The increase in child obesity in Switzerland is mainly due to migration from Southern Europe - a cross-sectional study.

BACKGROUND: Novel height, weight and body mass index (BMI) references for children in Switzerland reveal an increase in BMI compared to former percentile curves. This trend may be the result of children with parents originating from Southern European countries having a higher risk of being overweight compared to their peers with parents of Swiss origin. We examined the association of generational, migration-related and socioeconomic factors on BMI in Switzerland and expect the results to lead to more targeted prevention programs. METHODS: From contemporary cross-sectional data, we calculated subgroup-specific BMI percentiles for origin. Results for children of Swiss origin were compared with historical BMI data from Zurich. We tested for the association of overweight and obesity with origin and compared the distributions of BMI percentile ranks. Logistic regression analyses were applied to predict probabilities of being overweight or obese by origin and the Swiss neighborhood index of socioeconomic position (SSEP). RESULTS: Compared to the BMI from two generations ago, the newly calculated BMI increased only slightly for children with both parents from Switzerland; 1.2% of these girls and 1.6% of these boys are obese. In the Swiss population, 13% of the children have parents from Southern Europe and the proportion of obesity is 57 and 42% in these boys and girls, respectively. Their BMI medians correspond to those of their parents' countries of origin. For the probability of being overweight or obese, the SSEP differences are less important than the status of origin. CONCLUSION: We identified children with both parents from Southern Europe as the main influence driving the increase in BMI in Switzerland over the past 50 years. A differentiated consideration of the proportions of various migrant groups within cross-sectional samples is essential when monitoring BMI. Ignoring fluctuations can lead to false conclusions.

Prader-Willi Syndrome and Hypogonadism: A Review Article.

Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction and specific dysmorphisms. Hypothalamic dysfunction causes dysregulation of energy balance and endocrine deficiencies, including hypogonadism. Although hypogonadism is prevalent in males and females with PWS, knowledge about this condition is limited. In this review, we outline the current knowledge on the clinical, biochemical, genetic and histological features of hypogonadism in PWS and its treatment. This was based on current literature and the proceedings and outcomes of the International PWS annual conference held in November 2019. We also present our expert opinion regarding the diagnosis, treatment, care and counselling of children and adults with PWS-associated hypogonadism. Finally, we highlight additional areas of interest related to this topic and make recommendations for future studies.

Contemporary height, weight and body mass index references for children aged 0 to adulthood in Switzerland compared to the Prader reference, WHO and neighbouring countries.

Background: In 2011, WHO growth curves replaced those of Prader and colleagues (First Zurich longitudinal study) in Switzerland.Aim: To present contemporary height-, weight- and body mass index (BMI)-for-age references reflecting children's growth in modern Switzerland.Subjects and methods: Cross-sectional sample comprising 30,141 boys and girls aged 0-20 years measured between 2012 and 2019. Height, weight and BMI reference curves were created using the LMS method. Derived percentiles were compared with those of Prader, WHO and neighbouring countries.Results: Growth in the first 5 years is almost identical with Prader curves. Thereafter children are taller, yet their final height is only about 1 cm higher. Today's children, in particular boys, are considerably heavier. In comparison with WHO growth references, Swiss children are taller from the second year until adulthood; the WHO 3rd percentiles lie about 4 cm below those of our updated references. Weight and BMI median percentiles from our sample are similar to those of WHO and higher than the Prader curves. However, the course of the 97th BMI percentile WHO curves extends well below the 97th percentile of the updated Swiss curves.Conclusion: This study provides contemporary reference data for assessing individual growth based on height, weight and BMI of Swiss children.

Less physically active children are shorter.

