Severe Childhood Obesity Research Articles

Suboptimal Clinical Documentation in Young Children with Severe Obesity at Tertiary Care Centers.

Background and Objectives. The prevalence of severe obesity in children has doubled in the past decade. The objective of this study is to identify the clinical documentation of obesity in young children with a BMI ≥ 99th percentile at two large tertiary care pediatric hospitals. Methods. We used a standardized algorithm utilizing data from electronic health records to identify children with severe early onset obesity (BMI ≥ 99th percentile at age <6 years). We extracted descriptive terms and ICD-9 codes to evaluate documentation of obesity at Boston Children's Hospital and Cincinnati Children's Hospital and Medical Center between 2007 and 2014. Results. A total of 9887 visit records of 2588 children with severe early onset obesity were identified. Based on predefined criteria for documentation of obesity, 21.5% of children (13.5% of visits) had positive documentation, which varied by institution. Documentation in children first seen under 2 years of age was lower than in older children (15% versus 26%). Documentation was significantly higher in girls (29% versus 17%, p < 0.001), African American children (27% versus 19% in whites, p < 0.001), and the obesity focused specialty clinics (70% versus 15% in primary care and 9% in other subspecialty clinics, p < 0.001). Conclusions. There is significant opportunity for improvement in documentation of obesity in young children, even years after the 2007 AAP guidelines for management of obesity.

Melanocortin-4 Receptor Deficiency Phenotype with an Interstitial 18q Deletion: A Case Report of Severe Childhood Obesity and Tall Stature.

Childhood obesity is a growing health concern, associated with significant physical and psychological morbidity. Childhood obesity is known to have a strong genetic component, with mutations in the melanocortin-4 receptor (MC4R) gene being the most common monogenetic cause of obesity. Over 166 different MC4R mutations have been identified in persons with hyperphagia, severe childhood obesity, and increased linear growth. However, it is unclear whether the MC4-R deficiency phenotype is due to haploinsufficiency or dominant-negative effects by the mutant receptor. We report the case of a four-and-a-half-year-old boy with an interstitial deletion involving the long arm of chromosome 18 (46,XY,del(18)(q21.32q22.1)) encompassing the MC4R gene. This patient presented with tall stature and hyperphagia within his first 18 months of life leading to significant obesity. This case supports haploinsufficiency of MC4-R as it describes a MC4-R deficiency phenotype in a patient heterozygous for a full MC4R gene deletion. The intact functional allele with MC4-R haploinsufficiency has the potential to favor a therapeutic response to gastric surgery. Currently, small molecule MC4-R agonists are under development for pharmacologic therapy.

Pediatric obesity: Causes, symptoms, prevention and treatment.

Pediatric or childhood obesity is the most prevalent nutritional disorder among children and adolescents worldwide. Approximately 43 million individuals are obese, 21–24% children and adolescents are overweight, and 16–18% of individuals have abdominal obesity. The prevalence of obesity is highest among specific ethnic groups. Obesity increases the risk of heart diseases in children and adults. Childhood obesity predisposes the individual to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and kidney diseases and causes reproductive dysfunction in adults. Obesity in children is a major health concern of the developed world. The National Health and Nutrition Examination Survey has reported that the prevalence of obesity is on the increase in all the pediatric age groups, in males and females, and in various ethnic and racial groups. Factors, such as eating habits, genetics, environment, metabolism, and lifestyle play an important role in the development of obesity. Over 90% of obesity cases are idiopathic and less than 10% are associated with genetic and hormonal causes. Obesity occurs when the body consumes more calories than it burns, through overeating and underexercising. The symptoms of obesity include breathing disorders, sleep apnea, chronic obstructive pulmonary disease, certain types of cancer such as prostate, bowel, breast and uterine, coronary heart disease, diabetes (type 2 in children), depression, liver and gallbladder problems, gastro-esophageal reflux disease, high blood pressure, high cholesterol, stroke, and joint diseases such as osteoarthritis, pain in knees and lower back. Environmental, behavioral such as consumption of convenience foods, genetic, and family factors contribute to pediatric obesity. Obesity can be countered through lower calorie consumption, weight loss and diet programs, as well as increased physical activity. A number of endogenous molecules including leptin, hypothalamic melanocortin 4 receptor, and mitochondrial uncoupling proteins, are known to affect body weight. These molecules serve as potential targets for the pharmacological manipulation of obesity. Sibutramine and orlistat are primariliy used for the treatment of adult obesity, which produces modest weight loss, of 3–8% compared to placebo. For children and obese adolescents, metformin is used in the case of insulin resistance and hyperinsulinemia. Octreotide is used for hypothalamic obesity. Bariatric surgery is performed for the treatment of severe childhood obesity. The causes, symptoms, prevention and treatment of pediatric obesity are described in the present review.

