Optimizing Childhood Obesity Management: The Role of Edmonton Obesity Staging System in Personalized Care Pathways.

Childhood obesity, affecting 29% of 7-9-year-olds across 33 European countries, is a significant public health challenge. Its persistence into adulthood poses grave health risks influenced by genetic, environmental, and socio-economic factors. Belgium introduced a new care pathway in December 2023, based on the Edmonton Obesity Staging System for Pediatrics (EOSS-P), addressing four health domains and staging obesity severity. This pathway operates across three levels: primary care physicians, Paediatric Multidisciplinary Obesity Management Centres (PMOCs), and Centers of Expertise for Paediatric Obesity Management (CEPOs). Each stage of EOSS-P demands tailored interventions. Early stages involve dietary interventions, physical activity promotion, and behavior modifications. As obesity severity progresses, treatments intensify, encompassing psychological support, anti-obesity medications, and, in some cases, bariatric surgery. Throughout these stages, the involvement of multidisciplinary teams is crucial, emphasizing family-based approaches and continuous monitoring. This article provides detailed guidelines for healthcare professionals, delineating interventions and recommendations tailored to each EOSS-P stage. It emphasizes a holistic approach that extends beyond BMI-based diagnosis, promoting personalized care and prompt escalations between care levels, thereby ensuring optimal management of childhood obesity. This comprehensive framework aims to address the complexities of childhood obesity, emphasizing the importance of timely and targeted interventions for better health outcomes.

Near adult height and BMI changes in growth hormone treated short children with Noonan syndrome: the Belgian experience.

Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no mutation group). Results After a median (P10; P90) duration of 5.4 (2.2-10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.4; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta=0.90, p<0.001), mid-parental height SDS (beta =0.27; p=0.005), birth weight SDS (beta=0.15; p=0.051), age at start (beta=0.07; p=0032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p<0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.

Point-of-care applicable metabotyping using biofluid-specific electrospun MetaSAMPs directly amenable to ambient LA-REIMS.

In recent years, ambient ionization mass spectrometry (AIMS) including laser ablation rapid evaporation IMS, has enabled direct biofluid metabolome analysis. AIMS procedures are, however, still hampered by both analytical, i.e., matrix effects, and practical, i.e., sample transport stability, drawbacks that impede metabolome coverage. In this study, we aimed at developing biofluid-specific metabolome sampling membranes (MetaSAMPs) that offer a directly applicable and stabilizing substrate for AIMS. Customized rectal, salivary, and urinary MetaSAMPs consisting of electrospun (nano)fibrous membranes of blended hydrophilic (polyvinylpyrrolidone and polyacrylonitrile) and lipophilic (polystyrene) polymers supported metabolite absorption, adsorption, and desorption. Moreover, MetaSAMP demonstrated superior metabolome coverage and transport stability compared to crude biofluid analysis and was successfully validated in two pediatric cohorts (MetaBEAse, n = 234 and OPERA, n = 101). By integrating anthropometric and (patho)physiological with MetaSAMP-AIMS metabolome data, we obtained substantial weight-driven predictions and clinical correlations. In conclusion, MetaSAMP holds great clinical application potential for on-the-spot metabolic health stratification.

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.

BACKGROUND: Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. DESIGN: This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. RESULTS: Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p = .0278) and low INHB serum levels (p = .0130) were recorded after CT-HSCT, especially after myeloablative conditioning. CONCLUSION: The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.

Peripheral precocious puberty in Li-Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors.

INTRODUCTION: Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty. CASE PRESENTATION: Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li-Fraumeni syndrome. DISCUSSION: Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li-Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li-Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation. CONCLUSION: In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height.

Objectives: To improve adult height in pubertal girls with a poor height prediction, treatment with growth hormone (GH) can be used in combination with a gonadotropin releasing hormone agonist (GnRHa), to delay closure of the growth plates. However, there are few studies to support this practice, and they show conflicting results. The objective of this trial is to assess the safety and efficacy of this combination treatment in early pubertal girls with a short predicted height, in comparison with matched controls. Design patients and methods: We designed an open-label, multicenter, interventional case-control study. Early pubertal girls with predicted adult height (PAH) below -2.5 SDS, were recruited in tertiary care centers in Belgium. They were treated for four years with GH and GnRHa. The girls were followed until adult height (AH) was reached. AH vs PAH, AH vs Height at start, and AH vs Target Height (TH) were evaluated, as well as safety parameters. Control data were assembled from historical patient files or from patients who preferred not to participate in the study. Results: Sixteen girls with mean age ( ± SD) at start of 11.0 years (± 1.3) completed the study protocol and follow-up. Their mean height ( ± SD) increased from 131.3 ± 4.1 cm (-2.3 ± 0.7 SDS) at start of treatment to 159.8 ± 4.7 cm (-1.1 ± 0.7 SDS) at AH. In matched controls, height increased from 132.3 ± 4.2 cm (-2.4 ± 0.5 SDS) to 153.2 ± 3.4 cm (-2.1 ± 0.6 SDS) (p<0.001). AH surpassed initial PAH by 12.0 ± 2.6 cm in treated girls; and by 4.2 ± 3.6 cm in the controls (p<0.001). Most treated girls reached normal adult height (>-2SD) (87.5%) and 68.7% reached or superseded the target height (TH), which was the case in only a minority of the controls (37.5% and 6.2%, respectively) (p= 0.003 and 0.001). A serious adverse event possibly related to the treatment, was a fracture of the metatarsals. Conclusion: A four-year GH/GnRHa treatment in early pubertal girls with a poor PAH seems safe and results in a clinically relevant and statistically significant increase in AH compared with matched historical controls. Clinical trial registration: ClinicalTrials.gov, identifier NCT00840944.

Micro RNA in Semen/Urine from Non-Obstructive Azoospermia Patients as Biomarkers to Predict the Presence of Testicular Spermatozoa and Spermatogonia.

About half of testicular sperm extraction (TESE) procedures in men with non-obstructive azoospermia (NOA), including men with Klinefelter syndrome (KS), are unsuccessful. To avoid unnecessary invasive surgery, biomarkers for spermatozoa were studied. In addition, markers for spermatogonia in testis tissue were explored. This study aimed to find biomarkers in the semen and/or urine of NOA patients to predict the presence of spermatogonia in the testis. Differentially expressed miRNAs were identified (1) between samples from patients with and without a positive TESE procedure as well as (2) between TESE-negative patients with and without spermatogonia. A total of thirteen upregulated miRNAs (ten in seminal plasma and three in urine) were found in the TESE-negative/spermatogonia-positive group compared to the TESE-negative/spermatogonia-negative group. These miRNAs could be potential biomarkers for spermatogonia; however, more research is necessary to validate their predictive power.

Once-Weekly Semaglutide in Adolescents with Obesity.

BACKGROUND: A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking. METHODS: In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68. RESULTS: A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was -16.1% with semaglutide and 0.6% with placebo (estimated difference, -16.7 percentage points; 95% confidence interval [CI], -20.3 to -13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group. CONCLUSIONS: Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.).

Effect of nationwide reimbursement of real-time continuous glucose monitoring on HbA1c, hypoglycemia and quality of life in a pediatric type 1 diabetes population: The RESCUE-pediatrics study.

Objective: Real-time continuous glucose monitoring (RT-CGM) can improve metabolic control and quality of life (QoL), but long-term real-world data in children with type 1 diabetes (T1D) are scarce. Over a period of 24 months, we assessed the impact of RT-CGM reimbursement on glycemic control and QoL in children/adolescents with T1D treated with insulin pumps. Research design and methods: We conducted a multicenter prospective observational study. Primary endpoint was the change in HbA1c. Secondary endpoints included change in time in hypoglycemia, QoL, hospitalizations for hypoglycemia and/or ketoacidosis and absenteeism (school for children, work for parents). Results: Between December 2014 and February 2019, 75 children/adolescents were followed for 12 (n = 62) and 24 months (n = 50). Baseline HbA1c was 7.2 ± 0.7% (55 ± 8mmol/mol) compared to 7.1 ± 0.8% (54 ± 9mmol/mol) at 24 months (p = 1.0). Participants with a baseline HbA1c ≥ 7.5% (n = 27, mean 8.0 ± 0.3%; 64 ± 3mmol/mol) showed an improvement at 4 months (7.6 ± 0.7%; 60 ± 8mmol/mol; p = 0.009) and at 8 months (7.5 ± 0.6%; 58 ± 7mmol/mol; p = 0.006), but not anymore thereafter (endpoint 24 months: 7.7 ± 0.9%; 61 ± 10mmol/mol; p = 0.2). Time in hypoglycemia did not change over time. QoL for parents and children remained stable. Need for assistance by ambulance due to hypoglycemia reduced from 8 to zero times per 100 patient-years (p = 0.02) and work absenteeism for parents decreased from 411 to 214 days per 100 patient-years (p = 0.03), after 24 months. Conclusion: RT-CGM in pump-treated children/adolescents with T1D showed a temporary improvement in HbA1c in participants with a baseline HbA1c ≥ 7.5%, without increasing time in hypoglycemia. QoL was not affected. Importantly, RT-CGM reduced the need for assistance by ambulance due to hypoglycemia and reduced work absenteeism for parents after 24 months. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02601729].

Glycemic Variability Patterns Strongly Correlate With Partial Remission Status in Children With Newly Diagnosed Type 1 Diabetes.

OBJECTIVE: To evaluate whether indexes of glycemic variability may overcome residual ß-cell secretion estimates in the longitudinal evaluation of partial remission in a cohort of pediatric patients with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Values of residual ß-cell secretion estimates, clinical parameters (e.g., HbA1c or insulin daily dose), and continuous glucose monitoring (CGM) from 78 pediatric patients with new-onset type 1 diabetes were longitudinally collected during 1 year and cross-sectionally compared. Circadian patterns of CGM metrics were characterized and correlated to remission status using an adjusted mixed-effects model. Patients were clustered based on 46 CGM metrics and clinical parameters and compared using nonparametric ANOVA. RESULTS: Study participants had a mean (± SD) age of 10.4 (± 3.6) years at diabetes onset, and 65% underwent partial remission at 3 months. ß-Cell residual secretion estimates demonstrated weak-to-moderate correlations with clinical parameters and CGM metrics (r2 = 0.05-0.25; P < 0.05). However, CGM metrics strongly correlated with clinical parameters (r2 >0.52; P < 0.05) and were sufficient to distinguish remitters from nonremitters. Also, CGM metrics from remitters displayed specific early morning circadian patterns characterized by increased glycemic stability across days (within 63-140 mg/dL range) and decreased rate of grade II hypoglycemia (P < 0.0001) compared with nonremitters. Thorough CGM analysis allowed the identification of four novel glucotypes (P < 0.001) that segregate patients into subgroups and mirror the evolution of remission after diabetes onset. CONCLUSIONS: In our pediatric cohort, combination of CGM metrics and clinical parameters unraveled key clinical milestones of glucose homeostasis and remission status during the first year of type 1 diabetes.

Virtual Reality for Distraction and Relaxation in a Pediatric Hospital Setting: An Interventional Study With a Mixed-Methods Design.

Accumulating evidence supports the use of virtual reality (VR) as an effective pain and anxiety management tool for pediatric patients during specific medical procedures in dedicated patient groups. However, VR is still not widely adopted in everyday clinical practice. Feasibility and acceptability measures of clinicians' experiences are often missing in studies, thereby omitting an important stakeholder in VR use in a clinical setting. Therefore, the aim of this mixed-methods study was to investigate the feasibility, acceptability, tolerability (primary outcomes), and preliminary effectiveness (secondary outcome) of Relaxation-VR in both pediatric patients aged 4-16 years and clinicians. Relaxation-VR is a VR application prototype aimed to provide distraction and relaxation for a variety of patient populations and procedures and is used to reduce anxiety, stress (tension) and pain for children in hospital. Multiple measures of acceptability, feasibility and tolerability, and pre-to-post changes in measures of pain, anxiety, stress and happiness were assessed in pediatric patients. At the end of the study, acceptability and feasibility of VR use was assessed in clinicians. Results indicate that VR use (in particular, the Relaxation-VR prototype) for both distraction and relaxation is acceptable, feasible and tolerable for a variety of pediatric patients aged 4-16 years, as assessed in both patients and clinicians, and can reduce anxiety, pain and tension (stress), and increase happiness in a hospital setting.

Intermittent Scanning Glucose Monitoring or Predicted Low Suspend Pump Treatment: Does It Impact Time in Glucose Target and Treatment Preference? The QUEST Randomized Crossover Study.

Objective: To compare glycemic control and treatment preference in children with type 1 diabetes (T1D) using sensor augmented pump (SAP) with predictive low glucose suspend (SmartGuard®) or pump with independent intermittent scanning continuous glucose monitoring (iscCGM, Freestyle libre ®). Methods: In this open label, cross-over study, children 6 to 14 years of age, treated with insulin pump for at least 6 months, were randomized to insulin pump and iscCGM (A) or SAP with SmartGuard® (B) for 5 weeks followed by 5 additional weeks. The difference in percentages of time in glucose target (TIT), (3.9 - 8.0 mmol/l), <3 mmol/l, > 8 and 10 mmol/l, were analyzed using linear mixed models during the final week of each arm and were measured by blinded CGM (IPro2®). Results: 31 children (15 girls) finished the study. With sensor compliance > 60%, no difference in TIT was found, TIT: A 37.86%; 95% CI [33.21; 42.51]; B 37.20%; 95% CI [32.59; 41.82]; < 3 mmol/l A 2.27% 95% CI [0.71; 3.84] B 1.42% 95% CI [-0.13; 2.97]; > 8 mmol/l A 0.60% 95% CI [0.56, 0.67]; B 0.63% [0.56; 0.70]. One year after the study all participants were on CGM compared to 80.7% prior to the study, with a shift of 13/25 participants from iscCGM to SAP. Conclusions: In this study, no significant difference in glycemic control was found whether treated with SAP (SmartGuard®) or pump with iscCGM. The decision of all families to continue with CGM after the study suggests a positive impact, with preference for SmartGuard®. Clinical Trial Registration: [clinicaltrials.gov], identifier NCT03103867.

Testicular biopsy for fertility preservation in early-diagnosed Klinefelter patients: patient characteristics and long-term follow-up.

RESEARCH QUESTION: Which early-diagnosed Klinefelter syndrome patients have been offered cryopreservation of testicular tissue as part of fertility preservation before spermatogonial stem cell (SSC) loss? Do these Klinefelter syndrome patients present with behavioural, cognitive and/or psychological problems? Does a testicular biopsy procedure have long-term effects on the gonadal development of Klinefelter syndrome patients? DESIGN: Early-diagnosed Klinefelter syndrome patients followed between 2009 and 2020 and offered testicular tissue banking in an experimental context at the Universitair Ziekenhuis Brussel were included. The prevalence of behavioural, cognitive and/or psychological problems was determined. Changes in testicular volume and in gonadal function (LH, FSH, testosterone and inhibin B [INHB]) were studied. RESULTS: Of the 48 Klinefelter syndrome patients included, 22 had testicular tissue removed (biopsy group) and 26 had no surgical intervention (control group). The need for specialized education was significantly higher in prenatally (P = 0.0159) and prepubertally (P = 0.0002) diagnosed Klinefelter syndrome patients. Psychological problems were significantly more prevalent in Klinefelter syndrome patients who did not opt for fertility preservation (P = 0.0447). In the first 4.2 (1.9-9.1) years after testicular biopsy, no difference in testicular volume was observed between the biopsied and the contralateral non-biopsied testes (P > 0.9999). After pubertal onset, no differences in LH, FSH, testosterone and INHB were found between the biopsy and the control groups (P = 0.1324 for LH, P > 0.9999 for FSH, P = 0.5433 for testosterone, P > 0.9999 for INHB). CONCLUSION: Early-diagnosed Klinefelter syndrome patients presented with behavioural, cognitive and/or psychological problems. Only psychological problems seemed to influence the decision towards fertility preservation. Follow-up data confirm that harvesting testicular tissue does not have a long-term impact on the gonadal development of Klinefelter syndrome patients.

Intratesticular xenografting of Klinefelter pre-pubertal testis tissue as potential model to study testicular fibrosis.

RESEARCH QUESTION: Is intratesticular xenotransplantation a potential ex-vivo model for studying testicular fibrosis related to Klinefelter syndrome? STUDY DESIGN: First, a feasibility study of an ex-vivo model to study testicular fibrosis in patients with Klinefelter syndrome was performed. Testis tissue from boys with pre-pubertal Klinefelter syndrome (n = 3) and controls (n = 2) (<18 years) was grafted to the mouse testis (n = 12) and recovered after 2, 4, 6 and 8 weeks. Part two of this study consisted of a validation of this model, evaluating the effects of the mast cell blocker ketotifen on the histology of the grafts of Klinefelter syndrome (n = 5) and controls (n = 3), transplanted to mice (n = 10), after 4 weeks of ketotifen or saline treatment. Immunohistochemistry determined the histology of the grafts and the presence of mast cells and spermatogonia. RESULTS: The feasibility study showed that 4 weeks after transplantation, all Klinefelter syndrome grafts could be recovered. Later, degeneration was observed. Most recovered grafts showed an intact histology, with 67 ± 12% intact tubules for the Klinefelter syndrome grafts and 65 ± 15% of intact tubules for the control grafts. In the few remaining Klinefelter syndrome grafts, treatment with ketotifen improved testicular histology compared with non-treated grafts. Graft survival was patient dependent. No germ cell loss was observed after transplantation. CONCLUSION: Xenografting could become a model for the longitudinal study of the fibrotic process related to Klinefelter syndrome; however, the current model has a limited survival period and patient-specific differences in histology.

Endothelial function and its determinants in children born after maternal bariatric surgery.

BACKGROUND: Children born from mothers who underwent bariatric surgery were found to have an improved lipid profile and lower CRP levels compared to siblings born before surgery. We hypothesized that surgery before pregnancy might also influence endothelial function in the offspring. METHODS: Blood sample analysis, blood pressure (BP) measurement, and peripheral arterial tonometry (PAT) were performed in 142 children (median age 10.5 years), either born from mothers who underwent bariatric surgery (BS) before pregnancy (n = 36) from mothers with overweight/obesity (OW/OB) (n = 71) or from normal weight (NW) mothers (n = 35), allowing the determination of the Reactive Hyperemia Index (RHI) in 111 children. RESULTS: Children of the BS group had a higher diastolic blood pressure SDS and a lower RHI compared to the children of the OW/OB and NW group (1.32 versus 1.37 in OW/OB and 1.70 in NW; p = 0.004). After log transformation and correction for age, weight SDS, BMI SDS, body fat percentage, and diastolic BP SDS, RHI was comparable between the groups. CONCLUSIONS: Children of mothers who underwent bariatric surgery before pregnancy do not have a disturbed endothelial function before puberty, when their increased diastolic BP and degree of adiposity is taken into account. IMPACT: Children born after maternal bariatric surgery have a higher diastolic blood pressure without impaired endothelial function. To our knowledge, this is the first study that investigates the vascular function of children based on maternal characteristics during pregnancy. Adult offspring of mothers with obesity during pregnancy have an increased cardiovascular mortality. Since we cannot demonstrate a childhood-onset primary vascular dysfunction, this cardiovascular vulnerability might be more related to the hypertension and body adiposity. Thus, more emphasis should be made on the prevention of obesity and hypertension in the offspring at risk for development of obesity.

Paediatric obesity: a systematic review and pathway mapping of metabolic alterations underlying early disease processes.

BACKGROUND: The alarming trend of paediatric obesity deserves our greatest awareness to hinder the early onset of metabolic complications impacting growth and functionality. Presently, insight into molecular mechanisms of childhood obesity and associated metabolic comorbidities is limited. This systematic review aimed at scrutinising what has been reported on putative metabolites distinctive for metabolic abnormalities manifesting at young age by searching three literature databases (Web of Science, Pubmed and EMBASE) during the last 6 years (January 2015-January 2021). Global metabolomic profiling of paediatric obesity was performed (multiple biological matrices: blood, urine, saliva and adipose tissue) to enable overarching pathway analysis and network mapping. Among 2792 screened Q1 articles, 40 met the eligibility criteria and were included to build a database on metabolite markers involved in the spectrum of childhood obesity. Differential alterations in multiple pathways linked to lipid, carbohydrate and amino acid metabolisms were observed. High levels of lactate, pyruvate, alanine and acetate marked a pronounced shift towards hypoxic conditions in children with obesity, and, together with distinct alterations in lipid metabolism, pointed towards dysbiosis and immunometabolism occurring early in life. Additionally, aberrant levels of several amino acids, most notably belonging to tryptophan metabolism including the kynurenine pathway and its relation to histidine, phenylalanine and purine metabolism were displayed. Moreover, branched-chain amino acids were linked to lipid, carbohydrate, amino acid and microbial metabolism, inferring a key role in obesity-associated insulin resistance. CONCLUSIONS: This systematic review revealed that the main metabolites at the crossroad of dysregulated metabolic pathways underlying childhood obesity could be tracked down to one central disturbance, i.e. impending insulin resistance for which reference values and standardised measures still are lacking. In essence, glycolytic metabolism was evinced as driving energy source, coupled to impaired Krebs cycle flux and ß-oxidation. Applying metabolomics enabled to retrieve distinct metabolite alterations in childhood obesity(-related insulin resistance) and associated pathways at early age and thus could provide a timely indication of risk by elucidating early-stage biomarkers as hallmarks of future metabolically unhealthy phenotypes.

Clinical and biological correlates of morning serum cortisol in children and adolescents with overweight and obesity.

BACKGROUND AND AIM: A fraction of children with obesity have increased serum cortisol levels. In this study, we describe the clinical characteristics of obese children and adolescents with elevated morning serum cortisol levels and the relationship between the cortisol levels and components of the metabolic syndrome. METHODS: Retrospective medical record review study of children aged 4 to 18 years with overweight or obesity seen for obesity management in the Pediatric Obesity Clinic of the UZ Brussel between 2013 and 2015. RESULTS: A total of 234 children (99 boys and 135 girls) with overweight (BMI z-score > 1.3) without underlying endocrine or genetic conditions were included. Mean (SD) age was 10.1 (2.8) years, BMI SD-score 2.5 (0.6), and body fat percentage 37% (7.9). Serum fasting cortisol levels were elevated (>180 µg/L) in 49 children, normal (62-180 µg/L) in 168, and decreased (<62 µg/L) in 12. Serum fasting cortisol was not significantly correlated with gender, age, or degree of adiposity. But correlated significantly with fasting glucose (Rs = 0.193; p < 0.005), triglycerides (Rs = 0. 143; p < 0.05), fibrinogen (Rs = 0.144; p < 0.05) and leptin levels (Rs = 0.145; p < 0.05). After adjustment for serum insulin and leptin, the correlation between serum cortisol and fasting glucose remained significant. CONCLUSION: Elevated morning serum cortisol levels were found in 20% of overweight or obese children and adolescents, irrespective of the degree of adiposity, and were associated with higher fasting glucose, irrespective of underlying insulin resistance. The long-term cardiometabolic consequences of hypercortisolemia in childhood obesity needs further study.