BACKGROUND: Current concepts of linear growth include genetic, endocrine and nutritional factors. Limited and controversial results exist regarding the effect of physical activity (PA) on linear growth. In 2009, we showed that PA promotes foot length in hypoactive children with Prader-Willi-Syndrome. In the present study we tested the hypothesis that PA related epiphyseal loading has a positive modulating effect on linear growth in healthy school children. METHODS: In 99 healthy schoolchildren, we measured height, foot length and PA by tri-axial accelerometry. PA related epiphyseal loading was expressed as the product between mass (body weight) and acceleration (vector magnitude). Correlation between height, foot length and PA were calculated taking into account co-variables age, sex, parental height, lean and fat mass measured by DEXA. RESULTS: Height SDS (P<0.015, r=0.245) as well as foot length SDS (P<0.001, r=0.363) correlated with PA. Multiple linear regression models showed that muscle mass expressed by lean body mass has higher correlation with PA, height SDS and foot length SDS than fat mass. CONCLUSIONS: This study shows that physically less active children are shorter and have shorter feet. In analogy to the "muscle bone unit", we propose a "muscle epiphyseal unit" which regulates local bone growth as long as epiphyseal plates are still open.

Lean Body Mass in Boys With Prader-Willi Syndrome Increases Normally During Spontaneous and Induced Puberty.

CONTEXT: Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, and hypothalamic dysfunction combined with specific dysmorphisms. In PWS, growth hormone treatment is given primarily to improve body composition, yet lean body mass (LBM) does not normalize. Male hypogonadism is frequent in PWS and becomes evident during puberty. While LBM increases in normal boys during puberty, it is not known whether LBM and muscle mass concomitantly increase in PWS during spontaneous or induced puberty. OBJECTIVE: To describe the peripubertal increment in muscle mass in boys with PWS undergoing growth hormone treatment. DESIGN: Single-center, retrospective descriptive study, using data from 4 years before until 4 years after onset of puberty. SETTING: Primary referral centre for PWS. PATIENTS: Thirteen boys diagnosed with genetically proven PWS. The mean age at onset of puberty was 12.3 years; the mean observation period before (after) onset of puberty was 2.9 (3.1) years. INTERVENTION: Puberty was induced upon pubertal arrest. All boys received internationally standardized growth hormone treatment. MAIN OUTCOME MEASURE: Lean mass index (LMI) determined by dual energy X-ray absorptiometry. RESULTS: LMI increased by 0.28 kg/m2 per year before puberty and by 0.74 kg/m2 per year after the onset of puberty. The time before puberty explained less than 10% of the variation in LMI, whereas the time after puberty onset explained about 25%. CONCLUSION: Boys with PWS showed a recognizable increment in LMI during both spontaneous and induced puberty compared with the prepubertal phase, which was within the trajectories of normal boys. Therefore, timely testosterone substitution in the absence or at arrest of puberty during growth hormone treatment is important to optimize peak LBM in PWS.

Gonadal Hormone Substitution in People with Prader-Labhart-Willi Syndrome: An International Prader-Willi Syndrome Organisation Survey.

BACKGROUND: Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction, and specific dysmorphisms. Hypothalamic dysfunction causes growth hormone deficiency, dysregulation of energy balance, and hypogonadism. Although hypogonadism is prevalent in PWS, there are no clear guidelines for diagnosis and treatment. In particular, gonadal hormone substitution is a matter of debate due to concerns associated with the potentially induced aggressive behaviour, foremost in males, by sex steroids. METHODS: In 2019, a workshop dedicated to hypogonadism was held prior to the 10th International PWS Organization Conference. In this context, we designed a questionnaire to assess "the current standard of care" of hypogonadism in children and adults with PWS, which was sent out to physicians caring for people with PWS worldwide. RESULTS: Responses were received from a total of 24 centres located in 19 countries. Participating centres treat a total number of at least 1,000 children and adults with PWS. Responses showed limited consensus on who should be treated or at what age treatment should commence. Remarkably, very few behavioural problems were attributed to hormone substitution. CONCLUSION: Based on our findings, we make recommendations to progress the knowledge on hypogonadism in PWS and improve daily practice.

High-intensity training increases spontaneous physical activity in children: a randomized controlled study.

