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Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.
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Pueblo Asiatico , Metilación de ADN , Epigénesis Genética , Población Blanca , Humanos , Femenino , Metilación de ADN/genética , Embarazo , Recién Nacido , Población Blanca/genética , Pueblo Asiatico/genética , Fumar/genética , Fumar/efectos adversos , Masculino , Sangre Fetal , Adulto , Estudios de Cohortes , Islas de CpG , Efectos Tardíos de la Exposición Prenatal/genéticaRESUMEN
BACKGROUND: Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth. RESULTS: Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10-54) and South Asians (r = 0.66; p = 6.9 × 10-64). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts. CONCLUSIONS: These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.
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Pueblo Asiatico , Metilación de ADN , Epigénesis Genética , Sangre Fetal , Edad Gestacional , Población Blanca , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Pueblo Asiatico/genética , Canadá , Estudios de Cohortes , Islas de CpG/genética , Metilación de ADN/genética , Epigénesis Genética/genética , Sangre Fetal/química , Estudio de Asociación del Genoma Completo/métodos , Población Blanca/genéticaRESUMEN
BACKGROUND: Chronic stress is an important risk factor in the development of obesity. While research suggests chronic stress is linked to excess weight gain in children, the biological or behavioral mechanisms are poorly understood. OBJECTIVE: The objectives of the Family Stress Study are to examine behavioral and biological pathways through which chronic stress exposure (including stress from COVID-19) may be associated with adiposity in young children, and to determine if factors such as child sex, caregiver-child relationship quality, caregiver education, and caregiver self-regulation moderate the association between chronic stress and child adiposity. METHODS: The Family Stress Study is a prospective cohort study of families recruited from 2 Canadian sites: the University of Guelph in Guelph, Ontario, and McMaster University in Hamilton, Ontario. Participants will be observed for 2 years and were eligible to participate if they had at least one child (aged 2-6 years) and no plans to move from the area within the next 3 years. Study questionnaires and measures were completed remotely at baseline and will be assessed using the same methods at 1- and 2-year follow-ups. At each time point, caregivers measure and report their child's height, weight, and waist circumference, collect a hair sample for cortisol analysis, and fit their child with an activity monitor to assess the child's physical activity and sleep. Caregivers also complete a web-based health and behaviors survey with questions about family demographics, family stress, their own weight-related behaviors, and their child's mental health, as well as a 1-day dietary assessment for their child. RESULTS: Enrollment for this study was completed in December 2021. The final second-year follow-up was completed in April 2024. This study's sample includes 359 families (359 children, 359 female caregivers, and 179 male caregivers). The children's mean (SD) age is 3.9 years (1.2 years) and 51% (n=182) are female. Approximately 74% (n=263) of children and 80% (n=431) of caregivers identify as White. Approximately 34% (n=184) of caregivers have a college diploma or less and nearly 93% (n=499) are married or cohabiting with a partner. Nearly half (n=172, 47%) of the families have an annual household income ≥CAD $100,000 (an average exchange rate of 1 CAD=0.737626 USD applies). Data cleaning and analysis are ongoing as of manuscript publication. CONCLUSIONS: Despite public health restrictions from COVID-19, the Family Stress Study was successful in recruiting and using remote data collection to successfully engage families in this study. The results from this study will help identify the direction and relative contributions of the biological and behavioral pathways linking chronic stress and adiposity. These findings will aid in the development of effective interventions designed to modify these pathways and reduce obesity risk in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT05534711; https://clinicaltrials.gov/study/NCT05534711. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48549.
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COVID-19 , Estrés Psicológico , Aumento de Peso , Humanos , Estudios Prospectivos , Femenino , Masculino , Preescolar , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Niño , COVID-19/epidemiología , COVID-19/psicología , Obesidad Infantil/epidemiología , Obesidad Infantil/psicología , Ontario/epidemiología , Canadá/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada. METHODS: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders. RESULTS: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load. CONCLUSION: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada.
