Prepubertal Children Research Articles

Body composition in prepubertal children with idiopathic premature adrenarche: implications for cardiometabolic health.

Premature adrenarche (PA) has been reported as a potential precursor of metabolic disease. We aimed to explore the interaction between body composition and cardiometabolic health of prepubertal children with PA. This observational study comprised of 87 children with PA (15 boys, 8.0 ± 1.2 years) and 87 healthy sex- and age-matched controls. Body composition was measured by bioelectrical impedance analysis. Children with PA had a higher median BMI z-scores (P = 0.001), higher median fat percentage (P = 0.006), and lower muscle-to-fat z-scores (P = 0.050) compared to controls. There were no significant group differences in blood pressure percentiles and lipid profiles. Fat percentage of children with PA was positively correlated and the MFR z-score was negatively correlated with: BMI z-score, systolic blood pressure percentile, and atherogenic dyslipidemia index (P < 0.001 for all). There were significant correlations between parental and offspring MFR z-scores in the control group (father-child: r = 0.528, P = 0.020; mother-child: r = 0.359, P = 0.031), but none in the PA group. Children with PA exhibited an unfavorable body composition in association with their metabolic health even before the onset of puberty. Furthermore, while healthy children displayed heritable body composition traits, children with PA did not, possibly suggesting a relatively greater role for environmental factors in the PA group. Prepubertal children with premature adrenarche have a low muscle-to-fat ratio compared to healthy sex- and age- matched controls. The body composition of prepubertal children with premature adrenarche is associated with their systolic blood pressure percentile and atherogenic dyslipidemia index. Children with premature adrenarche and healthy weight exhibited higher adiposity compared to healthy weight controls, and those with overweight/obesity showed higher rates of elevated blood pressure and higher dyslipidemic atherogenic indices compared to overweight/obesity controls. These findings highlight the importance of early identification, intervention, and lifestyle changes for children with premature adrenarche to help prevent cardiometabolic complications.

An advantageous practical modification in mini-laparoscopic pyeloplasty for prepubertal children: Extracorporeal ureteral spatulation, suturing and stenting – EUSSS technique

BackgroundUreteral spatulation, the first ureteral suture, and double-J stenting may be challenging and time-consuming in laparoscopic pyeloplasty, especially in small children. We aimed to present our comparative results of the extracorporeal ureteral spatulation, suturing, and stenting (EUSSS) technique in mini-laparoscopic pyeloplasty (MLP) and the conventional intracorporeal technique in prepubertal children.MethodsThe data of 46 prepubertal pediatric patients (< 12 years) who underwent laparoscopic pyeloplasty by a single surgeon between January 2021 and October 2023 were retrospectively reviewed. The patients were divided into two groups: who underwent EUSSS-MLP (Group-1, n = 26) and who underwent conventional intracorporeal pyeloplasty (Group-2, n = 20).ResultsThe mean age of all patients was 5.3 years (4.8 ± 2.8 years in Group-1 and 6.0 ± 2.1 years in Group-2 p = 0.126). The mean duration of ureteral preparation plus double-J stenting was 5.7 ± 1.6 min in Group-1 and 19.2 ± 4.1 min in Group-2 (p < 0.0001). The mean duration of surgery was statistically significantly higher in Group-2 (p = 0.034). There was no significant difference in terms of postoperative complications (p = 0.482). Laparoscopic pyeloplasty was successful in 42 (91.3%) patients, with no statistically significant difference between the two groups (Group-1: 24 (92.3%), Group-2:18 (90%), p = 0.783).ConclusionExtracorporeal ureteral preparation and double-J stenting can be safely and effectively preferred in MLP for prepubertal children.

Comparison of growth hormone stimulation tests in prepubertal children with short stature according to response to growth hormone replacement.

Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement. We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS. At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST). The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.

An analysis of acid-labile subunit (ALS) levels in children with short stature born with normal weight.