Feasibility and Tolerance of Fingertip Peripheral Arterial Tonometry Measurements in School-Aged Children.

Background: Assessment of the endothelial function of the microvasculature by peripheral arterial tonometry (PAT) has gained increasing popularity in pediatrics. Discomfort or experienced pain during fingertip PAT has only been studied in adolescents and adults. Methods: In 142 children (aged 4-11 years old), a fingertip PAT with a commercial device (EndoPAT 2000®) as well as a caliper and ultrasound examination of peripheral skinfolds were performed as part of a cross-sectional cohort study. In 110 children, Faces Pain Scale (FPS-R) data were collected after PAT and skinfold measurements by caliper and ultrasound. Results: In 111 out of the 142 PAT measurements (78.2%), a reactive hyperemia index (RHI) could be obtained. The most frequent error messages by the software was a "too noisy" and/or a "poor quality" signal. The success rate was higher in children aged older than 6 years (83.1 vs. 44.4%; p < 0.001). Median (range) FPS-R after PAT was 0 (range 0-6) but was significantly higher than the median pain experienced after caliper measurements of peripheral skinfolds (p < 0.001). No pain was experienced by 59 of the 110 children (54.1%). Conclusion: PAT testing is feasible in the great majority of school-aged children, and the procedure is well-tolerated.

Psychogenic polydipsia in a female adolescent without a psychiatric background: A case report.

Psychological stress is a risk factor for primary polydipsia in adolescents without psychiatric comorbidity. Taking a detailed family and social history can help to distinguish primary polydipsia from diabetes insipidus in adolescents with challenging presentations of polydipsia and polyuria.

Adiposity, psychomotor and behaviour outcomes of children born after maternal bariatric surgery.

BACKGROUND: Bariatric surgery before pregnancy can result in improved maternal fertility. However, long-term data on the consequences at childhood age are currently lacking. METHODS: EFFECTOR is a prospective cohort study of children (aged 4 to 11 years) born to mothers who underwent bariatric surgery (BS) before pregnancy (n = 36), controls with overweight/obesity (OW/OB) matched on pre-pregnancy BMI (n = 36) and normal weight controls (NL) (n = 35). We performed prospective collection of anthropometric data, data on psychomotor development, school functioning and behaviour (Strengths and Difficulties Questionnaire (SDQ), Child Behaviour Checklist (CBCL)). RESULTS: The children born after bariatric surgery (BS) presented with the highest body-weight SDS (0.70 vs 0.14 in OW/OB and -0.09 in NL; P = .006) and BMI SDS (0.47 vs -0.02 in OW/OB and -0.42 in NL; P = .01). A higher excess in body fat percentage and waist circumference SDS were found in the BS group (5.7 vs 1.4 in OW/OB and -0.1 in NL; P < .001 and 0.61 vs 0.16 in OW/OB and -0.15 in NL; P = .04). The SDQ questionnaires revealed a higher amount of overall problems in the BS offspring (11.1 vs 7.5 in OW/OB and 8.1 in NL; P = .03), with a higher externalizing score at the CBCL (52.0 vs 44.2 in OW/OB and 47.0 in NL; P = .03). CONCLUSION: Maternal bariatric surgery does not appear to protect the offspring for childhood overweight and obesity. Parents reported more behaviour problems in these children, especially externally of nature.