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Diabetes Gestacional , Humanos , Femenino , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Embarazo , Canadá/epidemiología , Adulto , Estudios Transversales , Estudios de Cohortes , Carne Roja/efectos adversos , Factores de Riesgo , Productos de la Carne/efectos adversos , Dieta/efectos adversosRESUMEN
Childhood obesity is a global health concern affecting over 150 million children worldwide, with projections of a rise to 206 million by 2025. Understanding the mechanisms underlying this epidemic is crucial for developing effective interventions. In this study, we investigated circulating levels of Growth Differentiation Factor 10 (GDF10), a novel regulator of adipogenesis. Previous studies report diminished circulating GDF10 levels contribute to obesity and hepatic steatosis in mice. To further understand the role of plasma GDF10 in childhood obesity, a prospective case-control study was conducted. Using an enzyme-linked immunosorbent assay, plasma GDF10 levels were measured in children aged 5-17 years of age with normal (n = 36) and increased (n = 56) body mass index (BMI). Subsequently, plasma GDF10 levels were compared to various cardio-metabolic parameters. Children with increased BMI exhibit significantly lower levels of plasma GDF10 compared to children with normal BMI (p < 0.05). This study not only supports previous mouse data but is the first to report that lower levels of GDF10 is associated with childhood obesity, providing an important human connection for the relevance of GDF10 in obesity. Furthermore, this study revealed a significant correlation between low plasma GDF10 levels and elevated LDL-cholesterol and total cholesterol levels dependent on BMI (95% CI, p < 0.05). This study supports the hypothesis that children with obesity display lower plasma levels of GDF10, which correlates with elevated cholesterol levels. These insights shed light on potential mechanisms contributing to childhood obesity and may lead to future therapeutic interventions targeting GDF10 to mitigate adverse effects of adipogenesis in cardiometabolic health.
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Obesidad Infantil , Humanos , Niño , Animales , Ratones , Preescolar , Adolescente , Obesidad Infantil/etiología , Factor 10 de Diferenciación de Crecimiento , Estudios de Casos y Controles , Colesterol , Índice de Masa CorporalRESUMEN
CONTEXT: Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans. OBJECTIVE: To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome. METHODS: Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI). RESULTS: Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium. CONCLUSION: VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Adulto , Humanos , Masculino , Femenino , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estudios Transversales , ARN Ribosómico 16S , Triglicéridos , HDL-Colesterol , Glucosa/metabolismo , Tejido AdiposoRESUMEN
Association between obstructive lung function impairment with higher cIMT is present in childhood after accounting for common risk factors. This suggests that a developmental link between obstructive lung diseases and CVD may have its origin in early life. https://bit.ly/4657s2b.
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BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.
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Desarrollo Infantil , Efectos Tardíos de la Exposición Prenatal , Adolescente , Humanos , Embarazo , Lactante , Femenino , Preescolar , Canadá/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición Materna/efectos adversos , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
PURPOSE: 1) To explore how children with spina bifida (SB) and their parents understand bodyweight, health and weight management; and 2) To identify what services and supports children with SB and their families feel are most appropriate to help them manage their health and weight. METHODS: The study used interpretive description within a qualitative design. Participants were children with SB (aged 10-18) attending two Canadian SB clinics and their parents. Data were collected through individual interviews and analyzed using inductive thematic analysis. RESULTS: Five children and five parents participated in the study. Children and parents had a weight-centric approach to health, which was related to the child's mobility. Weight was considered to be under individual control and mostly through diet. Trusting relationships between healthcare providers, children and families were important to discuss weight in a non-judgemental manner. Children should be involved in setting meaningful and achievable weight management goals. CONCLUSION: Greater knowledge of how children with SB and their families understand weight and health offers opportunities for non-judgemental discussions about their needs and wishes. Helping families to place more value on health over weight may reduce feelings of stigma, while allowing children to develop some autonomy over health-related decisions.
Children with spina bifida and their parents do not recognise the complexity of factors contributing to weight regulation.Weight regulation was often seen as the child's responsibility, which could lead to feelings of guilt and shame through internalised weight stigmaHealthcare professionals working with children with spina bifida should explore their perceptions, beliefs, and behaviours related to weight, health and mobility to ensure they are not causing themselves physical and/or psychological harm.
