined with one behavioural lifestyle session delivered by a dietitian and/or a kinesiologist and (2) two behavioural lifestyle sessions alone. DBT skills training will consist of teaching mindfulness, emotion regulation, distress tolerance, interpersonal effectiveness and walking the middle path modules. Behavioural sessions will be guided by evidence-based practices for goal setting, dietary counselling, improving sleep, reducing screen time and structured physical activity. The main outcomes are enrolment rates, adherence to the intervention and retention rates for follow-up measurements. The secondary outcome will be changes in the quality of life (Pediatric Quality of Life Inventory) and daily physical activity levels between baseline and immediately post-intervention. Adolescents will participate in a focus group incorporating photo elicitation to explore satisfaction, acceptability and perceived benefits of the study arms. ETHICS AND DISSEMINATION:This study has received ethical approval from the University of Manitoba's Biomedical Research Ethics Committee (HS24295-H2020:427), Hamilton Health Sciences & McMaster University (HiREB 18159) and The Conjoint Health Research Ethics Board (CHREB), University of Calgary (REB24-1084). Results will be disseminated through publication in peer-reviewed journals and be relevant to researchers and clinicians involved in paediatrics and paediatric weight management. TRIAL REGISTRATION NUMBER:NCT05338944.

Few studies have characterized metabolically healthy (MHO) and unhealthy obesity (MUO) in pediatric populations over time. The objective of this study was to determine the prevalence of MHO in children and adolescents enrolled in a weight management program and examine changes in cardiometabolic indicators over 1 year. Methods: Participants from the CANadian Pediatric Weight management Registry were stratified by age (6-11-year-olds; 12-17-year-olds) and sex to determine MHO/MUO status at baseline and 1-year follow-up. Results: In this sample (n = 387), the baseline and 1-year follow-up prevalence of MHO were 35% and 34%, respectively. Obesity status remained stable in 72% of participants. Of the 387 participants, n = 55 transitioned from MHO to MUO, while n = 53 transitioned from MUO to MHO by 1 year. Patterns of change in MHO were generally similar across sexes and age groups. Conclusion: In this study, MHO was present in approximately one-third of children and adolescents, with one-quarter changing MHO to MUO or MUO to MHO status from baseline to 1-year follow-up.

Gestational diabetes (GDM) confers an increased risk of future type-2 diabetes (T2D). We aimed to identify determinants of the progression of GDM to T2D in South Asian women and develop a precision prognostics model for potential future clinical application. This study included 247 South Asian women with GDM from the prospective South Asian Birth Cohort (START) study in Ontario, Canada. Metabolomics was performed on 2nd trimester fasting serum samples by multisegment injection−capillary electrophoresis−mass spectrometry. We determined incidence of postpartum T2D through validated diagnostic codes using health administrative data. We used multivariable logistic regression to identify predictors of incident T2D through backward elimination. We assessed diagnostic performance of models using area under the receiver operating characteristic curve (AUC ROC) and 5-fold cross-validation to assess model stability. Of 247 South Asian women diagnosed with GDM with a mean age of 30.9 years and median total follow-up of 9.7 years, 45 (18.2

BACKGROUND:Health-related quality of life (HRQoL) can be impaired in children with obesity. Utilising data from the CANadian Paediatric Weight Management Registry (CANPWR), we examined changes in HRQoL up to 3-year after enrollment in paediatric weight management programs (PWMP) and demographic, socioeconomic, behavioural and health-related factors associated with it. METHODS:Data were collected from 2013 to 2020. Child (≥ 8 years) and parent-reported HRQoL data were assessed via questionnaire (PedsQL4.0) at baseline, 6-month, 1-, 2- and 3-year post-baseline in PWMP. Over time, HRQoL and associations with demographic, anthropometric, behavioural and health services data were examined using linear effects and mixed effects models. FINDINGS:A total of 1145 participants were included at baseline (47.8% male; age 12.4 ± 3.3 years; BMI z-score: 3.5 ± 1.2; 68.8% White), 793 (69%) at 1- and 615 (54%) at 3-year post-baseline. Total HRQoL improved from baseline to 6-month and was higher at 3-year (child-total score: 69.9 ± 15.2 vs. 74.6 ± 14.5, p < 0.001; parent-total score: 64.6 ± 17.4 vs. 68.6 ± 17.0; p < 0.001). Total child-reported HRQoL was higher in boys (ß: 2.71, CI: 1.2-4.2; p < 0.01), children who identified as non-White (ß: 2.63, CI: 0.8-4.5; p < 0.01), and those with higher household incomes (ß: 3.65, CI: 1.6-5.7; p < 0.01), independent of BMI z-score. Higher total child-reported HRQoL scores were positively related to higher hours of clinic attendance (ß: 0.09 CI: 0.06-0.12; p < 0.01). In contrast, sleep disturbance, lower physical activity, and higher screen time were associated with lower total child-reported HRQoL independent of BMI z-score. CONCLUSIONS:Both child- and parent-reported HRQoL scores improved over 3 years, and these changes were associated positively with clinic attendance and negatively with unhealthy behaviours.