The acid-labile subunit (ALS) is a protein best known for its function in stabilising the insulin like growth factor-1/2-insulin-like growth factor-1 binding protein 3/5 (IGF-1/2-IGFBP3/5) binary complex by creating the ternary complex and in consequence regulating the biological activity of IGF-1. The aim of the study was to assess ALS concentrations in a chosen population of children with short stature taking into account their clinical diagnosis. A total of 109 prepubertal children were involved in the study - 85 children in the study group and 24 in controls. In all the children IGF-1, IGFBP3, and ALS were measured. The study group was divided according to diagnosis into groups: growth hormone deficiency (GHD), constitutional delay of growth and puberty (CDGP), idiopathic short stature (ISS), and familial short stature (FSS). In the control group the ALS concentration ranged from 4.81 to 13.66 μg/mL. In the whole study group the ALS concentration ranged from 2.73 to 15.81 μg/mL. The difference between both groups was statistically significant (p < 0.0001, R = 0.39). A strong, statistically significant correlation between ALS levels and age was observed, but only in the study group (p < 0.0001, r = 0.59). The ALS standard deviation score (SDS) was not significantly different between the control and CDGP children (p = 0.0644). The ALS concentration was significantly lower in children with short stature. There was, however, no difference between the subgroups of the study group. There was no significant difference in ALS SDS between the control group and children with constitutional delay of growth and development. The usefulness of ALS in routine short stature diagnostics is uncertain, but it might play a role in the diagnosis of children with ISS and CDGP in the future.

Evaluation of insulin-like growth factor-1 in apparently healthy infants and prepubertal Egyptian children with different nutritional statuses

Objectivesto estimate insulin-like growth factor-1 (IGF-1) levels in apparently healthy infants and prepubertal children and compare results among different nutritional statuses.MethodsOur cross-sectional work is a sub-study of a screening project for anemia and nutritional status. We included 252 apparently healthy infants and children with a mean age of 3.7 ± 1.3 years (1.1–6.6), with equal gender distribution. Data retrieved included breastfeeding and anthropometric measures. We tested the stored blood samples for IGF-1 levels. The sample size was reached when all kits were consumed.Resultsabnormal anthropometric measures were detected in 32.9%, either a single or multiple, and 86.5% were breastfed. Girls had significantly higher serum IGF-1 levels than boys (P: <0.001), which was noticeable in girls with abnormal nutritional status detected with anthropometry. Breastfeeding showed no significant association with IGF-1 levels. No significant difference was observed between IGF-1 levels between children with normal versus those with abnormal growth measures. Children with overweight or obesity had significantly lower IGF-1 than children with other body mass index (BMI) categories. Serum IGF-1 levels correlated positively with arm muscle area Z scores in infants and toddlers and weight and BMI Z scores in children between three and four. Also, IGF-1 correlated positively with the triceps skinfold Z score and arm muscle area Z score between four and five.ConclusionsAmong studied infants and prepubertal children, serum IGF-1 was significantly higher in girls than boys and was considerably lower in children with overweight or obesity. Breastfeeding showed no association with IGF-1 levels.

Evaluation of antibodies to oxidized low-density lipoprotein in children with obesity of different degrees

Introduction. The interest in the study of anti-oxidized low-density lipoproteins (anti-oxLDL) is due to their association with the development and progression of atherosclerosis and metabolic syndrome. Purpose of the study. To study the level of antibodies of oxidized low-density lipoproteins (anti-oxLDL) in serum in obese children. Materials and Methods. 76 children aged 5 to 17 years participated in the study. A standard objective and laboratory examination was performed, including physical and sexual development, lipidogram and anti-oxLDL levels. To assess anthropometric data, the standard deviation coefficient was calculated using the Auxology application. The parameters of fat metabolism were determined according to the data of blood biochemical analysis. The content of anti-oxLDL was determined by immuno-enzymatic analysis using test kits “Biomedica”. Results. According to the results of the examination the patients were divided into three groups: group 1 included 36 children with constitutional-exogenous obesity and increased level of anti-oxLDL, group 2-30 patients with constitutional-exogenous obesity and normal level of anti-oxLDL, group 3-10 healthy children. The level of antibodies to oxidized low density lipoproteins (oxLDL) in obese children is 11.6 times higher compared to healthy children. The antibody titer in prepubertal children is 2206 [1809;2603] IU/mL, and in adolescents it is 1505.5 [1109;1902] IU/mL. The highest values of anti-oxLDL levels were observed in patients with 1st degree obesity 2623 [2245;3001] IU/mL and 3rd degree obesity 2914.5 [2678;3151] IU/mL. Conclusion. High of anti-oxLDL levels were found in pre-pubertal children with obesity, especially in 1st and 3rd degree obesity. In obese children, the level of anti-oxLDL has a direct correlation with the duration of the underlying disease and the increase in low-density lipoprotein (LDL) levels. Further studies are needed on the role of anti-OCOLDL as an early predictor of atherosclerosis in clidren with obesity.

