Development of a clinical pathway for bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity in the Netherlands.

Introduction In the Netherlands, bariatric surgery in adolescents is currently only allowed in the context of scientific research. Besides this, there was no clinical pathway for bariatric surgery in adolescents. In this paper, the development of a comprehensive clinical pathway for bariatric surgery in adolescents with severe obesity in the is described. Methods The clinical pathway for bariatric surgery in adolescents consists of an eligibility assessment as well as comprehensive peri- and postoperative care. Regarding the eligibility assessment, the adolescents need to be identified by their attending pediatricians and afterwards be evaluated by specialized pediatric obesity units. If the provided treatment is considered to be insufficiently effective, the adolescent will anonymously be evaluated by a national board. This is an additional diligence procedure specifically established for bariatric surgery in adolescents. The national board consists of independent experts regarding adolescent bariatric surgery, and evaluates whether the adolescents meet the criteria defined by the national professional associations. The final step is an assessment by a multidisciplinary team for adolescent bariatric surgery. The various disciplines (pediatrician, bariatric surgeon, psychologist, dietician) evaluate whether an adolescent is eligible for bariatric surgery. In this decision-making process, it is crucial to assess whether the adolescent is expected to adhere to postoperative behavioral changes and follow-up. When an adolescent is deemed eligible for bariatric surgery, he or she will receive preoperative counselling by a bariatric surgeon to decide on the type of bariatric procedure (Roux-en-Y gastric bypass or sleeve gastrectomy). Postoperative care consists of intensive guidance by the multidisciplinary team for adolescent bariatric surgery. In this guidance, several regular appointments are included and additional care will be provided based on the needs of the adolescent and his or her family. Furthermore, the multidisciplinary lifestyle intervention, in which the adolescents participated before bariatric surgery, continues in coordination with the multidisciplinary team for adolescent bariatric surgery, and this ensures long-term counselling and follow-up. Conclusion The implementation of bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity requires the development of a clinical pathway with a variety of disciplines.

Weight Loss and Glycemic Control After Bariatric Surgery in Adolescents With Severe Obesity: A Randomized Controlled Trial.

PURPOSE: Bariatric surgery is regarded as a valuable treatment option for adolescents with severe obesity. However, high-quality evidence of its superiority over prolonged conservative treatment with multidisciplinary lifestyle intervention (MLI) is limited. This study investigated the efficacy and safety of bariatric surgery in adolescents without sufficient weight loss after MLI for severe obesity. METHODS: A two-group randomized controlled trial was designed to assess one-year health effects of bariatric surgery in adolescents with severe obesity. The participants were referred by pediatricians after completing MLI without sufficient effects. Eligible for participation were adolescents aged 14-16 years with severe obesity (age- and sex-adjusted body mass index (BMI) using the International Obesity Task Force cutoffs: BMI ≥40 kg/m2, or ≥35 kg/m2 in combination with comorbidity). Participants were assigned to MLI combined with laparoscopic adjustable gastric banding (n = 29) versus only MLI (n = 30). Participants were included from 2011 to 2019. Main outcomes were weight change and sex- and age-specific BMI loss. Additionaly, glucose metabolism, blood pressure and lipid profile were analysed. RESULTS: 53 patients completed the 12-months follow-up (89.8%). Mean (±standard deviation [SD]) weight loss in the surgery group was 11.2 ± 7.8% after 12 months, compared to a weight gain of 1.7 ± 8.1% in the control group. The fasting insulin, insulin resistance score and lipid profile improved significantly in the surgery group. DISCUSSION: Bariatric surgery was associated with substantial weight loss and improvements in glucose and lipid metabolism after 12 months compared to conservative treatment in adolescents with severe obesity.

Promoting vegetable acceptance in toddlers using a contingency management program: A cluster randomised trial.

Children learn to accept novel foods by repeated exposure to these foods. In the current study, we investigated in toddlers whether a contingency management program (The Vegetable Box), comprising repeated vegetable taste exposure with contingent non-food rewards, is particularly potent at increasing recognition of and willingness to try vegetables. A total of 598 children (1-4 years old) recruited at 26 different day-care centres in the Netherlands took part. The day-care centres were randomly assigned to one of three conditions ('exposure/reward', 'exposure/no reward', or 'no exposure/no reward'). At the start and directly after the 3-month intervention period, all children were asked to identify various vegetables (recognition test; max score = 14) and whether they would like to taste and consume 1 or 2 bite-size pieces of tomato, cucumber, carrot, bell pepper, radish, and cauliflower (willingness to try test). Data were analysed with linear mixed-effects regression analyses (for recognition and willingness to try separately) with condition and time as independent variables, and adjusting for day-care centre clustering. Vegetable recognition significantly increased in both the 'exposure/reward' and the 'exposure/no reward' group, relative to the 'no exposure/no reward' control group. The willingness to try vegetables only increased significantly in the 'exposure/reward' group. Offering vegetables to children at day-care centres significantly increased toddlers' ability to identify various vegetables, but rewards contingent upon tasting vegetables appear particularly effective to also increase children's willingness to try (i.e., taste and consume) different vegetables. This result corroborates and strengthens previous findings demonstrating the efficacy of similar reward-based programs.

