Search

Extremely low birth weight (ELBW) survivors have higher rates of shyness, a risk factor for poorer outcomes across the life span. Due to advances in fetal and neonatal medicine, the first generation of ELBW survivors have survived to adulthood and become parents. However, no studies have investigated the transmission of their stress vulnerability to their offspring. We explored this phenomenon using a population-based cohort of ELBW survivors and normal birth weight (NBW) controls. Using data from three generations, we examined whether the shyness and parenting stress of ELBW and NBW participants (Generation 2) mediated the relation between the parenting style of their parents (Generation 1) and shyness in their offspring (Generation 3), and the extent to which exposure to perinatal adversity (Generation 2) moderated this mediating effect. We found that among ELBW survivors, parenting stress (in Generation 2) mediated the relation between overprotective parenting style in Generation 1 (grandparents) and child shyness in Generation 3. These findings suggest that perinatal adversity and stress may be transmitted to the next generation in humans, as reflected in their perceptions of their children as shy and socially anxious, a personality phenotype that may subsequently place their children at risk of later mental and physical health problems.

Background: The prevalence of overweight and obesity remains high in Canada, and the current standard for the treatment of childhood obesity is in-person, family-based, multidisciplinary interventions that target lifestyle behaviors (e.g., diet, physical activity, and sedentary behaviors). These programs are costly to operate, have limited success, and report recruitment and retention challenges. With recent advances in technology, mobile health or mHealth has been presented as a viable alternative to in-person interventions for behavior change, especially with teens., Purpose: The primary aim of this study is to test the efficacy of Aim2Be, a gamified app based on behavior change theory with health coaching to improve weight outcomes (i.e., decrease in standardized body mass index (zBMI)) and lifestyle behaviors (i.e., improve dietary quality, increase fruit and vegetable intake, reduce sugar-sweetened beverage intake, increase physical activity, and reduce screen time) among children 10- to 17-years old with overweight or obesity versus their peers randomized into a waitlist control condition. The secondary aims of this study are to 1) test whether supplementing the Aim2Be program with health coaching increases adherence and 2) examine the mediators and moderators of adherence to the Aim2Be intervention., Methods: We will employ a randomized controlled trial design and recruit 200 child and parent dyads to participate in the study (2019-2020). Participants will be recruited from Canadian pediatric weight management clinics and through online advertisements. Child participants must be between the ages of 10 and 17 years, have overweight or obesity, be able to read English at least at a grade 5 level, and have a mobile phone or home computer with internet access. Following baseline data collection, participants will be randomized into intervention and waitlist control groups. Intervention participants will receive access to Aim2Be, with access to health coaching. After having their data collected for 3 months, the control group will gain access to Aim2Be, with no access to health coaching. Participants will control their frequency and duration of app usage to promote autonomy., Discussion: Findings from this study will determine the efficacy of using Aim2Be in improving child weight outcomes and lifestyle behaviors and guide future mHealth interventions for pediatric weight management., Trial Registration: ClinicalTrials.gov, NCT03651284. Registered 29 August 2018.

Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1 -/- mast cells or selective mast cell deletion of Tph1 enhances uncoupling protein 1 (Ucp1) expression in white adipose tissue and protects mice from developing obesity and insulin resistance. These data suggest that therapies aimed at inhibiting mast cell Tph1 may represent a therapeutic approach for the treatment of obesity and type 2 diabetes.

To optimize infant nutrition, the nature of weight gain must be analyzed. This study aims to review publications and develop growth charts for fat and fat-free mass for preterm and term infants. Body composition data measured by air displacement plethysmography (ADP) and dual energy X-ray absorptiometry (DXA) in preterm and term infants until six months corrected age were abstracted from publications (31 December 1990 to 30 April 2019). Age-specific percentiles were calculated. ADP measurements were used in 110 studies (2855 preterm and 22,410 term infants), and DXA was used in 28 studies (1147 preterm and 3542 term infants). At term age, preterm infants had higher percent-fat than term-born infants (16% vs. 11%, p < 0.001). At 52 weeks postmenstrual age (PMA), both reached similar percent-fat (24% vs. 25%). In contrast, at term age, preterm infants had less fat-free mass (2500 g vs. 2900 g) by 400 g. This difference decreased to 250 g by 52 weeks, and to 100 g at 60 weeks PMA (5000 g vs. 5100 g). DXA fat-free mass data were comparable with ADP. However, median percent-fat was up to 5% higher with DXA measurements compared with ADP with PMA > 50 weeks. There are methodological differences between ADP and DXA measures for infants with higher fat mass. The cause of higher fat mass in preterm infants at term age needs further investigation., Competing Interests: The authors declare no conflict of interest.

Background: Despite recent declines in consumption of sugary beverages, energy drinks (ED) and sodas continue to contribute a substantial amount of sugar and caffeine to the diet of youth. Consumption of these beverages has been linked with electronic device use, however in-depth associations between sugar and caffeine intake from energy drinks and sodas with various electronic devices are not clear., Objective: Describe the relationship of soda and energy drink consumption and associated added sugar and caffeine intake with electronic device use among adolescents., Methods: Secondary data from the 2013-2016 cycles of Monitoring the Future Survey, a national, repeated, cross-sectional study, were analyzed. Information on energy drink and soda consumption by students in grades 8 and 10 (n = 32,418) from 252-263 schools randomly sampled from all US states was used., Results: Soda and energy drink consumption decreased each year from 2013-2016 while daily use of electronic devices remained stable. An additional hour/day of TV was linked to a 6.92g (6.31,7.48; p<0.001) increase in sugar intake and a 32% (OR = 1.32; 1.29,1.35; p < .001) higher risk of exceeding World Health Organization (WHO) recommended sugar intakes. Further, each hour/day of TV was linked to a 28% increased risk of exceeding caffeine recommendations (OR = 1.25-1.31; p<0.001). Each hour per day talking on a cellphone was associated with an increased risk of exceeding WHO sugar and caffeine intakes by 14% (OR = 1.11-1.16; p<0.001) and 18% (OR = 1.15-1.21; p<0.001) respectively. Video game use was only weakly linked to caffeine intake. Computer use for school was associated with lower likelihood of exceeding sugar intake cut-offs., Conclusion: While a trend towards reduced energy drink and soda intake from 2013-2016 was evident, greater electronic device use, especially TV time, was linked to higher intake of beverage-derived added sugar and caffeine amongst adolescents. Addressing these behaviours through counselling or health promotion could potentially help to reduce excess sugar and caffeine intake from sodas and energy drinks among this population., Competing Interests: The authors have declared that no competing interests exist.

Context: In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined., Objective: To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV ( i.e., BAT depot) and fat in the posterior neck region ( i.e., non-BAT)., Design: Cross-sectional., Setting: Clinical research center., Patients or Other Participants: Twelve healthy male volunteers aged 18 to 29 years [body mass index = 24.7 ± 2.8 kg/m 2 and body fat percentage = 25.0% ± 7.4% (both, mean ± SD)]., Interventions: Standardized whole-body cold exposure (180 minutes at 18°C) and immediate rewarming (30 minutes at 32°C)., Main Outcome Measures: Proton density fat fraction (PDFF) and T2* of the SCV and posterior neck fat pads. Acquisitions occurred at 5- to 15-minute intervals during cooling and subsequent warming., Results: SCV PDFF declined significantly after only 10 minutes of cold exposure [-1.6% (SE: 0.44%; P = 0.007)] and continued to decline until 35 minutes, after which time it remained stable until 180 minutes. A similar time course was also observed for SCV T2*. In the posterior neck fat (non-BAT), there were no cold-induced changes in PDFF or T2*. Rewarming did not result in a change in SCV PDFF or T2*., Conclusions: The rapid cold-induced decline in SCV PDFF suggests that in humans BAT is activated quickly in response to cold and that TAG is a primary substrate., (Copyright © 2019 Endocrine Society.)