7135 Changes in 11-oxygenated androgens in healthy prepubertal children from ages 4, 6, to 8 years: a prospective cohort study

Abstract Disclosure: Y. Lee: None. K. Lee: None. J. Kim: None. Y. Lim: None. J.I. Kim: None. B. Kim: None. Y. Hong: None. J. Song: None. C. Shin: None. Y. Lee: None. Background: 11-oxygenated androgens (11-oxyandrogens) have been recognized for their important role in adrenarche or androgen excess conditions. However, the trajectory during childhood remains understudied. Herein, we examined the longitudinal changes in 11-oxyandrogens among healthy prepubertal children. Methods: In an ongoing prospective cohort study, 172 prepubertal children with available blood samples at the ages of 4, 6, and 8 years were included. Serum concentrations of 14 adrenal androgens and precursors, including dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT) were assessed using liquid chromatography-tandem mass spectrometry. Repeated measures ANOVA was used to analyze the changes in adrenal androgens across age groups. Linear mixed model analysis was used to evaluate factors associated with adrenal hormone levels during 4 to 8 years of age. Results: Among 172 prepubertal children (107 boys, 65 girls), 11OHA4 was the predominant 11-oxyandrogen, exceeding concentrations of DHEA or A4. Serum 11KT level was higher than testosterone level from 6 years of age. Across age 4, 6, and 8 years, 11-oxyandrogens showed an increasing trend. Trajectories of 11OHA4, 11KA4, and 11KT significantly differed by sex (p for interaction &amp;lt; 0.05). Serum levels of 11OHA4 and 11KT consistently increased from 4, 6, to 8 years in both sexes, while 11OHT increased during 6-8 years (p &amp;lt; 0.05 for all). Serum 11KA4 levels increased during 4-6 years in boys and 6-8 years in girls (p &amp;lt; 0.05 for all). Girls showed higher levels of 11OHA4, 11KA4 at 4 years, 11OHT at 6 years, and 11KT at 4 and 6 years. Regarding classic adrenal androgens, DHEA, DHEAS, and A4 also exhibited increases in different patterns between sexes (p for interaction &amp;lt; 0.05) during 4-8 years. Girls had higher serum DHEA and A4 levels at 4 and 6 years, and DHEAS levels at 4 years (p &amp;lt; 0.05 for all). In boys, lower gestational age, lower birth weight z-score, and higher body mass index (BMI) z-score were correlated with elevated levels of DHEA and DHEA-S. Additionally, a higher BMI z-score was associated with increased levels of A4, 11OHT, and 11KT (p &amp;lt; 0.05 for all, multivariable models). In girls, a higher BMI z-score was linked to elevated DHEA levels, while a higher birth weight z-score was associated with increased A4 levels (p &amp;lt; 0.05 for all, multivariable models). Conclusion: In prepubertal children, 11-oxyandrogens showed increasing patterns similar to classic androgens, with sex-differences. Some 11-oxyandrogens were more predominant than classic androgens. This study suggests the importance of 11-oxyandrogens as biomarkers for zona reticularis development and adrenarche in prepubertal children. Presentation: 6/3/2024