Objective: The objectives of this study were to: (1) quantify toddlers' total physical activity (TPA) and guideline adherence using a machine learning method; and (2) explore socio-ecological predictors (e.g., sex, childcare) of TPA. Methods: Toddlers (n=103, 21.4 ± 6.9 months, 52% female) from the Hamilton, Canada region completed a gross motor assessment (Peabody Developmental Motor Scales 2nd ed; PDMS-2) and wore an ActiGraph wGT3X-BT accelerometer on the right hip for 4-8 days. Parents completed demographics and physical activity surveys. TPA was estimated using a validated machine learning model and reported using descriptive statistics. Multiple linear regression explored potential predictors of TPA: age, sex, household income, older sibling, BMI-for-age z-score, gross motor z-score, childcare arrangement, parent physical activity, and temperature, controlling for accelerometer wear time. Results: Toddlers had an average of 200.3 ± 44.0 minutes of daily TPA. Most (72%) met the PA guideline of 180 min/day when averaged across days, while only 27% met the guideline on all days. The regression model was significant and explained 57% of the variation in TPA (F13,79 = 8.09, p < 0.0001). Controlling for wear time, the only significant positive predictors were age and PDMS-2 z-score. Conclusion: Almost three quarters of toddlers met the TPA guidelines. Older toddlers and toddlers with more advanced gross motor skills for their age participated in more daily TPA. Future research should continue to apply machine learning methods in more diverse samples and could build on modifiable predictors (e.g., motor skill) to design interventions to improve toddlers' PA levels. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Canadian Institutes of Health Research (CIHR; funding reference numbers PJT-152877 and FBD-187487). SKD was supported by a CIHR postdoctoral fellowship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Hamilton integrated Research Ethics Board gave ethical approval for this work (HiREB #3674). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Context:To understand energy balance, whole-room indirect calorimetry (WRIC) allows for accurate measurement of energy expenditure (EE). Objective:To examine the relationship between cold-induced resting EE and brown adipose tissue (BAT) activity measured by magnetic resonance imaging (MRI) and to evaluate WRIC system (WRICS) performance and feasibility of use in children and adults. Methods:The WRICS was equipped with a Promethion High-Definition Room Calorimetry System. Technical validation utilized nitrogen (N2) and carbon dioxide (CO2) gas infusions. Healthy adults (n = 21) and children aged 8-17 years (n = 17) attended two 4-hour WRIC visits (one week apart) and one MRI visit. Resting EE at 25 °C (REE25) was compared between visits and to REE at 18 °C (REE18). Recruitment and completion rates were examined. BAT activity was assessed by MRI as the decline in supraclavicular proton density fat fraction during 18 °C cold exposure. Results:Gas infusion testing confirmed high accuracy (respiratory exchange ratio [RER] = 0.99; 95% CI 0.991-0.996). Study completion rates were high (adults: 20/21; children: 17/18). REE25 over a 10-minute period was consistent between visits (adults: 1.68 ± 0.462 vs 1.66 ± 0.301 kcal/min, P = 0.77; children: 1.50 ± 0.358 vs 1.58 ± 0.348 kcal/min, P = .25). Cold exposure increased fasting EE by 0.21 kcal/min (adults) and 0.14 kcal/min (children). BAT activity was correlated with REE18 in adults (r = 0.49, P = .04). Conclusion:WRICS use was feasible in adults and children. Changes in EE during cold (ie, cold-induced thermogenesis) were measurable and related to BAT activity, supporting the usefulness of this system in the assessment of EE in response to interventions in adults and children.