Purpose/aim: Antenatal corticosteroid (ACS) therapy has dramatically increased survival rates among extremely low birth weight (ELBW) infants. However, the long-term effects of ACS on autonomic nervous system function have not been explored. Using the world's oldest longitudinally followed cohort of ELBW infants we compared respiratory sinus arrhythmia (RSA) among ELBW survivors whose mothers received ACS (ELBW-S), those who did not (ELBW-NS) and normal birth weight (NBW) controls in their 20 and 30 s. Methods: Resting electrocardiogram (ECG) was recorded from ELBW-S ( n  = 28), ELBW-NS ( n  = 36), and matched NBW controls ( n  = 79) at 22-26 and 29-36 years. Resting RSA was compared across groups via analyses of covariance (ANCOVA), adjusting for sex, medication use, postnatal steroid exposure and the presence of chronic health conditions. RSA was also compared across assessments for each group. Results: At 29-36 years, resting RSA in ELBW-S was significantly lower than in NBW controls. RSA in the ELBW-NS group was intermediate between ELBW-S and NBW groups. Although the ELBW-S group also showed nominally reduced RSA compared to NBW controls at the 22-26-year visit, this difference was not statistically significant. Conclusions: ELBW survivors exposed to ACS had lower RSA than NBW controls during their 30 s, suggestive of a decline in parasympathetic input to heart. ELBW survivors who received ACS may be particularly vulnerable to cardiovascular problems in later life.

Background: Childhood obesity is a world-wide concern due to its growing prevalence and association with cardiometabolic risk factors in childhood and subsequent adult cardiovascular disease. In young pre-school children, there is uncertainty regarding which of the commonly used anthropometric measures of childhood obesity is best associated with cardiometabolic risk factors. This study compared the utility of common measures used in identifying obesity in these young children., Methods: The four commonly used metrics for identifying obesity in children: body fat percentage ≥ 90th percentile, waist circumference ≥ 90th percentile, BMI z score > 2 SD and waist-to-height ratio (WHtR) ≥ 0.5, were measured in a cohort of children born singleton, at full term and followed from birth (n = 761) to 5 years of age (n = 513). The utility of each in identifying cardiometabolic risk factors (fasting lipid profile, fasting blood glucose and blood pressure) was examined., Results: At age 5 years, children with percent body fat ≥ 90th percentile or waist circumference ≥ 90th percentile, were associated with higher levels of triglycerides, glucose, and systolic and diastolic blood pressures than those < 90th percentile, respectively. Such differences were not obvious at age 3 years or at birth. A BMI z-score > 2 SD was associated with higher levels of triglycerides and systolic and diastolic blood pressure but not glucose at age 5 years. Differences in HDL cholesterol, fasting glucose and systolic blood pressure were observed in children with BMI z score > 2 SD at age 3 years but not with the other indices of obesity. As almost all children had WHtR ≥ 0.5 at birth, ages 1 and 3 years, this measure could not differentiate increased cardiometabolic risk. At age 5 years, the differences were much more obvious, with significant differences in triglycerides and systolic and diastolic blood pressures between those with WHtR ≥ 0.5 and those with < 0.5., Conclusion: Each of the four commonly used measures of childhood obesity shows moderate associations with cardiometabolic risk factors at 5 years, with no advantage of one measure over the other. These associations were less consistent at 3 years of age or younger. These observations have not been reported previously., Competing Interests: The authors have declared that no competing interests exist.

Although prolonged engagement in paediatric weight management (PWM) is associated with positive treatment outcomes, little is currently known about enablers of long-term programme attendance. The purpose of our study was to explore families' reasons for and facilitators of their continued attendance at health services for PWM. Semi-structured, individual interviews were conducted with parents of children (10-17 year old; body mass index ≥85th percentile) who completed the active phase of treatment in one of four Canadian multidisciplinary clinics for PWM. Interview data were recorded digitally, transcribed verbatim and analysed thematically. Parents' (n = 40) reasons for continued clinic attendance included ongoing concerns (eg, parental concern about their child's health), actual and expected benefits from treatment (eg, lifestyle improvements) and perceived quality of care (eg, structured, comprehensive, tailored health services). Several logistical and motivational factors contributed to continued attendance, including flexible work schedules, flexible appointment times, financial resources and children's motivation for treatment. Helping families address treatment barriers and ensuring that weight management services meet families' treatment expectations are promising strategies to enhance retention in PWM to optimize health outcomes., (© 2019 World Obesity Federation.)

Background: Disease severity in paediatric obesity is usually defined using the body-mass index (BMI). Although informative at the population level, its usefulness on an individual level has limitations. The use of a clinical staging system-Edmonton Obesity Staging System for Pediatrics (EOSS-P)-in identifying health risk has been proposed. This study aimed to examine the association between BMI class and EOSS-P stage., Methods: This cross-sectional study was done in children with obesity aged 5-17 years who enrolled in the Canadian Pediatric Weight Management Registry (CANPWR) between May 31, 2013, and Oct 27, 2017, involving ten multidisciplinary paediatric weight management clinics in Canada. We classified participants into WHO BMI classes (class I as 2-3 SD scores, class II as >3 SD scores, and class III as >4 SD scores above the WHO growth standard median), and applied the EOSS-P staging system (stages 0, 1, and 2/3) based on the clinical assessment of coexisting metabolic, mechanical, mental health, and social milieu issues. Clinical information was extracted from medical records and reported using standardised case report forms. Associations of BMI class with EOSS-P stage were examined in children with complete data., Findings: Of the 847 children with complete data, 546 (64%) had severe obesity based on BMI class (ie, class II or III) and 678 (80%) were EOSS-P stage 2/3. Stage 2/3 obesity-related health issues were common; mental health concerns were most common (520 [61%] of 847 children), followed by metabolic (349 [41%] of 847 children), social milieu (179 [21%] of 847 children), and mechanical (86 [10%] of 847 children) health issues. Mental health issues (eg, anxiety and attention-deficit hyperactivity disorder) were equally distributed across BMI classes, metabolic health issues were slightly more common in higher BMI classes, and mechanical (eg, musculoskeletal issues and sleep apnoea) and social milieu (eg, bullying and low household income) issues increased with increasing BMI class. Of children with class I obesity, 206 (76%) of 270 had overall EOSS-P stage 2/3, compared with 195 (85%) of 229 with class III obesity., Interpretation: Physical and mental health issues were highly prevalent among children with obesity irrespective of BMI class. Participants with class III obesity carried the greatest health risk across subcategories of the EOSS-P. As BMI class increased, a concomitant increased disease burden in mechanical and social milieu issues was observed, whereas metabolic and mental health risks were high across BMI classes., Funding: Canadian Institutes of Health Research, Ontario Ministry of Health, McMaster University, and McMaster Children's Hospital., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Paediatric obesity management remains generalised to dietary and exercise modifications with an underappreciation for the contributions of eating behaviours and appetitive traits in the development of obesity., Objectives: To determine whether treatment-seeking children and adolescents with obesity cluster into phenotypes based on known eating behaviours and appetitive traits ("eating correlates") and how socio-demographic and clinical characteristics associate with different phenotypes., Methods: A cross-sectional, multi-centre questionnaire was administered between November 2015 and March 2017 examining correlates of eating in children and adolescents attending weight-management programmes in Canada. Latent profile analysis was used to cluster participants based on seven eating correlate scores obtained from questionnaires. Analysis of variance (ANOVA) was used to determine phenotype differences on socio-demographic and clinical characteristics. Multinomial logistic regression models assessed relative risk of specific characteristics associating with a disordered eating phenotype., Results: Participants were 247 children and adolescents (45.3% male, mean BMI z-score = 3.4 ± 1.0 kg/m 2 ) from six paediatric weight management centres in Canada. Seven eating correlates clustered into three distinct phenotypes: (1) loss of control eating, emotional eating, external eating, hyperphagia, impulsivity ("Mixed-Severe"; n = 42, 17%), (2) loss of control eating, emotional eating, external eating, hyperphagia ("Mixed-Moderate"; n = 138, 55.9%), and (3) impulsivity ("Impulsive"; n = 67; 27.1%). Social functioning scores and body esteem were significantly different across groups, with the Mixed-Severe participants having the poorest social functioning and lowest body esteem. Low body esteem indicated a greater risk of being in a multi-correlate group compared to the Impulsive group, while poor social function had a greater risk of clustering in the Mixed-Severe than Impulsive phenotype., Conclusions: Distinct eating phenotypes were found in treatment-seeking children and adolescents with obesity. Empirical evidence is needed, but these data suggest that tailored treatment approaches could be informed by these classifications to improve weight-management outcomes.

