Deeplasia: deep learning for bone age assessment validated on skeletal dysplasias.

BACKGROUND: Skeletal dysplasias collectively affect a large number of patients worldwide. Most of these disorders cause growth anomalies. Hence, evaluating skeletal maturity via the determination of bone age (BA) is a useful tool. Moreover, consecutive BA measurements are crucial for monitoring the growth of patients with such disorders, especially for timing hormonal treatment or orthopedic interventions. However, manual BA assessment is time-consuming and suffers from high intra- and inter-rater variability. This is further exacerbated by genetic disorders causing severe skeletal malformations. While numerous approaches to automate BA assessment have been proposed, few are validated for BA assessment on children with skeletal dysplasias. OBJECTIVE: We present Deeplasia, an open-source prior-free deep-learning approach designed for BA assessment specifically validated on patients with skeletal dysplasias. MATERIALS AND METHODS: We trained multiple convolutional neural network models under various conditions and selected three to build a precise model ensemble. We utilized the public BA dataset from the Radiological Society of North America (RSNA) consisting of training, validation, and test subsets containing 12,611, 1,425, and 200 hand and wrist radiographs, respectively. For testing the performance of our model ensemble on dysplastic hands, we retrospectively collected 568 radiographs from 189 patients with molecularly confirmed diagnoses of seven different genetic bone disorders including achondroplasia and hypochondroplasia. A subset of the dysplastic cohort (149 images) was used to estimate the test-retest precision of our model ensemble on longitudinal data. RESULTS: The mean absolute difference of Deeplasia for the RSNA test set (based on the average of six different reference ratings) and dysplastic set (based on the average of two different reference ratings) were 3.87 and 5.84 months, respectively. The test-retest precision of Deeplasia on longitudinal data (2.74 months) is estimated to be similar to a human expert. CONCLUSION: We demonstrated that Deeplasia is competent in assessing the age and monitoring the development of both normal and dysplastic bones.

Growth Patterns of Children With Short Stature in Adulthood According to Auxological Status and Maturity at Birth.

CONTEXT: Prematurity carries a risk for impaired postnatal growth and long-term growth restriction. Especially children born SGA seem vulnerable for poor growth, as a persistent short stature can be observed in app 10-15% of these children. OBJECTIVE: In this study we aimed to recognize differences in growth patterns of children according to sex, maturity, and auxological status at birth facilitating earlier identification of small-for-gestational-age (SGA) children with adult short stature. METHODS: The growth data of 44 791 infants born between January 1, 1980, and December 30, 2012, among 2 pediatric cohorts with follow-up through December 31, 2020, were analyzed. A total of 5698 children with birth data had measurements at near final height (nfh) and at least 2 further points. RESULTS: Preterm children (gestational age < 37 weeks) had a significantly lower mean nfh SDS than term children (preterm, -0.61; term, -0.18) and a higher likelihood of nfh < third percentile (preterm, 20.5%; term, 12.2%). SGA born children also had a lower mean nfh SD score (SDS) than children born appropriate for gestational age (AGA) (SGA, -1.06; AGA, -0.15) and a higher likelihood of nfh < third percentile (SGA, 28.2%; AGA 10.1%). Of 1204 SGA children, 672 (56%) showed successful catch-up growth (CUG) to nfh greater than or equal to the 10th percentile (SGA-CU), and 532 children (44%) did not (SGA-S). The difference in their mean nfh SDS (SGA-CU, -0.12; SGA-S -2.26) can only partly be explained by the differences in mean mid-parental height SDS (SGA-CU, -0.3; SGA-S, -1.19). During the first year, SGA-CU showed higher CUG (SGA-CU, +1.2 SDS; SGA-S, +0.45 SDS), which helps to discriminate between groups earlier. CONCLUSION: Final growth outcome was influenced by prematurity and auxological status at birth, but not by sex. Height/length SDS increments during year 1 are instrumental to discern SGA children with later normal or short stature. While observing CUG until year 2 and 3 can add specificity, discrimination thereafter becomes difficult.

The Influence of Body Mass Index on the Growth Hormone Peak Response regarding Growth Hormone Stimulation Tests in Children.