Atherosclerosis begins in youth and is directly linked to the presence and severity of cardiovascular risk factors, including dyslipidemia. Timely identification and management of dyslipidemia in childhood can slow atherosclerotic progression and decrease risk for future cardiovascular disease, especially in children with a genetic disorder predisposing to dyslipidemia (e.g., familial hypercholesterolemia, which is frequently undiagnosed). Existing screening strategies can identify cases of paediatric dyslipidemia effectively but should be conducted both earlier and more broadly. Evaluating for secondary causes of dyslipidemia in children, including medication use and systemic disorders, is essential. First-line therapy centres on lifestyle modifications and dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and assessment for cardiovascular risk on an individual basis.

Résumé L’athérosclérose, qui se manifeste pendant l’enfance, est directement liée à la présence et à la gravité des facteurs de risque cardiovasculaires, y compris la dyslipidémie. La détection et la prise en charge rapides de la dyslipidémie pendant l’enfance peuvent ralentir l’évolution de l’athérosclérose et réduire le risque de future maladie cardiovasculaire, particulièrement chez les enfants atteints d’un trouble génétique qui les prédispose à la dyslipidémie (p. ex., l’hypercholestérolémie familiale qui, souvent, demeure non diagnostiquée). Les stratégies de dépistage existantes peuvent permettre de détecter les cas de dyslipidémie avec efficacité en pédiatrie, mais devraient être à la fois plus globales et adoptées plus tôt. Il est essentiel d’évaluer les causes secondaires de la dyslipidémie chez les enfants, y compris la prise de médicaments et les troubles systémiques. Les traitements de première ligne sont axés sur les modifications au mode de vie et à l’alimentation en fonction du phénotype de la dyslipidémie. Les indications relatives à la médication dépendent de la gravité de la dyslipidémie et de l’évaluation du risque cardiovasculaire individuel.

BACKGROUND:Obesity is a complex, chronic, stigmatized disease whereby abnormal or excess body fat may impair health or increase the risk of medical complications, and can reduce quality of life and shorten lifespan in children and families. We developed this guideline to provide evidence-based recommendations on options for managing pediatric obesity that support shared decision-making among children living with obesity, their families, and their health care providers. METHODS:We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We used the Guidelines International Network principles to manage competing interests. Caregivers, health care providers, and people living with obesity participated throughout the guideline development process, which optimized relevance. We surveyed end users (caregivers, health care providers) to prioritize health outcomes, completed 3 scoping reviews (2 on minimal important difference estimates; 1 on clinical assessment), performed 1 systematic review to characterize families' values and preferences, and conducted 3 systematic reviews and meta-analyses to examine the benefits and harms of behavioural and psychological, pharmacologic, and surgical interventions for managing obesity in children. Guideline panellists developed recommendations focused on an individualized approach to care by using the GRADE evidence-to-decision framework, incorporating values and preferences of children living with obesity and their caregivers. RECOMMENDATIONS:Our guideline includes 10 recommendations and 9 good practice statements for managing obesity in children. Managing pediatric obesity should be guided by a comprehensive child and family assessment based on our good practice statements. Behavioural and psychological interventions, particularly multicomponent interventions (strong recommendation, very low to moderate certainty), should form the foundation of care, with tailored therapy and support using shared decision-making based on the potential benefits, harms, certainty of evidence, and values and preferences of children and families. Pharmacologic and surgical interventions should be considered (conditional recommendation, low to moderate certainty) as therapeutic options based on availability, feasibility, and acceptability, and guided by shared decision-making between health care providers and families. INTERPRETATION:This guideline will support children, families, and health care providers to have informed discussions about the balance of benefits and harms for available obesity management interventions to support value- and preference-sensitive decision-making.