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BACKGROUND: Recruitment of participants continues to be a challenge that researchers must overcome to yield successful study results. Over the past decade, there has been a dramatic increase in the use of social media platforms to recruit research participants. We conducted a secondary analysis of the Aim2Be randomized controlled trial (RCT) to examine if there was variability between participants recruited via social media versus pediatric obesity clinics. METHODS: Parents and their children living with overweight or obesity were recruited through social media (i.e., Facebook advertisements) (n = 119) or pediatric obesity management clinics (n = 95) to participate in the Aim2Be RCT. We compared recruitment costs, recruitment rate, participant retention, intervention engagement, obesity-related risk factors, and behavioral habits. RESULTS: Facebook recruitment resulted in more participant contacts, but higher attrition during 'high effort' stages of the recruitment process. Group differences emerged regarding costs (Facebook: $407 versus clinics: $699). There were no group differences in participant retention or intervention engagement. Families recruited from Facebook were younger parents (42.6 versus 46.0 years; p < 0.001) and children (12.2 versus 13.9 years; p < 0.001), a higher percentage male children, and fewer had previously participated in a pediatric weight management program. Parents recruited from Facebook self-reported greater screen time for themselves, and their children reported lower physical activity levels and higher caloric and sugar intake. CONCLUSIONS: Social media and clinical site recruitment are complementary strategies that appear to draw in families with different profiles, but regardless of how they were recruited, all families had the potential to benefit from pediatric obesity management.
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OBJECTIVES: The prevalence of pediatric diabetes is increasing. Dyslipidemia is an important modifiable cardiovascular disease risk factor often present in children with diabetes. In this study, we evaluated the adherence to Diabetes Canada 2018 lipid screening guidelines in a pediatric diabetes program to determine the prevalence of dyslipidemia in youth with diabetes and to identify risk factors related to dyslipidemia. METHODS: This retrospective chart review included patients at McMaster Children's Hospital with diabetes (types 1 and 2), who were at least 12 years of age as of January 1, 2019. Extracted data included age, sex, family history of diabetes or dyslipidemia, date of diagnosis, body mass index, glycemia monitoring system used, lipid profile, glycated hemoglobin (A1C), and thyroid-stimulating hormone values at the time the lipid profile was measured. Statistical methods included descriptive statistics and logistic regression modelling. RESULTS: Of the 305 patients included, 61% had a lipid profile measured according to guidelines, 29% had lipid screening completed outside of the recommended window, and 10% had no lipid profile on record. Among screened patients, 45% had dyslipidemia, most commonly hypertriglyceridemia (35%). Dyslipidemia was highest amongst those with type 2 diabetes, obesity, older age, short duration of diabetes, higher A1C, and those who used capillary blood glucose for monitoring (p<0.05). CONCLUSIONS: A high proportion of patients were screened for dyslipidemia, but many outside the recommended window. Dyslipidemia is highly prevalent in this patient population and was associated with the presence of obesity, but 44% of patients without obesity also had dyslipidemia.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Adolescente , Humanos , Niño , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada , Estudios Retrospectivos , Factores de Riesgo , Obesidad/complicaciones , Dislipidemias/epidemiología , Lípidos , Triglicéridos , HDL-ColesterolRESUMEN
Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.
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Background: Children with disabilities are twice as likely to have overweight/obesity than their typically developing peers. Higher weights in these individuals may compound challenges already experienced with their disability, including mobility and activities of daily living. However, children with disabilities often find it challenging accessing weight management care. It is therefore important to understand the experiences and needs of the health care professionals (HCPs) who work in specialized pediatric weight management clinics about providing weight-related care to children with disabilities. Methods: Employing an interpretive description approach, purposeful sampling was used to recruit 17 HCP participants working in pediatric weight management settings in Canada. Qualitative semistructured interviews were conducted online or via telephone. All interview recordings were transcribed and a reflexive thematic analysis approach was used to develop themes from the data. Results: Four themes were developed: (1) infrequent referrals leads to a lack of experience with children with disabilities; (2) adapting group-based clinics can be challenging; (3) perceived lack of disability-specific knowledge causes moral distress; and (4) disability-specific training and greater interdisciplinary collaboration are desired. Conclusions: This work identifies the urgent need for more evidence-based, specialized, weight-related treatment options for children with disabilities, as well as more support for HCPs working in existing programs.