INTRODUCTION: Several studies have analyzed the association between the maximal growth hormone serum level obtained during a growth hormone stimulation test (GHMax) and the body mass index-standard deviation score (BMI-SDS). However, as sample sizes were quite small, our study aimed to analyze the association between GHMax and BMI-SDS within a large cohort of 991 children. Further, we investigated other influencing factors, like test type, age, sex, puberty, and preterm birth. METHODS: Children with short stature (height <10th percentile) received growth hormone stimulation tests with arginine or glucagon at the Department of Paediatric Endocrinology of the University of Leipzig Medical Center. The study population included a total of 1,438 tests (633 tests on girls, 805 tests on boys), with the majority consisting of prepubertal children (tests = 1,138). The mean age at testing was 7.74 years. Analyses were carried out on the entire cohort as well as stratified by test types. We performed univariate and multivariate analyses using linear mixed-effect models to assess the effects on GHMax. RESULTS: GHMax and BMI-SDS were significantly negatively associated with an effect size of ß = -1.10 (p < 0.001), independent from the test type. The GHMax values were significantly (p < 0.001) higher for glucagon (mean value: 9.65 ng/mL) than those for arginine tests (mean value: 8.50 ng/mL). Age, sex, premature birth, and puberty were not significantly related to GHMax values. CONCLUSION: We confirmed the negative association between GHMax and weight status of short children found in previous studies. Therefore, considering BMI-SDS may be helpful in the assessment of growth hormone stimulation tests in short-statured children, but it should not be the determining factor for a treatment decision.

[Community-based prevention of obesity in children]. / Gemeinwesen-basierte Prävention und kindliche Adipositas.

Besides individual determinants, obesity is also caused by obesogenic environmental conditions. Thus, prevention of obesity in children should aim at creating health-promoting environments. This is especially important for children of socially disadvantaged families and communities who are hardly reached and often profit less by behavior-oriented interventions. The main question is which environmental conditions should be changed and how in order to be accepted and sustainable? According to our experiences from the project "Grünau moves" (Grünau bewegt sich), the consideration of environmental and social conditions in the intervention field as well as the inclusion of the professional expertise of local agents and the lifeworld perspective (subjective meanings and realities) of families and children are crucial. Based on the fact that the understanding and weighting of health varies between individuals, the starting points for interventions and environmental change must be sought according to the interests and resources of the local community. Combining a medical and social work perspective and focusing on the community work approach can help to link and bundle different perspectives and interests in order to create appropriate and context-specific health-promoting environments.

Age- and weight group-specific weight gain patterns in children and adolescents during the 15 years before and during the COVID-19 pandemic.

BACKGROUND/OBJECTIVES: There is a concern that measures aiming to limit a further spread of COVID-19, e.g., school closures and social distancing, cause an aggravation of the childhood obesity epidemic. Therefore, we compared BMI trends during the 15 years before and during the COVID-19 pandemic. SUBJECTS/METHODS: To assess the change in weight dynamics during the first months of COVID-19, we compared the trends of 3-month change in BMI-SDS (ΔBMI-SDS) and the proportions of children showing a high positive (HPC) or high negative (HNC) weight change between 2005 and 2019 and the respective changes from 2019 (pre-pandemic) to 2020 (after the onset of anti-pandemic measures) in more than 150,000 children (9689 during the pandemic period). The period of 3 months corresponds approximately to the first lockdown period in Germany. RESULTS: During the COVID-19 pandemic, we found a substantial weight gain across all weight and age groups, reflected by an increase in the 3-month change in BMI-SDS (ß = 0.05, p < 0.001), an increase in the proportion of children showing HPC (OR = 1.4, p < 0.001), and a decrease in the proportion of children showing HNC (OR = 0.7, p < 0.001). Besides, we found the same trends since 2005 on a low but stable level with a yearly increase of ΔBMI-SDS by ß = 0.001 (p < 0.001), the odds of HPC increased by ORhigh_pos = 1.01 (p < 0.001), and the odds of HNC decreased by ORhigh_neg = 0.99 (p < 0.001). These rather small effects accumulated to ß = 0.02, ORhigh_pos = 1.14, and ORhigh_pos = 0.85 over the whole period 2005-2019. Alarmingly, both the long-term and the short-term effects were most pronounced in the obese subgroup. CONCLUSIONS: There are positive dynamics in different measures of weight change, indicating a positive trend in weight gain patterns, especially within the group of children with obesity. These dynamics are likely to be escalated by COVID-19-related measures. Thus, they may lead to a significant further aggravation of the childhood obesity pandemic.

Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values.