Psychological stress changes both behaviour and metabolism to protect organisms. Adrenaline is an important driver of this response. Anxiety correlates with circulating free fatty acid levels and can be alleviated by a peripherally restricted β-blocker, suggesting a peripheral signal linking metabolism with behaviour. Here we show that adrenaline, the β3 agonist CL316,243 and acute restraint stress induce growth differentiation factor 15 (GDF15) secretion in white adipose tissue of mice. Genetic inhibition of adipose triglyceride lipase or genetic deletion of β-adrenergic receptors blocks β-adrenergic-induced increases in GDF15. Increases in circulating GDF15 require lipolysis-induced free fatty acid stimulation of M2-like macrophages within white adipose tissue. Anxiety-like behaviour elicited by adrenaline or restraint stress is eliminated in mice lacking the GDF15 receptor GFRAL. These data provide molecular insights into the mechanisms linking metabolism and behaviour and suggest that inhibition of GDF15–GFRAL signalling might reduce acute anxiety. Anxiety-like behaviour in mice, as a result of psychological stress, is shown to be mediated by GDF15 release in response to adipose tissue lipolysis.

GLP1R-based obesity therapies can reduce lean muscle and energy expenditure via adaptive thermogenesis (also known as metabolic adaptation), leading to weight plateaus and regain. Defining the role of muscle energy expenditure in mediating these effects is critical to improving next-generation treatments and sustaining long-term weight loss.

INTRODUCTION:Childhood obesity is a public health concern. Studies have investigated the effects of metal mixtures on childhood obesity but none have identified periods of heightened susceptibility of exposure. We identified the periods by investigating the association of metal mixture, measured at four time points, with adiposity. MATERIALS AND METHODS:Using data from the Maternal-Infant Research on Environmental Chemicals Research Platform, we included 234 child-parent pairs. We measured whole blood metal concentrations during the first and third trimesters, early and late childhood. Outcomes were late childhood body mass index z-score (zBMI), body fat percentage (%BF) and waist circumference z-score (zWC). We used treed distributed lag mixture models (TDLMM) to investigate associations between metal mixture and adiposity. We also investigated associations using linear regression and conducted sex-specific analysis. RESULTS:Among females, arsenic was positively associated with zBMI and zWC. Regression results show that each doubling in third trimester arsenic concentrations was associated with 0.16 (95% CI: 0.02, 0.31) and 0.13 (95% CI: 0.01, 0.25) increase in zBMI and zWC, respectively. TDLMM results were similar but attenuated. We also observed negative associations between third trimester cadmium and zWC, null associations between other metals and adiposity and among males and no metal interactions. CONCLUSION:Third trimester is a period of heightened susceptibility to obesogenic effects of arsenic exposure in females.

OBJECTIVE:Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of behavioural and psychological interventions for managing paediatric obesity. METHODS:Eligible studies, published between 1985 and 2022, included 0 to 18 year olds with outcomes reported ≥3 months post-baseline, including patient-reported outcome measures (PROMs), cardiometabolic and anthropometric outcomes, and adverse events (AEs). We pooled data using a random effects model and assessed certainty of evidence (CoE) related to minimally important difference estimates for outcomes using GRADE. RESULTS:We included 73 unique RCTs (n = 6305 participants, 53% female). Intervention types included physical activity (n = 1437), nutrition (n = 447), psychological (n = 1336), technology-based (n = 901) or multicomponent (≥2 intervention types, n = 2184). Physical activity had a small effect on health-related quality of life (HRQoL), varying effects ranging from moderate to very large on blood pressure, lipids and insulin resistance, and a small effect on BMIz. Nutrition had a small effect on lipids, insulin resistance and BMIz. Psychological interventions showed a small effect on HRQoL and triglycerides and moderate benefits on depressive symptoms, while technology interventions showed small benefits on blood pressure and BMIz. Multicomponent interventions had a large benefit on anxiety, small benefit on depressive symptoms, with large to very large benefits on lipids, and small benefits for diastolic blood pressure, insulin resistance and BMIz. AEs were reported infrequently, and when reported, were described as mild. CONCLUSION:Physical activity and multicomponent interventions showed improvements in PROMs, cardiometabolic and anthropometric outcomes. Future trials should consistently measure PROMs, evaluate outcomes beyond the intervention period, and study children <6 years of age.