12256 Sustained Efficacy Of Weekly Somapacitan In Children With GHD: 3-year Results From Phase 3 REAL4 Study

Abstract Disclosure: B.S. Miller: Consulting Fee; Self; Abbvie, Ascendis Pharma, BioMarin, Bristol-Myers Squibb, EMD Serono, Endo Pharmaceuticals, Novo Nordisk, Orchard Therapeutics, Pfizer, Provention Bio, Tolmar. Grant Recipient; Self; Alexion, Abbvie, Aeterna Zentaris, Amgen, Amicus, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health Pfizer, Prevail Therapeutics, Sangamo Therapeutics. J.C. Blair: Advisory Board Member; Self; Novo Nordisk. Speaker; Self; Novo Nordisk, Ipsen. Other; Self; Novo Nordisk. M. Højby Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. A. Maniatis: Research Investigator; Self; Novo Nordisk, Ascendis, OPKO, Pfizer. J. Mori: Advisory Board Member; Self; Novo Nordisk. Consulting Fee; Self; JCR. Speaker; Self; Novo Nordisk, Pfizer, JCR. V. Böttcher: Advisory Board Member; Self; Merck. Speaker; Self; Novo Nordisk, Merck. Other; Self; Ferring, Lilly, Merck, Novo Nordisk. H. Kim: None. M. Polak: Advisory Board Member; Self; Ipsen, Novo Nordisk, Pfizer. Grant Recipient; Self; Ipsen, Novo Nordisk, Pfizer, Sandoz, Merck, Sanofi. Speaker; Self; Novo Nordisk, Pfizer, Ipsen. R. Horikawa: Advisory Board Member; Self; Novo Nordisk, Pfizer, Ascendis, Lumos Pharma. Grant Recipient; Self; Sandoz. Speaker; Self; Novo Nordisk, Pfizer, JCR. Growth hormone (GH) replacement therapy for children with GH deficiency (GHD) traditionally required daily subcutaneous injections. Somapacitan (Novo Nordisk A/S) is a reversible albumin-binding GH derivative administered once-weekly and the only long-acting GH (LAGH) approved for the treatment of both adults and children with GHD. REAL4 is a randomized, open-label, multi-national, phase 3 trial, consisting of a 52-week main phase and a three-year (week 52 to 208) extension period (NCT03811535). The trial included 200 GH-treatment-naïve, prepubertal children with GHD. Participants received either once-weekly somapacitan (0.16 mg/kg; n=132) or once-daily GH (Norditropin® 0.034 mg/kg; n=68) for 52 weeks. Afterwards, participants receiving daily GH switched to 0.16 mg/kg/week somapacitan (switch group), while those receiving somapacitan continued treatment (soma/soma group). Growth-related endpoints included height velocity (HV), HV standard deviation score (SDS), height SDS, and bone age. The 3-year (156-week) results are presented here. A total of 188 participants (125 in the soma/soma group and 63 in the switch group) completed 3 years of treatment. Improvements in HV, HV SDS, height SDS, and bone age were similar between the groups. In year 3 (week 104 to 156), mean (SD) HV was 7.4 (1.5) cm/year in the soma/soma group and 7.8 (1.4) cm/year in the switch group. The mean (SD) change in height SDS from baseline to week 156 was 2.04 (0.85) in the soma/soma group and 2.38 (1.14) in the switch group, with mean (SD) height SDS at week 156 of -0.95 (0.98) and -1.08 (0.93) in the soma/soma and switch groups, respectively. Mean BMI SDS remained within normal range in both groups at week 156. No safety or tolerability issues were identified. During the extension period (week 52 to 156), a low proportion of the participants reported injection site reactions. No neutralizing antibodies were detected at any of the visits. In conclusion, once-weekly somapacitan showed sustained efficacy and tolerability for three years, as well as for two years following the switching from daily GH treatment in this pivotal phase 3 REAL4 trial. The safety profile of somapacitan was similar to the well-known safety profile of daily GH. Presentation: 6/3/2024

7772 A Study on Role of Anti-Mullerian Hormone and Inhibin B in 46,XY Disorders Of Sexual Development

Abstract Disclosure: N. Kudugunti: None. S. Bangaru: None. R.K. Sahay: None. Background: In pre-pubertal period, a major part of the testicular tissue is constituted by Sertoli cells for which AMH, Inhibin B are specific biomarkersHigh AMH, Inhibin B levels in the prepubertal period is via FSH stimulation, which is mistakenly considered to be silent due to its reduced activity Aim &amp; Objectives: To assess AMH and Inhibin B measurements in the diagnostic workup of prepubertal children with different subtypes of 46,XY DSD and comparing with normal controls To assess Sertoli cell function with AMH and Inhibin B and to assess correlation between testosterone elevation after hCG stimulation, basal AMH and Inhibin B Patients and methods: Pilot study-Single centered, Cross-sectional Observational study. After ethical committee approval, 40 children with 46,XY DSD &amp; 40 healthy age matched, boys as controls recruited after taking assent. All children with DSD underwent karyotyping, assessment of hCG stimulated testosterone, DHT and androstenedione. Basal AMH and inhibin B were measured in both cases and controls. Data were analysed using IBM SPSS version 25. Results: The mean age at presentation was 4.09 years.The diagnosis was made clinically and biochemically, genetic analysis done in few patients. Out of 40 cases, 26 had normal hCG stimulated testosterone of &amp;gt;100 ng/dl (17 cases were 5 alpha reductase type 2 deficiency [5αR2D], 9 cases were PAIS) &amp; 14 had low hCG stimulated testosterone of &amp;lt;100 ng/dl (8 cases were 17βHSD3 deficiency, 4 cases were Partial gonadal dysgenesis [PGD], 2 cases were Vanishing testis syndrome). In the low testosterone group, mean AMH in 17βHSD3 deficiency-279.95 ng/ml, in PGD-31.16 ng/ml which is statistically significant in differentiating these disorders(p-0.002)&amp; mean Inhibin B in 17βHSD3 deficiency-186.41 pg/ml, in PGD-35.95 pg/ml which is statistically significant in differentiating these disorders (p-0.007). In vanishing testis syndrome, AMH &amp; Inhibin B were helpful in confirming the absent functioning testicular tissue Whereas in normal testosterone group, mean AMH in PAIS-235.65 ng/ml, in 5αR2D-289.08 ng/ml difference is not statistically significant(p-0.36)&amp; mean Inhibin B in PAIS-204.50 pg/ml, in 5αR2D-190.91 pg/ml difference is not statistically significant(p-0.72) There was significant correlation between basal AMH and hCG stimulated testosterone (r=0.434; p-0.002), Inhibin B and hCG stimulated testosterone(r=0.438; p-0.001), AMH and Inhibin B(r=0.770; p&amp;lt;0.001). Conclusion: AMH and Inhibin B are valuable in differentiating PGD, 17βHSD3 deficiency in low hCG stimulated testosterone patients, but not helpful in differentiating PAIS, 5αR2D in normal hCG stimulated testosterone patients. Especially in PGD they may have a role with respect to fertility prospects and malignancy risk assessment. Presentation: 6/3/2024

9318 Growth Response To Oral Growth Hormone Secretagogue LUM-201 In Children With Moderate GH Deficiency (GHD) Is Dependent On The Pattern Of Pulsatile GH Secretion Induced By LUM-201

