Search

Background: Pediatric obesity has been linked to the components of metabolic syndrome (MetS: abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance). Data on the role of muscle mass in the development of MetS are sparse. We explored the interaction between the muscle-to-fat ratio (MFR) and MetS components in children with overweight or obesity. Methods: An observational study of 210 pediatric subjects (88 boys, mean age [±standard deviation (SD)] 11.9 ± 3.1 years, BMI z-score range 1.036-3.140) from January 2018 to January 2021. Body composition was measured by bioelectrical impedance analysis (Tanita MC-780 MA and GMON Professional Software), and MFR z-scores were calculated. Results: The 148 subjects (70%) who had MetS components were older ( p  = 0.008), had lower socioeconomic positions, higher triglyceride/high-density lipoprotein-cholesterol ratios, fat percentages (FATP), truncal FATPs (TRFATPs), and lower MFR z-scores ( p  < 0.001 for all parameters) than those without MetS components. The correlation between the MFR z-score and the BMI z-score was stronger in subjects with obesity than in subjects with overweight ( r  = -0.556 vs. r  = -0.440, p  < 0.001 for both). The risk for MetS components increased by 1.4 for every 3% increase in FATP or TRFATP [odds ratio (OR) = 1.4, confidence interval ([CI] 1.20, 1.64), p  < 0.001]. The risk for MetS components was tripled for every 1 SD decrease in MFR z-scores [OR = 3.3, CI (1.74, 6.27), p  < 0.001]. Conclusions: Given the strong predictive value of the MFR z-score in the development of early-onset MetS components, preventive strategies should apply interventions for improving the body composition parameters of both adiposity and muscle.

Objectives: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes, diagnosed before age 6 months. We aimed to describe the clinical characteristics, molecular genetics, and long-term follow-up of NDM patients from a single pediatric endocrine center in Israel., Methods: Retrospective study (1975-2020) of all patients diagnosed with diabetes before 6 months of age, who tested negative for pancreatic autoantibodies. Medical records were reviewed for demographic, familial and medical history, and clinical and biochemical features; a genetic analysis was performed., Results: Of 24 patients, nine had transient neonatal diabetes (TNDM) and 15 permanent neonatal diabetes (PNDM), of whom five had rare syndromic causes. Genetic etiology was revealed in 87.5% of the NDM cohort, and the most common causes were ABCC8 mutations in TNDM and KCNJ11 and insulin gene mutations in PNDM. The switch from insulin to off-label sulfonylurea therapy was successful for 5/9 (56%) of the qualifying candidates. Severe hypoglycemia and diabetic ketoacidosis developed in 2 (8%) patients, and chronic diabetes complications in 5 (21%) patients with more than 10 years NDM. At last follow-up, weight and height of all but two syndromic PNDM patients were normal. The median height-SDS of the TNDM subgroup was significantly taller and the mean weight-SDS significantly heavier than those of the PNDM subgroup (-0.52 (-0.67, -0.09) vs. -0.9 (-1.42, -0.3) (p = 0.035) and 0.22 ± 0.69 vs. -0.89 ± 1.21 (p = 0.02), respectively). PNDM patients showed no incremental change in mean weight SDS over the time., Conclusion: The Israeli NDM cohort has clinical and genetic characteristics comparable with other populations. Patients with TNDM were taller and heavier than those diagnosed with PNDM, although both show rapid catch-up growth and reached normal growth parameters. Chronic diabetes complications developed in patients with long-standing NDM., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the incidence and severity of ketoacidosis (DKA) at type 1 diabetes diagnosis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Israel., Research Design and Methods: A population-based study the product of a national collaboration of Israeli pediatric diabetes centers investigated the presentation of childhood-onset type 1 diabetes. The frequencies of DKA and severe DKA observed during the COVID-19 period from March 15, 2020 (commencement of the first nationwide lockdown) until June 30, 2020 were compared with the same periods in 2019, 2018, and 2017 using multivariable logistic regression, adjusting for age, sex, and socioeconomic position., Results: During the COVID-19 period, DKA incidence was 58.2%, significantly higher than in 2019 (adjusted OR [aOR] 2.18 [95% CI, 1.31-3.60], P = 0.003); 2018 (aOR 2.05 [95% CI, 1.26-3.34], P = 0.004); and 2017 (aOR, 1.79 [95% CI, 1.09-2.93], P = 0.022). The incidence of severe DKA was 19.9%, significantly higher than in 2018 (aOR, 2.49 [95% CI, 1.20-5.19], P = 0.015) and 2017 (aOR, 2.73 [95% CI, 1.28-5.82], P = 0.009). In 2020, admissions and duration of stay in the intensive care unit were higher than in previous years (P = 0.001). During the COVID-19 pandemic, children aged 6-11 years had higher incidences of DKA (61.3% vs. 34.0%, 40.6%, and 45.1%, respectively, P = 0.012), and severe DKA (29.3% vs. 15.1%, 10.9%, and 5.9%, respectively, P = 0.002)., Conclusions: The dramatic increase in DKA at presentation of childhood-onset type 1 diabetes during the COVID-19 pandemic mandates targeted measures to raise public and physician awareness., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pregnancy and parturition reflect the complex interaction between physiological conditions of the mother and her offspring, and fetal health characteristics may affect maternal health throughout pregnancy and delivery. We aimed to investigate the characteristics of the mother-infant dyad of term infants detected as having congenital hypothyroidism (CH). Methods: A retrospective cohort study of 108,717 term infants delivered liveborn at Lis Maternity and Women's Hospital between 2010 and 2017. Infants were detected by the National Newborn Screening Program as having CH (131, 0.12%). Three years of surveillance in the Pediatric Endocrine Clinic revealed that 65 infants had transient CH and 66 had permanent CH. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital's electronic database. Results: Mode of delivery differed: a higher proportion of deliveries of CH infants required vacuum assistance, and more infants with CH were born through a cesarean section compared with the general population ( p  < 0.001). Medication during labor also differed, with higher rates of oxytocin ( p  < 0.001) and antibiotics ( p  = 0.008) administered to mothers of CH infants. A multivariate logistic regression model revealed an increased demand for oxytocin administration during the labor of a CH infant in a hypothyroidism severity-dependent manner, expressed as a threefold risk associated with permanent but not transient CH. Conclusions: Our findings of increased utilization of medical interventions during the labor and delivery of CH infants suggest that the prenatal fetal thyroid function may affect the development and progress of labor and delivery, in response to oxytocin.

Background: West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published., Methods: In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy (< 2 years), early childhood (2-6 years), and childhood/adolescence (6-18 years)., Results: The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [p = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [p < 0.001], hypertriglyceridemia 71 % vs. 40 % [p = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [p = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [p < 0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients (p = 0.008, p = 0.001, and p = 0.037, respectively), and higher triglyceride levels during early childhood (p = 0.050), with no significant group differences during childhood/adolescence., Conclusions: Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation., (© 2021. The Author(s).)

Introduction: The preventive measures taken in attempt to prevent COVID-19 spread lead to closure of schools and leisure time activities. The impact of the pandemic on pediatric weight status is unclear, reports from around the world predict grave consequences with increasing obesity. We aimed to examine the change in body composition parameters of children and adolescents during the pandemic. Materials and Methods: An observational study of 220 pediatric subjects (109 boys; mean current age 11.8 ± 3.3 years; 37 with underweight, 123 with normal weight, and 60 with overweight/obesity) who underwent height and body composition measurements by bioelectrical impedance analysis, Tanita MC-780MA, GMON Professional Software before and during the pandemic. Height, body mass index (BMI) and muscle-to-fat ratio (MFR) z-scores were calculated. Data collected from the participants' medical files included home address for socioeconomic position calculation, pubertal stage, and self-reported sleep duration and physical activity performance. Results: The vast majority of the cohort (81.8%) had stable or improved MFR z-scores during the pandemic. MFR z-scores significantly increased in subjects with underweight ( p = 0.05) and normal weight ( p = 0.008), but not in subjects with overweight/obesity ( p = 0.169). There were significant associations in BMI z-scores ( r = 0.961, p < 0.001) and MFR z-scores ( r = 0.854, p < 0.001) before and during the pandemic. A multivariate linear regression model identified socioeconomic position, pre-pandemic BMI z-scores, pre-pandemic MFR z-scores, and physical activity levels during the pandemic as predictors for delta MFR z-scores ( F = 12.267, p < 0.001). Age, sex, pre-pandemic physical activity, and the time that had elapsed between initiation of the first nationwide lockdown and the BIA assessment during the pandemic did not emerge as predictors for delta MFR z-score. Conclusions: Our encouraging findings demonstrate improvement in body composition parameters of subjects with underweight and normal weight and stability in subjects with overweight/obesity. Engagement in physical activity during the pandemic predicted improvement, while lower socioeconomic position predicted deterioration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Azoulay, Yackobovitch-Gavan, Yaacov, Gilboa, Lopez, Sheppes, Waksman, Lebenthal and Brener.)