Studies on prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and cardiometabolic health in childhood have produced inconsistent results. In this study, we evaluated associations between prenatal PFAS exposures, individually and as a mixture, and cardiometabolic outcomes including insulin resistance, beta cell function, blood lipids, blood pressure and central adiposity during middle childhood (7-9 years of age) in a Canadian maternal-child cohort (n = 281). We also explored effect measure modification based on child sex and physical activity. We quantified maternal second trimester plasma concentrations of six PFAS and measured 11 offspring cardiometabolic outcomes at a 7-9-year follow-up. In single-exposure models, ten-fold higher prenatal PFDA (β: -0.82, 95% CI: -1.36, -0.28), PFNA (β: -0.8, 95% CI: -1.41, -0.19), and PFOA (β: -0.69, 95% CI: -1.18, -0.19) concentrations were associated with lower diastolic blood pressure z-scores. This association did not persist when considering PFAS exposures as a mixture using quantile g-computation. Associations between PFAS exposures, individually or as a mixture, and other cardiometabolic outcomes were null. We observed no effect measure modification by child sex or physical activity (p-values for interaction ≥0.2). Our results contradict existing studies that suggest prenatal PFAS exposures are associated with adverse childhood cardiometabolic outcomes. Future studies should consider alternative markers of cardiometabolic health, trajectories in cardiometabolic health throughout childhood, and further explore potentially protective health behaviors.

Contexte L'ob & eacute;sit & eacute; est une maladie chronique complexe et stigmatisante caract & eacute;ris & eacute;e par une accumulation anormale ou excessive de graisse corporelle susceptible de nuire & agrave; la sant & eacute;, d'accro & icirc;tre le risque de complications m & eacute;dicales et de r & eacute;duire l'esp & eacute;rance de vie des enfants, leur qualit & eacute; de vie ainsi que celle de leur famille. Ce guide de pratique clinique a donc & eacute;t & eacute; & eacute;labor & eacute; afin de proposer des recommandations fond & eacute;es sur des donn & eacute;es probantes quant aux options de prise en charge de l'ob & eacute;sit & eacute; p & eacute;diatrique et ce, afin de soutenir une prise de d & eacute;cision partag & eacute;e entre les enfants concern & eacute;s, leur famille et les professionnels de la sant & eacute;.M & eacute;thodes Nous avons utilis & eacute; le syst & egrave;me GRADE (Grading of Recommendations, Assessment, Development and Evaluation) d'& eacute;valuation des donn & eacute;es probantes pour l'& eacute;laboration et la classification des recommandations. Nous avons & eacute;galement appliqu & eacute; les principes du Guidelines International Network pour g & eacute;rer les conflits d'int & eacute;r & ecirc;ts. Pour optimiser la pertinence et l'applicabilit & eacute; des recommandations, des parents/tutrices ou tuteurs, des prestataires de soins de sant & eacute; et des personnes vivant avec l'ob & eacute;sit & eacute; ont & eacute;t & eacute; impliqu & eacute;s tout au long du processus d'& eacute;laboration du guide de pratique clinique. Nous avons r & eacute;alis & eacute; un sondage aupr & egrave;s d'utilisatrices et d'utilisateurs primaires (parents/tutrices ou tuteurs et prestataires de soins de sant & eacute;) pour hi & eacute;rarchiser les indicateurs de sant & eacute;. Nous avons effectu & eacute; 3 & eacute;tudes de port & eacute;e (2 sur les estimations des diff & eacute;rences minimales importantes et 1 sur l'& eacute;valuation clinique). Nous avons r & eacute;alis & eacute; 1 revue syst & eacute;matique pour caract & eacute;riser les valeurs et les pr & eacute;f & eacute;rences des familles. Nous avons effectu & eacute; 3 revues syst & eacute;matiques et m & eacute;ta-analyses pour examiner les effets b & eacute;n & eacute;fiques et ind & eacute;sirables des interventions comportementales et psychologiques, pharmacologiques et chirurgicales dans la prise en charge de l'ob & eacute;sit & eacute; chez les enfants. Les membres du panel ont formul & eacute; des recommandations ax & eacute;es sur une approche individualis & eacute;e des soins, en utilisant le syst & egrave;me GRADE pour la prise de d & eacute;cision fond & eacute;e sur les donn & eacute;es probantes. Ils ont aussi tenu compte des valeurs et des pr & eacute;f & eacute;rences des enfants vivant avec l'ob & eacute;sit & eacute; et de leur famille.Recommandations Notre guide de pratique clinique comporte 10 recommandations et 9 & eacute;nonc & eacute;s de bonnes pratiques pour la prise en charge de l'ob & eacute;sit & eacute; chez l'enfant. La prise en charge de l'ob & eacute;sit & eacute; p & eacute;diatrique doit & ecirc;tre guid & eacute;e par une & eacute;valuation exhaustive de l'enfant et de sa famille, en fonction de nos & eacute;nonc & eacute;s de bonnes pratiques. Les interventions comportementales et psychologiques, et en particulier les interventions multimodales (forte recommandation, certitude tr & egrave;s faible & agrave; mod & eacute;r & eacute;e), doivent constituer la base des soins, avec des traitements et du soutien sur mesure s & eacute;lectionn & eacute;s de mani & egrave;re conjointe en fonction des effets b & eacute;n & eacute;fiques et ind & eacute;sirables potentiels, du degr & eacute; de certitude & agrave; l'& eacute;gard des donn & eacute;es probantes et des valeurs et pr & eacute;f & eacute;rences de l'enfant et de sa famille. Les interventions pharmacologiques et chirurgicales doivent & ecirc;tre consid & eacute;r & eacute;es (recommandation conditionnelle, certitude faible & agrave; mod & eacute;r & eacute;e) comme des options th & eacute;rapeutiques selon leur accessibilit & eacute;, faisabilit & eacute; et acceptabilit & eacute;, et guid & eacute;es par une prise de d & eacute;cision partag & eacute;e entre les prestataires de soins de sant & eacute; et les familles.Interpr & eacute;tation Ce guide de pratique clinique aidera les enfants, les familles et les professionnels de la sant & eacute; & agrave; avoir des discussions & eacute;clair & eacute;es sur l'& eacute;quilibre entre les b & eacute;n & eacute;fices et les risques des interventions disponibles pour la prise en charge de l'ob & eacute;sit & eacute;, afin de soutenir une prise de d & eacute;cision fond & eacute;e sur les valeurs et les pr & eacute;f & eacute;rences des enfants et leur famille.