BACKGROUND: Obesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes. METHODS: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020). FINDINGS: Children with obesity were significantly taller than normal-weight peers, differing at maximum by 7·6 cm (1·4 height, standard deviation scores or SDS) at age 6-8 years. Already at birth, children with obesity were slightly taller and thereafter had increased growth velocities by up to 1·2 cm/year. This growth acceleration was unrelated to parental height, but was accompanied by increased levels of insulin-like growth factor-1 (IGF-1), insulin and leptin. During puberty, children with obesity showed a catch-down in height SDS. The reduction in pubertal growth velocity by up to 25% coincided with a decrease in levels of IGF-1 (by 17%) and testosterone (by 62%) in boys and estradiol (by 37%) in girls. We confirmed these alterations in growth in the independent CrescNet cohort and furthermore provide height reference values for children with obesity for open access. INTERPRETATION: Dynamics of linear growth are altered distinctively in different developmental phases in children with obesity. Early emergence before other profound comorbidities implies predisposition, environmental, and/or endocrine factors affecting growth in early life. Height reference values for children with obesity may enhance the precision of clinical health surveillance. FUNDING: German Research Foundation, German Diabetes Association, EU, ESF, ERDF, State of Saxony, ESPE, Hexal, Novo Nordisk, Pfizer Pharma.

COVID-19 pandemic and families' utilization of well-child clinics and pediatric practices attendance in Germany.

OBJECTIVE: The COVID-19 pandemic and the measures implemented to stop the pandemic had a broad impact on our daily lives. Besides work and social life, health care is affected on many levels. In particular, there is concern that attendance in health care programs will drop or hospital admissions will be delayed due to COVID-19-related anxieties, especially in children. Therefore, we compared the number of weekly visits to 78 German pediatric institutions between 2019 and 2020. RESULTS: We found no significant differences during the first 10 weeks of the year. However, and importantly, from April, the weekly number of visits was more than 35% lower in 2020 than in 2019 (p = 0.005). In conclusion, the COVID-19 pandemic seems to relate to families´ utilization of outpatient well-child clinics and pediatric practice attendance in Germany.

[Primordial prevention in childhood to avoid chronic diseases]. / Primordiale Prävention im Kindesalter zur Vermeidung chronischer Erkrankungen.

Primordial prevention targets the healthy population. It aims at supporting people in developing and maintaining a healthy lifestyle to minimize the development of risk factors for noncommunicable diseases. Childhood offers special starting points and opportunities for this. Essentially for this is the creation of health-promoting conditions. This requires the participation of medical and non-medical professionals. Community organizing can significantly foster this process of interdisciplinary and setting-related work. Primordial prevention in childhood cannot be achieved without the active participation of pediatricians.

"Movement-enhancing footpaths" - A natural experiment on street design and physical activity in children in a deprived district of Leipzig, Germany.

Despite the beneficial effects of physical activity (PA), only 26% of children in Germany meet the WHO's recommendations. Because active play contributes to PA and is accepted by families, the creation of "playable" environments could promote PA. This study is a natural experiment that was conducted to investigate whether slight changes in the physical environment can increase PA in children. In autumn 2016, 140 students from two primary schools located in a deprived district of Leipzig (Germany) gathered ideas on PA-promoting street designs. After protracted negotiations with the city administration, two footpaths were decorated with colored markings (hopscotch grids, labyrinths, "mirror me") in September 2019. 48 observations were made before (August 2019) and after (September/October 2019) the implementation using the System for Observing Play and Recreation in Communities (SOPARC). Age, gender, activity level, bike use, and interactions with the colored markings were recorded. A total of 5455 individuals (including 1099 cyclists) were observed. Almost one fifth of the observed children (0 to 12 years) interacted with the markings. There was a slight increase in vigorous activity in all observed individuals after the implementation (2.9% vs. 6.4%, p < 0.001). The chance for vigorous activity was higher on decorated footpaths (OR 2.45, CI 1.54-3.89, p < 0.001), for children (OR 19.32, CI 13.07-28.56, p < 0.001), and on Sundays (OR 3.39, CI 2.33-4.94, p < 0.001). The participatory development and design of footpaths that support spontaneous active play "on the way" might be one component that can be used to support changes in children's PA behaviors and social interactions.

Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study.