Aims: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of paediatric individuals with type 1 diabetes (T1D)., Methods: An observational multicentre real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e. change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100)., Results: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6 ± 5.3 years, and diabetes duration 6.0 ± 4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9 ± 16.0, p < 0.001 vs. 59.0 ± 17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180-250 mg/dl range, higher daily insulin dose, and single-parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively., Conclusions: Paediatric and young adult patients with T1D benefited from a telehealth visit during COVID-19. However, this modality is not yet suitable for a considerable proportion of patients.

Background: Physical growth during childhood and adolescence is influenced by both genetic and environmental factors. Heritability, the proportion of phenotypic variance explained by genetic factors, has been demonstrated for stature and weight status. The aim of this study was to explore the heritability of body composition., Methods: A real-life, observational study of the children and adolescents referred to the Endocrine Unit in a tertiary medical center. In January 2018, body composition by means of bioimpedance analysis (BIA) was implemented as part of the standard intake assessment of subjects referred for endocrine consultation. The clinic BIA database was searched for subjects with the term "observation of growth" as the sole reason for referral. BIA of 114 triads of healthy subjects aged 5-18 years and their parents were analyzed. The BIA report included the following data: fat mass, fat percentage, truncal fat percentage and muscle mass. Calculated variables included: appendicular skeletal muscle mass (ASMM = the sum of muscle mass of four limbs), muscle-to-fat ratio [MFR = ASMM (kg)/fat mass (kg)] and sarcopenic index [(SI = ASMM(kg)/height (meter)²]. Data collection from medical files included pubertal stage and home address for socioeconomic position grading., Results: There were sex differences in body composition parameters in both the prepubertal and pubertal subjects. The boys among the prepubertal subjects had a lower fat percentage on average than girls (p = 0.020). Among the adolescents, boys on average had lower fat percentage (p = 0.011), higher sarcopenic index (p = 0.021), and higher muscle-to-fat ratio (p < 0.001), than adolescent girls. Correlation analyses between body composition parameters of all participants revealed significant correlations in the sarcopenic index of prepubertal children and their parents (boys-fathers: r = 0.380, p = 0.050; boys-mothers: r = 0.435, p = 0.026; girls-fathers: r = 0.462, p = 0.012; girls-mothers: r = 0.365, p = 0.050) and adiposity indices (fat percentage, truncal fat percentage and muscle-to-fat ratio) of prepubertal boys and their mothers (r = 0.438, p = 0.025; r = 0.420, p = 0.033, and r = 0.478, p = 0.014, respectively). There were no associations between body composition parameters of adolescents and their parents. Socioeconomic position adversely affected fat percentage in adolescent girls and mothers., Conclusions: Heritable body composition traits were demonstrated in childhood but not in adolescence, suggesting that environmental influence has a more telling effect during teenage years.

