Abnormal blood pressure and pediatric obesity phenotype: Red flags for clinical practice.

BACKGROUND AND AIMS: systolic and diastolic blood pressure values identify different subtypes of Primary Hypertension. In pediatric age, hypertension is often related to obesity. Characterization of an individual's Blood Pressure (BP) status needs multiple measurements in the course of time, but this is rarely the case, principally in everyday pediatrics. Thus, the finding of abnormal BP values even in a single routine check visit should need a special attention. The aim of this study was to evaluate if even a single abnormal measurement could be a marker of metabolic risk, according to clinical and/or metabolic phenotype and subtypes of hypertension in a population of overweight/obese children and adolescents. METHODS AND RESULTS: We reviewed data from 489 overweight-obese children and adolescents. BP values were classified according to American Academy of Pediatrics Guidelines (2017). Considering study design, we used the term "Abnormal" instead of "High" BP. Data on lipid profile, glucose metabolism and ultrasonographic pattern of the liver were recorded. Mean age was 9.4 ± 2.5 years: 76.9% had normal BP values. Children with Abnormal BP harbored more frequently an unfavorable metabolic profile. Children with Abnormal Systolic-Diastolic BP values had higher BMI z-score and Waist to Height ratio (p = 0.022 and p = 0.032). Hepatic Steatosis was detected in 4.5%, 14.8 % and 17.6 % of children with normal, abnormal systolic and abnormal systo-diastolic blood pressure, respectively. (p < 0.001). CONCLUSION: Identification of abnormal BP subtypes even in a single measurement could be useful for identification of specific clinical-metabolic phenotypes allowing an individual targeted management of obesity-related comorbidities.

Relationship between salt consumption and iodine intake in a pediatric population.

PURPOSE: The World Health Organization recommends reduction of salt intake to < 5 g/day and the use of iodized salt to prevent iodine deficiency states. A high prevalence of excess salt consumption and an inadequate iodine intake has been previously shown in an Italian pediatric population. It was appropriate, therefore, to analyse in the same population the relationship occurring between salt consumption and iodine intake. METHODS: The study population was made of 1270 children and adolescents. Estimates of salt consumption and iodine intake were obtained by measuring 24 h urinary sodium and iodine excretion. RESULTS: The iodine intake increased gradually across quartiles of salt consumption independently of sex, age and body weight (p < 0.001). Median iodine intake met the European Food Safety Authority adequacy level only in teenagers in the highest quartile of salt consumption (salt intake > 10.2 g/day). We estimated that approximately 65-73% of the total iodine intake was derived from food and 27-35% from iodized salt and that iodized salt made actually only 20% of the total salt intake. CONCLUSION: In this pediatric population, in face of an elevated average salt consumption, the use of iodized salt was still insufficient to ensure an adequate iodine intake, in particular among teenagers. In the perspective of a progressive reduction of total salt intake, the health institutions should continue to support iodoprophylaxis, in the context of the national strategies for salt reduction. In order for these policies to be successful, in addition to educational campaigns, it is needed that the prescriptions contained in the current legislation on iodoprophylaxis are made compelling through specific enforcement measures for all the involved stakeholders.

Anthropometric characteristics of newborns with Prader-Willi syndrome.

This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader-Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11-13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p < .0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.

Adjusting insulin doses in patients with type 1 diabetes who use insulin pump and continuous glucose monitoring: Variations among countries and physicians.

AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Nearly half of the adolescents in an Italian school-based study exceeded the recommended upper limits for daily caffeine consumption.

AIM: No data are available on caffeine consumption among Italian adolescents. We investigated caffeine intake from coffee, soft drinks and energy drinks in a sample of Italian adolescents and determined if they exceeded the recommended limits. METHODS: The study comprised 1213 adolescents with a mean age of 15.1 years (range 12-19) from four schools in Foggia, southern Italy. Caffeine intake was assessed using an anonymous self-reported questionnaire during the 2013/2014 school year. We calculated the percentage of daily caffeine consumers, their mean intake of caffeine from beverages and the contribution of each beverage category to the total caffeine intake. RESULTS: Approximately 76% of the sample consumed caffeine every day, amounting to 125.5 ± 69.2 mg/day and 2.1 ± 1.2 mg/kg/day. When we applied the reference values from the Academy of Pediatrics, we found that 46% of the adolescents exceeded the recommended upper limits. Coffee was the most frequently consumed caffeinated drink and the main contributor to daily caffeine intake. CONCLUSION: More than three quarters (76%) of the Italian adolescents in our study drank coffee on a daily basis and nearly half (46%) exceeded the recommended upper limits. Strategies are needed to reduce caffeine consumption by adolescents.

A multi-modal training programme to improve physical activity, physical fitness and perceived physical ability in obese children.

Actual and perceived physical abilities are important correlates of physical activity (PA) and fitness, but little research has explored these relationships over time in obese children. This study was designed: (a) to assess the feasibility of a multi-modal training programme promoting changes in PA, fundamental motor skills and real and perceived physical abilities of obese children; and (b) to explore cross-sectional and longitudinal relationships between real and perceived physical competence in boys and girls. Forty-one participants (9.2 ± 1.2 years) were assessed before and after an 8-month intervention with respect to body composition, physical fitness, self-reported PA and perceived physical ability. After treatment, obese children reported improvements in the body mass index, PA levels, gross motor performance and actual and perceived physical abilities. Real and perceived physical competence was correlated in boys, but not in girls. Results indicate that a multi-modal programme focused on actual and perceived physical competence as associated with the gradual increase in the volume of activity might be an effective strategy to improve adherence of the participants and to increase the lifelong exercise skills of obese children.

Children's diet assessed with the Mediterranean Diet Index: the finding of new eating habits and their impact on a cohort of Italian children.

OBJECTIVES: Mediterranean Diet (MD) has been inversely associated with many diseases: it reduces total mortality and lowers cardiovascular risk. Despite the known benefits of MD, variations of dietary habits have occurred in recent years especially in young people. The aim of our study is to evaluate MD adherence in a cohort of Italian children and adolescents living in Southern Italy. METHODS AND RESULTS: Adherence to MD was evaluated with the Mediterranean Diet Index (KIDMED). Sex, age, and anthropometric measures were recorded on a population of 132 children; of those 71.2% showed poor adherence to MD, 26.5% average adherence and only 2.3% good adherence. Higher prevalence of poor adherence was recorded in obese children and there was statistically significant inverse correlation between age and adherence score. CONCLUSIONS: Our results highlight low adherence to MD in a cohort of Italian children. These findings support the importance of monitoring dietary habits, especially in adolescents.

The Italian registry for patients with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients' care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. MATERIALS AND METHODS: The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. RESULTS: A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019-2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. CONCLUSIONS: The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.

Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes.

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1-5% of patients with diabetes. Some of these variants are harbored by genes whose altered function can be tackled by specific actions ("actionable genes"). In suspected patients, molecular diagnosis allows the implementation of effective approaches of precision medicine so as to allow individual interventions aimed to prevent, mitigate or delay clinical outcomes. This review will almost exclusively concentrate on the clinical strategy that can be specifically pursued in carriers of mutations in "actionable genes", including ABCC8, KCNJ11, GCK, HNF1A, HNF4A, HNF1B, PPARG, GATA4 and GATA6. For each of them we will provide a short background on what is known about gene function and dysfunction. Then, we will discuss how the identification of their mutations in individuals with this form of diabetes, can be used in daily clinical practice to implement specific monitoring and treatments. We hope this article will help clinical diabetologists carefully consider who of their patients deserves timely genetic testing for monogenic diabetes.

Early Signs of Autonomic Nervous System Imbalance in Children with High Cardiometabolic Risk.

OBJECTIVE: Autonomic nervous system is involved in many disorders, and changes in its modulation are the known risk factors for cardiovascular diseases. Its role in metabolic disarrangements in children at high cardio-metabolic risk is not known. Aim of the study is to analyze the relation between clinical-metabolic parameters and autonomic nervous system in children. MATERIALS AND METHODS: Children affected by type 1 diabetes (group 1), obesity (group 2), and control group (group 3) were enrolled. Autonomic nervous system functionality was assessed with dynamic tests (The Expiration to Inspiration indexes-E/I delta and ratio, 30:15 Ratio Test, Systolic blood pressure response to standing-deltaPA), and ultrasonography was performed to evaluate Intima Media Thickness (cIMT). Clinical parameters were recorded. RESULTS: The study popultaion had a total of 75 children with mean age of 12.5 ± 2.8 years: 26 in group 1, 28 in group 2, 21 in group 3. Obese children had higher cIMT z-score (P < .001). Diabetic patients had lower EI delta values (P < .001) and 30:15 ratio test (P = .01). There was an inverse correlation between E/I delta and microalbuminuria levels (rho -0.955, P < .001) and 30:15 ratio test and microalbuminuria (rho -0.936, P < .001) in group 1, even after adjustment for age. DeltaPA was higher in obese (P = .032) and correlated with BMI z-score and homeostatic model assessment. CONCLUSION: Our results highlight imbalances in sutonomic nervous system function in children at high metabolic risk, in particular with involvement of parasympathetic function in type 1 Diabetes Mellitus and sympathetic one in obesity. An early screening could lead to a prompt identification of these alterations and could have a predictive role on cardio-metabolic risk.

Iodine Requirements in Pediatrics: From Fetal Life to Adolescence.

The aim of this mini-review is to present the current knowledge on iodine requirements in developmental age, from conception to adolescence. It is based on the analysis of updated national and international guidelines on iodine intake and the prevention of iodine deficiency. Health policy initiatives carried out in industrialized countries in previous decades have led to a dramatic improvement in nutritional iodine status in the general population. However, the prevention of iodine deficit continues to be a concern, especially for vulnerable categories, like adolescents and pregnant women.

Is sunlight enough for sufficient vitamin D status in children and adolescents? A survey in a sunny region of southern Italy.

OBJECTIVES: Because it is involved in calcium homeostasis, vitamin D is a prohormone with many implications for health, especially bone health. Hypovitaminosis D is considered pandemic worldwide, with important health health consequences. The aim of our study was to evaluate vitamin D levels in children living in a southern region of Italy with high exposure to sunlight for at least 5 mo a year along with contributing factors. METHODS: A total of 1484 children and adolescents (age 0.02-17.74 y) living in the Apulia region (Southern Italy) were studied. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were assessed and vitamin status defined as follows: deficiency with serum 25(OH)D < 20 ng/mL, insufficiency from 20 to 29.9 ng/mL, and sufficiency with serum 25(OH)D from 30 to 100 ng/mL. RESULTS: The median serum 25(OH)D levels were 20.2 ng/mL (interquartile range, 14.5-26.4 ng/mL): 48.9% of the overall population had 25(OH)D < 20 ng/mL and only 15% had sufficient 25(OH)D values. There was an inverse association between blood levels of 25(OH)D and age (P < 0.001, ρ: -0.113). Significant 25(OH)D variations were recorded according to the season in which blood samples were drawn, but even during summer only 32.6% of analyzed children had sufficient 25(OH)D levels. CONCLUSIONS: More than 80% of our population had 25(OH)D less than sufficiency cutoff levels. Results highlight a high prevalence of 25(OH)D deficiency in our area, even during summer. It is important to establish screening, supplementation guidelines, and pediatric cutoff levels to optimize vitamin D status in children, taking into account age, nutritional status, and seasonality.

Obesity-Related Hypertension in Pediatrics, the Impact of American Academy of Pediatrics Guidelines.

The prevalence of primary hypertension in pediatric patients is increasing, especially as a result of the increased prevalence of obesity in children. New diagnostic guidelines for blood pressure were published by the American Academy of Pediatrics (AAP) in 2017 to better define classes of hypertension in children. The aim of our study is to evaluate the impact of new guidelines on diagnosis of hypertension in pediatrics and their capacity to identify the presence of cardiovascular and metabolic risk. Methods: Retrospective clinical and laboratory data from 489 overweight and obese children and adolescents were reviewed. Children were classified according to the 2004 and 2017 AAP guidelines for systolic and diastolic blood pressure. Lipid profile and glucose metabolism data were recorded; triglyceride/HDL ratio (TG/HDL) was calculated as an index of endothelial dysfunction. Hepatic steatosis was detected using the ultrasonographic steatosis score. Results: Children with elevated blood pressure increased from 12.5% with the 2004 AAP to 23.1% with the 2017 AAP criteria (p < 0.001). There was a statistically significant increase in children with high blood pressure in all age groups according to the new cut-off values. Notably, the diagnosis of hypertension according to 2017 AAP criteria had a greater positive association with Hepatic Steatosis (rho 0.2, p < 0.001) and TG/HDL ratio (rho 0.125, p = 0.025). Conclusions: The 2017 AAP tables offer the opportunity to better identify overweight and obese children at risk for organ damage, allowing an earlier and more impactful prevention strategy to be designed.

EEG Patterns in Patients with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, and it is characterized by hypotonia, hyperphagia, obesity, short stature, hypogonadism, craniofacial dysmorphisms, and cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical, and neuroimaging data. The demographic, clinical, genetic, EEG, and neuroimaging data of seventy-four patients were collected. Associations among the presence of paroxysmal EEG abnormalities, genotype, and clinical and neuroimaging features were investigated. Four patients (5.4%) presented drug-sensitive epilepsy. Interictal paroxysmal EEG abnormalities-focal or multifocal-were present in 25.7% of the cases, and the normalization of the EEG occurred in about 25% of the cases. In 63.2% of the cases, the paroxysmal abnormalities were bilaterally localized over the middle-posterior regions. Brain magnetic resonance imaging (MRI) was performed on 39 patients (abnormal in 59%). No relevant associations were found between paroxysmal EEG abnormalities and all of the other variables considered. Interictal paroxysmal EEG abnormalities-in particular, with a bilateral middle-posterior localization-could represent an important neurological feature of PWS that is not associated with genotype, cognitive or behavioral endophenotypes, MRI anomalies, or prognosis.

Physical Activity and Physical Competence in Overweight and Obese Children: An Intervention Study.