Objective: We sought to explore various correlates of blood pressure (BP) and hypertension, and to identify the most important aggregate combination of correlates for BP in South Asian children., Design: Cross-sectional study SETTING: Community-based recruitment in two Canadian cities PARTICIPANTS: South Asian children (n=762) provided a range of physiological, lifestyle and social variables. BP was assessed using an automated device. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and BP were transformed to z-scores using published standards., Outcome Measures: Linear and logistic regression analyses were used to explore associations between the range of variables with BP z-scores and hypertension while stepwise regression was used to identify aggregate factors that provided explanatory capacity for systolic BP (SBP) and diastolic BP (DBP) z-scores., Results: A range of variables were associated with BP z-score and hypertension in unadjusted analysis. On adjustment for confounders, the association between age (β=-0.054, 95% CI=-0.078 to 0.029), female sex (β=-0.208, 95% CI=-0.350 to -0.067), height (β=0.022, 95% CI=0.011 to 0.033), weight (β=0.047, 95% CI=0.040 to 0.055), BMI z-score (β=0.292, 95% CI=0.249 to 0.336), WC z-score (β=0.273, 95% CI=0.219 to 0.326), WHtR z-score (β=0.289, 95% CI=0.236 to 0.342), heart rate (β=0.016, 95% CI=0.010 to 0.022), child's perception of body image (β=0.183, 95% CI=0.128 to 0.239) and grip strength (β=0.025, 95% CI=0.007 to 0.043) with SBP z-score remained. In stepwise regression, age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of SBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the DBP z-score variance., Conclusion: Our findings suggest that variables, such as age, sex, height, adiposity and heart rate, provide stronger explanatory capacity to BP variance and hypertension risk than other variables in South Asian children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Given the South Asian phenotype of higher body fat at similar body mass index (BMI) relative to Caucasians, we sought to explore the association between prominent adiposity indicators with blood pressure (BP) and hypertension, to compare the accuracy of these indicators in estimating hypertension, and to provide cut-off values associated with adverse hypertension risk in South Asian children., Design: Cross-sectional study., Setting: Community-based recruitment in two Canadian cities (Hamilton and Surrey)., Participants: South Asian children (n=762) were recruited from two Canadian cities. Waist circumference, waist to height ratio and BMI were determined. Body fat percentage was assessed by bioelectrical impedance analysis and BP was assessed using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards., Outcome Measures: Linear and Poisson regression was used to explore associations between the adiposity indicators with BP z-score and hypertension. Receiver operating curve (ROC) analysis was used to explore the strength of the adiposity indicators in estimating hypertension risk and sex-stratified optimal adiposity cut-off values associated with hypertension risk., Results: Significant associations were detected in adjusted and unadjusted models between the adiposity indicators with BP z-score and hypertension (p<0.01 for all). The area under the curve (AUC) values for the adiposity indicators for boys and girls ranged from 0.74 to 0.80, suggesting that the adiposity indicators are fair measures of estimating hypertension risk. Sex-stratified cut-off associated with adverse risk of hypertension for girls and boys, respectively, were at the 92nd and 82nd percentile for BMI z-scores, 65th and 80th percentile for WC z-score, 63rd and 67th percentile for WHtR z-score and at 29.8% and 23.5% for body fat., Conclusion: Our results show associations between adiposity indicators with BP and hypertension and suggests that South Asian children might be at adverse risk of hypertension at levels of adiposity considered normal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Various aspects of human cytomegalovirus (HCMV) pathogenesis, including its ability to replicate in specific cells and tissues and the mechanism(s) of horizontal transmission, are not well understood, predominantly because of the strict species specificity exhibited by HCMV. Murine CMV (MCMV), which contains numerous gene segments highly similar to those of HCMV, has been useful for modeling some aspects of CMV pathogenesis; however, it remains essential to build relevant human cell-based systems to investigate how the HCMV counterparts function. The salivary gland epithelium is a site of persistence for both human and murine cytomegaloviruses, and salivary secretions appear to play an important role in horizontal transmission. Therefore, it is important to understand how HCMV is replicating within the glandular epithelial cells so that it might be possible to therapeutically prevent transmission. In the present study, we describe the development of a salivary epithelial model derived from primary human "salispheres." Initial infection of these primary salivary cells with HCMV occurs in a manner similar to that reported for established epithelial lines, in that gH/gL/UL128/UL130/UL131A (pentamer)-positive strains can infect and replicate, while laboratory-adapted pentamer-null strains do not. However, while HCMV enters the lytic phase and produces virus in salivary epithelial cells, it fails to exhibit robust spread throughout the culture and persists in a low percentage of salivary cells. The present study demonstrates the utility of these primary tissue-derived cells for studying HCMV replication in salivary epithelial cells in vitro IMPORTANCE Human cytomegalovirus (HCMV) infects the majority of the world's population, and although it typically establishes a quiescent infection with little to no disease in most individuals, the virus is responsible for a variety of devastating sequelae in immunocompromised adults and in developing fetuses. Therefore, identifying the viral properties essential for replication, spread, and horizontal transmission is an important area of medical science. Our studies use novel human salivary gland-derived cellular models to investigate the molecular details by which HCMV replicates in salivary epithelial cells and provide insight into the mechanisms by which the virus persists in the salivary epithelium, where it gains access to fluids centrally important for horizontal transmission., (Copyright © 2019 American Society for Microbiology.)

Background: Individuals born extremely preterm are exposed to significant perinatal stresses that are associated with an increased risk of psychopathology. However, a paucity of longitudinal studies has prevented the empirical examination of long-term, dynamic effects of perinatal adversity on mental health. Here, internalizing and externalizing problems from adolescence through adulthood were compared in individuals born at extremely low birth weight (ELBW; <1,000 g) and normal birth weight (NBW; >2,500 g)., Methods: Internalizing and externalizing data were collected over 20 years in three waves, during adolescence, young adulthood, and adulthood. Growth models were used to compare longitudinal trajectories in a geographically based sample of 151 ELBW survivors and 137 NBW control participants born between 1977 and 1982 matched for age, sex, and socioeconomic status at age 8., Results: After adjusting for sex, socioeconomic and immigrant status, and family functioning, ELBW survivors failed to show the normative, age-related decline in internalizing problems over time relative to their NBW peers (β = .21; p < .01). Both groups exhibited small declines in externalizing problems over the same period. Self-esteem (but not physical health, IQ, or maternal mood) partially mediated the association between ELBW status and internalizing problems., Conclusions: Extremely low birth weight survivors experienced a blunting of the expected improvement in depression and anxiety from adolescence to adulthood. These findings suggest that altered physiological regulatory systems supporting emotional and cognitive processing may contribute to the maintenance of internalizing problems in this population., (© 2018 Association for Child and Adolescent Mental Health.)

