Health equity in action: using community-engaged research to update an intervention promoting a healthy home food environment to Black/African American families.

PURPOSE: Describe the method for conducting community-engaged research to identify needed changes for an existing evidence-based intervention, and prepare it for implementation in a community setting within the Dan L Duncan Comprehensive Cancer Center catchment area in an effort to achieve more equitable outcomes in diet-related disease risk factors. METHODS: The intervention, Family Eats, was developed over 10 years ago. It works directly with parents of Black/African American 9-12 year old children to create a healthy home food environment to support prevention of obesity and related cancers. Data collection with community stakeholders occurred through a series of  Community Advisory Board (CAB) meetings guided by the Delphi Technique, an iterative approach for gaining group consensus on a topic. RESULTS: Key information on needed changes and potential implementation strategies were identified. Perceived level of engagement among CAB members was high overall and in terms of both quantity and quality. CONCLUSION: The Delphi Technique shows promise as a method for conducting community-engaged research that promotes engagement and identifies key information needed to adapt and implement an existing intervention in a community setting.

Validation of Variables for Use in Pediatric Obesity Risk Score Development in Demographically and Racially Diverse United States Cohorts.

OBJECTIVE: To evaluate the performance of childhood obesity prediction models in four independent cohorts in the United States, using previously validated variables obtained easily from medical records as measured in different clinical settings. STUDY DESIGN: Data from four prospective cohorts, Latinx, Eating, and Diabetes; Stress in Pregnancy Study; Project Viva; and Center for the Health Assessment of Mothers and Children of Salinas were used to test childhood obesity risk models and predict childhood obesity by ages 4 through 6, using five clinical variables (maternal age, maternal prepregnancy body mass index, birth weight Z-score, weight-for-age Z-score change, and breastfeeding), derived from a previously validated risk model and as measured in each cohort's clinical setting. Multivariable logistic regression was performed within each cohort, and performance of each model was assessed based on discrimination and predictive accuracy. RESULTS: The risk models performed well across all four cohorts, achieving excellent discrimination. The area under the receiver operator curve was 0.79 for Center for the Health Assessment of Mothers and Children of Salinas and Project Viva, 0.83 for Stress in Pregnancy Study, and 0.86 for Latinx, Eating, and Diabetes. At a 50th percentile threshold, the sensitivity of the models ranged from 12% to 53%, and specificity was ≥ 90%. The negative predictive values were ≥ 80% for all cohorts, and the positive predictive values ranged from 62% to 86%. CONCLUSION: All four risk models performed well in each independent and demographically diverse cohort, demonstrating the utility of these five variables for identifying children at high risk for developing early childhood obesity in the United States.

Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays.

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

Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.

BACKGROUND: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. METHODS: The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. RESULTS: Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. CONCLUSIONS: Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.

Metabolomic data presents challenges for epidemiological meta-analysis: a case study of childhood body mass index from the ECHO consortium.

INTRODUCTION: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility. OBJECTIVE: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework. METHODS: We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure. RESULTS: Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coefmeta = 0.40 [95% CI 0.10,0.70], Pmeta = 9.7 × 10-3), guanidinoacetate (Coefmeta = - 0.28 [- 0.54, - 0.02], Pmeta = 0.033), 3-ureidopropionate (Coefmeta = 0.22 [0.017,0.41], Pmeta = 0.033), 1-methylhistidine (Coefmeta = - 0.18 [- 0.33, - 0.04], Pmeta = 0.011), serine (Coefmeta = - 0.18 [- 0.36, - 0.01], Pmeta = 0.034), and lysine (Coefmeta = - 0.16 [- 0.32, - 0.01], Pmeta = 0.044). No associations were robust to multiple testing correction. CONCLUSIONS: Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

Interactive effects of gestational diabetes and high pre-pregnancy body mass index on adverse growth patterns of offspring.

AIMS: To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre-pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. MATERIALS AND METHODS: One thousand six hundred and eighty one mother-child pairs were followed for 8 years in Tianjin, China. Group-based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre-pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut-off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre-pregnancy BMI for adverse growth patterns. RESULTS: Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre-pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74-3.25 & 4.92, 2.26-10.73). GDM greatly enhanced the adjusted OR of high pre-pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25-5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. CONCLUSIONS: Maternal high pre-pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre-pregnancy BMI for LOGP.