OBJECTIVE: To test the hypothesis that resistance training may increase spontaneous physical activity in children. STUDY DESIGN: Two junior ice hockey teams were randomly assigned to unchanged training schedules (team ZSC, 21 boys; mean age, 13.2 years) or to participate twice weekly in guided resistance training for 4 months (team GCK, 25 boys; mean age, 13.4 years). Spontaneous physical activity energy expenditure (SpAEE; 3-axial accelerometry for 7 days), muscle strength, and body composition (dual energy x-ray absorptiometry) were measured at 0, 4, and 12 months. RESULTS: Baseline measures did not differ in the groups, except for higher leg and trunk strength in team ZSC. In the intervention group compared with the control group, SpAEE significantly (P < or = .02) increased at 4 months (+25.5% versus 0%) and 12 months (+13.5% versus -9.5%). Leg and arm strength increased because of training intervention; all other variables were unchanged. None of these variables correlated with changes in SpAEE. CONCLUSION: In boys who play ice hockey, spontaneous physical activity is inducible with resistance training; this effect seems to be independent of changes in body composition and strength. If this was confirmed in unselected children, resistance training might be a new strategy for childhood obesity prevention programs.

Association between foot growth and musculoskeletal loading in children with Prader-Willi syndrome before and during growth hormone treatment.

OBJECTIVE: To explore how foot growth relates to musculoskeletal loading in children with Prader-Willi syndrome (PWS). STUDY DESIGN: In 37 children with PWS, foot length (FL) before and after 6 years of growth hormone therapy (GHT) was retrospectively evaluated with parental and sibling's FL, height, and factors reflecting musculoskeletal loading, such as weight for height (WfH), lean body mass (LBM; dual energy X-ray absorptiometry, deuterium labeled water), physical activity (accellerometry), and walk age. Because of the typically biphasic evolution of body mass and the late walk age in PWS, 2 age groups were separated (group 1, >2.5 years; group 2, < or =2.5 years). RESULTS: Children with PWS normalized height, but not FL after 6 years of GHT. Parental FL correlation with PWS's FL was lower than with sibling's FL. In group 1, FL positively correlated with WfH, LBM, and physical activity. In group 2, FL negatively correlated with age at onset of independent ambulation. Foot catch-up growth with GHT was slower in group 2 compared with group 1. CONCLUSION: In PWS, FL is positively associated with musculoskeletal loading. Small feet in children with PWS before and during long-term GHT may be more than just another dysmorphic feature, but may possibly reflect decreased musculoskeletal loading influencing foot growth and genetic and endocrine factors.

Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies.

CONTEXT: The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency. OBJECTIVES: Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations. DESIGN: The LHX4 gene sequence was determined from patient DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins were characterized using structural predictions, pituitary gene transcription assays, and DNA binding experiments. PATIENTS: A total of 253 patients from 245 pedigrees with GH deficiency and deficiency of at least one additional pituitary hormone was included in the study. RESULTS: In five patients, three types of heterozygous missense mutations in LHX4 that result in substitution of conserved amino acids were identified. One substitution is between the LIM domains (R84C); the others are in the homeodomain (L190R; A210P). The patients have GH deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant pituitary morphology. Structural models predict that the aberrant L190R and A210P LHX4 proteins would have impaired DNA binding and gene activation properties. Consistent with these models, EMSAs and transfection experiments using pituitary gene promoters demonstrate that whereas the R84C form has reduced activity, the L190R and A210P proteins are inactive. CONCLUSIONS: LHX4 mutations are a relatively rare cause of combined pituitary hormone deficiency. This report extends the range of phenotypes associated with LHX4 gene mutations and describes three novel exonic mutations in the gene.

Association between short sleeping hours and physical activity in boys playing ice hockey.