Background: To address gaps in knowledge of the longitudinal trajectory of dysglycemia in children with obesity, this study aimed to: (1) describe the changes in glycemic status over 2 years; (2) establish a predictive model for development of prediabetes among children with euglycemia; and (3) evaluate the influence of change in body mass index (BMI) z-score on glycemic status., Methods: Children aged 5 to 17 years entered this prospective, longitudinal study at the time of entry to a weight management program. Measures included a 75-g oral glucose tolerance test (OGTT), fasting blood glucose, hemoglobin A1c (HbA1c), lipid profile, liver enzymes and anthropometric measures at baseline, 1 and 2 years. Cox proportional hazard was used to build a predictive model for prediabetes., Results: The cohort included 270 children, mean age: 11.6 ± 2.7 years and BMI z-score: 3.1. The baseline prevalence of prediabetes, based upon elevated 2-hour glucose in OGTT or HbA1c, was 100/270 (37.0%). Among children with prediabetes at baseline, 53 (53.0%) continued to have prediabetes over the following 2 years, 15 (15.0%) were euglycemic at 1 year and had prediabetes at 2 years, 20 (20.0%) became euglycemic and remained so. Change in BMI z-score predicted dysglycemic status at 2 years. Among those euglycemic at baseline, the incidence of prediabetes was 14 (8.2%) after 1 year, 20 (12.8%) at 2 years. Predictors of incident prediabetes were baseline BMI z-score; hazard ratio (HR): 1.72, 95th confidence interval (CI: 1.08, 2.74) and baseline HbA1c HR: 1.26, 95th CI (1.02-1.56) when controlling for age, family history of diabetes and sex., Conclusion: Prediabetes presents significant morbidity in children with obesity. Family-based lifestyle interventions might delay prediabetes progression., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is increasing recognition of the value of "real-world evidence" in evaluating health care services. Registry-based, observational studies conducted in clinical settings represent a relevant model to achieve this directive. Starting in 2010, we undertook a longitudinal, observational study (the CANadian Pediatric Weight management Registry [CANPWR]), which is embedded in 10 multidisciplinary, pediatric weight management clinics across Canada. The objective of this paper was to share the lessons our team learned from this multi-centre project., Methods: Data sources included a retrospective review of minutes from 120 teleconferences with research staff and investigators, notes taken during clinical site visits made by project leaders, information from quality control processes to ensure data accuracy and completeness, and a study-specific survey that was sent to all sites to solicit feedback from research team members (n = 9). Through an iterative process, the writing group identified key themes that surfaced during review of these information sources and final lessons learned were developed., Results: Several key lessons emerged from our research, including the (1) value of pilot studies and central research coordination, (2) need for effective and regular communication, (3) importance of consensus on determining outcome measures, (4) challenge of embedding research within clinical practice, and (5) difficulty in recruiting and retaining participants. The sites were, in spite of these challenges, enthusiastic about the benefits of participating in multi-centre collaborative studies., Conclusion: Despite some challenges, multi-centre observational studies embedded in pediatric weight management clinics are feasible and can contribute important, practical insights into the effectiveness of health services for managing pediatric obesity in real-world settings.

The capacity to match carbohydrate (CHO) oxidation with CHO availability (deemed metabolic flexibility (MetFlex)) may be important for type 2 diabetes prevention. In adults, impaired MetFlex is associated with insulin resistance (IR), which can be improved with as little as 7 days of exercise. Whether this occurs similarly in children is unknown. We hypothesized that 7 consecutive days of exercise would improve MetFlex and IR in children with obesity. Twelve children (8 boys, 4 girls) completed 2 study visits before (PRE) and 2 study visits after (POST) exercise training. At visit 1, fasting blood was collected, and anthropometry and maximal oxygen uptake were assessed. At visit 2, a 13 C-enriched CHO drink was ingested before exercise (3 × 20 min) at ∼59% maximal oxygen uptake. Exogenous CHO oxidative efficiency, used as a surrogate measurement of MetFlex, was calculated from breath samples. During training, participants alternated between continuous and high-intensity interval cycling sessions at home under supervision. In spite of good training adherence, there was no improvement in MetFlex (PRE: 20.7% ± 1.8%, POST: 18.9% ± 4.9%, p = 0.22) or homeostasis model assessment of insulin resistance (PRE: 8.7 ± 4.6, POST: 8.1 ± 6.0, p = 0.51). Future research should investigate exercise volume, sex, and pubertal effects on the early responsiveness of MetFlex to exercise therapy.

The activation of brown adipose tissue (BAT) is associated with reductions in circulating lipids and glucose in rodents and contributes to energy expenditure in humans indicating the potential therapeutic importance of targetting this tissue for the treatment of a variety of metabolic disorders. In order to evaluate the therapeutic potential of human BAT, a variety of methodologies for assessing the volume and metabolic activity of BAT are utilized. Cold exposure is often utilized to increase BAT activity but inconsistencies in the characteristics of the exposure protocols make it challenging to compare findings. The metabolic activity of BAT in response to cold exposure has most commonly been measured by static positron emission tomography of 18 F-fluorodeoxyglucose in combination with computed tomography ( 18 F-FDG PET-CT) imaging, but recent studies suggest that under some conditions this may not always reflect BAT thermogenic activity. Therefore, recent studies have used alternative positron emission tomography and computed tomography (PET-CT) imaging strategies and radiotracers that may offer important insights. In addition to PET-CT, there are numerous emerging techniques that may have utility for assessing BAT metabolic activity including magnetic resonance imaging (MRI), skin temperature measurements, near-infrared spectroscopy (NIRS) and contrast ultrasound (CU). In this review, we discuss and critically evaluate the various methodologies used to measure BAT metabolic activity in humans and provide a contemporary assessment of protocols which may be useful in interpreting research findings and guiding the development of future studies., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Children who are overweight and obese display lower physical activity levels than normal weight peers. Measures of weight status, perceived motor competence, and motor skill performance have been identified as potential correlates explaining this discrepancy. 1881 children (955 males; 926 females; 9.9 years) were assessed as part of the Physical Health Activity Study Team project. The age, habitual physical activity participation (PAP), body mass index (BMI), socioeconomic status (SES), motor performance (MP), and perceived athletic competence (PAC) of each child included were assessed. Gender-specific linear regression analyses (main effects model) were conducted to identify the percent variance in PAP explained by the following variables: BMI, MP, and PAC. For males, 18.3% of the variance in PAP was explained by BMI, MP, and PAC. PAC explained 17% of the variance, while MP, BMI, and SES only accounted for 0.6%, 0.7%, and 0.5%, respectively. PAC explained 17.5% of PAP variance in females; MP explained 0.8%. BMI, SES, and chronological age were not significant correlates of PAP in girls. An established repertoire of motor skill performance has been seen as a vehicle to PAP in children; however, this study indicates that PAC should not be overlooked in intervention strategies to promote increased PAP.