Cardiometabolic Risks and Severity of Obesity in Children and Young Adults

BackgroundThe prevalence of severe obesity among children and young adults has increased over the past decade. Although the prevalence of cardiometabolic risk factors is relatively low among children and young adults who are overweight or obese, those with more severe forms of obesity may be at greater risk.MethodsWe performed a cross-sectional analysis of data from overweight or obese children and young adults 3 to 19 years of age who were included in the National Health and Nutrition Examination Survey from 1999 through 2012 to assess the prevalence of multiple cardiometabolic risk factors according to the severity of obesity. Weight status was classified on the basis of measured height and weight. We used standard definitions of abnormal values for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, glycated hemoglobin, and fasting glucose and report the prevalence of abnormal values in children and young adults according to weight status.ResultsAmong 8579 children and young adults with a body-mass index at the 85th percentile or higher (according to the Centers for Disease Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Mean values for some, but not all, cardiometabolic variables were higher with greater severity of obesity in both male and female participants, and the values were higher in male participants than in female participants; for HDL cholesterol, the mean values were lower with greater severity of obesity. Multivariable models that controlled for age, race or ethnic group, and sex showed that the greater the severity of obesity, the higher the risks of a low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels.ConclusionsSevere obesity in children and young adults was associated with an increased prevalence of cardiometabolic risk factors, particularly among boys and young men.

Complications of Childhood Obesity Appear Early

Because severe childhood obesity is a growing public health problem, understanding obesity-associated cardiovascular risk factors has importance for

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 – 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 – 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

Growth hormone signaling pathways

Over 20years ago, our laboratory showed that growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway; 4) signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown that SH2B1β is recruited to and phosphorylated by JAK2 in response to GH. SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight.

Links and risks associated with adenotonsillectomy and obesity.

Adenotonsillectomy (A&T) is a very common surgical procedure in children. Over the past 20 years the principal indication for A&T in children has changed from recurrent adenotonsillitis to obstructive sleep apnea. The physiopathology of obstructive sleep apnea syndrome (OSAS) is multifactorial and obesity has been shown to be one of the main factors correlated with its occurrence. On the other hand, the prevalence and severity of childhood obesity have become a veritable epidemic problem in the past 30 years. So the increasing prevalence of obesity in children and high prevalence of obstructive sleep apnea in obese children implies that an increasing number of these children will present for A&T. Due to more prevalent anatomical alterations of the oronasopharyngeal airways, it is often difficult to predict operation success in obese children. However, previous studies supports that although the risk of presence of residual symptoms of OSAS and airway-related perioperative complication in obese may be more than nonobese group, A&T is effective to reduce obstructive symptoms and improve quality of life in obese children with OSAS.

Does Identifying Severe Obesity in Children Predict Cardiometabolic Risk

The prevalence of severe obesity in children is increasing and there is growing concern over the long term health complications these children may face. The purpose of this study was to determine if children with severe obesity present to weight management treatment centres with higher cardiometabolic risk factors compared to children with moderate obesity.

Adoption of the children's obesity clinic's treatment (TCOCT) protocol into another Danish pediatric obesity treatment clinic.

BackgroundTreating severe childhood obesity has proven difficult with inconsistent treatment results. This study reports the results of the implementation of a childhood obesity chronic care treatment protocol.MethodsPatients aged 5 to 18 years with a body mass index (BMI) above the 99th percentile for sex and age were eligible for inclusion. At baseline patients’ height, weight, and tanner stages were measured, as well as parents’ socioeconomic status (SES) and family structure. Parental weight and height were self-reported. An individualised treatment plan including numerous advices was developed in collaboration with the patient and the family. Patients’ height and weight were measured at subsequent visits. There were no exclusion criteria.ResultsThree-hundred-thirteen (141 boys) were seen in the clinic in the period of February 2010 to March 2013. At inclusion, the median age of patients was 11.1 years and the median BMI standard deviation score (SDS) was 3.24 in boys and 2.85 in girls. After 1 year of treatment, the mean BMI SDS difference was −0.30 (95% CI: −0.39; −0.21, p < 0.0001) in boys and −0.19 (95% CI: −0.25; −0.13, p < 0.0001) in girls. After 2 years of treatment, the mean BMI SDS difference was −0.40 (95% CI: −0.56; −0.25, p < 0.0001) in boys and −0.24 (95% CI: −0.33; −0.15, p < 0.0001) in girls. During intervention 120 patients stopped treatment. Retention rates were 0.76 (95% CI: 0.71; 0.81) after one year and 0.57 (95% CI: 0.51; 0.63) after two years of treatment. Risk of dropout was independent of baseline characteristics. Median time spent by health care professionals was 4.5 hours per year per patient and the mean visit interval time was 2.7 months. The reductions in BMI SDS were dependent on gender, parental BMI, and family structure in girls, but independent of baseline BMI SDS, age, co-morbidity, SES, pubertal stage, place of referral, hours of treatment per year, and mean visit interval time.ConclusionsThe systematic use of the TCOCT protocol reduced the degree of childhood obesity with acceptable retention rates with a modest time-investment by health professionals.

Prevalence of severe childhood obesity in England: 2006–2013

BackgroundInternational evidence shows that severe paediatric obesity results in an increased risk of ill health and may require specialised weight management strategies, yet there remains a lack of data on...

Evaluation and Treatment of Severe Obesity in Childhood.

Pediatric obesity is highly prevalent in developed countries globally (and worsening in developing countries) and threatens to shorten the lifespan of the current generation. At highest risk for weight-related comorbidities including Type 2 diabetes mellitus, non-alcoholic fatty liver disease and dyslipidemia is a sub-set of children with severe obesity, often defined as a body mass index (BMI) percentile ≥99th percentile for age and sex. The pathophysiology of severe obesity in childhood is complex, resulting from the dynamic interplay of a myriad of individual and societal factors including genetic predisposition and health behaviors contributing to energy imbalance. Approximately 4–6% of children have severe obesity, representing a common scenario encountered by providers, and intervention is critical to halt ongoing weight gain and, when possible, reverse the trend. Clinical approaches promoting behavioral weight loss may result in modest, albeit clinically significant, reductions in BMI; however, such changes are often difficult to maintain long-term. Data regarding the impact of targeted pharmacotherapy including agents such as orlistat are limited in the pediatric population and again only suggest modest results. However, increasing evidence suggest that surgical treatment, as an adjunct to ongoing lifestyle changes, may be a promising option in carefully-screened adolescents with severe obesity and weight-related comorbidities who are motivated to adhere to the long-term treatment needs.

Is there an Association between Cardio Metabolic Risk and Severity of Obesity in Children and Young Adults?

Skinner et al. performed a cross-sectional analysis from overweight or obese children and young adults (3 to 19 years) to assess the prevalence of multiple cardiometabolic risk factors according to the severity of obesity. It was found that 8579 children and young adults with a body mass index in the 85th percentile or higher, 6.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Cardiometabolic variables were higher with more severe obesity in both sexes, and the values were higher in male participants; for HDL cholesterol, the mean values were lower with more severe obesity. Multivariate models demonstrated that the greater the degree of obesity, the greater the risk of a low level of HDL cholesterol, high systolic and diastolic blood pressure, and high triglycerides and glycated hemoglobin levels [7].

How many steps are our children taking each day?

The increasing prevalence and severity of obesity in children and adolescents has focused our attention on the components of energy balance, diet, and physical activity. With this in mind, it is interesting that there are so few normative data on activity in these age groups. In this issue of The Journal, Barreira et al report on an analysis of NHANES data to evaluate activity levels. In NHANES, accelerometers were used to measure activity levels. Barreira et al used those measures to determine steps per day and, thus, develop sex- and age-specific normative values for the number of steps. Although these values reflect the current situation and should not necessarily be interpreted as healthful levels of activity, they do provide useful information to clinicians and researchers from which comparisons can be made.Article page 139▶ The increasing prevalence and severity of obesity in children and adolescents has focused our attention on the components of energy balance, diet, and physical activity. With this in mind, it is interesting that there are so few normative data on activity in these age groups. In this issue of The Journal, Barreira et al report on an analysis of NHANES data to evaluate activity levels. In NHANES, accelerometers were used to measure activity levels. Barreira et al used those measures to determine steps per day and, thus, develop sex- and age-specific normative values for the number of steps. Although these values reflect the current situation and should not necessarily be interpreted as healthful levels of activity, they do provide useful information to clinicians and researchers from which comparisons can be made. Article page 139▶ Normative Steps/Day and Peak Cadence Values for United States Children and Adolescents: National Health and Nutrition Examination Survey 2005-2006The Journal of PediatricsVol. 166Issue 1PreviewTo provide sex-and-age specific normative values for children and adolescents' accelerometer-determined steps/day, and peak 60-minute cadence adjusted to a pedometer-based scale. Full-Text PDF

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Severe obesity prevalence in 8- to 9-year-old Italian children: a large population-based study.

Little information is available on severe obesity in childhood. This study estimates the prevalence of severe obesity in 8- to 9-year-old children resident in Italy and its association with gender, age, geographical area and parents' nutritional status and education using the World Health Organization (WHO) and International Obesity Task Force (IOTF) criteria. A nationally representative sample of grade 3 Italian students was measured in 2010 (N=42,431) using standardized instruments and methodology. Severe obesity in children was assessed using definitions provided by the WHO and by the IOTF. Prevalence was estimated within categories of sociodemographic variables and their independent effects were estimated using multivariate logistic regression. The estimated prevalence of severe obesity in 2010 was 4.5% (95% confidence interval (CI): 4.2-4.7) according to the WHO definition and 2.7% (95% CI: 2.5-2.9) with IOTF cutoffs. These values were slightly lower than those observed in 2008. The prevalence was higher in males, in 8-year-old children and in the South. Parental low education and high body mass index were strongly associated with childhood severe obesity. According to the definition used, between 30,000 and 50,000 children aged 8-9 years suffer severe obesity in Italy.

Inpatient treatment of children and adolescents with severe obesity in the Netherlands: a randomized clinical trial.

Severe childhood obesity has become a major health problem, and effective, evidence-based interventions are needed. The relative effectiveness of inpatient compared with ambulatory treatment remains unknown. To determine whether an inpatient treatment program is more effective than an ambulatory treatment program at achieving a sustained weight loss in children and adolescents with severe obesity. We conducted a randomized clinical trial with a 2-year follow-up at a tertiary referral center for pediatric obesity in the Netherlands. We recruited 90 children and adolescents aged 8 to 18 years with severe obesity (body mass index [BMI] z score, ≥3.0 or >2.3 with obesity-related health problems). Patients were randomly assigned to an inpatient (6 months of hospitalization on working days) or an ambulatory (12 days of hospital visits at increasing intervals during a 6-month period) treatment program. Both treatment programs involved an intensive, family-based, lifestyle intervention, including exercise, nutritional education, and behavior modification for the patients and their caregiver(s). Change in BMI z score. Secondary outcomes included fasting insulin, fasting plasma glucose, 2-hour plasma glucose, and lipid levels, insulin sensitivity, liver function test results, waist circumference, blood pressure, body composition, and aerobic fitness (peak oxygen consumption, Vo₂). Outcomes were analyzed by intention to treat. Immediately after treatment, reductions in the BMI z score were significantly larger for the inpatient than the ambulatory groups (mean [SE] difference, -0.26 [0.12; 95% CI, -0.59 to -0.01]; P = .04). Change from baseline for the BMI z score in the inpatient group was -18.0% (P = .001) immediately after treatment, -8.5% (P = .008) at 18 months, and -6.3% (P = .38) at 30 months; in the ambulatory group, changes from baseline were -10.5% (P = .001), -6.2% (P = .39), and -1.5% (P > .99), respectively. The favorable outcomes of the inpatient group could not be sustained at 12 and 24 months after treatment. In addition, significant differences in favor of the inpatient group immediately after treatment were found for levels of fasting insulin (-6.37 IU/L; P = .02), total cholesterol (-19.51 mg/dL; P = .01), low-density lipoprotein cholesterol (-13.48 mg/dL; P = .03), and triglycerides (-25.39 mg/dL; P = .01), and insulin sensitivity (-1.37; P = .02), fat mass (-3.31%; P = .03), and peak Vo₂ (378.2 mL/min; P = .01). In severely obese children and adolescents, inpatient treatment was superior to ambulatory treatment immediately after treatment, but effects were not sustained at long-term follow-up. These findings stress the need to further study maintenance strategies for sustainable weight loss. trialregister.nl Identifier: NTR1172.

Severe obesity among children in New York City public elementary and middle schools, school years 2006-07 through 2010-11.

IntroductionAlthough studies have shown that childhood obesity overall is on the decline among New York City (NYC) public school children, the prevalence of severe childhood obesity has not been studied.MethodsWe used height and weight measurements of 947,765 NYC public school students aged 5 to 14 years in kindergarten through 8th grade (K–8), from school years 2006–07 through 2010–11. We used age- and sex-specific body mass index (BMI) percentiles according to Centers for Disease Control and Prevention growth charts to define childhood obesity (BMI ≥ 95th percentile) and severe childhood obesity (BMI ≥120% of 95th percentile) and to identify biologically implausible values (BIV). Multivariable logistic models tested for trends in obesity and severe obesity prevalence. To evaluate misclassification, we recalculated prevalence estimates for the most recent school year (2010–11) including the student records identified as BIV who were also declared severely obese (BMI ≥ 120% of 95th percentile). We refer to this subgroup of BIVs as “high BIV.”ResultsSevere obesity among NYC public school students in grades K–8 decreased 9.5% from the 2006–07 school year (6.3%) to the 2010–11 school year (5.7%), and obesity decreased 5.5% (from 21.9% to 20.7%). The prevalence of severe obesity and obesity was highest among minority, poor, and male children. Severe obesity declined in prevalence among every subgroup, with the greatest effect among white students and wealthy students. Severe obesity prevalence increased with age, and obesity prevalence peaked among those aged 7 to 10 years. For the 2010–11 school year, including high BIVs increased severe obesity prevalence from 5.7% to 6.6% and increased obesity prevalence from 20.7% to 21.5%.ConclusionAmong all subgroups of NYC public school children in grades K–8, the reduction in severe obesity was greater than the reduction in overall obesity. Efforts to decrease obesity in NYC have affected the severely obese; however, monitoring of this specific subgroup should continue because of differences in trends and greater health risks.

Personality profile of obese children and adolescents

Personality traits can affect eating behaviors, the development of obesity, and obesity treatment failure. Because of the scarcity of research on the relationship between personality traits and childhood obesity and its importance in obesity treatment outcome, the current study aimed to assess the personality profile of obese children and adolescents, investigate the relationship between patterns of temperament and character as well as psychopathology in obese youths and explore the relationship between personality traits and severity of childhood obesity and its metabolic complications independent of the impact of psychopathology. After exclusion of children with comorbid psychiatric disorders, 40 obese children were enrolled from the Pediatrics Obesity Clinic, Ain Shams University. They were compared with a matched control group of nonobese children (n=20). The Junior Temperament and Character Inventory was used to assess the personality profile, and Child Behavioral Checklist was used to assess psychopathology. Obese children were found to have significantly higher novelty seeking and harm avoidance behavior compared with nonobese controls. Among obese children, high novelty seeking was associated with externalizing problems, and low self-transcendence was associated with internalizing problems. Higher BMI was associated with higher novelty seeking and lower persistence. Personality traits related to metabolic complications of obesity were persistence, self-transcendence, and self-directedness. Personality traits may contribute to health outcome through their association with obesity and its progression. These data underscore the future potential usefulness of personality assessment in obesity management and suggest the use of cognitive behavioral therapy targeting these personality traits to achieve better treatment outcome.

Pediatric severe obesity: time to establish serious treatments for a serious disease.

Pediatric severe obesity: time to establish serious treatments for a serious disease.