BACKGROUND: Recombinant human growth hormone has been used for more than 30 years and its indications have increased worldwide. There is concern that this treatment might increase mortality, but published data are scarce. We present data from the entire dataset of all eight countries of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium, with the aim of studying long-term overall and cause-specific mortality in young adult patients treated with recombinant human growth hormone during childhood and relating this to the underlying diagnosis. METHODS: This cohort study was done in eight European countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK). Patients were classified a priori based on pre-treatment perceived mortality risk from their underlying disease and followed up for cause-specific mortality. Person-years at risk of mortality and expected rates from general population data were used to calculate standardised mortality ratios (SMRs). FINDINGS: The cohort comprised 24 232 patients treated with recombinant human growth hormone during childhood, with more than 400 000 patient-years of follow-up. In low-risk patients with isolated growth hormone deficiency or idiopathic short stature, all-cause mortality was not significantly increased (SMR 1·1, 95% CI 0·9-1·3). In children born small for gestational age, all-cause mortality was significantly increased when analysed for all countries (SMR 1·5, CI 1·1-1·9), but this result was driven by the French subcohort. In patients at moderate or high risk, mortality was increased (SMR 3·8, 3·3-4·4; and 17·1, 15·6-18·7, respectively). Mortality was not associated with mean daily or cumulative doses of recombinant human growth hormone for any of the risk groups. Cause-specific mortality from diseases of the circulatory and haematological systems was increased in all risk groups. INTERPRETATION: In this cohort, the largest, to our knowledge, with long-term follow-up of patients treated with recombinant human growth hormone during childhood, all-cause mortality was associated with underlying diagnosis. In patients with isolated growth hormone deficiency or idiopathic short stature, recombinant human growth hormone treatment was not associated with increased all-cause mortality. However, mortality from certain causes was increased, emphasising the need for further long-term surveillance. FUNDING: European Union.

A Comprehensive Cohort Analysis Comparing Growth and GH Therapy Response in IGF1R Mutation Carriers and SGA Children.

CONTEXT: IGF1 receptor mutations (IGF1RM) are rare; however, patients exhibit pronounced growth retardation without catch-up. Although several case reports exist, a comprehensive statistical analysis investigating growth profile and benefit of recombinant human growth hormone (rhGH) treatment is still missing. OBJECTIVE AND METHODS: Here, we compared IGF1RM carriers (n = 23) retrospectively regarding birth parameters, growth response to rhGH therapy, near final height, and glucose/insulin homeostasis to treated children born small for gestational age (SGA) (n = 34). Additionally, health profiles of adult IGF1RM carriers were surveyed by a questionnaire. RESULTS: IGF1RM carriers were significantly smaller at rhGH initiation and had a diminished first-year response compared to SGA children (Δ height standard deviation score: 0.29 vs. 0.65), resulting in a lower growth response under therapy. Interestingly, the number of poor therapy responders was three times higher for IGF1RM carriers than for SGA patients (53 % vs. 17 %). However, most IGF1RM good responders showed catch-up growth to the levels of SGA patients. Moreover, we observed no differences in homeostasis model assessment of insulin resistance before treatment, but during treatment insulin resistance was significantly increased in IGF1RM carriers compared to SGA children. Analyses in adult mutation carriers indicated no increased occurrence of comorbidities later in life compared to SGA controls. CONCLUSION: In summary, IGF1RM carriers showed a more pronounced growth retardation and lower response to rhGH therapy compared to non-mutation carriers, with high individual variability. Therefore, a critical reevaluation of success should be performed periodically. In adulthood, we could not observe a significant influence of IGF1RM on metabolism and health of carriers.

[Neighbourhood deprivation and community nutrition environment: associations between the social and built environment and food availability]. / Stadtteildeprivation und Lebensmittelumwelt: Zusammenhänge von sozialen und baulichen Merkmalen der Wohnumgebung und Lebensmittelverfügbarkeit.

OBJECTIVE: Eating habits are influenced by individual socioeconomic status (SES). As the association between neighbourhood characteristics and food availability is still unclear, we investigated the community nutrition environment in different neighbourhoods. METHODS: Using official data of the city of Leipzig, we selected three neighbourhoods which differed in terms of their social (2 deprived vs. 1 affluent) and built (1 large housing estates vs. 2 historic buildings) environment. Data on food outlets were assessed via direct observation (ground truthing). RESULTS: Social and residential environment characteristics are associated with food availability. The proportion of fast food outlets is higher in deprived neighbourhoods compared to the affluent one (25%, 30.4% vs. 13.5%). Neighbourhoods with historic buildings offer a greater variety of food outlets. CONCLUSION: The greater availability of unhealthy food may contribute to the development of obesity. Preventive measures should consider the physical and social environment.