A Systematic Review of Instruments Measuring the Division of Care Responsibilities between Children with Type 1 Diabetes and their Parents.

BACKGROUND: The division of care responsibilities between parents and children with type 1 diabetes, and an optimal transfer of responsibilities from parent to child over time are assumed to be key for optimal diabetes outcomes during childhood and adolescence. However, an overview of instruments assessing this division as well as their psychometric qualities is currently lacking. OBJECTIVE: The study aims to 1) identify all existing instruments, 2) evaluate their psychometric properties, and 3) provide an overview of scoring methods. METHODS: Pubmed and PsycINFO were searched using a priori-defined search string. Peerreviewed studies in English using an instrument assessing the division of diabetes care responsibilities between children (6-18 years) and parents were included. In total, 84 of 725 articles qualified, covering 62 unique samples. RESULTS: Thirteen questionnaires were identified. The Diabetes Family Responsibility Questionnaire (DFRQ) was most frequently used across studies. Instructions, content and number of tasks, response options, and scoring methods varied across questionnaires. Recent studies often adapted questionnaires, contributing to the heterogeneity across measures. Overall, reporting and quality of psychometric properties was suboptimal. CONCLUSION: The division of diabetes care responsibilities can be operationalized with various instruments, each having its strengths and weaknesses but all with limited psychometric support. To measure the division of diabetes care responsibilities more adequately, an updated version of the popular DFRQ or a new scale needs to be developed and evaluated.

Human total, basal and activity energy expenditures are independent of ambient environmental temperature.

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.

Parents' and Children's Experiences with a Coordinating Professional in Integrated Care for Childhood Overweight and Obesity-A Novel Dutch Approach.

BACKGROUND: In the new integrated program of care for childhood overweight and obesity (ICCO), a Youth Health Care (YHC) nurse has the role of a coordinating professional. After a broad assessment of strengths and weaknesses in the family setting, this coordinating professional makes a plan of action with the child and parents and involves other professionals when needed. The aim of this study was to explore the experiences of parents and children with the coordinating professional in the ICCO. MATERIAL & METHODS: Semi-structured interviews were conducted with eight families. Interview data were analyzed using content analysis. In addition, descriptive data on involved professionals and referrals was collected with an online questionnaire in 38 families. RESULTS: In total, eight families (8 mothers, 2 fathers, four boys and three girls aged 10-12 yrs) were interviewed and 38 children and parents filled in (three consecutive) online questionnaires. FINDINGS: The main themes related to the experiences of parents and children with the CP: parents and children felt supported and understood by the coordinating professional. They appreciated the broad perspective and personal approach. Contacts with the coordinating professional were not always frequent. Major points of improvement concerned the intensity of the follow-up and collaboration. Only few parents experienced collaboration between the coordinating professional and other professionals in the ICCO. CONCLUSIONS: Parents and children appreciated the personal approach of the Youth Health Care nurse as a CP. The role of the coordinating professional, however, appears not fully implemented yet. Strengthening the promising role of the coordinating professional in the ICCO is recommended.

Weight Gain in Children during the COVID-19 Pandemic and the Protective Effect of Lifestyle Intervention in Children with Obesity.

INTRODUCTION: School closures due to the COVID-19 pandemic affect children's daily structure, mealtimes, physical activity, and sleeping habits, possibly exacerbating weight gain, particularly in vulnerable children with overweight and obesity. This study aimed to evaluate both perceived and objectively measured weight gain in children in the Netherlands during the COVID-19 pandemic and the effect of prior lifestyle intervention. METHODS: A total of 150 children of the Children, Obesity and Lifestyle during COVID-19 (COLC) study (cohort A) reported perceptions of weight change during the COVID-19 pandemic. Anthropometric data of 65 children with overweight and obesity were collected at the expertise Centre for Overweight Adolescent and Children's Healthcare in the same period (COACH; cohort B). RESULTS: In cohort A, 43% of children with overweight and obesity perceived weight gain during the pandemic, compared to 15% of lean children. In cohort B, the BMI z-score increased significantly (+0.065 SD) within 5 months. Participation in a lifestyle intervention for >1 year and having parents with Dutch background was associated with less weight gain, specifically in children with obesity. DISCUSSION/CONCLUSION: In particular, children with overweight and obesity seem to be at risk for accelerated weight gain during the COVID-19 pandemic. Prior long-term participation in a lifestyle intervention protects against this weight gain, which emphasizes the importance of strong support for vulnerable populations during health crises and pleads for wide implementation of lifestyle interventions for children.