OBJECTIVES: To determine physical activity in healthy boys and how physical activity relates to training and daily awake hours. STUDY DESIGN: In 66 boys (5 to 15 years) affiliated with an ice-hockey club, we measured total daily energy expenditure (TDEE, doubly-labeled water) and basal metabolic rate (ventilated-hood method). Physical activity energy expenditure for the whole day (DAEE), during training, and during spontaneous physical activity was measured by accelerometry and activity protocols. Univariate (UA) and multivariate (MA) correlation analysis was applied. RESULTS: Physical activity level, DAEE, and TDEE for prepubertal (2.0 and 2.2 Mcal/d) and pubertal (bone age >or=13 years; 1.8 and 2.8 Mcal/d) boys were matched to literature data from normal boys of equal age. In prepubertal boys DAEE correlated positively with awake hours (r(UA) = 0.55, r(MA) = 0.39, P < .01). In pubertal boys this correlation was not significant, the slopes between the 2 groups being significantly different (P = .025). In prepubertal boys spontaneous physical activity expenditure correlated significantly positively with training activity expenditure (r(UA) = 0.72, r(MA) = 0.52, P < .001). CONCLUSION: Contrary to findings in adults, where short sleepers had lower physical activity and intensive training was negatively compensated reducing spontaneous physical activity, in physically active prepubertal boys, total daily and spontaneous physical activity relate positively to awake hours and training; suggesting child-specific control of physical activity.

Developmental profiles in young children with Prader-Labhart-Willi syndrome: effects of weight and therapy with growth hormone or coenzyme Q10.

Muscle hypotonia and failure to thrive are key symptoms of Prader-Willi syndrome (PWS) allowing diagnosis during infancy already. Improved general care as well as Coenzyme Q(10) (CoQ(10)) and growth hormone (GH) are administered to improve PWS children's outcome. This study aims to investigate psychomotor development of young PWS children in relation to body weight and body composition at baseline as well as to the effects of GH or CoQ(10) therapy. Twenty-six young children (age 1.0 +/- 0.1 years, mean +/- SEM) with PWS genetically proven at age 0.1 +/- 0.1 years (17 deletions, 8 maternal disomy) were divided into three groups: Group 1 on GH therapy (started in 1994-1996, 6 mg/kg/week) tolerating low body weight (<50th centile), group 2 on GH (1997-2000) and group 3 on CoQ(10) (2001-2002, 2.5 mg/kg/day orally), both combined with active early weight management to achieve weight >50th centile. Anthropometry, body composition and Griffith's developmental scores (DQs) were assessed before therapy and after 12 months. DQs were not related to infants' weight, lean mass or genetic background. DQs improved significantly with chronological age and were best in the most recently diagnosed group. Improved psychomotor development, mainly due to progress in locomotor development, did not differ between GH and CoQ(10) treated groups. In conclusion, while only GH has significant effects on growth and body composition, GH and CoQ(10) therapy act equally on psychomotor development of PWS infants. However, improving psychomotor development may merely reflect an age-related phenomenon additionally depending on early diagnosis and introduction of appropriate care.

Clinical effects of treatment for hypogonadism in male adolescents with Prader-Labhart-Willi syndrome.

BACKGROUND: In boys with Prader-Labhart-Willi syndrome (PWS), hypogonadism causes pubertal arrest and reduces pubertal muscle growth. Formerly, it was assumed that therapy with gonadal hormones accentuates behaviour abnormalities in PWS. Our aim was to assess the clinical effects of human chorionic gonadotropin (hCG) therapy on pubertal development, muscle mass and behaviour in adolescents with PWS. METHODS: 6 peripubertal boys with PWS undergoing long-term treatment with growth hormone were examined 6-monthly for at least 2 years before and after pubertal arrest (13.5 +/- 0.3 years, mean +/- SEM) and the beginning of hCG therapy (500-1,500 IU twice weekly, intramuscularly). Height, weight, pubertal stage, bone age, body composition (by dual-energy X-ray absorptiometry), testosterone levels and behaviour abnormalities (obtained from parents) were assessed. RESULTS: Testicular volume and lean mass were reduced in pubertal boys with PWS. During hCG therapy, testosterone levels and lean mass significantly increased (at the beginning and after 2 years of hCG therapy: 2.3 +/- 0.9 and 10.7 +/- 1.3 nmol/l, -3.1 +/- 0.3 and -1.4 +/- 0.6 SD, respectively), and fat mass stabilized at 38%. The characteristically observed PWS-associated problems, mood instability, aggressiveness and difficulties in social interaction, did not deteriorate during therapy. CONCLUSION: In the present study, timely application of hCG to treat hypogonadism in boys with PWS promoted virilization and normalized muscle mass without detrimental effects on behaviour. Larger studies comparing hCG therapy with testosterone replacement would be useful.

Hypothalamic and gonadal components of hypogonadism in boys with Prader-Labhart- Willi syndrome.

CONTEXT: The specific form of hypogonadism in Prader-Labhart-Willi syndrome (PWS), central or peripheral, remains unexplained. OBJECTIVES: The objectives of this study were to investigate the cause of hypogonadism in PWS and determine whether human chorionic gonadotropin (hCG) treatment can restore pubertal development. DESIGN: This was a clinical follow-up study, divided into two samples, over a duration of 1.5 and 4.5 yr. PATIENTS: Eight male infants and six peripubertal boys (age at start of observation, 0.06-0.93 and 8.1-10.8 yr, respectively) with genetically confirmed PWS were studied. INTERVENTION: hCG (500-1500 U twice weekly) was given from age 13.5 yr to the present. MAIN OUTCOME MEASURES: Serum FSH, LH, inhibin B, and testosterone levels and pubertal development were the main outcome measures. RESULTS: Infants with PWS presented normal LH (2.3 +/- 0.7 U/liter) and testosterone (2.5 +/- 0.9 nmol/liter) levels (mean +/- sem at 5 months) compared with the reference range. However, two thirds of the boys displayed cryptorchidism. Inhibin B levels were at the lowest level of the normal range and decreased significantly between infancy and puberty (at 13 yr, 72 +/- 17 pg/ml), whereas FSH secretion increased (9.9 +/- 2.6 U/liter). Pubertal maturation stopped at an average bone age of 13.9 yr. hCG therapy increased testosterone (11 +/- 2 nmol/liter) and reduced FSH (at 16 yr, 1.1 +/- 0.9 U/liter) levels. Testicular volume (5.6 +/- 1 ml) and inhibin B (26.5 +/- 11.9 pg/ml) remained low. CONCLUSION: Children with PWS display a specific form of combined hypothalamic (low LH) and peripheral (low inhibin B and high FSH) hypogonadism, suggesting a primary defect in Sertoli and/or germ cell maturation or an early germ cell loss. hCG therapy stimulates testosterone production and virilization.

A daily comprehensive muscle training programme increases lean mass and spontaneous activity in children with Prader-Willi syndrome after 6 months.

UNLABELLED: The reduction of spontaneous physical activity (PA) and of muscle tissue are thought to be major causes of fat accretion and metabolic deterioration in Prader-Labhart-Willi syndrome (PWS). We investigated whether a generalized physical training programme in a home setting improves these parameters. The prospective study included 11 prepubertal children (mean age 8.7 years, range 5.9-11.8) with documented PWS and under continuous growth hormone treatment for at least 2.8 years. Seven children were enrolled in a training programme for several muscle groups during 4-10 minutes daily. Twelve matched children with PWS served as controls (average age 8.8 years, 6.1-11.3). Before and after training, at 6 months, PA was assessed by measuring walking distance by pedometer registration and by an activity score, and body composition by DEXA expressed as standard deviation scores (SDS) related to height. After training, lean mass (LM) increased from -1.83 to -1.48 SDS, p <0.05, whereas the controls showed no change. In the training group, walking distance and PA increased from 4.2 to 4.7 km/d and from 255 to 266 points, respectively, and these rises significantly exceeded those observed in controls. CONCLUSION: Children with PWS can be motivated by their families to follow a short daily training, which has general effects on PA and does increase, but not normalize LM.

Behavioral phenotypes in four mental retardation syndromes: fetal alcohol syndrome, Prader-Willi syndrome, fragile X syndrome, and tuberosis sclerosis.

Behavioral phenotypes were studied in four mental retardation syndromes using the Developmental Behavior Checklist (DBC). The four samples comprised fetal alcohol syndrome (FAS), Prader-Willi syndrome (PWS), fragile X syndrome (FRAX), and tuberosis sclerosis (TSC). Both on the item and the subscale level, there were clear behavioral differentiations across the four syndromes. FAS and FRAX proved to be most clearly differentiated from the other two samples, with PWS and TSC showing lower scores and less abnormal behavior profiles. Neither intelligence nor gender nor age contributed to variations in the number of behavior abnormalities. It was concluded that the DBC as a quantitative approach contributes significantly to the differentiation of behavioral phenotypes in various mental retardation syndromes.