Acceleration of BMI in Early Childhood and Risk of Sustained Obesity.

BACKGROUND: The dynamics of body-mass index (BMI) in children from birth to adolescence are unclear, and whether susceptibility for the development of sustained obesity occurs at a specific age in children is important to determine. METHODS: To assess the age at onset of obesity, we performed prospective and retrospective analyses of the course of BMI over time in a population-based sample of 51,505 children for whom sequential anthropometric data were available during childhood (0 to 14 years of age) and adolescence (15 to 18 years of age). In addition, we assessed the dynamics of annual BMI increments, defined as the change in BMI standard-deviation score per year, during childhood in 34,196 children. RESULTS: In retrospective analyses, we found that most of the adolescents with normal weight had always had a normal weight throughout childhood. Approximately half (53%) of the obese adolescents had been overweight or obese from 5 years of age onward, and the BMI standard-deviation score further increased with age. In prospective analyses, we found that almost 90% of the children who were obese at 3 years of age were overweight or obese in adolescence. Among the adolescents who were obese, the greatest acceleration in annual BMI increments had occurred between 2 and 6 years of age, with a further rise in BMI percentile thereafter. High acceleration in annual BMI increments during the preschool years (but not during the school years) was associated with a risk of overweight or obesity in adolescence that was 1.4 times as high as the risk among children who had had stable BMI. The rate of overweight or obesity in adolescence was higher among children who had been large for gestational age at birth (43.7%) than among those who had been at an appropriate weight for gestational age (28.4%) or small for gestational age (27.2%), which corresponded to a risk of adolescent obesity that was 1.55 times as high among those who had been large for gestational age as among the other groups. CONCLUSIONS: Among obese adolescents, the most rapid weight gain had occurred between 2 and 6 years of age; most children who were obese at that age were obese in adolescence. (Funded by the German Research Council for the Clinical Research Center "Obesity Mechanisms" and others; ClinicalTrials.gov number, NCT03072537 .).

Growth prediction of small for gestational age infants within the first weeks after birth.

ABSTRACT: Being born small for gestational age (SGA) in length is a sign of growth failure due to malnutrition in pregnancy or other serious disorders. In previous publications it was shown that SGA born neonates may experience a compensatory growth spurt (catch-up growth) in infancy and childhood (Olbertz et al. in press). The timing of this growth spurt, however, was not well described. We analyzed longitudinal data of 5,138 SGA infants and children, collected by licensed physicians in Germany and centrally stored in the Database Management System of CrescNet at the University of Leipzig. We confirm that SGA born infants undergo a catch-up in height SDS after birth and up to 2 years of life. 2,712 SGA newborns out of 2,846 showed catch-up in length SDS. The catch-up occurred already during the 4th to 16th postnatal weeks. We analyzed infants who did not show a catch-up within this time period, or even had a loss in height SDS. These infants have a significant lower height SDS throughout the first 5 years after birth and especially in the timeframe of 60th to 64th month after birth (-1.33 mean height SDS in catch-up group, -2.49 in non-catch-up group, p-value < 0.001, CI = [0.827, 1.483]). Even though the medical reasons for the lack of catch-up growth in young SGA infants may not be known, absence of this catch-up within the 4th to 16th postnatal week can be used to early identify SGA infants with high risk of growth failure within the following 5 years.

Challenges in doing multi-disciplinary health promotion research in Germany.

Health problems such as obesity are increasingly addressed by complex intervention programmes which operate at multiple levels of influence (e.g. families, schools, neighbourhoods) involving partners from various academic, professional and cultural backgrounds. Following a complex participatory health promotion approach is challenging, because conflicting interests as well as contextual constraints may occur which are rarely discussed empirically. Process evaluations of some programmes investigate factors influencing the implementation process. However, researchers' perspectives on inter- and transdisciplinary work are mostly neglected. This paper aims at illustrating and critically analysing challenges that arose in the planning and implementation of a health promotion project in a socially deprived neighbourhood in Germany. Drawing on minutes, email conversations, and research diary entries we reflect on discrepancies and difficult interactions within the research team, with collaborating (academic) institutions (interdisciplinary work) and with the community partners (transdisciplinary work) respectively. Differences in language, interests, success criteria, professional preferences and habits as well as contextual factors are worked out and coping strategies or solutions are proposed. According to our experiences, bringing to light researchers' positions, preferences and interactions with the community is necessary to find a balance between research and practice, to develop adequate solutions for challenging situations and to evaluate the process, effectiveness and transferability of a programme. Health promotion research should report not only on the effectiveness of interventions but also on struggles, unsuccessful attempts and useful (or useless) strategies to fuel discourse on opportunities in and the efficacy and transferability of health promotion projects.