Although the developmental course of self-esteem has been examined in general population samples, there is a lack of research examining the trajectory of self-esteem in populations who experience unique developmental challenges. We compared the trajectory of self-esteem in extremely low birth weight (ELBW; <1000 grams) survivors and normal birth weight (NBW) controls from mid-adolescence through their early 30s. Self-esteem was reported during three follow-up periods (age 12-16, age 22-26, age 30-35). Adjusting for sex, chronic health problems, socioeconomic status, and social support, no difference was noted in self-esteem in the two groups in adolescence, but birth weight status predicted rate of change of self-esteem from adolescence to adulthood. The NBW controls showed the expected, normative increases in self-esteem from mid-adolescence to young adulthood, while ELBW individuals displayed stable, low levels of self-esteem into young adulthood. Our findings highlight that ELBW survivors may not experience the normative trajectory of self-esteem into young adulthood.

Existing methods for diagnosing diabetes and for identifying risk of diabetes development are completed under resting conditions and based on adult data. Studying additional methods to identify metabolic risk in children is warranted. Our objective was to examine the validity and reliability of a metabolic flexibility (MetFlex) test for screening glycemia and insulin resistance (IR) in children. We hypothesized higher MetFlex during exercise would be correlated with lower fasting glucose and homeostasis model assessment of insulin resistance (HOMA-IR) and higher whole body insulin sensitivity index (WBISI) and insulin secretion-sensitivity index-2 (ISSI-2). Thirty-four children with obesity (14 boys, 20 girls) attended two visits. At visit 1, an oral glucose tolerance test (OGTT) was followed by anthropometric and aerobic fitness (V̇o 2max ) assessments. Insulin and glucose during the OGTT were used to calculate HOMA-IR, WBISI, and ISSI-2. At visit 2, a 13 C-enriched carbohydrate drink was ingested before 60 min of exercise at 45% V̇o 2max . Breath measurements were collected to calculate area under the curve exogenous carbohydrate to measure MetFlex. Pearson's r correlation showed no significant association between MetFlex during exercise with fasting glucose ( r = -0.288, P = 0.110). MetFlex was associated with log-HOMA-IR ( r = -0.597, P = 0.024), log-WBISI ( r = 0.575, P = 0.051), and log-ISSI-2 ( r = 0.605, P = 0.037) in boys but not girls. When repeated ( n = 18), MetFlex was deemed a reliable test (intraclass correlation coefficient = 0.692). MetFlex during exercise was negatively associated with IR and β-cell function in boys. Further research is required to explore clinical utility of the MetFlex test and explain the lack of association in girls. NEW & NOTEWORTHY This study is the first to investigate the validity and reliability of a novel noninvasive metabolic flexibility (MetFlex) test for identifying insulin resistance in children with obesity. MetFlex was measured during exercise using [ 13 C]glucose stable isotope methodology. Findings showed that MetFlex was negatively associated with insulin resistance in boys but not in girls with obesity. Future work is required to investigate these sex differences. MetFlex test results were deemed reliable when repeated on a separate day.

Background: The genetic influence on child obesity has not been fully elucidated., Objective: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old., Methods: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed., Results: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10 -3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10 -3 and 5.08 × 10 -3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10 -6 and 3.75 × 10 -5 , respectively)., Conclusions: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs., (© 2016 World Obesity Federation.)

Objective: To explore parents' recommendations to enhance enrollment in multidisciplinary clinical care for managing pediatric obesity., Study Design: Data for this interpretative description study were collected through individual, semistructured interviews that were audiorecorded, transcribed verbatim, and analyzed thematically. Parents (n = 79) were recruited from 4 multidisciplinary weight management clinics in Canada located in Edmonton, Hamilton, Montreal, and Vancouver., Results: Most interviewed parents had children with obesity (body mass index ≥95th percentile; 84.2%), were female (87.3%), had postsecondary education (69.6%), and were white (75.9%). Parents' recommendations referred to enrollment opportunities, information about obesity services, motivation for treatment, and accessibility to obesity services. Specifically, parents recommended to increase referral options and follow-up contacts with families during the enrollment process, inform referring physicians and families about the availability and characteristics of obesity services, enhance families' motivation for treatment, prevent families from getting discouraged, make services more appealing to families, and address accessibility issues (eg, offering multiple options for appointment times, providing support for transportation)., Conclusions: Parents' recommendations support the need for family-centered approaches to enhance enrollment; however, their feasibility, acceptability, and effectiveness remain to be tested empirically., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Early life microbial colonization and succession is critically important to healthy development with impacts on metabolic and immunologic processes throughout life. A longitudinal prospective cohort was recruited from midwifery practices to include infants born at full term gestation to women with uncomplicated pregnancies. Here we compare bacterial community succession in infants born vaginally, with no exposure to antibiotics (n = 53), with infants who were exposed to intrapartum antibiotic prophylaxis (IAP) for Group B Streptococcus (GBS; n = 14), and infants born by C-section (n = 7). Molecular profiles  of the 16 S rRNA genes indicate that there is a delay in the expansion of Bifidobacterium, which was the dominate infant gut colonizer, over the first 12 weeks and a persistence of Escherichia when IAP for GBS exposure is present during vaginal labour. Longer duration of IAP exposure increased the magnitude of the effect on Bifidobacterium populations, suggesting a longer delay in microbial community maturation. As with prior studies, we found altered gut colonisation following C-section that included a notable lack of Bacteroidetes. This study found that exposure of infants to IAP for GBS during vaginal birth affected aspects of gut microbial ecology that, although dramatic at early time points, disappeared by 12 weeks of age in most infants.

Objective: Birth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Significant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight., Setting: Four multiethnic birth cohorts based in Canada (the NutriGen Alliance)., Participants: 3997 full-term mother-infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores-plant-based, Western and health-conscious-and birth weight data., Results: No associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=-67.6 g per 1-unit increase; P<0.001), and an interaction with non-white ethnicity and birth weight was observed. Ethnically stratified analyses demonstrated that among white Europeans, maternal consumption of a plant-based diet associated with lower birth weight (β=-65.9 g per 1-unit increase; P<0.001), increased risk of small-for-gestational age (SGA; OR=1.46; 95% CI 1.08 to 1.54;P=0.005) and reduced risk of large-for-gestational age (LGA; OR=0.71; 95% CI 0.53 to 0.95;P=0.02). Among South Asians, maternal consumption of a plant-based diet associated with a higher birth weight (β=+40.5 g per 1-unit increase; P=0.01), partially explained by cooked vegetable consumption., Conclusions: Maternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Previous genome wide association studies (GWAS) identified associations of multiple common variants with diastolic and systolic blood pressure traits in adults. However, the contribution of these loci to variations of blood pressure in early life is unclear. We assessed the child and parental contributions of 33 GWAS single-nucleotide polymorphisms (SNPs) for blood pressure in 1,525 participants (515 children, 406 mothers and 237 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) study followed-up for 5 years. Two genotype scores for systolic (29 SNPs) and diastolic (24 SNPs) blood pressure were built. Linear mixed-effect regressions showed significant association between rs1378942 in CSK and systolic blood pressure (β = 0.98±0.46, P = 3.4×10-2). The child genotype scores for diastolic and systolic blood pressure were not associated in children. Nominally significant parental genetic effects were found between the SNPs rs11191548 (CYP17A1) (paternal, β = 2.78±1.49, P = 6.1×10-2 for SBP and β = 3.60±1.24, P = 3.7×10-3 for DBP), rs17367504 (MTHFR) (paternal, β = 2.42±0.93, P = 9.3×10-3 for SBP and β = 1.89±0.80, P = 1.8×10-2 for DBP and maternal, β = -1.32±0.60, P = 2.9×10-2 and β = -1.97±0.77, P = 1.0×10-2, for SBP and DBP respectively) and child blood pressure. Our study supports the view that adult GWAS loci have a limited impact on blood pressure during the five first years of life. The parental genetic effects observed on blood pressure in children may suggest epigenetic mechanisms in the transmission of the risk of hypertension. Further replication is needed to confirm our results.