The division and transfer of care responsibilities in paediatric type 1 diabetes: A qualitative study on parental perspectives.

AIM: To determine which factors other than child age play a role in the division and transfer of diabetes care responsibilities between parents and children with type 1 diabetes. DESIGN: Qualitative focus group study. METHODS: Across four sites in the Netherlands, 18 parents (13 mothers) of children (9-14 years) with type 1 diabetes participated in four focus groups in 2015-2016, as part of the research project 'Whose diabetes is it anyway?'. Qualitative content analysis and the constant comparison method were used to analyse the data. RESULTS: According to parents, the transfer process included both direct and indirect tasks, had different levels (remembering, deciding, performing), was at times a difficult and stressful process, and showed large variation between families. A large number of child, parent and context factors were identified that affected the division and transfer of diabetes care responsibilities according to parents. Both positive and negative consequences of the transfer process were described for parental and child health, behaviour and well-being. Parental final evaluations of the division and transfer of diabetes care responsibilities appeared to be dependent on parenting values. CONCLUSION: How families divide and transfer diabetes care tasks appeared to be affected by a complex interplay of child, parent and context characteristics, which had an impact on several parent and child domains. IMPACT: Parents struggle with the right timing of transfer, which calls for more support from diabetes nurses. The identified factors can be used as input for integrating a more family-based approach into current age-based guidelines, to improve regular care.

Laparoscopic roux-en-Y gastric bypass versus sleeve gastrectomy for teenagers with severe obesity - TEEN-BEST: study protocol of a multicenter randomized controlled trial.

BACKGROUND: Recent data support the use of bariatric surgery in adolescents with severe obesity following unsuccessful non-surgical treatments. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have demonstrated reasonably similar weight loss and reduction of obesity related comorbidities in randomized trials in adults. SG has internationally become the most commonly used procedure in adolescents, yet long-term outcome data are lacking. No randomized controlled trial comparing SG and RYGB has been performed in adolescents. OBJECTIVE: Determine whether SG is non-inferior to RYGB in terms of total body weight (TBW) loss in adolescents with severe obesity. METHODS: A multicenter randomized controlled non-inferiority trial. Two hundred sixty-four adolescents aged 13-17 (Tanner stage ≥IV) with severe obesity (corrected for age and sex) will be included. Adolescents agreeing to participate will be randomized to either RYGB or SG. The primary outcome is the proportion of participants achieving 20% TBW loss at 3 years postoperatively. Secondary outcomes include (i) change in body weight, body mass index (BMI) and BMI standard deviation score, (ii) incidence of adverse health events and need for additional surgical intervention, (iii) resolution of obesity-related comorbidities, (iv) prevalence of cardio metabolic risk factor measures, (v) bone health measures and incidence of bone fractures, (vi) quality of life including psychosocial health, patient satisfaction and educational attainment and (vii) body composition. Follow-up will extend into the long term. RESULTS: Not applicable. DISCUSSION: This study will, to our knowledge, be the first randomized controlled trial comparing SG and RYGB in adolescents with severe obesity. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register on July 26th, 2018 - NTR7191 - https://www.trialregister.nl/trial/7191 (protocol version 5.0 - February 3th 2020).

The evaluation of an integrated network approach of preventive care for children with overweight and obesity; study protocol for an implementation and effectiveness study.

BACKGROUND: Children with overweight often do not receive appropriate integrated care. An innovative integrated network approach of preventive care for overweight children aged 4-12 years old has been developed and implemented in four neighbourhoods of 's-Hertogenbosch, The Netherlands. This new approach focusses on self-management of the family and is based on the principles of stepped and matched care. Youth health care (YHC) nurses support the families in their new role as central care providers. The aim of this study is to evaluate the implementation and effectiveness of this network approach. METHODS: The implementation of the new approach (reach, functioning of the central care provider, network functioning and patient satisfaction) is assessed by interviews and checklists with professionals and parents of 4-12 year old overweight or obese children. To evaluate effectiveness, we aim to compare 120 overweight or obese children in 's-Hertogenbosch with 60 overweight or obese children outside 's-Hertogenbosch during one year of YHC involvement. Quality of life, psychosocial problems of the child and parental empowerment are the main outcomes of the effectiveness study. Outcomes are measured with digital questionnaires at inclusion, at three months and one year after inclusion. BMI measurements and referrals are distracted from medical files. DISCUSSION: Integrated care for overweight and obese children is high on the agenda of many municipalities in The Netherlands. The new approach is expected to have beneficial effects for overweight children, their parents and professionals. With the results of this study, we can optimize the support for overweight and obese children and their parents. The first results are expected to be available in 2019. TRIAL REGISTRATION: This study is registered in the Dutch Trial Register on 10 November 2017 (NTR number NTR6813). https://www.trialregister.nl/trial/6596 Word count: 281 (max 350).

Overweight and Obesity in Children: More Than Just the Kilos.

A new model of diagnostics and treatment for overweight in children is used for implementation of a new approach toward childhood obesity. Although based in a hospital setting, it is part of a cure and care network with other professionals. By psycho-education about the body at a 6-year-old level, parents and children become informed and competent partners. This knowledge increases their autonomy and ability to make choices. Collaboration with the family's support group or network reduces isolation and increases the feeling of being connected and supported. Together with their support network, they can maintain this healthier lifestyle or adjust it where needed. Family workbooks and worksheets support the child and parents and increase their autonomy, self management skills, and motivation to take part in the cure and care network. The approach is a based on the three basic needs that determine motivation, namely autonomy, competence, and connectedness.

The relationship between parenting stress and parent-child interaction with health outcomes in the youngest patients with type 1 diabetes (0-7 years).

UNLABELLED: To test whether parenting stress and the quality of parent-child interaction were associated with glycemic control and quality of life (QoL) in young children (0-7 years) with type 1 diabetes (T1DM), we videotaped 77 families with a young child with T1DM during mealtime (including glucose monitoring and insulin administration). Parent-child interactions were scored with a specifically designed instrument. Questionnaires assessed general and disease-related parenting stress and (diabetes-specific (DS)) QoL. HbA(1c) (glycemic control) was extracted from the medical records. Both general and disease-related parenting stress were associated with a lower (DS)QoL (r ranged from -0.39 to -0.70, p < 0.05), but not with HbA(1c) levels. Furthermore, with regard to the parent-child interaction, emotional involvement of parents (r = 0.23, p < 0.05) and expressed discomfort of the child (r = 0.23, p < 0.05) were related to suboptimal HbA(1c) levels. There was no clear pattern in the correlations between parent-child interaction and (DS)QoL. CONCLUSION: The results support the notion that diabetes does not only affect the child with T1DM: T1DM is a family disease, as parenting factors (like stress and parent-child interactions) are associated with important child outcomes. Therefore, it is important for health-care providers to not only focus on the child with T1DM, but also on the family system.

[A neonate with an interlabial cyst]. / Een neonaat met een interlabiale cyste.

During a routine physical examination of a term, healthy neonate of Somalian origin we observed an anteriorly located interlabial yellow cyst with visible vascularisation on the outer surface. It caused lateralisation of the urinary meatus without notable obstruction. A Skene's duct cyst, or paraurethral cyst, was clinically diagnosed with spontaneous regression. This is a self-limiting phenomenon of unknown origin that rarely requires surgical drainage in case of urinary obstruction.

METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents - study protocol of a randomized controlled study.

BACKGROUND: The prevalence of childhood obesity and insulin resistance is rising, increasing the risk of diabetes mellitus type 2. To prevent these complications, lifestyle intervention is the corner stone in treatment. However, long-term efficacy of lifestyle intervention is questionable. In addition to lifestyle intervention, pharmacological treatments have been explored. Metformin has been shown to be moderately effective to reduce BMI in obese adolescents with hyperinsulinemia. However, data on pharmacokinetics and long-term efficacy and safety are lacking as well as an evidence-based dosing regimen for this age group. The primary objective of the METFORMIN study is to determine the effect of adding metformin treatment to lifestyle intervention in reducing BMI in obese adolescents with insulin resistance. In addition, the pharmacokinetics of metformin in obese adolescents will be studied. METHODS/DESIGN: The METFORMIN study is a multi-centre prospective study that consists of two 18-month phases: a double-blind randomized placebo-controlled trial (part 1) and an open-label follow-up study (part 2). During part 1, the participants will be given metformin 1,000 mg or placebo twice daily and will be offered a lifestyle intervention programme; 144 participants will be included, 72 in each arm. Primary endpoints are reduction in body mass index, insulin resistance, and percentage body fat. DISCUSSION: This study will provide data on short- and long-term efficacy and safety of metformin and on the pharmacokinetics of metformin in obese adolescents. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01487993; EudraCT nr. 2010-023980-17. Registration date: 06-01-2011.

Qualitative observation instrument to measure the quality of parent-child interactions in young children with type 1 diabetes mellitus.

BACKGROUND: In young children with type 1 diabetes mellitus (T1DM), parents have complete responsibility for the diabetes-management. In toddlers and (pre)schoolers, the tasks needed to achieve optimal blood glucose control may interfere with normal developmental processes and could negatively affect the quality of parent-child interaction. Several observational instruments are available to measure the quality of the parent-child interaction. However, no observational instrument for diabetes-specific situations is available. Therefore, the aim of the present study was to develop a qualitative observation instrument, to be able to assess parent-child interaction during diabetes-specific situations. METHODS: First, in a pilot study (n = 15), the observation instrument was developed in four steps: (a) defining relevant diabetes-specific situations; (b) videotaping these situations; (c) describing all behaviors in a qualitative observation instrument; (d) evaluating usability and reliability. Next, we examined preliminary validity (total n = 77) by testing hypotheses about correlations between the observation instrument for diabetes-specific situations, a generic observation instrument and a behavioral questionnaire. RESULTS: The observation instrument to assess parent-child interaction during diabetes-specific situations, which consists of ten domains: "emotional involvement", "limit setting", "respect for autonomy", "quality of instruction", "negative behavior", "avoidance", "cooperative behavior", "child's response to injection", "emphasis on diabetes", and "mealtime structure", was developed for use during a mealtime situation (including glucose monitoring and insulin administration). CONCLUSIONS: The present study showed encouraging indications for the usability and inter-rater reliability (weighted kappa was 0.73) of the qualitative observation instrument. Furthermore, promising indications for the preliminary validity of the observation instrument for diabetes-specific situations were found (r ranged between |.24| and |.45| for significant correlations and between |.10| and |.23| for non-significant trends). This observation instrument could be used in future research to (a) test whether parent-child interactions are associated with outcomes (like HbA1c levels and psychosocial functioning), and (b) evaluate interventions, aimed at optimizing the quality of parent-child interactions in families with a young child with T1DM.

Diagnostic procedures and treatment of childhood obesity by pediatricians: 'The Dutch approach'.

Child Public Health professionals in the Netherlands refer obese children to a pediatrician to check for underlying causes and comorbidity. What happens to these children in terms of diagnostics and treatment when they visit a pediatrician? To get an overview of the diagnostic procedures and treatment methods a questionnaire was developed and sent to all 583 pediatricians in the Netherlands. Data was obtained of 290 pediatricians from 85% of the general hospitals and all (8) academic hospitals. To define childhood obesity Dutch pediatricians most often use the adult Body Mass Index, only 34% use the sex and age specific IOTF-BMI-criteria. 11% of the (non-obese) overweight children visiting a pediatrician have already comorbidities. All pediatricians perform at least weight and height measurements. Waist circumference is measured by only 42%, ninety-five percent measure blood pressure. To treat obese children without comorbidity thirty different intervention programs were reported. A large variation in diagnostics and interventions of childhood obesity exist. Guidelines in pediatric obesity for diagnostics and treatment are urgently needed.

Changes and tracking of fat mass in pubertal girls.

Puberty is a critical period in body composition development. The influence of puberty on the development of fat mass asks for further investigation. We investigated the development of fat mass during puberty in a longitudinal prospective study in 152 healthy nonobese white girls, initial ages between 9 to 12 years. The influence of menarcheal age and the existing of tracking of fat mass have been analyzed. In 10 years time, participants were measured on eight time points. Various anthropometric data were collected, breast development was staged according to Tanner and body composition was determined with the dual-energy X-ray absorptiometry (DXA) scan. Calculations were made with the use of a linear mixed model. Fat mass increases from 7.9 kg (23.6%) at B1 to 18.5 kg (29.3%) at B5. Fat mass is higher in girls with an early menarche than in girls with a late menarche from B2. Girls in the quartile with initially the lowest fat mass have a chance of being in the same quartile after 10 years of 77% (P < 0.001). Girls in the quartile with initially the highest fat mass, have a risk of staying in the highest quartile of 55% (P < 0.001). Menarcheal age is of great influence on the development of fat mass. Girls with an early menarche, will have a bigger fat mass, especially at the end of puberty. Tracking of fat mass exists: a high amount of fat mass in early puberty will continue to exist at young adulthood.

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. SETTING: We conducted a multicenter prospective trial. DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial.

BACKGROUND: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. OBJECTIVES: The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. DESIGN: We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GH-treated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated. RESULTS: Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. CONCLUSIONS: Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months.