Growth and Final Height Among Children With Phenylketonuria.

BACKGROUND AND OBJECTIVES: Growth is an important criterion to evaluate health in childhood and adolescence, especially in patients depending on special dietary treatment. Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism. Patients with PKU depend on a special phenylalanine-restricted diet, low in natural protein. The study aimed to evaluate growth, growth rate, and target height in 224 patients with PKU. METHODS: Retrospective, longitudinal analysis of standardized, yearly measurements of height, weight, and calculated growth rate (SD score [SDS]) of patients with PKU aged 0 to 18 years were conducted by using the national computerized CrescNet database. Inclusion was restricted to patients carried to term with a confirmed diagnosis of PKU or mild hyperphenylalaninemia determined by newborn screening and early treatment initiation. RESULTS: From birth to adulthood, patients with PKU were significantly shorter than healthy German children (height SDS at 18 years: -0.882 ± 0.108, P < .001). They missed their target height by 3 cm by adulthood (women: P = .02) and 5 cm (men: P = .01). In patients receiving casein hydrolysate during childhood, this was more pronounced compared with patients receiving amino acid mixtures (P < .001). Growth rate was significantly reduced during their first 2 years of life and in puberty (growth rate SDS: -1.1 to -0.5 m/year, P < .001 and -0.5; P < .02). CONCLUSIONS: Early diagnosed, treated, and continuously monitored patients with PKU showed reduced height from birth onward. During the last 2 decades, this phenomenon attenuated, probably because of advances in PKU therapy related to protein supplements and special low-protein foods.

Further stabilization and even decrease in the prevalence rates of overweight and obesity in German children and adolescents from 2005 to 2015: a cross-sectional and trend analysis.

OBJECTIVE: Recently several industrialized countries reported a stabilization or even a decrease in childhood overweight and obesity prevalence rates. In Germany, this trend started in 2004. The present study therefore aimed to evaluate whether this trend has continued or even leads in a clear direction. Design/Setting/Subjects BMI (>90th percentile (overweight), >97th percentile (obesity)) from the CrescNet database was analysed in 326 834 children and adolescents according to three age groups (4-7·99, 8-11·99 and 12-16 years), gender and between time points (2005-2015). RESULTS: Trend analysis from 2005 to 2010 demonstrated that the prevalence of overweight and obesity decreased significantly in boys and girls in the entire group (4-16 years) and in 4-7·99-year-olds. From 2010 to 2015 there was a significant decrease in boys for overweight and obesity in the entire group and for overweight among 8-11·99-year-olds. Within the cross-sectional analysis, prevalence rates for overweight decreased significantly for both genders in the age groups of 4-7·99 and 8-11·99 years (2005 v. 2015). For obesity, prevalence rates showed a significant decrease for boys (2005 v. 2015) and girls (2005 v. 2010) in 4-7·99-year-olds. CONCLUSIONS: We observed a further stabilization of overweight and obesity prevalence rates for all age groups and even a decrease in the rates for the younger ages (4-7·99 years, 8-11·99 years). As other industrialized countries have also reported similar trends, it seems that the epidemic of childhood overweight and obesity is reaching a turning point in the industrial part of the world.

Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity.

CONTEXT: Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. OBJECTIVE: We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents. PATIENTS AND METHODS: We measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset <3 years of life from our Leipzig childhood obesity cohort (n = 1204). Sanger sequencing of the leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin <90%. RESULTS: The mean levels of bioactive and immunoreactive leptin were almost identical (41.1±25.2 vs. 41.1±25.4ng/mL). In three probands with the lowest bioactive leptin proportion (<90%) we did not identify mutations in the leptin gene. Compared to immunoreactive leptin, bioactive leptin showed similar and slightly better statistical associations with indices of insulin resistance in correlation and multivariate analyses. CONCLUSION: In our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin. Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels.