Body composition in pediatric celiac disease and metabolic syndrome component risk-an observational study.

BACKGROUND: Celiac disease (CD) in children and adolescents has been linked with increased susceptibility for cardiometabolic disease in adulthood. We explored the interaction between body composition and metabolic syndrome (MetS) components in pediatric CD. METHODS: We conducted a retrospective observational study of patients with CD followed at our Pediatric Endocrine and Gastroenterology Units between 1/2018-1/2022. Data on sociodemographic, clinical, laboratory, and body composition parameters (bioelectrical impedance analysis, BIA) were collected. RESULTS: Forty-four patients with MetS components and 67 patients without them were enrolled. The cohort's mean age at BIA assessment was 11.5 ± 3.6 years. Individuals with MetS components were older (P = 0.045), had higher BMI z-scores (P < 0.001), higher total and truncal fat percentage levels (P < 0.001), lower muscle-to-fat ratio z-scores (P = 0.018), higher sarcopenic indices (P = 0.05), higher systolic blood pressure percentiles (P = 0.001), higher triglycerides levels (P = 0.009), and higher triglycerides/HDL-c ratios (P < 0.001) than those without MetS components. A sex- and age-adjusted model revealed that the diagnosis of MetS components was positively associated with fat percentage (odds ratio = 1.087, confidence interval [1.010-1.171], P = 0.027), but not with BMI z-scores (P = 0.138). CONCLUSIONS: We found that fat percentage but not weight status is associated with risk for MetS components in individuals with childhood-onset CD. Preventive interventions should target an improvement in body composition. IMPACT: The literature on cardiometabolic risk in pediatric patients with celiac disease (CD) is sparse. Our analysis revealed that at least one metabolic syndrome (MetS) component was present in two out of every five children and adolescents with CD. An increase in fat percentage but not in body mass index z-scores predicted the presence of MetS components in our cohort. These findings suggest that the weight status of children and adolescents with CD does not mirror their risk for MetS components. Body composition analysis should be considered as an integral part of the clinical evaluation in young patients with CD.

Beyond Body Mass Index - Body Composition Assessment by Bioimpedance in Routine Endocrine Practice.

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.

Blood pressure dynamics after pubertal suppression with gonadotropin-releasing hormone analogs followed by estradiol treatment in transgender female adolescents: a pilot study.

OBJECTIVES: The benefits of gonadotropin-releasing hormone analogues (GnRHa) in the treatment of central precocious puberty are well established, and their use is regarded as both safe and effective. Possible adverse effects on blood pressure (BP) and cardiac outcomes, body composition, bone health and brain development, however, continue to be of some concern. The aim of this study was to analyze BP changes in transgender female adolescents before and after receiving GnRHa and after adding estrogen treatment. METHODS: This was a retrospective pilot study. We analyzed systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding estrogen. RESULTS: Nineteen transgender female adolescents received GnRHa and 15 continued to estrogen treatment. Their baseline SBP and DBP percentiles did not change significantly after either GnRHa or the addition of estrogen treatment. CONCLUSIONS: Blood pressure is apparently not affected by GnRHa or GnRHa + estrogen treatment in transgender female adolescents. Further larger studies are indicated to confirm these findings.

Paediatricians' practices and knowledge of corticosteroids: A national survey.

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 (ß = 2.271, P = 0.032); medical practice only in a subspecialty (ß = 1.909, P = 0.041) or in both general paediatrics and a subspecialty (ß = 2.023, P = 0.014), compared to general paediatrics alone and medical studies in Israel (ß = 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.

Type 1 diabetes outcomes of children born in Israel of Eritrean asylum seekers.

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.

Blood Pressure Dynamics After Pubertal Suppression with Gonadotropin-Releasing Hormone Analogs Followed by Testosterone Treatment in Transgender Male Adolescents: A Pilot Study.

Purpose: We analyzed blood pressure (BP) changes in transgender male adolescents treated with gonadotropin-releasing hormone analogs (GnRHa) and after adding testosterone treatment. Methods: This was a retrospective pilot study. Outcome measures included systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding testosterone. Results: Fifteen transgender male adolescents received GnRHa. DBP percentiles increased significantly after GnRHa treatment (from 55.9% ± 26.4 to 73.6% ± 9.4, p = 0.019). BP levels did not meet criteria for hypertension. DBP percentiles were restored after adding testosterone. Conclusion: GnRHa may increase DBP in transgender male adolescents, and testosterone treatment may restore it. Further larger studies are indicated.

CHILDREN AND ADOLESCENTS WITH GENDER DYSPHORIA IN ISRAEL: INCREASING REFERRAL AND FERTILITY PRESERVATION RATES.

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD). Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (<18 years) referred to and followed at the multidisciplinary Israeli Pediatric Gender Dysphoria Clinic from March 2013 through December 2018. Results: Of the 106 patients, 10 were prepubertal (9 prepubertal transgender females), and 96 were pubertal (38 pubertal transgender females). The GD population increased 11-fold since the establishment of our clinic in 2013. The subject's median age at referral was 15.5 years (range, 4.6 to 18 years). At the time of referral, 91 (95%) of the pubertal group had completed sexual maturation in their assigned gender at birth. Thirteen (13.5%) patients had attempted suicide, and 11 (11.5%) reported having had suicidal thoughts. Fourteen (45%) pubertal transgender females and 3 (6.5%) pubertal transgender males completed fertility preservation. Gonadotropin-releasing hormone analog treatment was prescribed in 77 (80%) patients at a mean age of 15.9 ± 1.6 years. Gender-affirming hormones were prescribed in 61 (64%) patients at a mean age of 16.5 ± 1.3 years. No severe side effects were recorded. Two (2%) of the pubertal group expressed regret about medical treatment. Conclusion: Children and adolescents with GD are presenting for medical attention at increasing rates. Israeli adolescents with GD have high fertility preservation rates, perhaps attributable to cultural perspectives. Taking advantage of the option to preserve fertility can be achieved when proper counseling is both available and promoted by medical personnel. Abbreviations: GAH = gender-affirming hormone; GD = gender dysphoria; GnRHa = gonadotropin-releasing hormone analog; MHP = mental health professional.

Higher C-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment.

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.

HEALTH-RELATED QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS WITH NONCLASSIC CONGENITAL ADRENAL HYPERPLASIA.

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.

Fever Phobia as a Reason for Pediatric Emergency Department Visits: Does the Primary Care Physician Make a Difference?

BACKGROUND: Fever is a source of considerable parental anxiety. Numerous studies have also confirmed similar anxiety among health care workers. This study analyzed caregiver knowledge of fever, and beliefs concerning children with a febrile illness, with an emphasis on the referring physician. METHODS: This was a cross-sectional study of 100 caregivers of children 3 months to 12 years old, treated at an urban tertiary care pediatric emergency department for fever. Caregiver knowledge was assessed with a questionnaire. RESULTS: Most caregivers correctly defined the threshold for fever as >38.0-38.3°C. Caregivers commonly believed that fever can cause brain damage and epilepsy; the frequency of this belief was not affected by whether they were referred to the emergency department by their pediatrician/family physician or by another physician or arrived without a referral. For a comfortable-appearing child with a temperature not above 38.0°C, both groups reported that they would give antipyretics in similar proportions (mean 31%). The majority of parents in both groups believed that teething could cause fever (mean 74%). CONCLUSION: Caregivers in this study had limited knowledge of fever and its management in children, even if referred by their primary care physician. We suggest that there is a need for aggressive educational interventions to reduce parents' fever phobia, in clinics as well as in pediatric emergency departments, and that this need may extend to the education of medical personnel as well.

The diagnostic accuracy of the 'classic meningeal signs' in children with suspected bacterial meningitis.

To prospectively determine the diagnostic accuracy of nuchal rigidity, Kernig's sign, and Brudzinski's sign in children with suspected bacterial meningitis. Children 3 months to 17 years old diagnosed with bacterial meningitis and matched controls without bacterial meningitis were enrolled. The diagnostic accuracy was calculated independently for each test and for a combinations of tests. Of 86 children, 40 (46.5%) had bacterial meningitis. The sensitivity, specificity, LR+, and LR- were 64.5%, 53.5%, 1.4, and 0.7 for nuchal rigidity, 52.6%, 77.5%, 2.3, and 0.6 for Brudzinski's sign, and 51.4%, 95.0%, 10.3, and 0.5 for Kernig's sign. The three tests did not yield any better results in the subsets of children with moderate or severe meningeal inflammation, nor in relation to any of the causative pathogens. In children with suspected meningitis, the three classic signs did not have a high diagnostic value and better bedside diagnostic signs are required.