The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Infrared thermography is a promising way to quantify BAT; however, a standardized methodology has not been established. This study aims to establish a standardized and reproducible protocol to measure thermal response to cold in the supraclavicular area using thermographic imaging. In Phase 1, we compared the thermal response to 12 °C cold after acclimation at either 32 °C or room temperature using thermographic imaging. Repeatability of the 32 °C acclimation trial was studied in a second group in Phase 2. Phase 1 included 28 men (mean age 23.9 ± 5.9 y; mean BMI 25.2 ± 3.9 kg/m 2 ) and Phase 2 included 14 men (mean age 20.9 ± 2.4 y; mean BMI 23.6 ± 3.1 kg/m 2 ). The thermal response was greater after 32 °C than after room temperature acclimation (0.22 ± 0.19 vs 0.13 ± 0.17 °C, p = 0.05), was not related to outdoor temperature (r = -0.35, p = 0.07), did not correlate with supraclavicular fat (r = -0.26, p = 0.21) measured with dual-energy x-ray absorptiometry and was repeatable [ICC 0.69 (0.14-0.72)]. Acclimation at 32 °C followed by cold generates a reproducible change in supraclavicular skin temperature measurable by thermal imaging that may be indicative of BAT metabolic activity.

Introduction: The long allele of the DRD4 gene can confer different behavioral and emotional phenotypes depending upon environmental exposure, although the physiological changes underlying these phenotypes are not fully known. We sought to extend this work by assessing the interaction of the DRD4 gene and exposure to perinatal adversity (indexed by extremely low birth weight [ELBW]) on resting respiratory sinus arrhythmia (RSA), a neurophysiological measure of emotion regulation, in adulthood., Methods: We examined the interaction between the DRD4 gene and perinatal adversity on RSA at age 30-35 in a longitudinal cohort of ELBW survivors (n = 49) and NBW controls (n = 63). Buccal DNA samples were genotyped for short and long carriers of the exon III DRD4 VNTR gene. Resting RSA was assessed by electrocardiogram., Results: We report an interaction between birth weight status and DRD4 gene (F = 9.42, p = 0.003) in predicting RSA, such that DRD4 long carriers had the highest and lowest resting RSA depending on whether they were born NBW or ELBW, respectively. DRD4 short carriers were less sensitive to birth weight. Additionally, reduced RSA was correlated with a history of major depressive disorder, suggesting it was a reliable index of emotion dysregulation., Discussion: These results suggest that the perinatal environment influences autonomic nervous system functioning in individuals with genotypes that confer additional sensitivity. Whether the long-term autonomic outcomes of this environmental sensitivity are beneficial or detrimental appears to depend on the quality of the early life environment, and may influence the development of emotion regulatory and psychiatric problems in adulthood., (© 2017 Wiley Periodicals, Inc.)

Extremely low birth weight (ELBW; <1000 g) infants have been exposed to stressful intrauterine and early postnatal environments. Even greater early adversity has been experienced by ELBW survivors who were also born small for gestational age (SGA; <10th percentile for GA) compared to those born appropriate for GA (AGA). ELBW survivors, particularly those born SGA, face increased risk for internalizing problems compared to normal BW (NBW; ≥2500 g) controls. Internalizing problems are related to allelic variations in the promoter region of the serotonin transporter linked polymorphic region gene (5-HTTLPR). We followed the oldest longitudinal cohort of ELBW survivors to adulthood. Participants provided buccal cells and reported on internalizing problems, using the Young Adult Self-Report when they were in their mid-20s (ELBW/SGA, N = 28; ELBW/AGA, N = 60; NBW, N = 81) and mid-30s (ELBW/SGA, N = 27; ELBW/AGA, N = 58; NBW, N = 76). The findings indicate that ELBW/SGAs carrying the 5-HTTLPR short allele reported increased internalizing problems, particularly depression, during the third and fourth decades of life. This is the first known report on gene-environment interactions predicting psychopathology among ELBW survivors. Our findings elucidate putative neurobiological pathways that underlie risk for psychopathology.

There is a growing need to curb paediatric obesity. The aim of this study is to untangle associations between video-game-use attributes and obesity as a first step towards identifying and examining possible interventions. Cross-sectional time-lagged cohort study was employed using parent-child surveys (t1) and objective physical activity and physiological measures (t2) from 125 children/adolescents (mean age = 13.06, 9-17-year-olds) who play video games, recruited from two clinics at a Canadian academic children's hospital. Structural equation modelling and analysis of covariance were employed for inference. The results of the study are as follows: (i) self-reported video-game play duration in the 4-h window before bedtime is related to greater abdominal adiposity (waist-to-height ratio) and this association may be mediated through reduced sleep quality (measured with the Pittsburgh Sleep Quality Index); and (ii) self-reported average video-game session duration is associated with greater abdominal adiposity and this association may be mediated through higher self-reported sweet drinks consumption while playing video games and reduced sleep quality. Video-game play duration in the 4-h window before bedtime, typical video-game session duration, sweet drinks consumption while playing video games and poor sleep quality have aversive associations with abdominal adiposity. Paediatricians and researchers should further explore how these factors can be altered through behavioural or pharmacological interventions as a means to reduce paediatric obesity., (© 2017 World Obesity Federation.)

Background: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH., Methods: Children with HeFH (age, 6-<18 years) and low-density lipoprotein cholesterol >4.9 mmol/L or >4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6-<10 years) or 20 mg (age, 10-<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings. P values were adjusted for age, sex, carotid artery site, and family relations., Results: At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P =0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings ( P =0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively; P =0.2)., Conclusions: In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675., (© 2017 American Heart Association, Inc.)

Objective: To explore parents' reasons for discontinuing tertiary-level care for paediatric weight management., Methods: Participants were parents of 10-17year olds (body mass index [BMI] ≥85th percentile) who were referred for paediatric weight management. Parents were recruited from three Canadian sites (Vancouver, BC; Edmonton, AB; Hamilton, ON) and were eligible if their children attended at least one clinical appointment and subsequently discontinued care. Data were collected using semi-structured individual interviews that were digitally recorded, transcribed, and analysed using an inductive manifest content analysis., Results: Parents (n=29) of children [mean age: 14.7±1.8years; mean BMI percentile: 98.9±1.6; n=17 (58.6%) boys] were primarily female (n=26; 89.7%), Caucasian (n=22; 75.9%), and had a university degree (n=23; 79.3%). Reasons for discontinuing care were grouped into three categories: (i) family factors (e.g., perceived lack of progress, lack of family support, children's lack of motivation), (ii) logistical factors (e.g., monetary costs, distance, scheduling), and (iii) health services factors (e.g., unmet expectations of care, perceived limited menu of services, no perceived need for further support)., Conclusions: A range of multi-level factors influenced attrition from tertiary-level paediatric weight management. Our data suggest that experimental research is needed to examine whether addressing reasons for attrition can enhance families' retention in care and ultimately improve health outcomes for children living with obesity., (Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Experts recommend that clinicians assess motivational factors before initiating care for pediatric obesity. Currently, there are no well-established clinical tools available for assessing motivation in youth with obesity or their families. This represents an important gap in knowledge since motivation-related information may shed light on which patients might fail to complete treatment programs. Our study was designed to evaluate the measurement properties and utility of the Readiness and Motivational Interview for Families (RMI-Family), a structured interview that utilizes a motivational interviewing approach to (i) assess motivational factors in youth and their parents, and (ii) examine the degree to which motivation and motivation-related concordance between youth and parents are related to making changes to lifestyle habits for managing obesity in youth., Methods: From 2016 to 2020, this prospective study will include youth with obesity (body mass index [BMI] ≥97th percentile; 13-17 years old; n = 250) and their parents (n = 250). The study will be conducted at two primary-level, multidisciplinary obesity management clinics based at children's hospitals in Alberta, Canada. Participants will be recruited and enrolled after referral to these clinics, but prior to initiating clinical care. Each youth and their parent will complete the RMI-Family (~1.5 h) at baseline, and 6- and 12-months post-baseline. Individual (i.e., youth or parent) and family-level (i.e., across youth and parent) responses to interview questions will be scored, as will aspects of interview administration (e.g., fidelity to motivational interviewing tenets). The RMI-Family will also be examined for test-retest reliability. Youth data collected at each time point will include demography, anthropometry, lifestyle habits, psychosocial functioning, and health services utilization. Cross-sectional and longitudinal associations between individual and family-level interview scores on the RMI-Family and these clinical measures will be examined., Discussion: As a measurement tool drawing on family-centered care and motivational interviewing, the RMI-Family was designed to increase understanding of the role of motivational factors in pediatric obesity management, allowing healthcare providers and policymakers to manage pediatric obesity more effectively and efficiently. Findings will help to create an innovative, tailored model of health care delivery that uses resources judiciously and is designed to best meet families' needs.