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The study objective is to evaluate the influence of attrition from a paediatric weight management program (PWM) on health indicators over a 2-year period. In this observational study, children and youth with obesity were recruited at entry into a family-based behaviour modification PWM and had four research study visits, independent of clinic visits, over 2 years. Participants were divided into attrition groups based on length of clinic enrolment. Body composition, cardiometabolic health and health-related quality of life (HRQoL) were assessed. Among 269 children enrolled, 19% had no clinic treatment visit, 16% had treatment visits only up to 6 months, 23% up to 1 year and 42% had at least one clinic visit after 1 year (No Attrition). Greater declines in BMI z-score and body fat were seen at 2 years in children with No Attrition, while improvements in HRQoL were similar for all attrition groups. Children who attended at least one treatment visit reported improved HRQoL up to 2 years, regardless of duration in clinic. In contrast, declines in body fat and BMI z-score were greater at 2 years for those with at least one visit after 1 year. Continued efforts to reduce attrition are likely to improve anthropometric health outcomes during PWM.
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Obesidad , Calidad de Vida , Adolescente , Humanos , Niño , Índice de Masa Corporal , Obesidad/terapia , Antropometría , Composición CorporalRESUMEN
To examine the (i) relationships between various body mass index (BMI)-derived metrics for measuring severe obesity (SO) over time based the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) references and (ii) ability of these metrics to discriminate children and adolescents based on the presence of cardiometabolic risk factors. In this cohort study completed from 2013 to 2021, we examined data from 3- to 18-year-olds enrolled in the CANadian Pediatric Weight management Registry. Anthropometric data were used to create nine BMI-derived metrics based on the CDC and WHO references. Cardiometabolic risk factors were examined, including dysglycemia, dyslipidemia, and elevated blood pressure. Analyses included Pearson correlations, intraclass correlation coefficients (ICC), and receiver operator characteristic area-under-the-curve (ROC AUC). Our sample included 1,288 participants (n = 666 [52%] girls; n = 874 [68%] white). The prevalence of SO varied from 60-67%, depending on the definition. Most BMI-derived metrics were positively and significantly related to one another (r = 0.45-1.00); ICCs revealed high tracking (0.90-0.94). ROC AUC analyses showed CDC and WHO metrics had a modest ability to discriminate the presence of cardiometabolic risk factors, which improved slightly with increasing numbers of risk factors. Overall, most BMI-derived metrics rated poorly in identifying presence of cardiometabolic risk factors. Conclusion: CDC BMI percent of the 95th percentile and WHO BMIz performed similarly as measures of SO, although neither showed particularly impressive discrimination. They appear to be interchangeable in clinical care and research in pediatrics, but there is a need for a universal standard. WHO BMIz may be useful for clinicians and researchers from countries that recommend using the WHO growth reference. What is Known: ⢠Severe obesity in pediatrics is a global health issue. ⢠Few reports have evaluated body mass index (BMI)-derived metrics based on the World Health Organization growth reference. What is New: ⢠Our analyses showed that the Centers for Disease Control and Prevention BMI percent of the 95th percentile and World Health Organization (WHO) BMI z-score (BMIz) performed similarly as measures of severe obesity in pediatrics. ⢠WHO BMIz should be a useful metric to measure severe obesity for clinicians and researchers from countries that recommend using the WHO growth reference.
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Obesidad Mórbida , Obesidad Infantil , Femenino , Adolescente , Niño , Humanos , Masculino , Estados Unidos , Índice de Masa Corporal , Obesidad Mórbida/complicaciones , Estudios de Cohortes , Salud Global , Benchmarking , Canadá/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/prevención & control , Organización Mundial de la Salud , Centers for Disease Control and Prevention, U.S. , Sistema de Registros , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & controlRESUMEN
BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.
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Sobrepeso , Obesidad Infantil , Niño , Preescolar , Humanos , Femenino , Masculino , Sobrepeso/epidemiología , Adiposidad , Estudios Transversales , Obesidad Infantil/epidemiología , Glutamina , Canadá/epidemiología , Aminoácidos Aromáticos , Metaboloma , GlutamatosRESUMEN
Worldwide, rates of metabolic diseases are rapidly increasing and environmental exposure to pesticides, pollutants and/or other chemicals may play a role. Reductions in Brown Adipose Tissue (BAT) thermogenesis, mediated in part by uncoupling protein 1 (Ucp1), are associated with metabolic diseases. In the current study, we investigated whether the pesticide deltamethrin (0.01-1 mg/kg bw/day) incorporated into a high-fat diet and fed to mice housed at either room temperature (21°C) or thermoneutrality (29°C) would suppress BAT activity and accelerate the development of metabolic disease. Importantly, thermoneutrality allows for more accurate modeling of human metabolic disease. We found that, 0.01 mg/kg bw/day of deltamethrin induced weight loss, improved insulin sensitivity and increased energy expenditure, effects that were associated with increases in physical activity. In contrast, exposure to 0.1 and 1 mg/kg bw/day deltamethrin had no effect on any of the parameters examined. Deltamethrin treatment in mice did not alter molecular markers of BAT thermogenesis, despite observing suppression of UCP1 expression in cultured brown adipocytes. These data indicate that while deltamethrin inhibits UCP1 expression in vitro, 16wks exposure does not alter BAT thermogenesis markers nor exacerbates the development of obesity and insulin resistance in mice.
Asunto(s)
Resistencia a la Insulina , Masculino , Humanos , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Obesidad/inducido químicamente , Obesidad/metabolismo , Tejido Adiposo Pardo , Metabolismo Energético , Termogénesis , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Studies investigating neonatal outcomes following intrapartum antibiotic exposure show conflicting results. METHODS: Data were collected prospectively in pregnancy to 1-year-of-age, from 212 mother-infant pairs. Adjusted multivariable regression models estimated relationships following exposure to intrapartum antibiotics among vaginally-born, full-term infants and outcomes related to growth, atopic disease, gastrointestinal symptoms, and sleep at 1-year. RESULTS: Intrapartum antibiotic exposure (n = 40) was not associated with mass, ponderal index, BMI z-score (1- year), lean mass index (5-months) or height. Antibiotic exposure in labour ≥4-h was associated with increase in fat mass index at 5-months (ß 0.42 [95% CI: 0.03, 0.80], p = 0.03). Intrapartum antibiotic was associated with atopy in the first year (OR: 2.93 [95% CI: 1.34, 6.43], p = 0.007). Antibiotic exposure during intrapartum or day 1-7 was associated with newborn fungal infection requiring antifungal therapy (OR 3.04 [95% CI: 1.14, 8.10], p = 0.026), and number of fungal infections (IRR: 2.90 [95% CI: 1.02, 8.27], p = 0.046). CONCLUSION: Intrapartum and early life exposure to antibiotics were independently associated with measures of growth, atopy, and fungal infections suggesting that intrapartum and early neonatal antibiotics be used prudently following careful risk-benefit analysis. IMPACT: This prospective study: Shows a shift in fat mass index at 5 months associated with antibiotic administration ≥4 h in labour; an earlier age than previously reported; Shows atopy reported less frequently among those not exposed to intrapartum antibiotics; Supports earlier research of increased likelihood of fungal infection following exposure to intrapartum or early-life antibiotics; Adds to growing evidence that antibiotics used intrapartum and in early neonatal periods influence longer-term outcomes for infants. Suggests that use of intrapartum and early neonatal antibiotics should be used prudently after careful consideration of risk and benefit.