Abstract Disclosure: A. Roslan: None. R. Roman: None. A. Avila: None. D. Said: None. I. Baier: None. E. Brincks: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. A. Bruchey: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. J. McKew: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. P. Pitukcheewanont: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc.. M. Johnson: None. T. Garner: Consulting Fee; Self; Lumos Pharma, Inc.. Grant Recipient; Self; Novo Nordisk. M.O. Thorner: Consulting Fee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. P.E. Clayton: Advisory Board Member; Self; Lumos Pharma, Inc.. Consulting Fee; Self; Lumos Pharma, Inc.. Grant Recipient; Self; Novo Nordisk. A. Stevens: Consulting Fee; Self; Lumos Pharma, Inc. F. Cassorla: Consulting Fee; Self; Lumos Pharma, Inc.. Background: Oral GH secretagogue, LUM-201, increases growth rates in children with moderate GHD in Phase 2 trials (OraGrowtH210 and 212) [ENDO 2023, OR21-06]. GH pulse profiles at baseline (D1) and 6 months (6M) were assessed in OraGrowtH212. This study aims to understand relationships between pulse profiles and growth response to LUM-201. Methods: The OraGrowtH212 trial is being conducted at a single site (Chile). 22 prepubertal children (M 14: F 8) with moderate GHD (peak GH level on two stimulation tests &amp;gt;3 and &amp;lt;10ng/ml), who had basal IGF-I &amp;gt;30ng/ml and an acute GH response to 0.8mg/kg LUM-201 of ≥5ng/ml, were randomised to receive LUM-201 1.6 or 3.2 mg/kg/day. 10min samples over 12hrs (08.00-20.00) were collected at D1 and M6 for measurement of GH concentration (ng/ml), with GH secretion rates (ng/ml/min) derived by deconvolution analysis. A univariate Spearman’s rank correlation matrix was used to screen for relationships (significant at p&amp;lt;0.05) between D1 characteristics, D1 height velocity, 6M annualised height velocity (AHV) and interpulse, pulsatile and total GH secretion at D1 and M6.The pattern of pulsatile GH secretion in the 12hr profile was characterised using Functional Principal Component Analysis (FPCA) - used to explore the dominant modes of variation in functional data, in this case the GH time series. Subjects were grouped into tertiles based on 6M AHV (High [mean 8.9cm/yr], Medium [7.7], and Low [6.7]), and the 12hr profiles were divided into three 4hr intervals. The interquartile range (IQR) for mean GH secretion (representing variation in amount) and principal components [PCs] (variation in pattern) for all subjects in each AHV tertile at D1 and M6 were generated. Results: All GH secretion parameters increased significantly from D1 to M6 (p&amp;lt;0.01). Age was negatively associated with 6m AHV (rs= -0.46), and D1 pulsatile GH secretion was positively associated with D1 AHV (rs = +0.51). However, GH secretion at D1 and M6 was not correlated with 6m AHV. In the FPCA, the difference in IQR for mean GH secretion from D1 to 6M was highest over 0-4hrs for subjects in the high and medium AHV tertiles (5- and 3.3-fold greater respectively compared to the other time intervals), while subjects with low AHV had the highest difference over 8-12hrs (42-fold greater). Using the first PC (which accounts for ∼50% of total variation), the change in IQR was highest over 0-4 and 4-8hrs in the high AHV tertile (3-fold greater compared to other time intervals), over 0-4hrs in the medium tertile (46-fold greater) and over 8-12hrs in the low tertile (3.4-fold greater). Conclusions: Oral LUM-201 stimulates significant increases in GH secretion over 6 months in children with moderate GH deficiency. Complex relationships exist between growth response and both the amount and pattern of GH secretion, with the highest growth responses to LUM-201 associated with the greatest pulsatile activity early in the profile. Presentation: 6/3/2024

Effect of Volleyball Small Side Games on Body Mass Index and Physiological Conditions on Pre Pubertal Children

Effect of Volleyball Small Side Games on Body Mass Index and Physiological Conditions on Pre Pubertal Children

Fertility Treatment and Preservation Options for Transgender and Gender Diverse People.

Years of growing research demonstrate that transgender and gender diverse (TGD) people desire fertility counseling and family building, however social and medical factors can impact future fertility options. Fortunately, TGD individuals have many viable options for family building using their own gametes and/or reproductive organs. However, the nuanced ways in which different gender affirming treatments affect reproduction, the interplay with non-treatment related infertility factors, and mitigation of likely dysphoria triggers are all critical to actual utilization. This review focuses on fertility treatment and preservation options for TGD patients and highlights these influential social and medical factors. Fertility treatments may be associated with worsening gender dysphoria in TGD people, and an affirming clinical environment and conscientious provider approach is paramount to treatment success. However, reducing gender dysphoria can also require specific changes to medically assisted reproduction and sperm collection protocols, some which carry the potential for diminished outcomes or unknown effects. Adolescents undergoing fertility preservation treatments may need more support or additional protocol modifications, and outcomes may be poorer in this age group compared with adults. Testicular and ovarian tissue cryopreservation may present a fertility preservation option for prepubertal TGD children, however in-vitro gamete maturation remains experimental in this situation.