The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array. Genotype scores (GS) were calculated for TC, HDL-C, LDL-C and TG. Linear and mixed-effects regressions adjusted for sex, age and population stratification were performed. The GS was associated with LDL-C level at 3 and 5 years (β = 0.017 ± 0.003, P = 2.9 × 10 -8 ; β = 0.020 ± 0.003, P = 5.7 × 10 -9 ) and from birth to 5 years (β = 0.013 ± 0.003, P = 2.6 × 10 -7 ). The GS was associated with TC level at 3 and 5 years (β = 0.009 ± 0.002, P = 9.1 × 10 -7 ; β = 0.009 ± 0.002, P = 7.7 × 10 -6 ). CETP rs3764261 was associated with the HDL-C level from birth to 5 years (β = 0.064 ± 0.014, P =  7.4 × 10 -6 ). AMPD3 rs2923084 was associated with the HDL-C level at 5 years (β = 0.096 ± 0.024, P = 9.7 × 10 -5 ). Known loci associated with blood lipids in adults are associated with TC, LDL-C and HDL-C, but not TG in early life. Genetically predisposed children may benefit from early lipid lowering preventative strategies.

Aim: To examine the extent to which the theory of planned behavior (TPB) predicts academic clinicians' intent to treat pediatric obesity., Methods: A multi-disciplinary panel iteratively devised a Likert scale survey based on the constructs of the TPB applied to a set of pediatric obesity themes. A cross-sectional electronic survey was then administered to academic clinicians at tertiary care centers across Canada from January to April 2012. Descriptive statistics were used to summarize demographic and item agreement data. A hierarchical linear regression analysis controlling for demographic variables was conducted to examine the extent to which the TPB subscales predicted intent to treat pediatric obesity., Results: A total of 198 physicians, surgeons, and allied health professionals across Canada (British Columbia, Alberta, Manitoba, Saskatchewan, Nova Scotia, Ontario and Quebec) completed the survey. On step 1, demographic factors accounted for 7.4% of the variance in intent scores. Together in step 2, demographic variables and TPB subscales predicted 56.9% of the variance in a measure of the intent to treat pediatric obesity. Perceived behavioral control, that is, confidence in one's ability to manage pediatric obesity, and subjective norms, congruent with one's context of practice, were the most significant predictors of the intent to treat pediatric obesity. Attitudes and barriers did not predict the intent to treat pediatric obesity in this context., Conclusion: Enhancing self-confidence in the ability to treat pediatric obesity and the existence of supportive treatment environments are important to increase clinician's intent to treat pediatric obesity., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Background: The success of behavioural interventions to optimize cardiovascular health is dependent on adequate cognitive functioning beginning in early life. In this study we aimed to systematically review studies that examined associations between childhood cognition and cardiovascular disease (CVD) events in adulthood., Methods: This study followed the Meta-analysis Of Observational Studies in Epidemiology guidelines to systematically examine associations between childhood cognition and adult CVD, coronary heart disease, and stroke hospitalization or mortality events. Literature was retrieved from EMBASE, MEDLINE, PsycInfo, and CINAHL., Results: Five longitudinal studies that examined links between childhood cognition and CVD in adulthood were included. Pooled estimates of unadjusted CVD events indicated a relative risk of 1.23 (95% confidence interval, 1.12-1.34) per standard deviation decrease in childhood IQ, whereas the pooled estimate adjusted for biopsychosocial confounding factors indicated an overall relative risk of 1.16 (95% confidence interval, 1.07-1.26)., Conclusions: Lower childhood IQ is associated with an increased risk of cardiovascular events in adulthood, even after adjustment for confounding variables. Future research should examine the behavioural mechanisms by which these risks are mediated to optimize cardiovascular health., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: The effects of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) on maternal and offspring obesity traits, as well as the maternal and offspring genetic contribution to GWG and postpartum weight retention, were examined., Methods: Blood samples from mothers (n = 608) and offspring (n = 541) were genotyped for 83 BMI-associated SNPs and 47 waist-to-hip ratio (WHR)-associated SNPs. Linear regression and mixed-effects regression models were performed to examine clinical epidemiological and genetic associations with unweighted and weighted BMI and WHR genetic risk scores (GRS)., Results: Prepregnancy BMI was positively associated with offspring weight and BMI Z-score from birth to 5 years. GWG was positively associated with maternal postpartum weight retention at 1 and 5 years and with offspring weight Z-score from birth to 5 years old. The maternal unweighted BMI GRS was associated with prepregnancy BMI, postpartum weight retention at 5 years, and offspring weight Z-score from birth to 5 years old, but not associated with GWG. Both maternal and offspring unweighted WHR GRSs were negatively associated with GWG., Conclusions: Maternal BMI-associated SNPs may contribute to the genetic link between prepregnancy BMI variation, long-term postpartum weight retention, and offspring birth weight and longitudinal weight. Maternal and offspring WHR-associated SNPs may contribute to GWG variation., (© 2016 The Obesity Society.)

Objectives: To compare the health-related quality of life (HRQL) trajectories of a regional cohort of extremely low birth weight (ELBW, <1000 g) survivors (births from 1977 to 1982) and a group of normal birth weight (NBW) controls, at 3 ages: 12-16 years, 22-26 years, and 29-36 years, spanning over 20 years. We hypothesized that the HRQL of the ELBW cohort would be significantly compromised compared with their NBW peers, and that neurosensory impairments (NSI) would have an additional negative effect., Study Design: We used the Health Utilities Index Mark 3, in which health status was self-assessed and utility scores were derived from community preferences; multilevel modeling was used to delineate trajectories of HRQL among ELBW survivors with (n = 37) and without NSI (n = 116), and NBW controls (n = 137)., Results: Adjusting for participant sex and socioeconomic status at age 8 years, ELBW survivors with NSI had consistently lower HRQL compared with both ELBW survivors without NSI and NBW controls, from adolescence through to adulthood (β = -0.264; P < .001). ELBW survivors without NSI also had significantly lower HRQL compared with NBW controls (β = -0.092; P < .01). At all ages, differences seen in the Health Utilities Index Mark 3 scores between ELBW participants and NBW controls were clinically important, though there was no differential rate of decline between the 2 groups., Conclusions: ELBW survivors manifest meaningfully poorer HRQL from their early teens through their mid-30s. Individuals with NSI appear to represent a distinct group of ELBW survivors with substantially lower HRQL at all ages. Information on HRQL can be helpful in prioritizing research and intervention strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.