Obesity and diabetes are interlinked diseases, but it was unclear how obesity vs. diabetes modifies the risk and severity of gut bacterial infection. We aimed to determine how obesity or hyperglycemia, indicative of diabetes, altered metabolic endotoxemia and severity of enteric infection. Metabolic endotoxemia was determined using TLR4 activity reporter assay in serum from humans with obesity or diabetes, and from hyperglycemic Akita+/- mice and genetically obese ob/ob mice. Diarrhea severity during Escherichia coli infection was determined in humans during a previous community outbreak. The enteropathogen Citrobacter rodentium was used to define the mechanisms of action that altered the severity of enteric infection in ob/ob and Akita+/- mice. We found that elevated blood glucose, indicative of diabetes, was associated with increased occurrence and severity of diarrhea during an E. coli outbreak in humans. Metabolic endotoxemia occurred in a separate cohort of people with obesity who were normoglycemic or hyperglycemic, and in mice with either obesity or hyperglycemia. Hyperglycemia, not obesity, increased mortality during infection with the diarrhea-causing pathogen C. rodentium in mouse models of type 1 and type 2 diabetes. Common indicators of poor prognosis, such as gut pathology, systemic bacteraemia, or metabolic endotoxemia, did not predict worse outcomes during enteric infection in diabetic mice. Hyperglycemia activated intestinal Wnt/β-catenin and increased mortality, which could be reversed by blocking Wnt/β-catenin, lowering blood glucose, or restoring fluid balance during infection. The increased severity of infection via overactivation of intestinal Wnt/β-catenin during hyperglycemia may be a potential target for therapeutics.NEW & NOTEWORTHY We show that elevated blood glucose is associated with worse diarrhea during an Escherichia coli outbreak in humans. Obesity or hyperglycemia was sufficient to promote metabolic endotoxemia in humans and mice. Hyperglycemia promotes worse enteric infection outcomes independent of obesity. Finally, we showed that blocking of Wnt/β-catenin, lowering blood glucose, or restoring fluids improved enteric infection outcomes in hyperglycemic mice.