With the current obesity epidemic and the decline of fitness among school-aged children, the importance of obesity interventions to promote physical activity and healthy habits has become indisputable. The purpose of this study was to assess the efficacy of a school-based multicomponent intervention in increasing physical activity (PA) levels, actual physical abilities, and perceived physical abilities in clinical and nonclinical samples of overweight/obese boys and girls aged 10-12 years. The clinical intervention group (n = 35) participated in a 7-month after-school program in addition to curricular physical education lessons, while the nonclinical control group (n = 29) received usual curricular lessons. Measures included levels of PA and fitness and individual's perceptions of physical ability. After treatment, the intervention group showed improved PA levels, perceived physical ability, and throwing and jumping task performances compared to the control group. Results indicate that a multicomponent program can improve levels of PA, fitness, and perceived competence of overweight participants. Findings highlight the importance of a comprehensive healthy lifestyle program that includes physical, psychosocial, and behavioral factors and suggest practical implications for educators, trainers, and teachers in identifying best practices targeting childhood obesity.

Caring and living with Prader-Willi syndrome in Italy: integrating children, adults and parents' experiences through a multicentre narrative medicine research.

OBJECTIVES: Prader-Willi syndrome (PWS) significantly impacts health-related quality of life; however, its relational and existential aspects remain unknown in Italian clinical and social debate. The project aimed to investigate the impact of PWS on illness experience through narrative medicine (NM) to understand the daily life, needs and resources of patients with PWS and their caregivers, and to furnish insights for clinical practice. DESIGN AND SETTING: The project involved 10 medical centres of the Italian Network for Rare Diseases and PWS family associations and targeted underage and adult patients with PWS and their caregivers. Written interviews, composed by a sociodemographic survey and a narrative, were collected through the project's website. Three dedicated illness plots employed evocative and open words to facilitate individual expression and to encourage reflection. Narratives were analysed through NVivo software. Researchers discussed the results with the project's steering committee. PARTICIPANTS: Twenty-one children and adolescents and 34 adults with PWS joined the project, as well as 138 caregivers. A PWS diagnosis or the caregiving of a patient with PWS older than 5 years represented the eligibility criteria, as well as the willingness to share their illness experience by writing and the ability to communicate in Italian. RESULTS: The analysis of narratives led to understanding the PWS social and relational issues concerning diagnosis and current management, PWS daily experiences and social contexts, PWS implications in the working sphere and participants' future perspectives. Narratives demonstrated that PWS management affects relationships and work-life balance and that social stigma remains present. CONCLUSION: The project represented the first effort to investigate the impact of PWS on illness experience in Italy through NM while considering the perspectives of patients with PWS and their caregivers. The findings indicated that a multiprofessional approach is fundamental to ensure adequate treatment and provided elements for its improvement.

Iodine deficiency among Italian children and adolescents assessed through 24-hour urinary iodine excretion.

BACKGROUND: Iodine is an essential micronutrient for intellectual development in children. Information on iodine intakes based on 24-h urinary iodine excretion (UIE) is scant, because iodine status is only assessed by the measurement of urinary iodine concentration (UIC) in spot urine samples. OBJECTIVES: The aim of our study was to evaluate the iodine intake of school-age children and adolescents, using UIE measurement in 24-h urine collections. METHODS: The study population included 1270 healthy subjects (677 boys, 593 girls) aged 6-18 y (mean age ± SD: 10.3 ± 2.9) from 10 Italian regions. Daily iodine intake was estimated as UIE/0.92, based on the notion that $\sim$92% of the dietary iodine intake is absorbed. The adequacy of intakes was assessed according to the Dietary Reference Values for iodine of the European Food Safety Authority (EFSA). Body mass index (BMI) and UIC were also measured for each subject. RESULTS: Based on the scientific opinion of EFSA, 600 of 1270 subjects (47.2%) had a lower than adequate iodine intake, with a higher prevalence among girls (54.6%) compared with boys (40.2%) (P < 0.001). Although UIE and 24-h urinary volumes increased with age (P < 0.001), a progressive decrease in the percentage of subjects with iodine excretion <100 µg/24 h (P < 0.001) was observed, without any significant difference in the percentage of subjects with UIC <100 µg/L. No significant association was detected between BMI z-score and UIE (P = 0.603) or UIC (P = 0.869). CONCLUSIONS: A sizable proportion of our population, especially girls, appeared to be at risk of iodine inadequacy. The simple measurement of UIC could lead to underestimation of the occurrence of iodine deficiency in younger children, because of the age-related smaller urine volumes producing spuriously higher iodine concentrations.

Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment.

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m2/week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated with higher sensitivity to GH. In case of these risk factors, we recommend a more accurate titration of the dose to avoid overtreatment and its potential side effects.