Background: The intestinal microbiota influences metabolic, nutritional, and immunologic processes and has been associated with a broad range of adverse health outcomes including asthma, obesity and Type 2 diabetes. Early life exposures may alter the course of gut microbial colonization leading to differences in metabolic and immune regulation throughout life. Although approximately 50 % of low-risk full-term infants born in Canada are exposed to intrapartum antibiotics, little is known about the influence of this common prophylactic treatment on the developing neonatal intestinal microbiota. The purpose of this study is to describe the intestinal microbiome over the first 3 years of life among healthy, breastfed infants born to women with low-risk pregnancies at full term gestation and to determine if at 1 year of age, the intestinal microbiome of infants exposed to intrapartum antibiotics differs in type and quantity from the infants that are not exposed., Methods: A prospectively followed cohort of 240 mother-infant pairs will be formed by enrolling eligible pregnant women from midwifery practices in the City of Hamilton and surrounding area in Ontario, Canada. Participants will be followed until the age of 3 years. Women are eligible to participate in the study if they are considered to be low-risk, planning a vaginal birth and able to communicate in English. Women are excluded if they have a multiple pregnancy or a preterm birth. Study questionnaires are completed, anthropometric measures are taken and biological samples are acquired including eight infant stool samples between 3 days and 3 years of age., Discussion: Our experience to date indicates that midwifery practices and clients are keen to participate in this research. The midwifery client population is likely to have high rates of breastfeeding and low rates of intervention, allowing us to examine the comparative development of the microbiome in a relatively healthy and homogenous population. Results from this study will make an important contribution to the growing understanding of the patterns of intestinal microbiome colonization in the early years of life and may have implications for best practices to support the establishment of the microbiome at birth.

Adults born preterm at very low birth weight (VLBW; <1500 g) have higher blood pressure than those born at term. It is not known whether all VLBW adults are at risk or whether higher blood pressure could be attributed to some of the specific conditions underlying or accompanying preterm birth. To identify possible risk or protective factors, we combined individual-level data from 9 cohorts that measured blood pressure in young adults born at VLBW or with a more stringent birth weight criterion. In the absence of major heterogeneity, we performed linear regression analysis in our pooled sample of 1571 adults born at VLBW and 777 controls. Adults born at VLBW had 3.4 mm Hg (95% confidence interval, 2.2-4.6) higher systolic and 2.1 mm Hg (95% confidence interval, 1.3-3.0) higher diastolic pressure, with adjustment for age, sex, and cohort. The difference in systolic pressure was present in men (1.8 mm Hg; 95% confidence interval, 0.1-3.5) but was stronger in women (4.7 mm Hg; 95% confidence interval, 3.2-6.3). Among the VLBW group, blood pressure was unrelated to gestational age, maternal smoking, multiple pregnancy, retinopathy of prematurity, or bronchopulmonary dysplasia. Blood pressure was higher than that of controls among VLBW adults unexposed to maternal preeclampsia. Among those exposed, it was even higher, especially if born appropriate for gestational age. In conclusion, although female sex and maternal preeclampsia are additional risk factors, the risk of higher blood pressure is not limited to any etiologic subgroup of VLBW adults, arguing for vigilance in early detection of high blood pressure in all these individuals., (© 2016 American Heart Association, Inc.)

Background: Young adults born with extreme prematurity have increased blood pressure and insulin resistance. This study documents their metabolic health as they enter their fourth decade of life. The study objective was to compare body composition, glycemia, lipid levels, and blood pressure in adults born with extremely low birth weight (ELBW) versus age- and sex- matched normal birth weight (NBW) control subjects and to examine related previous and current exposures., Methods: The study examines one of the oldest regionally representative cohorts of ELBW subjects (birth weight <1 kg) and NBW individuals born between 1977 and 1982. The primary outcome was dysglycemia (type 2 diabetes or prediabetes) based on results of a 75-g oral glucose tolerance test. Secondary outcomes include body composition, insulin resistance, fasting lipid profile, and blood pressure. Potential predictive factors included birth weight, maternal antenatal corticosteroid exposure, retinopathy of prematurity, growth parameters, and smoking history., Results: Adults (mean age, 31.8 years) born ELBW (n = 100) had a higher percent body fat (P = .004) and lower lean mass for height (P = .018) but similar waist circumference (P = .54) and BMI (P = .61) compared with NBW control subjects. ELBW adults had a 4.0-fold (95% confidence interval, 1.53-10.66) increased risk of developing dysglycemia. Adults born ELBW also had higher systolic (P = .004) and diastolic (P = .02) blood pressures compared with NBW control subjects, but there were no differences in lipid profile., Conclusions: By their fourth decade, these adults born extremely premature had increased body fat, lower lean mass, and a 4-fold increased risk of developing dysglycemia., (Copyright © 2016 by the American Academy of Pediatrics.)

We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT (n = 22) or IGT (n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a (13)C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) (P = 0.90) despite lower whole body insulin sensitivity in IGT at rest (P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT (P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT., (Copyright © 2016 the American Physiological Society.)

Premature birth in conjunction with extremely low birth weight (<1 kg, ELBW) is associated with insulin resistance and increased cardiometabolic health risk compared to birth at full term with normal birth weight (NBW). However, little is known regarding the biologic mediators of these effects. Abdominal and ectopic lipid accumulation is linked to insulin resistance and metabolic dysfunction, yet whether ELBW survivors are predisposed to aberrant lipid deposition in adulthood is unknown. We used magnetic resonance imaging in a cohort of 16 NBW and 29 ELBW participants to determine if ELBW survivors have differences in pancreatic, hepatic, subcutaneous and visceral fat distribution compared to NBW participants. ELBW individuals had a higher proportion of liver and pancreatic fat compared to NBW subjects (P < 0.05). Abdominal subcutaneous fat, but not visceral fat, area was higher in ELBW survivors compared to NBW individuals. In multivariate analyses, tissue fat measures were most highly related to BMI and sex, but not preterm birth. This work highlights that fat deposition is enhanced in adults born preterm and suggests that ectopic fat accretion driven by their relatively greater adiposity may contribute to the higher rates of metabolic dysfunction seen in ELBW survivors.

Objective: Although parents are uniquely positioned to offer first-hand insights that can be used to improve health services for managing pediatric obesity, their perspective is underexplored. Our objective was to characterize parents' recommendations for enhancing tertiary-level health services for managing pediatric obesity in Canada., Methods: Semistructured, one-on-one interviews were conducted with parents of children who initiated treatment at 1 of 4 Canadian tertiary-level, multidisciplinary weight management clinics. Parent perspectives were elicited regarding the strengths and weaknesses of the health services they received as well as areas for potential improvement. Interviews were audio-recorded and transcribed verbatim. We used qualitative description as the methodological framework and manifest content analysis as the analytical strategy., Results: Parents (n = 65; 88% female; 72% Caucasian; 74% with at least some postsecondary education; 52% >$50,000 CDN household income) provided a range of recommendations that were organized according to health care: 1) accessibility, 2) content, and 3) delivery. The most common recommendations included increasing scheduling options (44%; n = 29), tailoring services to families' needs and circumstances (29%; n = 19), placing greater emphasis on physical activity (29%; n = 19), altering program duration (29%; n = 19), incorporating interactive elements (25%; n = 16), information provision (25%; n = 16), and providing services at sites closer to participants' homes (24%; n = 15)., Conclusions: Parents' recommendations to enhance health services for managing pediatric obesity concerned modifiable factors related to accessibility, content, and delivery of care. Further research is needed to evaluate whether implementing suggested recommendations improves clinically relevant outcomes including attrition, quality of care, and success in weight management., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)