Objective: To explore the body composition of pediatric patients referred for endocrine evaluation., Methods: This real-life observational study conducted between January 2018 and January 2020 included 10 001 clinic visits of 3500 children and adolescents; first visits of 5 to 18-year-old patients were included. Anthropometric data, blood pressure levels, pubertal status, and bioelectrical impedance analysis (BIA, Tanita MC-780 MA) were extracted from medical files. Excluded from the analysis were patients participating in other studies., Results: A total of 1001 patients (48% boys, mean age 11.3 ± 3.4 years, 33.5% prepubertal) were included. Mean anthropometric z-scores were normal and similar for boys and girls. Sex differences in body composition were as follows: boys had lower fat percentage, lower truncal fat percentage, higher appendicular skeletal muscle mass, and a higher muscle-to-fat ratio (MFR) than girls (P < .001 for all). MFR correlated with body mass index-standard deviation scores (BMI-SDS) in overweight/obese patients (r = -0.558, P < .001), although not in underweight patients. Systolic blood pressure (SBP) correlated with BMI-SDS in overweight/obese patients (r = 0.262, P < .001), although not in underweight patients. Diastolic blood pressure (DBP) did not correlate with BMI-SDS in either group of extreme weight status. MFR correlated with SBP and DBP in overweight/obese patients (r = -0.230, P < .001 and r = -0.141, P = .018, respectively) as well as in underweight patients (r = 0.331, P < .001 and r = 0.264, P = .005, respectively)., Conclusions: Our findings support BIA for a more refined characterization of patients referred for endocrine evaluation than BMI-SDS. MFR may be a better surrogate marker of blood pressure levels than BMI-SDS in both underweight and overweight/obese pediatric patients., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Burosumab, a recombinant anti-FGF23 monoclonal antibody, was recently introduced as a treatment for X-linked hypophosphatemia (XLH). Burosumab normalizes blood phosphate levels, thereby healing rickets, decreasing leg bowing, and reducing pain. We aimed to explore the body composition and cardiometabolic health of pediatric patients with XLH treated with burosumab., Methods: This observational real-life study was conducted on growing children and adolescents. The outcome measures included changes in sex- and age-adjusted anthropometric and body composition parameters [fat mass (FM), fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), muscle-to-fat ratio (MFR)], blood pressure, laboratory evaluation, and radiographic rickets severity [Thacher Rickets Severity Score (TRSS)]. Body composition was assessed by bioelectrical impedance analysis (BIA). Percentiles for FFM% and ASMM% were calculated according to BIA pediatric reference curves. The delta variable was calculated as the variable at 12 months minus the variable at baseline., Results: A total of 15 pediatric patients with XLH are treated in our clinic; included in the analyses were 7 children and adolescents (3 males, mean age 8.7 ± 3.2 years) with XLH without comorbidities. Baseline BIA revealed an unfavorable physique, with increased body fat percentage in five patients and decreased muscle mass in six. Indices of lean body mass significantly increased after 6 and 12 months of treatment: FFM(kg) ( p  = 0.001, p  = 0.046, respectively) and ASMM(kg) ( p  = 0.012, p  = 0.034, respectively), without any significant change in FM(kg). The percentile of ASMM% increased significantly after 6 months of treatment ( p  = 0.006) and stabilized thereafter. TRSS improved significantly after 12 months of therapy ( p  = 0.005). Age was positively correlated with delta TRSS ( r  = 0.814, p  = 0.026), and delta TRSS was negatively correlated with delta MFR ( r  = -0.826, p  = 0.022)., Conclusions: There was a heretofore unrecognized improvement in body composition of growing children and adolescents with XLH who were treated with burosumab. These findings highlight the need to initiate burosumab treatment at a younger age when rickets is less severe., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: The impact of gonadotropin-releasing-hormone-analogue (GnRHa) treatment on weight and body composition is controversial. Exploring the nutritional, psychological patterns of this population may aid to clarify this propensity to gain weight. This prospective observational study aimed to evaluate longitudinal changes in adiposity, nutrition and quality of life in girls with central precocious/early-fast puberty (CPP/EFP) during GnRHa treatment., Methods: Thirty-two GnRHa-treated girls with CPP/EFP and 27 prepubertal girls (7-10 years) were included in the analysis. Outcome measures assessed at baseline for CPP/EFP and the control groups and during up to two years of GnRHa treatment for the CPP/EFP group, included anthropometrics, body-composition, basal-metabolic-rate (BMR), 3-day food-diaries, child eating-behavior questionnaire, and pediatric quality-of-life questionnaire (PedsQL)., Results: Girls with CPP/EFP had higher pretreatment BMI-SDS, fat percentages, waist circumference and waist-per-height ( p<0.01 for all), and lower psychosocial functioning than controls (p<0.05). Changes in anthropometric and body composition measurements indicated a gradual increase in adiposity and a decrease in muscle mass (p<0.001 for all). Dynamics in body composition could not be explained by the participants' self-reported dietary patterns and physical activity levels or by the measured BMR, which revealed an adequate and relatively low energy intake as compared to energy requirements. A gradual decline in physical functioning (PedsQL) after one and two years of GnRHa treatment was observed (p<0.001)., Conclusions: Our findings highlight the need for comprehensive surveillance in girls with CPP/EFP. Dynamics in weight status and body composition during GnRHa treatment indicate the need for tailored nutritional and physical activity counseling aimed at preventing obesity., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Aim: To explore corticosteroid prescription practices and knowledge among paediatricians., Methods: The Paediatricians Corticosteroids Survey, a cross-sectional, web-based survey distributed to Israeli paediatricians between February and July 2018., Results: Three hundred and forty-nine paediatricians (105 general paediatricians, 207 subspecialists and 37 paediatric endocrinologists) participated. Two hundred and three (58.2%) had >10 years of paediatric clinical experience and treated >60 patients/wk on average, 175/318 (55%) prescribed corticosteroids to >10% of their patients. On knowledge items, 11/266 (4.1%) responded 'not sure' when tapering of steroids is required, 22/268 (8.2%) to what 'stress dose' meant and 27/268 (10.1%) when a stress dose is required. Multivariate linear analysis showed higher scores were associated with training in paediatric endocrinology (β = 2.271, P = 0.032); medical practice only in a subspecialty (β = 1.909, P = 0.041) or in both general paediatrics and a subspecialty (β = 2.023, P = 0.014), compared to general paediatrics alone and medical studies in Israel (β = 1.059, P = 0.035). Overall, 96.2% thought continued medical education (CME) sessions would be helpful., Conclusion: Our findings suggest that despite clinical experience with corticosteroid usage, respondents demonstrated gaps in knowledge for potentially life-threatening situations. Corticosteroid-based CME programs are warranted to improve paediatricians' knowledge and patient management., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims: Disparities in health outcomes in pediatric type 1 diabetes (T1D) based on race/ethnicity and socioeconomic position (SEP) have been reported. We compared T1D characteristics between Eritrean status-less children living in Israel and native-born Israeli children., Methods: This observational study compared 7 Eritrean and 28 Israeli children (< 8 years old at T1D diagnosis) who were diagnosed in a single diabetes center during 2015-2019. Sociodemographic and diabetes-related data from diagnosis until the last clinic visit were retrieved from their medical files., Results: At diagnosis, the mean age was 4.8 ± 2.2 years, 17 (48.6%) had diabetic ketoacidosis with a mean HbA1c level of 10.5 ± 2.1% (91.3 mmol/mol) and 29 (82.9%) had ≥ 2 pancreatic autoantibodies. The mean T1D duration of follow-up was 2.7 ± 1.4 years. Overall glycemic control during follow-up (> 6 months from diagnosis, mean number of samples 10.6 ± 5.2) was good, with mean, best, and peak HbA1c levels of 7.4 ± 0.8% (57.4 mmol/mol), 6.7 ± 0.7% (49.7 mmol/mol), and 8.1 ± 1.1% (65 mmol/mol), respectively. Thirty-two children (91.4%) used continuous glucose monitoring devices (CGMs), and the mean time from diagnosis to CGM initiation was 10.8 ± 14.1 months. CGM metrics: time CGM active: 95.4 ± 3.8%, mean glucose level: 170.0 ± 27.0 mg/dl (9.4 mmol/L), time-in-range: 56.4 ± 14.7%, time-below-range: 5.5 ± 5.7%, and time-above-range: 38.6 ± 16.1%. Diabetes-related parameters at diagnosis and during follow-up were similar between groups. Eritrean children had significantly lower SEPs (P < 0.001) and parental education levels (P < 0.001). Correlations between SEP and diabetes parameters and SEP and growth parameters were not significant., Conclusions: Eritrean status-less children in Israel achieved glycemic targets similar to those of Israeli children, perhaps reflecting uniformity in the standard of care and CGM usage.

Background: Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis., Aim: To examine risk factors for dyslipidemia in young subjects with T1D., Methods: Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models., Results: At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (β[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (β[SE] = 11.4[4.7], P = 0.003) and family history of CVD (β[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (β[SE] = 23.8[9.1], P = 0.010) and family history of CVD (β[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (β[SE] = 4.8[2.1], P = 0.022])., Conclusion: Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia., Competing Interests: Conflict-of-interest statement: All authors confirm that no potential conflicts of interest relevant to this article were reported., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Younger age at diagnosis of type 1 diabetes (T1D) may affect the clinical course and outcome. We examined whether age at diagnosis was associated with glycemic control and metabolic outcome in young adulthood., Methods: This observational study included 105 young adults with T1D (current mean age: 21.2 ± 3.0 years, mean age at diagnosis 12.0 ± 4.0 years) followed during 2012 to 2019. Data on HbA1c, glucose variability, continuous glucose monitoring (CGM) metrics, body mass index (BMI), blood pressure (BP), and body composition were collected from medical records from age 18 years until last visit, and the association between age at diagnosis and outcomes was assessed., Results: Age at T1D diagnosis was negatively associated with HbA1c levels (r = -0.368, P = .001), BMI (r = -0.218, P = .026), and diastolic BP (r = -0.215, P = .028). Younger age at diagnosis predicted poorer glycemic control after controlling for T1D duration, sex, socioeconomic status, BMI, and CGM use (r 2 = 0.19, P = .002). There was a 0.1% greater HbA1c reduction for every yearly increase in age at diagnosis (β = -0.090, P = .042). The mean metabolic age of females diagnosed at <10 years of age was older than their chronological age (P = .049)., Conclusions: Younger age at T1D diagnosis predicts worse glycemic control at young adulthood, independent of recognized confounding risk factors (disease duration, sex, socioeconomic status, weight, and use of diabetes technology). Female patients diagnosed at a young age have an older metabolic age, indicating the need for lifestyle alteration to improve their basal metabolic rate., (© 2020 John Wiley & Sons Ltd.)

The genetic causes of multiple congenital anomalies are incompletely understood. Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (WBP11) gene in seven unrelated families with a variety of overlapping congenital malformations, including cardiac, vertebral, tracheo-esophageal, renal and limb defects. WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger RNA splicing. We generated a Wbp11 null allele in mouse using CRISPR-Cas9 targeting. Wbp11 homozygous null embryos die prior to E8.5, indicating that Wbp11 is essential for development. Fewer Wbp11 heterozygous null mice are found than expected due to embryonic and postnatal death. Importantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans. LoF WBP11 variants should be considered as a possible cause of VACTERL association as well as isolated Klippel-Feil syndrome, renal agenesis or esophageal atresia., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: Billions of people have been under lockdown in an attempt to prevent COVID-19 spread. Lifestyle changes during lockdown could lead to deterioration of glycemic control in type 1 diabetes (T1D). We aimed to assess the impact of COVID-19 lockdown on the glycemic control of pediatric patients with T1D., Methods: This observational real-life study from the AWeSoMe Group assessed continuous glucose monitoring (CGM) metrics of 102 T1D patients (52.9% males, mean age 11.2 ± 3.8 years, mean diabetes duration 4.2 ± 3.8 years) who used  Dexcom G5. The data were accessed without any interface between patients, caregivers, and the diabetes team. Study variables from CGM metrics were: mean glucose level, time-in-range (TIR, 70-180 mg/dL; 3.9-10 mmol/L), hypoglycemia (< 54 mg/dL; < 3 mmol/L), hyperglycemia (> 250 mg/dL; > 13.3 mmol/L), coefficient of variation (CV), and time CGM active before and during lockdown. Delta-variable = lockdown variable minus before-lockdown variable., Results: The mean TIR was 60.9 ± 14.3% before lockdown, with no significant change during lockdown (delta-TIR was 0.9 ± 7.9%). TIR during lockdown was significantly correlated with TIR before lockdown (r = 0.855, P < 0.001). Patients with improved TIR (delta-TIR > 3%) were significantly older than patients with stable or worse TIR (P = 0.028). Children aged < 10 years had a significantly higher CV before lockdown and during lockdown than children aged ≥ 10 years (P = 0.02 and P = 0.005, respectively). Among children aged < 10 years, a multiple linear regression model revealed associations of age and lower socioeconomic cluster with delta-TIR (F = 4.416, P = 0.019) and with delta-mean glucose (F = 4.459, P = 0.018)., Conclusions: CGM metrics in pediatric patients with T1D were relatively stable during a nationwide lockdown. Intervention plans should focus on younger patients with lower socioeconomic position.