A comprehensive team approach to the management of patients with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by extreme obesity accompanied by other, multisystem clinical manifestations encompassing both physical and behavioral/cognitive abnormalities. The multi-dimensional problems of patients with PWS cannot be treated with a single intervention and benefit from a team approach to management to optimize outcomes. Childhood stature below target height and reduced final height are some defining characteristics of PWS, and compelling evidence from growth hormone (GH) treatment trials suggests that hypothalamic GH deficiency exists. Treatment with GH has been shown to increase height velocity in children with PWS, decrease weight-for-height index values and body fat mass, and have a positive effect on lean body mass during at least the first year of therapy. In addition to medical concerns, the behavioral manifestations, including an uncorrectable deficit in appetite control, and cognitive limitations associated with PWS, require long-term multidisciplinary management.

Parent preference in Switzerland for easy-to-use attributes of growth hormone injection devices quantified by willingness to pay.

Sustained treatment adherence, usually over long periods of time, is critical to the success of growth hormone (GH) therapy. However, adherence rates are often poor which may result in suboptimal clinical outcomes. The type of device used by patients to administer their GH can influence adherence. Offering patients a choice of device maximizes the chance of adherence to treatment. Multiple factors will influence a patient's choice of device, depending on individual priorities. This study evaluated the most preferred features of GH injection devices by parents using a web-based questionnaire and as assessed by their willingness to pay for specific device features. The results show that parents are willing to pay for device features facilitating ease of use.

Strength training and physical activity in boys: a randomized trial.

BACKGROUND: In developed societies levels of daily physical activity (PA) among school-age children are decreasing. This implies risk factors for cardiovascular and metabolic diseases. Specific strategies to improve levels of PA are needed. In prepubertal boys there is evidence that strength training increases spontaneous PA outside of training. METHODS: A total of 102 schoolchildren (age 10-14 years) in Switzerland were randomly assigned to physical education classes or to participate twice weekly at a guided strength training program for 19 weeks. Spontaneous PA energy expenditure (PAEE; 3axial accelerometry for 7 days), leg and arm strength, and body composition (dual energy radiograph absorptiometry) were measured at baseline, after 19 weeks of training intervention, and after 3 months of washout. RESULTS: There were no significant differences between the groups at baseline. In the intervention group, PAEE increased by 10% from baseline to end of training in boys (P = .02), but not in girls. Leg and arm strength were increased owing to training intervention in both boys and girls. All other variables were unchanged. Baseline PAEE was significantly negatively correlated with changes of PAEE. CONCLUSIONS: Targeted strength training significantly increases daily spontaneous PA behavior in boys. The less active children showed the greatest increase in spontaneous PAEE. Girls showed a similar increase in strength, but not in spontaneous PAEE. This may be explained by their earlier pubertal development. Strength training may be a promising strategy in schools to counteract decreasing levels of PA.

Deaths in children with Prader-Willi syndrome. A contribution to the debate about the safety of growth hormone treatment in children with PWS.

Irrespective of GH treatment, children with Prader-Willi syndrome (PWS) suffer more frequently and more seriously from respiratory problems than healthy children. The pathogenesis of such respiratory problems in PWS seems to be multifactorial in origin, but mainly related to insufficiency of respiratory muscles and pharyngeal narrowness. Deaths of children with PWS are reported among GH treated as well as untreated children. Our data show that also disturbed body composition plays an important role in fatal outcomes, possibly enhancing the ventilation disorder. For several years, in our recommendations we have pointed out the secondary risks of increasing obesity. In addition, it is recommended for all children with PWS, in particular before institution of GH therapy, to have polysomnography and an otorhinolaryngologic examination performed, and tonsillectomy in the case of enlarged tonsils. Furthermore, upper airway infections should be treated aggressively.