Variety of High and Very Low-Energy Density Foods among Preschool-Aged Children and Associations with Food Intake, Diet Quality, and Weight Status.

BACKGROUND: Energy density (ED) and the variety of foods are 2 factors that may have a combined effect on preschool-aged children's ability to regulate food intake. However, little is known about the variety of foods consumed within different ED categories by children in the United States. OBJECTIVE: Therefore, we explored the variety of high ED (HED, 4-9 kcal/g) and very low ED (VLED, <0.6 kcal/g) foods consumed by a nationally representative sample of children aged 2-5 y in the United States and the relationship between variety with food intake, diet quality, and weight status. METHODS: ED, variety, and diet quality were assessed using two 24-h dietary recalls collected as part of the National Health And Nutrition Examination Survey 2011-2018 cycles (n = 1682). We assessed associations between HED and VLED varieties with energy intake, volume of food, diet quality, and weight status using multivariable linear and logistic regressions. RESULTS: The HED variety was positively associated with energy intake (P < 0.0001). The VLED variety was positively associated with the volume of food (P < 0.0001) and diet quality (P < 0.0001). VLED was negatively associated with the odds of having obesity in minimally adjusted models [odds ratio (OR): 0.62; 95% confidence interval (CI): 0.31, 0.87]; however, the relationship was not significant in fully adjusted models. Patterns of variety intake were differently associated with energy, volume, and diet quality. Children consuming the high VLED variety and the low HED variety had lower odds of obesity [OR: 0.43; 95% CI: 0.21, 0.90]; however, this pattern was rare (10%). CONCLUSIONS: These findings suggest that the variety of HED foods is associated with higher average energy intake per day, and the variety of VLED foods is associated with a higher volume of food consumed per day and diet quality in a nationally representative sample of preschool-aged children.

Obesity Influences T CD4 Lymphocytes Subsets Profiles in Children and Adolescent's Immune Response.

BACKGROUND: OBJECTIVES: Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation in adults with the disease. Because the profile of these cells is poorly understood in the pediatric population, this study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. METHODS: Using flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines, and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n = 20) with those with eutrophy group (EU group, n = 16). Plasma levels of cytokines in both groups were determined by CBA. RESULTS: The OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared with the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, whereas CTLA-4 is decreased in all subpopulations compared with the EU group. Furthermore, Th2, Th17, and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. CONCLUSIONS: CD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

Early childhood (1-5 years) obesity prevention: A systematic review of family-based multicomponent behavioral interventions.

INTRODUCTION: Globally 38.9 million children under age 5 have overweight or obesity, leading to type 2 diabetes, cardiovascular complications, depression, and poor educational outcomes. Obesity is difficult to reverse and lifestyle behaviors (healthy or unhealthy) can persist from 1.5 years of age. Targeting caregivers to help address modifiable behaviors may offer a viable solution. OBJECTIVE: Evaluate the impact of multicomponent family interventions on weight-based outcomes in early childhood and explore related secondary behavior outcomes. METHODS: Four databases were searched (1/2017-6/2022) for randomized controlled trials (RCTs) of obesity-prevention interventions for children (1-5 years). Eligible studies included an objectively measured weight-based outcome, family interventions targeting the caregiver or family, and interventions including at least two behavioral components of nutrition, physical activity, or sleep. RESULTS: Eleven interventions were identified consisting of four delivery modes: self-guided (n = 3), face-to-face group instruction (n = 3), face-to-face home visits (n = 2), and multiple levels of influence (n = 3). The reviewed studies reported almost no significant effects on child weight-based outcomes. Only two studies (one was an underpowered pilot study) resulted in significant positive child weight-management outcomes. Seven of the interventions significantly improved children's dietary intake. CONCLUSION: Except for one, the reviewed studies reported that family based interventions had no significant effects on child weight-based outcomes. Future studies of this type should include measurements of age and sex-based body mass index (BMI) and trajectories, and also examine other important benefits to the children and families.

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is a multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed to estimate the connection between relative leucocyte telomere lengths (rLTL) - biomarker of cellular ageing with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both sexes. The results suggested that rLTL are significantly shorter in obese, compared with lean group (P < 0·01). Negative correlation of rLTL with total oxidant status (TOS) (Spearman's ρ = -0·365, P < 0·001) as well as with C-reactive protein (Spearman's ρ = -0·363, P < 0·001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35 % of total variability; antioxidant factor with 30 % of total variability and lipid antioxidant - biological ageing factor with 12 % of the total variability. The most important predictor of BMI > 30 kg/m2 according to logistic regression analysis was PCA-derived antioxidant factor's score (OR: 1·66, 95th Cl 1·05-2·6, P = 0·029). PCA analysis confirmed that oxidative stress importance in biological ageing is caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homoeostasis deepness, even before any overt disease occurrence.

Association between postterm birth and adverse growth outcomes in children aged 3-6 years: A national retrospective cohort study.

BACKGROUND: Gestational age significantly influences children's growth and development. Yet, the effect of postterm birth (gestation beyond 42 weeks) on children's growth outcomes remains underexplored. OBJECTIVES: This study aimed to assess the impact of postterm birth on adverse growth outcomes in children using a nationally representative sample from China. METHODS: A retrospective cohort study was conducted in China from 1 April 2018, to 31 December 2019. The final analysis included 141,002 children aged 3-6 years from 551 cities. Postterm birth was defined as children with postterm birth at a gestational age of 42 weeks or more. Obesity, overweight and thinness were assessed using body mass index-for-age (BMI-for-age) z-scores, based on the World Health Organization (WHO) Child Growth Standards. Generalised additive models were employed to investigate the non-linear relationship between maternal gestational age and BMI-for-age z scores. Poisson regression models and subgroup analyses with forest plots were performed to examine the associations between postterm birth and the risks of obesity, overweight and thinness in children. RESULTS: We included 141,002 mother-child pairs, of whom 7314 (5.2%) children were classified as postterm births. There exists a non-linear relationship between gestational age and BMI-for-age z scores. Children born postterm exhibited a 46% increased risk of obesity, a 27% increased risk of combined overweight/obesity and a 13% increased risk of thinness. Similar associations were observed in most cases when further sensitivity and subgroup analysis were conducted. CONCLUSIONS: Postterm birth was associated with elevated risks of obesity, overweight and thinness in children aged 3-6 years, independent of sex. These findings underscore the importance of further research across diverse populations to understand the implications of postterm births on child health outcomes.

Effect of a higher protein diet and lifestyle camp intervention on childhood obesity (The COPE study): results from a nonrandomized controlled trail with 52-weeks follow-up.

PURPOSE: In adults, diets rich in protein seem beneficial in relation to satiety, weight loss, and weight management; however, studies investigating dietary protein and weight development in children are scarce and inconsistent. This nonrandomized controlled trial aimed to investigate the effect of a higher protein diet during lifestyle intervention on anthropometry and metabolic biomarkers in children with overweight and obesity. METHODS: Children (n:208) were recruited from two multicomponent lifestyle camps. One camp was assigned as the intervention group. In the intervention group, carbohydrates-rich foods at breakfast and two in-between-meals were replaced with protein-containing foods to increase the amount of protein from ~ 10-15 energy percent (E%) per day to ~ 25E% per day. Other components were similar between groups. Anthropometry and biochemical measurements were collected at baseline, 10 weeks (after camp) and 52 weeks. RESULTS: The intervention group had a non-significant improvement in BMI-SDS (- 0.07 SD (- 0.19; 0.05), p = 0.24) compared to the control group, but in general, there was no effect of a higher protein diet on anthropometry and metabolic biomarkers. Overall, 10 weeks at camp resulted in a more favorable body composition [- 6.50 kg (p < 0.00), - 0.58 BMI-SDS (p < 0.00), and - 5.92% body fat (p < 0.00)], and improved metabolic health, with most changes maintained at 52 weeks. CONCLUSION: A higher protein diet had no significant effect on body composition and metabolic health; however, these lifestyle camps are an efficiatious treatment strategy for childhood obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov with ID: NCT04522921. Preregistered August 21st 2020.

Growth patterns in infants born to women with pregestational overweight/obesity supplemented with docosahexaenoic acid during pregnancy.

BACKGROUND: Previous studies of maternal docosahexaenoic acid (DHA) supplementation during pregnancy have controversial and contrasting results on the short and long-term effects on early child growth. The impact of this nutritional intervention on the postnatal growth patterns in the offspring of women with pregestational overweight/obesity (PGO) also remains controversial. OBJECTIVE: To analyze the postnatal growth patterns during the first 4 months of life in the offspring of women with PGO randomly supplemented with 800 mg/day (PGO-800) compared with normative doses of 200 mg/day (PGO-200) of DHA during pregnancy (<15 weeks of gestation until delivery). METHODS: This study evaluated the growth patterns during the first 4 months of life of 169 infants of the women that participated in the MIGHT study (NCT02574767). We included the infants of women from the PGO-200 (n = 81) and PGO-800 group (n = 88). The growth patterns (weight, length, and head circumference) and change in z-score (World health Organization charts) were evaluated. RESULTS: Throughout the first 4 months of life, the infants of the PGO-800 group had lower weight-for-length z-score (coef. -0.65, 95% confidence interval [CI] -1.07, -0.22, p = 0.003) and lower body mass index-for-age z-score (coef. -0.56, 95% CI -0.99, -0.12, p = 0.012) compared with the PGO-200 group adjusted by maternal body mass index, gestational weight gain, gestational age, insulin in cord blood and infant feeding (exclusive breastfed, not breastfed, and partially breastfed). CONCLUSIONS: Maternal supplementation with DHA during pregnancy could beneficially limit the offspring's postnatal weight gain during the first 4 months of life.

Serum stromal cell-derived factor-1 concentrations are increased and associated with nonalcoholic fatty liver disease in children with obesity.

INTRODUCTION: Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children. METHODS: Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound. RESULTS: Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis. CONCLUSION: These results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders.

The evaluation of kidney function estimation during lifestyle intervention in children with overweight and obesity.

BACKGROUND: Children with overweight and obesity are at risk for developing chronic kidney disease (CKD). During lifestyle adjustment, the first step in the treatment of childhood obesity, body proportions are likely to change. The aim of this study was to examine how lifestyle intervention affects creatinine-based kidney function estimation in children with overweight and obesity. METHODS: This longitudinal lifestyle intervention study included 614 children with overweight and obesity (mean age 12.17 ± 3.28 years, 53.6% female, mean BMI z-score 3.32 ± 0.75). Loss to follow-up was present: 305, 146, 70, 26, and 10 children were included after 1, 2, 3, 4, and 5 (about yearly) follow-up visits, respectively. Serum creatinine (SCr) was rescaled using Q-age and Q-height polynomials. RESULTS: At baseline, 95-97% of the children had a SCr/Q-height and SCr/Q-age in the normal reference range [0.67-1.33]. SCr/Q significantly increased each (about yearly) follow-up visit, and linear mixed regression analyses demonstrated slopes between 0.01 and 0.04 (corresponding with eGFR FAS reduction of 1.1-4.1 mL/min/1.73 m2) per visit. BMI z-score reduced in both sexes and this reduction was significantly higher in males. No correlation between change in rescaled SCr and BMI z-score reduction could be demonstrated. CONCLUSIONS: Rescaled serum creatinine (SCr/Q) slightly increases during multidiscipline lifestyle intervention in this cohort of children with overweight and obesity. This effect seems to be independent from change in BMI z-score. Whether this minor decrease in estimated kidney function has clinical consequences in the long term remains to be seen in trials with a longer follow-up period. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov; Registration Number: NCT02091544.

Individualized morphometric similarity predicts body mass index and food approach behavior in school-age children.

Childhood obesity is associated with alterations in brain structure. Previous studies generally used a single structural index to characterize the relationship between body mass index(BMI) and brain structure, which could not describe the alterations of structural covariance between brain regions. To cover this research gap, this study utilized two independent datasets with brain structure profiles and BMI of 155 school-aged children. Connectome-based predictive modeling(CPM) was used to explore whether children's BMI is reliably predictable by the novel individualized morphometric similarity network(MSN). We revealed the MSN can predict the BMI in school-age children with good generalizability to unseen dataset. Moreover, these revealed significant brain structure covariant networks can further predict children's food approach behavior. The positive predictive networks mainly incorporated connections between the frontoparietal network(FPN) and the visual network(VN), between the FPN and the limbic network(LN), between the default mode network(DMN) and the LN. The negative predictive network primarily incorporated connections between the FPN and DMN. These results suggested that the incomplete integration of the high-order brain networks and the decreased dedifferentiation of the high-order networks to the primary reward networks can be considered as a core structural basis of the imbalance between inhibitory control and reward processing in childhood obesity.

Associations among body mass index, working memory performance, gray matter volume, and brain activation in healthy children.

To investigate the neural mechanisms underlying the association between poorer working memory performance and higher body mass index (BMI) in children. We employed structural-(sMRI) and functional magnetic resonance imaging (fMRI) with a 2-back working memory task to examine brain abnormalities and their associations with BMI and working memory performance in 232 children with overweight/obesity (OW/OB) and 244 normal weight children (NW) from the Adolescent Brain Cognitive Development dataset. OW/OB had lower working memory accuracy, which was associated with higher BMI. They showed smaller gray matter (GM) volumes in the left superior frontal gyrus (SFG_L), dorsal anterior cingulate cortex, medial orbital frontal cortex, and medial superior frontal gyrus, which were associated with lower working memory accuracy. During the working memory task, OW/OB relative to NW showed weaker activation in the left superior temporal pole, amygdala, insula, and bilateral caudate. In addition, caudate activation mediated the relationship between higher BMI and lower working memory accuracy. Higher BMI is associated with smaller GM volumes and weaker brain activation in regions involved with working memory. Task-related caudate dysfunction may account for lower working memory accuracy in children with higher BMI.

Associations between body mass index, sleep-disordered breathing, brain structure, and behavior in healthy children.

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9-11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.

Obesity is associated with decreased gray matter volume in children: a longitudinal study.

Childhood obesity has become a global health problem. Previous studies showed that childhood obesity is associated with brain structural differences relative to controls. However, few studies have been performed with longitudinal evaluations of brain structural developmental trajectories in childhood obesity. We employed voxel-based morphometry (VBM) analysis to assess gray matter (GM) volume at baseline and 2-year follow-up in 258 obese children (OB) and 265 normal weight children (NW), recruited as part of the National Institutes of Health Adolescent Brain and Cognitive Development study. Significant group × time effects on GM volume were observed in the prefrontal lobe, thalamus, right precentral gyrus, caudate, and parahippocampal gyrus/amygdala. OB compared with NW had greater reductions in GM volume in these regions over the 2-year period. Body mass index (BMI) was negatively correlated with GM volume in prefrontal lobe and with matrix reasoning ability at baseline and 2-year follow-up. In OB, Picture Test was positively correlated with GM volume in the left orbital region of the inferior frontal gyrus (OFCinf_L) at baseline and was negatively correlated with reductions in OFCinf_L volume (2-year follow-up vs. baseline). These findings indicate that childhood obesity is associated with GM volume reduction in regions involved with reward evaluation, executive function, and cognitive performance.

Associations of prenatal and concurrent exposure to phenols mixture with anthropometric measures and blood pressure during childhood: A time-varying mixture approach.

BACKGROUND: Environmental phenols were recognized as endocrine disrupting chemicals (EDCs). However, their impact on childhood anthropometric measures and blood pressure (BP) is still inconclusive. Limited studies have simultaneously considered prenatal and childhood exposures in analyzing mixtures of phenols. OBJECTIVE: We investigated the relationships between combined prenatal and childhood exposures (two periodic exposures) to phenol mixtures and anthropometric measure and BP, to further identify the vulnerable periods of phenol exposure and to explore the important individual contribution of each phenol. METHODS: We analyzed 434 mother-child dyads from the Sheyang Mini Birth Cohort Study (SMBCS). The urinary concentrations of 11 phenolic compounds were measured using gas chromatography tandem mass spectrometry. Generalized linear regression models (GLMs) and hierarchical Bayesian Kernel Machine Regression (hBKMR) were used to examine the effects of individual phenolic compounds at each period and of two periodic exposures. RESULTS: In the single-chemical analysis, prenatal or childhood exposure to specific phenols, especially Benzopheone-3 (BP3), 4-tert-Octylphenol (4-tOP), and Benzyl paraben (BePB) were associated with BMI z-scores (BAZ), Waist-to-height ratio (WHtR), and BP. In the hBKMR models, two periodic exposures to phenol mixtures had a U-shaped association with WHtR, primarily driven by childhood BePB exposure. Moreover, among the phenol mixtures analysis, childhood 4-tOP exposure was identified as the primary contributor to the positive association with diastolic BP. Concurrent exposure to phenol mixtures resulted in greater susceptibility. CONCLUSIONS: We found that prenatal and childhood exposure to phenol mixtures might influence childhood obesity and elevate blood pressure levels. Concurrent exposure to 4-tOP may be the primary driver of the positive associations with BP.