Insulin-like growth factor-1 (IGF-1) is an anabolic hormone with myotrophic effects on muscle tissue. Patients with spinal muscular atrophy (SMA) sustain early-onset sarcopenia, which contributes to an increased prevalence of insulin resistance. Our aim was to determine the IGF-1 status in 5q-SMA patients and its association with insulin resistance. Real-life clinical and laboratory data of 34 patients (15 males; age 3 months-24 years) included: anthropometric measurements [weight, height/length, body mass index or weight-to-length ratio, delta-height standard deviation score (∆Ht SDS) as the difference between height/length SDS and mid-parental height (MPHt) SDS] and laboratory measurements [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and IGF-1]. HOMA-IR levels categorized patients as insulin-resistant [HOMA-IR ≥1.9 (n = 20)] or insulin-sensitive [HOMA-IR <1.9 (n = 14)]. The collective height/length SDS was -0.29±1.34 and ∆Ht SDS was -0.11±1.47. IGF-1 levels were within the normal population range for all patients. Insulin-resistant patients had higher IGF-1 SDS levels compared to insulin-sensitive patients (0.87±0.78 vs. -0.67±0.96, respectively, P<0.001). The IGF-1 SDS was significantly associated with HOMA-IR for all subjects (r = 0.547, P = 0.001), and linear growth parameters (height/length SDS, ∆Ht SDS) were significantly associated with IGF-1 SDS in the insulin-resistant subgroup (r = 0.649, P = 0.002 and r = 0.605, P = 0.005, respectively). Our findings suggest that IGF-1 status is associated with insulin resistance in patients with early-onset sarcopenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To explore incidental findings on brain magnetic resonance imaging (MRI) studies of pediatric patients referred due to endocrine disorders., Methods: A retrospective, observational study conducted in a tertiary referral center. The neuroimaging database of 17,445 brain MRI studies of 11,011 pediatric patients were searched for cases with endocrine referrals and without medical history of malignancy, genetic syndromes, and/or neurologic comorbidities. This database was linked to the pediatric neurosurgical database. Clinical data were retrieved from medical files., Results: In total, 524 patients (50.2% males, mean age 8.5±3.5 years) were referred to brain MRI due to growth disturbances (n = 313), pubertal disorders (n = 183), prolactin hypersecretion (n = 18), central diabetes insipidus (n = 8), and obesity (n = 1). Incidental findings were found in 128 (24.4%) cases. Chiari type 1 malformation was more prevalent in patients with growth disturbances (P<.001). Small pituitary cysts were observed in 20 (3.8%) patients, and pineal cysts in 25 (4.8%) patients, mostly girls (68%, P<.001). White matter lesions were diagnosed in 30 (5.7%) patients, none with clinical evidence of neurologic disease. Brain asymmetry without clinical significance and developmental venous anomalies were observed in 14 (2.7%) and 8 (1.5%) patients, respectively. Twelve patients were diagnosed with intracranial tumors, and 5 required surgical intervention for a histopathologic diagnosis of juvenile pilocytic astrocytoma (n = 3), choroid plexus papilloma (n = 1), or inconclusive (n = 1). The rest were managed conservatively., Conclusion: Incidental findings on brain MRIs of pediatric patients referred by endocrinologists are common and raise dilemmas. The spectrum ranges from structural disruptions to tumors. Decision-making is individualized and patient-centered., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

Sleep-disordered breathing (SDB) during pregnancy has been linked to adverse fetal outcomes. Since the intrauterine milieu plays a critical role in childhood growth, we explored the interactions between maternal SDB and offspring growth and adiposity patterns during infancy. Fifty-eight healthy women with uncomplicated pregnancies underwent an objective sleep study and laboratory evaluation during the third trimester, their offspring underwent a 3-year growth surveillance. The 14 (24.1%) women with SDB had a higher body mass index (BMI) (P = 0.003), elevated C-reactive protein levels (P = 0.003), and decreased HDL-cholesterol levels (P = 0.009) than the women without SDB. A general linear model evaluated the interactions between maternal SDB and offspring growth and adiposity measurements after controlling for gestational age and maternal and paternal BMIs. The offspring of mothers with SDB had a significantly smaller head circumference at birth (P = 0.004), with a distinctive pattern of catchup growth by the end of the first year of life (P = 0.018). Their growth pattern was distinguished by compromised birth weight-to-length, rapid catch-up growth, and an increase in both weight-to-length and triceps thickness by the age of three (P < 0.001 and P = 0.001, respectively). Our findings suggest that maternal SDB during pregnancy affects head circumference growth and adiposity acquisition from birth through infancy.

Objective: To report the first successful oocyte cryopreservation in a prepubertal girl., Design: Case report and review of the literature., Setting: Tertiary medical center., Patient(s): A 7-year-old prepubertal girl with Turner syndrome mosaicism (45,X[37]/47,XXX[15]) who underwent a novel fertility preservation procedure after fertility preservation counseling and informed decision of the parents., Intervention(s): Controlled ovarian hyperstimulation with daily administration of 100 IU recombinant human follicle-stimulating and 50 IU recombinant human luteinizing hormone per milliliter, injection of 250 μg human chorionic gonadotropin was given 36 hours before the follicular aspiration procedure, and oocytes retrieved by a transabdominal ultrasound guided approach., Main Outcome Measure(s): Mature oocyte cryopreservation., Result(s): The first cryopreservation cycle with use of a gonadotropin-releasing hormone agonist trigger failed to yield oocytes. The second cycle with human chorionic gonadotropin trigger was successful. Six oocytes were retrieved, and all were mature metaphase 2. The patient was discharged in good condition with no complications., Conclusion(s): This novel procedure bypasses the timely physiologic progression of pubertal maturation of the hypothalamic-pituitary-ovarian axis to directly target the ovaries and achieve mature ovarian follicles. This innovative approach offers a new treatment modality for prepubertal girls who need fertility preservation such as in Turner syndrome or in cases that ovarian tissue cryopreservation is contraindicated., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Females with the severe classic forms of congenital adrenal hyperplasia reportedly have a higher frequency of atypical gender identity, nonheterosexual sexual relationships, and cross-gender role behavior. Comparable data and quality-of-life measures among those with the milder, more prevalent form, nonclassic congenital adrenal hyperplasia, are scarce. We aimed to assess health-related quality of life, gender identity, role, and sexual orientation in women with nonclassic congenital adrenal hyperplasia via a prospective, questionnaire-based, case-control study. Methods: Thirty-eight women with nonclassic congenital adrenal hyperplasia (median age 34 years; range, 18 to 44 years) and 62 age-matched female controls were recruited. Outcome measures included the Multi-Gender Identity, Sexuality, and World Health Organization (WHO) quality-of-life questionnaires. Results: Sociodemographic parameters (marital status, number of children, and educational level) were similar for both groups, as were most measures of the Multi-Gender Identity, Sexuality, and WHO quality-of-life questionnaires. However, "sometimes-feeling-as-a-man and sometimes-feeling-as-a-woman" were more frequently reported in the study group compared to the controls (7/38 [18.4%] vs. 3/62 [4.8%], respectively; P = .02). Furthermore, more nonclassic congenital adrenal hyperplasia women reported first falling in love with a woman (4/37 [10.8%] vs. 0/58 [0%]; P = .02). Conclusion: Our findings suggest possible subtle differences in gender identity and sexual orientation between adult nonclassic congenital adrenal hyperplasia females and controls. Quality of life was not impaired in individuals within the study group. The impact of exposure to mildly elevated androgen levels during childhood and adolescence on the female brain warrants more in-depth assessment in further studies. Abbreviations: CAH = congenital adrenal hyperplasia; Multi-GIQ = Multi-Gender Identity Questionnaire; NCCAH = nonclassic congenital adrenal hyperplasia; QoL = quality of life.

The aim of the study was to characterize factors that may serve as clinical tools to identify neonates with transient neonatal hyperinsulinism hypoglycemia (HH) who may benefit from diazoxide treatment. This retrospective study included 141 neonates with transient HH (93 males) of whom 34 (24%) were treated with diazoxide. Diazoxide treatment was started at median age of 13 days (range 5-35) and discontinued at median age of 42 days (range 14-224). The maximal dose was 7.1 ± 2.3 mg/kg/day. Diazoxide-treated neonates required a higher glucose infusion rate (GIR) compared with non-treated neonates (16.6 ± 3.4 vs. 10.4 ± 4.0 mg/kg/min, respectively, P < .01), had a longer duration of intravenous fluids (15.9 ± 9.3 vs. 7.8 ± 6.5 days, P < .01), a longer hospitalization (32.8 ± 22.7 vs. 20.4 ± 13.4 days, P < .01), a longer duration of carbohydrate supplementation (38.9 ± 40.4 vs. 17.8 ± 21.4 days, P < .01), and higher mean C-peptide levels on "critical sample" (1.4 ± 0.9 vs. 0.8 ± 0.5 ng/ml, P < .01). Their insulin levels also tended to be higher (3.5 ± 2.9 vs. 2.2 ± 3.8 μU/ml, P = .07). A stepwise logistic regression model revealed that significant predictors of prolonged HH were maximal GIRs (odds ratio (OR) 1.56, 95%; confidence interval (CI) 1.3-1.88, P < .001) and C-peptide levels (OR 3.57, 95%; CI 1.3-12.1, P = .005).Conclusion: Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.What is Known:• Neonates with transient hyperinsulinism usually do not require treatment beyond glucose supplementation due to its self-limited clinical course, but some may benefit from diazoxide treatment.What is New:• Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.• The incidence of prolonged neonatal HH is higher than the currently accepted figures.

The introduction of nusinersen, the first therapeutic modality for Spinal Muscular Atrophy (SMA) patients has raised hopes and led to construction of a multi-professional medical SMA service, including pediatric endocrinology. Our study aimed to provide a comprehensive description of the endocrine manifestations of SMA patients with variable degree of sarcopenia. Real-life clinical and laboratory data of 62 SMA patients (age range 3 months to 31 years, 24 type 1, 21 type 2, 17 type 3) were collected including: weight-status, self-reported information on puberty, current pubertal stage, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), basal gonadotropin and androgen levels. Precocious pubarche (mean age at onset 3.9 ± 2.8 years) was found in 24% (15/62) of the SMA cohort [45.9%(11/24) type 1 and 19%(4/21) type 2]. A higher HOMA-IR predicted precocious pubarche after adjustment for SMA type and age (OR=1.42; 95% CI, 1.05, 1.93, P = 0.025). Bilateral cryptorchidism was found in 60% of type 1 and 30% of type 2 boys; type 3 young adult males attained full puberty. Most of the young women had normal pubertal development and regular menses, regardless of degree of obesity. Our findings suggest that isolated precocious pubarche is associated with early-onset insulin resistance linked to severity of muscular atrophy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia ® ) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups ( p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12-18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (-0.34 and -0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (-0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation., Competing Interests: The study design was carried out by the investigators and the sponsor’s representatives. Data collection and the statistical analysis of results were performed by the external CRO. Data interpretation and writing were carried out by the investigators and the sponsor’s representatives. E.C.L. is on the advisory board of Kamada. D.E., M.S., and N. T. are employees of Kamada. No other potential conflicts of interest relevant to this article are reported.

Introduction: Classical congenital adrenal hyperplasia is associated with an increased risk of obesity and cardiometabolic disease. The aim of the study was to determine if this is also true for non-classical congenital adrenal hyperplasia (NCCAH). Methods: A retrospective, cross-sectional, single-center study design was used. Data were collected on 114 patients (92 female) with NCCAH diagnosed during childhood/adolescence at a tertiary medical center. Patients were classified by treatment status at the last clinic visit. Outcome measures were assessed at diagnosis and the last clinic visit: weight status, body composition, blood pressure, lipid profile, and glucose metabolism. The prevalence of overweight/obesity was compared to the parental prevalence, and for patients aged 11-20 years, to the Israeli National Survey. Results: Mean age was 7.9 ± 4.2 years at diagnosis and 17.1 ± 6.9 years at the last follow-up. At the last clinic visit, 76 patients were under treatment with glucocorticoids, 27 were off-treatment (previously treated), and 11 had never been treated. The rate of obesity (11.4%) was similar to the parental rates, and the rate of overweight was significantly lower. In patients 11-20 years old, rates of obesity or obesity + overweight were similar to the general Israeli population (11.4 vs. 15.1%, P = 0.24 and 34.2 vs. 41.6% P = 0.18, respectively). No significant difference was found between glucocorticoid-treated and off-treatment patients in any of the metabolic or anthropometric parameters evaluated, except for a lower mean fat mass (% of body weight) in off-treatment patients (23.0 ± 7.7% vs. 27.8 ± 6.8%, P = 0.06). Systolic hypertension was found in 12.2% of NCCAH patients either treated or untreated. Conclusion : NCCAH diagnosed in childhood, whether treated or untreated, does not pose an increased risk of overweight, obesity, or metabolic derangements in adolescence and early adulthood., (Copyright © 2019 de Vries, Lebenthal, Phillip, Shalitin, Tenenbaum and Bello.)

Objective: Nonclassic congenital adrenal hyperplasia (NCCAH) is a late-onset milder form of congenital adrenal hyperplasia that differs dramatically from the classic form. Health-related quality of life (HRQOL) in pediatric patients with the sole diagnosis of NCCAH has not been determined; therefore, in this study, we aimed to determine whether HRQOL is compromised in comparison to the general population. Methods: Single-center, cross-sectional, case-control study. Twenty-three hydrocortisone-treated children and adolescents (7 males) diagnosed with NCCAH by cosyntropin stimulation test and CYP21A2 gene mutation analysis were recruited to this study; 6 healthy siblings were also recruited. HRQOL was assessed by the child and parent-proxy PedsQL Inventory and compared between NCCAH subjects and healthy siblings. HRQOL scores of NCCAH subjects were compared with known standards from the U.S. and Israeli general healthy populations. Anthropometric measurements of children and parents were performed and compared between NCCAH subjects and healthy siblings. Pearson correlation coefficients were calculated. Results: HRQOL scores of the participants and parents did not differ between NCCAH subjects and healthy siblings. The HRQOL emotional domain scores of the NCCAH patients and parent were significantly lower than the healthy U.S. pediatric population ( P = .046) but not different from established standards of the healthy Israeli population ( P = .583). Anthropometric measurements were within the normal range and did not differ between NCCAH subjects and their siblings. Total, school functioning, and psychosocial HRQOL domain scores were positively correlated with body mass index-standard deviation score in NCCAH subjects. Conclusion: HRQOL was not adversely affected by NCCAH among adequately treated children and adolescents. Abbreviations: BMI = body mass index; CAH = congenital adrenal hyperplasia; HRQOL = health-related quality of life; NCCAH = nonclassic congenital adrenal hyperplasia; PedsQL = Pediatric Quality of Life Inventory; SDS = standard deviation score.

Context: Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging., Objective: To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy., Design: Retrospective, single-center observational study from 2003-2018., Setting: Tertiary endocrine center., Patients: One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH., Main Outcome Measures: AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt)., Results: Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001)., Conclusions: Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS., (Copyright © 2019 Endocrine Society.)

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood., Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents., Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations., Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809-0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941-0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728-0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035-1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001)., Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Context: Growth hormone (GH) treatment of short healthy children is based on the belief that short stature is associated with psychosocial problems and a diminished quality of life., Objective: To determine the impact of GH therapy on psychosocial well-being and the ability of psychological metrics to define short stature-related distress., Methods: Sixty prepubertal boys with idiopathic short stature (age: 10.0 ± 1.4 years, height-SDS: -2.38 ± 0.3) were enrolled in this 4-year intervention study (1-year double-blinded, randomized, placebo-controlled [GH/placebo-2:1] and 3-year open-labelled GH therapy). Explicit (conscious/voluntary) psychological metrics (Pediatric Quality of Life Inventory [PedsQL], Silhouette Apperception Test [SAT], Rosenberg Self-Esteem Scale [RSES], Child Behavior Checklist [CBCL]) and implicit (unconscious/involuntary) psychological metrics (Single-Category Implicit Association Test for height [SC-IAT-H], Height Perception Picture Test [HPPT]). Psychosocial evaluations were performed at study entry, after 1 and 4 years., Results: At study entry, PedsQL of boys with idiopathic short stature was lower than Israeli norms (P = 0.001). After 1-year blinded intervention, only the GH-treated boys improved their actual and anticipated adult height perception (SAT, P < 0.001 and P = 0.022) with reduced short stature-related distress (SC-IAT-H, P < 0.001). At study end, RSES and SC-IAT-H improved significantly (P < 0.001), with no change in PedsQL and CBCL., Conclusions: Our finding of improved psychosocial functioning only in the GH-treated boys after 1-year blinded intervention suggests that it was the GH therapy, rather than being enrolled in a clinical trial, which contributed to the outcome. Long-term open-labelled GH treatment significantly improved height perception and self-esteem. Future studies are needed to fully assess the relevance of complementing the routinely used explicit self-report measures with the implicit measures., (© 2019 John Wiley & Sons Ltd.)

Aims/hypothesis: Maternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort., Methods: The HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at ~28 weeks gestation 10-14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA 1c values during pregnancy., Results: Fully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA 1c measures, ORs for each child adiposity outcome were in the range of 1.05-1.16 for maternal fasting glucose, 1.11-1.19 for 1 h glucose, 1.09-1.21 for 2 h glucose and 1.12-1.21 for HbA 1c . Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls., Conclusions/interpretation: Exposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

Objective: Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort., Research Design and Methods: HAPO Follow-up Study (FUS) included 4,160 children ages 10-14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index., Results: For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78-1.52) for IFG and 1.96 (1.41-2.73) for IGT. GDM was positively associated with child's 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference -76.3 [95% CI -130.3 to -22.4] and -0.12 [-0.17 to -0.064]), respectively, but not insulinogenic index., Conclusions: Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT., (© 2019 by the American Diabetes Association.)

Objective: This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort., Research Design and Methods: HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10-14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT., Results: Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased., Conclusions: Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes., (© 2019 by the American Diabetes Association.)

Objective: To assess clinical variables, including early thyroid scintigraphy, in predicting the outcome (permanent vs transient) in term infants with congenital hypothyroidism (CH)., Methods: In a retrospective study, 142 full-term infants with CH diagnosed between 2000 and 2012 were categorized into three groups: agenesis/ectopic thyroid and permanent CH; eutopic thyroid and permanent CH; and eutopic thyroid and transient CH. All underwent early thyroid scintigraphy and were under regular follow-up in our tertiary Pediatric Endocrine Institute., Results: Thyroid scan showed agenesis/ectopic thyroid in 58 (41%) and eutopic thyroid in 84 (59%) infants. Imaging findings were similar in eutopic-permanent and eutopic-transient groups. At initial evaluation, TSH levels were higher in the agenesis/ectopic group than in the eutopic-permanent and eutopic-transient groups (71.5 ± 11.2 mIU/L vs 49.1 ± 27.9 mIU/L and 42.5 ± 29.1 mIU/L, respectively; P < 0.001). Higher l-T4 doses were required from the third month in the agenesis/ectopic than in the eutopic-permanent group (P < 0.001) and from the sixth month in the eutopic-permanent than in the eutopic-transient group (P < 0.01). Initial TSH >63.5 mU/L (P < 0.001) and l-T4 dose >4.6 μg/kg/d at age >6 months (P < 0.001) were found to be predictors for an agenesis/ectopic gland using receiver operating characteristic analysis, as was an l-T4 dose >2.2 μg/kg/d at age >6 months (P < 0.01) for permanent CH in patients with a eutopic gland., Conclusions: Although early thyroid scintigraphy is reliable in predicting permanent CH when detecting agenesis or ectopic gland, it cannot differentiate between permanent and transient CH in cases with a eutopic thyroid. Confirmatory TSH at diagnosis and the l-T4 dose through treatment may better distinguish between permanent and transient CH.

Unfortunately, the co-author name was misspelled as "Avivit Brenner" instead of "Avivit Brener" in the original publication and the correct author name is updated here.

Aims: Frequent glucose testing is required for optimal management of type 1 diabetes (T1D). Limited data are available regarding real-world experience of the novel technology for monitoring by continuous interstitial fluid glucose (IFG), using flash glucose-sensing technology (FSL-CGM). We aimed to assess the effect of FSL-CGM in a real-life clinical setting on glycemic control parameters, compliance, and adverse events among pediatric and young adult T1D patients., Methods: This observational multi-center study assessed FSL-CGM use (6-12 months) in T1D patients (mean ± SD age 13.4 ± 4.9 years) who purchased the device out-of-pocket. Outcome measures included HbA1c, mean IFG levels, CGM metrics [time in hypoglycemia (< 54 mg/dL; < 3 mmol/L), in target range (70-180 mg/dL; 3.9-10 mmol/L), and in hyperglycemia > 240 mg/dL; > 13.3 mmol/L)], frequency of self-monitoring of blood glucose, acute complications, skin reactions, and reasons for initiation/discontinuation., Results: Among patients with regular use of the FSL-CGM (n = 59), mean HbA1c decreased from 8.86 ± 0.23 to 8.05 ± 0.2% (73.3-64.5 mmol/mol) in 3 months (p = 0.0001) and plateaued thereafter. A clinically significant reduction in HbA1c (defined as a decrease of ≥ 0.5%) was associated with shorter diabetes duration. Of 71 patients who initiated use of the FSL-CGM, 12 (16.9%) discontinued during the study period. No statistically significant changes were found after FSL-CGM use, in mean and standard deviation IFG levels, and in time of glucose levels in target, hypoglycemia, and hyperglycemia ranges. One patient with hypoglycemia unawareness was found dead-in-bed while using FSL-CGM., Conclusions: Real-life observational data in a self-selected young T1D population demonstrated a significant and sustained reduction in HbA1c with FSL-CGM in one-third of the participants. Surveillance of glucose monitoring should be individualized, especially for patients with hypoglycemia unawareness.

Importance: The sequelae of gestational diabetes (GD) by contemporary criteria that diagnose approximately twice as many women as previously used criteria are unclear., Objective: To examine associations of GD with maternal glucose metabolism and childhood adiposity 10 to 14 years' postpartum., Design, Setting, and Participants: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study established associations of glucose levels during pregnancy with perinatal outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers and 4832 children; study visits occurred between February 13, 2013, and December 13, 2016)., Exposures: Gestational diabetes was defined post hoc using criteria from the International Association of Diabetes and Pregnancy Study Groups consisting of 1 or more of the following 75-g oral glucose tolerance test results (fasting plasma glucose ≥92 mg/dL; 1-hour plasma glucose level ≥180 mg/dL; 2-hour plasma glucose level ≥153 mg/dL)., Main Outcomes and Measures: Primary maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes or prediabetes). Primary outcome for children: being overweight or obese; secondary outcomes: obesity, body fat percentage, waist circumference, and sum of skinfolds (>85th percentile for latter 3 outcomes)., Results: The analytic cohort included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was 11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall and by 14.1% (683/4832) of mothers of participating children. Among mothers with GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1% (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14]; risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers without GD. Adjusted for maternal body mass index during pregnancy, the OR was 1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD was 3.7% (95% CI, -0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was 1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI, 0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to 1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%)., Conclusions and Relevance: Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.

Promising findings of α-1 antitrypsin (AAT) intervention in mice models of Type 1 diabetes (T1D) led researchers to investigate AAT as a therapeutic modality for β-cell preservation in recent-onset T1D patients. Our prospective, open-label Phase I/II extension study demonstrated that the administration of multiple repeated AAT infusions (up to 36) to AAT-sufficient pediatric T1D patients is safe and well-tolerated. Long-term surveillance of participants (up to 5 years) from diabetes onset revealed normal growth and pubertal progression through adolescence to attainment of full puberty and near adult height. No serious adverse events, clinical or laboratory abnormalities were reported. Given its safety profile, AAT may be an individualized-tailored innovative immunotherapy in AAT-sufficient pediatric patients with diverse immune-related medical conditions. ClinicalTrials.gov Identifier: NCT01661192.

Aims: The transition of emerging adults with type 1 diabetes (T1D) from pediatric diabetes clinics to adult clinics between 18 and 21 years of age could result in decreased clinic attendance and thus worsen glycemic control. Our institutional policy offering surveillance till age 30 enabled us to evaluate clinic attendance without the confounding effect of transition. Our aim was to determine the association between glycemic control (HbA1c) and attendance rate., Methods: The medical records of 261 (54% males) young adult T1D patients (median age 22.9 years) were reviewed. Patients were stratified according to the attainment/nonattainment of glycemic targets (HbA1c ≤ 7% versus HbA1c > 7% (53 mmol/mol)). The attendance rate was calculated as the number of clinic visits/number of scheduled appointments., Results: Median annual number of scheduled visits was 3 (3, 4); attendance rate was 75% (53.6%, 100%). Seventy-four (28.4%) patients attained glycemic targets (median HbA1c 6.5% (48 mmol/mol) (6.3%, 6.8% (45.51 mmol/mol)); 187 (71.6%) patients had a median HbA1c of 7.8% (62 mmol/mol) (7.4%, 8.4% (57.68 mmol/mol)). The attainment of the treatment target was more prevalent in older patients ( P = 0.006), in male patients ( P = 0.007), and in patients with higher education ( P = 0.017). Higher attendance rate ( β (2.483), P < 0.001) and male gender ( β (0.746), P = 0.015) were associated with better metabolic control., Conclusions: In emerging adults with T1D during the ongoing stable phase of diabetes management, higher attendance rate, rather than absolute number of clinic visits, was associated with the attainment of glycemic targets.

Aims: Nutrition and sleep are prerequisites for linear growth and we addressed the under-researched role of sleep in this equation., Methods: This was a prospective randomised, double-blinded, placebo-controlled study of nutritional supplements in 164 healthy lean, short, prepubertal children with 83 in the supplement group and 81 in the placebo group. From November 2010 to November 2013, we focussed on children aged three to nine years referred for specialist growth assessments to the Schneider Children's Medical Center, Israel. Progress was assessed using anthropometric measurements, sleep questionnaires and three-day food diaries at baseline and after the six-month intervention., Results: Children in the supplement group who took at least 50% of the recommended dose had shorter sleep latency than those who did not (p = 0.046). Children who fell asleep in less than 15 minutes had significantly improved standard deviation scores for weight (0.25 ± 0.34 versus 0.07 ± 0.36, p = 0.044) and height (0.09 ± 0.13 versus 0.03 ± 0.13, p = 0.057) than those who took longer to fall asleep. Positive correlations were found between mean sleep duration and caloric and macronutrient intake per kilogram., Conclusion: Adequate nutritional intake was associated with better sleep patterns and may enhance linear growth., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Few studies have evaluated the impact of diabetic ketoacidosis (DKA) at diabetes onset on long-term glycemic control in patients with type 1 diabetes (T1D)., Objective: We aimed to determine any differences in long-term glycemic control between children/adolescents with T1D presenting with DKA at diabetes onset and those without., Methods: This retrospective study comprised 335 patients diagnosed with T1D from September 2007 to December 2012, among which 132 (39.4%) presented with DKA. Variables compared between patients with DKA at onset and those without: yearly hemoglobin A1c (HbA1c) levels, daily insulin dose, yearly rates of severe hypoglycemia and DKA, percent of patients achieving target HbA1c levels., Results: After the first year of diabetes, the mean daily insulin dose and HbA1c level were significantly higher in the group with DKA at onset (0.74 ± 0.26 vs 0.69 ± 0.27 units/kg/d, P = .049, and 7.85 ± 1.13% vs 7.49 ± 0.94%, P = .01, respectively), despite similarity of therapy (multiple daily injections or continuous subcutaneous insulin infusion), with a similar but not statistically significant trend subsequently. Mean HbA1c since onset was significantly higher in the DKA group (8.08 ± 0.95% vs 7.86 ± 0.95%, P = .025). A significantly higher percentage of patients in the group without DKA at onset achieved a mean level of HbA1c since onset within glycemic targets (32% vs 20.5%, P = .02). In the DKA group, the frequency of subsequent DKA episodes per diabetes years was significantly higher (P = .042)., Conclusions: DKA at diagnosis was associated with less favorable long-term glycemic control as assessed by HbA1c and the rate of DKA episodes. T1D patients presenting with DKA may therefore need stricter treatment and tight follow-up., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Patients with Turner syndrome (TS) are at increased risk for metabolic disorders. We aimed to delineate the occurrence and evolution of metabolic comorbidities in TS patients and to determine whether these differ in 45,X monosomy and other karyotypes., Methods: A longitudinal and cross-sectional retrospective cohort study was conducted in a tertiary pediatric endocrine unit during 1980-2016. Ninety-eight TS patients, 30 with 45,X monosomy were followed from childhood to early adulthood. Outcome measures included weight status, blood pressure (BP), glucose metabolism, and lipid profile., Results: Longitudinal analysis showed a significant change in body mass index (BMI) percentiles over time [ F (3,115) = 4.8, P  = 0.003]. Age was associated with evolution of elevated BP [systolic BP: odds ratio (OR) = 0.91, P  = 0.003; diastolic BP: OR = 0.93, P  = 0.023], impaired glucose metabolism (HbA1c: OR = 1.08, P  = 0.029; impaired glucose tolerance: OR = 1.12, P  = 0.029), and abnormal lipid profile (cholesterol: OR = 1.06, P  = 0.01; low-density lipoprotein cholesterol: OR = 1.07, P  = 0.041; high-density lipoprotein cholesterol: OR = 1.07, P  = 0.033). The occurrence of metabolic comorbidities was similar in 45,X monosomy and other karyotypes. Coexistence of multiple metabolic comorbidities was significantly higher in 45,X monosomy [ F (1,72) = 4.81, P  = 0.032]. BMI percentiles were positively correlated with metabolic comorbidities (occurrence and number) in each patient ( r  = 0.35, P  = 0.002 and r  = 0.383, P  = 0.001, respectively)., Conclusion: Our longitudinal study provides unique insights into the evolution of weight gain and metabolic disorders from childhood to early adulthood in TS patients. Since overweight and increasing age aggravate the risk for metabolic comorbidities, careful surveillance is warranted to prevent and control obesity already from childhood. The more prominent clustering of metabolic comorbidities in 45,X monosomy underscores the importance of a more vigorous intervention in this group.

Phenotypic variability in maturity-onset diabetes of the young (MODY) makes screening criteria for genomic analysis challenging. We describe the clinical spectrum in a large pedigree with HNF1A-MODY; as generations progressed, the course and outcome became poorer. Although uncommon, pancreatic autoantibodies and diabetes ketoacidosis should not exclude the diagnosis of MODY., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background/aims: The objective was to evaluate endocrine complications in survivors of hematopoietic stem cell transplantation (HSCT) performed during childhood., Methods: Endocrine dysfunction and metabolic syndrome parameters were assessed by chart review of 178 childhood HSCT survivors (median age at evaluation, 15.5 [range: 3.8-29.8] years; median follow-up, 8.5 [range: 2-23.4] years)., Results: The following statistically significant associations were identified (p < 0.05 for all): growth hormone deficiency (17.4%) was associated with cranial/craniospinal irradiation, total body irradiation (TBI), allogeneic HSCT, and longer follow-up. Short adult stature (23.3% of patients who had attained adult height) was associated with cranial/craniospinal irradiation and, in females, with younger age at HSCT. Primary gonadal failure was more prevalent in females (52.6 vs. 24.1%), and was associated with TBI in males and with a primary diagnosis of hematological malignancy in females. Hypothyroidism (25.2%) was associated with previous neck/mediastinal irradiation. Metabolic disturbances included obesity (3.9%), type 2 diabetes (2.2%), impaired glucose tolerance (2.8%), and dyslipidemia (18.5%). Dyslipidemia was associated with a primary diagnosis of hematological malignancy, TBI, and a positive family history of dyslipidemia. Endocrine dysfunction was less frequent in patients who had received fludarabine., Conclusions: Patients after HSCT require long-term surveillance for the detection of endocrine and metabolic disorders. Nonmyeloablative conditioning regimens may reduce the incidence of these complications., (© 2018 S. Karger AG, Basel.)

Background: Lifestyle weight loss interventions represent the mainstay of treating children with obesity. Long-term follow-up studies of intervention programs are scarce. This study assessed the long-term effects and identified factors associated with significant weight loss., Methods: This prospective, observational study involved 165 children with body mass index (BMI) z-score ≥1.5 who participated in after-school intervention program., Main Outcome Measure: change in BMI z-scores; decreased BMI z-score ≥0.5 units was defined as clinically significant., Results: At baseline, 55/165 (33.3%) had BMI z-score 1.5-2 and 98 (59.4%) had BMI z-score >2. At follow-up (mean 5.4±1.4 years), 80 (48.5%) had a clinically significant reduction in BMI z-score, while 56 (33.9%) reported a mildly decrease in BMI z-score of 0-0.5 and 29 (17.6%) reported increased BMI z-score. Lower BMI z-score at baseline and participation in sport activity at follow-up were associated with long-term decrease in BMI z-score. Participation in additional post-intervention weight control programs was correlated with weight gain., Conclusions: Intervention program was associated with long-term improvement in weight control, especially in children with mild obesity. Physical activity was related to long-term success. Participation in an additional intervention program was associated with failure of weight control., (Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objectives: Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex- and BMI-percentiles for children and adolescents., Methods: Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1.2 million children and adolescents per study year). These children and adolescents were categorized according to sex- and age-stratified BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight (85th-95th percentile) and 26,417 obese (≥95th percentile) individuals. Excluded were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves were computed., Results: Obese children had a lipid profile pattern throughout childhood and adolescence similar to that of normal weight subjects but with a significant upward shift in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol (HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P < 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels, 11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001)., Conclusions: Across a large, nationally representative cohort of children and adolescents, lipoprotein levels were found to vary in relation to weight status. On the basis of these findings, it is suggested that when evaluating the lipid profile in the pediatric population, in addition to sex-based curves, clinical decision making may require consideration of BMI-stratified curves.

Background: Survivors of acute lymphoblastic leukemia (ALL) may experience endocrine dysfunction. This study evaluated growth and pubertal patterns in survivors of childhood ALL., Methods: Longitudinal assessment of anthropometric measurements and pubertal status was performed in a retrospective cohort of survivors (n=183). Median age at last endocrine visit was 16.1 years (range 8.2-27.6); median follow-up time was 8.7 years (range 3-21.4)., Results: Treatment with chemotherapy+prophylactic cranial radiation (pCRT, n=29) was associated with lower mean height standard deviation score (SDS) than chemotherapy alone (n=154) (p=0.001) and higher prevalence of adult short stature (13% vs. 2.2%). Mean age at pubertal onset was normal (girls: 10.3±1.3 years; boys: 12.0±1.3 years). Precocious puberty, diagnosed in 8.7% of patients, was more prevalent in pCRT-treated girls. Rates of overweight and obesity were 22.9% and 9.3%, respectively. Predictors of endocrine disorders were pCRT (p=0.031) and female gender (p=0.041); of obesity, higher body mass index (BMI)-SDS at diagnosis (p=0.001); and of short stature, lower height-SDS at diagnosis (p=0.038)., Conclusions: Most childhood ALL survivors given chemotherapy alone attain normal adult height and puberty. Childhood ALL survivors are at increased risk of overweight, especially those with increased BMI at diagnosis. Clinicians should screen for overweight early in survivorship and introduce early interventions.

Aim: This study explored whether using the suggested diagnostic serum basal level of 17-hydroxyprogesterone (6.0 nmol/L) would lead to underdiagnosis of nonclassical congenital adrenal hyperplasia., Methods: We retrospectively studied 123 patients with nonclassical congenital adrenal hyperplasia, defined as an adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level of more than 45 nmol/L. Of these 13 had basal 17-hydroxyprogesterone levels of less than 6.0 nmol/L and 110 exceeded that level. The 42 controls had idiopathic premature pubarche. Clinical and laboratory data were reviewed and compared., Results: There were no differences between patients with 17-hydroxyprogesterone levels of <6.0 nmol/L or ≥6.0 nmol/L based on age at presentation, gender, anthropometric measurements, bone age advancement, age at glucocorticoid initiation and hydrocortisone dosage. Patients with basal 17-hydroxyprogesterone <6.0 nmol/L had significantly lower stimulated 17-hydroxyprogesterone levels (p = 0.02) and higher stimulated serum cortisol levels (p < 0.008). Children with nonclassical congenital adrenal hyperplasia and premature pubarche were clinically indistinguishable from controls with idiopathic premature pubarche. Androgen levels were significantly higher in the nonclassical congenital adrenal hyperplasia group., Conclusion: A basal 17-hydroxyprogesterone threshold of 6.0 nmol/L was not a sensitive predictive marker for diagnosing nonclassical congenital adrenal hyperplasia. Children whose clinical presentation suggests nonclassical congenital adrenal hyperplasia should undergo diagnostic adrenocorticotropic hormone stimulation testing., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Childhood obesity is a major health concern. Excess adiposity during childhood affects growth and puberty. Our aim was to assess whether genetic adult height is compromised in adolescents with obesity., Methods: In a retrospective study of 190 obese patients followed at our Pediatric Endocrinology Institute, adult height and delta height (the difference between adult height and mid-parental height) were compared to those of 150 healthy age-matched normal-weight controls. Review of medical files yielded the relevant clinical and anthropometric data of patients, controls, and parents., Results: Of the 190 obese adolescents, 150 were morbidly obese. The median adult height of morbidly obese males was 174.3 cm, of obese males 174 cm, and of normal-weight males 176 cm (p = 0.025). Delta height of morbidly obese males was -0.5 cm, of obese males -0.8 cm, and of normal-weight males, 3 cm (p < 0.0001). The median adult height of morbidly obese females was 161.3 cm, of obese females 162.8 cm, and of normal-weight females 162 cm (p = 0.37). Delta height of morbidly obese females was -1.85 cm, of obese females -0.95 cm, and of normal-weight females 0.7 cm (p = 0.019). Impairment of potential genetic height was not associated with obesity-related comorbidities., Conclusion: Adolescents with obesity showed impairment of potential genetic adult height as compared to that of normal-weight subjects., (© 2017 S. Karger AG, Basel.)