Factors beyond Body Mass Index Associated with Cardiometabolic Risk among Children with Severe Obesity.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements, and bioimpedance analysis (BIA)-derived parameters to identify potential cardiometabolic complications associated with severe obesity. Methods: This study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting the criteria for severe obesity based on BMI thresholds for different age groups. The patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests, and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR) but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. The metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in the pubertal children. A negative correlation between HDL and triglycerides was observed only in the boys. The prepubertal children exhibited more significant correlations, despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Adiposity and cardiac autonomic function in children with a family history of obesity.

Data on associations between adiposity and heart rate variability (HRV) in prepubertal children are limited. We examined the associations between adiposity indices and HRV, independent of lifestyle behaviors, comparing multiple indicators of adiposity, and explored differences between boys and girls. Data stem from 469 participants of the QUALITY cohort (630 children aged 8-10 years with a parental history of obesity). Adiposity indices included waist-to-height ratio, body mass index (BMI) percentiles and categories (overweight, obesity), dual-energy x-ray absorptiometry (DEXA) defined fat mass percentage and android/gynoid ratio. HRV indices in the frequency and the spectral domain were derived from a daytime 3-h Holter recording. Multivariable linear regression models were adjusted for age, sex, Tanner stage, physical activity, screen time, and fitness. Interactions between sex and adiposity were tested. Greater adiposity was associated with decreased parasympathetic modulation and increased sympathetic dominance. Waist-to-height ratio was associated with lower parasympathetic activity: root mean square of the successive differences (RMSSD) [B = -23.32, 95% confidence interval (CI) -42.42, -4.22], pNN50 (B = -16.93, 95% CI - 28.58, - 5.27), LF/HF ratio (B = 1.83, 95% CI 0.97-2.70). Patterns of association were similar for android/gynoid ratio. Overweight was not associated with altered HRV. Obesity was negatively associated with RMSSD and pNN50 and positively with LF/HF ratio. Greater fat mass percentage was associated with lower RMSSD, pNN50, and HF, and increased LF/HF ratio. There were no differences between boys and girls. Specific markers of adiposity relate to altered HRV in childhood, with waist-to-height ratio being potentially a more relevant marker of HRV than BMI and more pragmatic than percent body fat. NCT03356262, 11 November 2017.

Associations between Biological Maturation, Chronological Age, Body Mass Index, Sex, and Motor Competence in Prepubertal Children: A Network Analysis.

The development of motor competence (MC) during childhood is crucial for future physical activity and health outcomes, and it is affected by both biological and psychosocial factors. Most MC research has focused on children's age, with fewer studies examining separate associations between MC and biological maturation. This cross-sectional study used network analysis to assess the nonlinear associations between biological maturation (the child's percentage of predicted mature stature to indicate somatic maturation), chronological age, sex, BMI, and MC (Test of Gross Motor Development, third edition) in 218 children (100 boys, 118 girls) aged 7-9 years. Biological maturation was not significantly associated with MC in boys and weakly associated with MC in girls for the dribble, under-hand throw, and gallop. Age was positively associated with MC in girls and boys. Centrality measures indicated that the gallop and slide in girls and the dribble, catch, and run in boys were the most important network variables. Positive associations were observed between maturation and BMI for girls (r = 0.579) and, to a lesser degree, for boys (r = 0.267). The findings suggest that age, rather than biological maturation, is positively associated with MC in 7- to 9-year-olds. Centrality measures showed that some skills may influence other skills.

Somapacitan in Children Born SGA: 52-week Efficacy, Safety, and IGF-I Response Results from the Phase 2 REAL5 Study.

Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in short children born small for gestational age (SGA). Evaluate efficacy, safety, tolerability as well as total and bioactive insulin-like growth factor-I (IGF-I) response of once-weekly somapacitan compared to daily GH in children born SGA. REAL5 is a randomized, multi-center, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension, and an ongoing 4-year safety extension (NCT03878446). Thirty-eight sites across 12 countries. Sixty-two GH-treatment-naïve, prepubertal short children born SGA were randomized; 61 completed 52-weeks of treatment. Patients randomized (1:1:1:1:1) to somapacitan (0.16, 0.20 or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day), all administered subcutaneously. Estimated mean height velocity (HV; cm/year) at week 52 was 8.5, 10.4 and 10.7 cm/year for somapacitan 0.16, 0.20 and 0.24 mg/kg/week, respectively, and 9.3 and 11.2 cm/year for daily GH 0.035 and 0.067 mg/kg/day, respectively. Dose-dependent increases in total IGF-I as well as peak IGF-I bioactivity were observed for both treatments and were similar between comparator groups. For somapacitan, exposure-response modelling indicated highest efficacy with 0.24 mg/kg/week after 52 weeks of treatment. Similar safety and tolerability were demonstrated across all groups. A sustained dose-dependent growth response was demonstrated for somapacitan after 52 weeks of treatment. Overall, somapacitan 0.24 mg/kg/week provides similar efficacy, safety, and tolerability, as well as comparable bioactive and total IGF-I response, as daily GH (0.067 mg/kg/day) in children born SGA.

Hormonal and inflammatory responses in prepubertal vs. pubertal male children following an acute free-weight resistance training session.

Examine the acute hormonal and cytokine responses to free-weight resistance training in trained prepubertal and pubertal male children. Prepubertal (n = 21; age 11.4 ± 1.1years; Tanner I-II) and pubertal male children (n = 20; age 15.8 ± 0.7years; Tanner III-V) conducted a moderate-intensity free-weight resistance training program to failure with venous blood sampling before (pre), immediately after (post) and during the recovery phase of the program (post-15,-30min). Growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, testosterone, IL-6, and TNF-α were analyzed in serum samples. Biological maturation was assessed according to the stages of the Tanner scale. There was a significant time-by-group interaction in IGF-I response (p = 0.044; η2 = 0.209) and testosterone (p < 0.001; η2 = 0.508), indicating a greater change in the pubertal group compared to the prepubertal group. Both groups significantly increased post-exercise GH levels (p < 0.05). Only the prepuberal group significantly increased levels of IL-6 at all post-exercise time points (p < 0.05). Both groups showed a significant (p < 0.05) increase in TNF-α levels compared to resting levels. These data suggest that acute testosterone and IGF-I response following resistance training differ between trained prepubertal and pubertal male children. Moderate-intensity resistance training performed to failure may thus have different effects in trained prepubertal and pubertal male children, which should be considered when giving training advice. Clinical trials number: NCT05022992.

Elevated systemic venous pressures as a possible pathology in prepubertal pediatric idiopathic intracranial hypertension

BackgroundPediatric idiopathic intracranial hypertension (IIH) is a rare and challenging condition. As implied by the nomenclature, the etiologies remain unknown, and multiple etiologies are being investigated. In this study, we explored the potential role of increased systemic or cerebral venous pressure in the pathogenesis.MethodAn observational cohort study following the STROBE guidelines, including prepubertal children with clinical symptoms and imaging findings consistent with IIH referred to the neurosurgical department, was conducted. The patients underwent a comprehensive diagnostic protocol, including MRI, continuous intracranial pressure (ICP) monitoring, and endovascular venography with venous pressure measurements.ResultsThe study included 11 consecutive patients (six boys and five girls) with an average age of 2.3 years, and an average BMI of 18.4. Among these, one patient was found to have venous stenosis with a gradient; the other 10 patients presented with normal intracranial anatomy. All patients exhibited elevated venous pressures, with an average superior sagittal sinus pressure of 18.9 mmHg, average internal jugular vein pressure of 17.0 mmHg, and average central venous pressure of 15.9 mmHg. Daytime ICP averaged 12.9 mmHg, whereas nighttime ICP averaged 17.2 mmHg with either A- or B-waves in 10 of the 11 patients. Despite pathological ICP, only three patients had papilledema.ConclusionsAll patients had an increased systemic venous pressure, indicating a possible pathological factor for prepubertal IIH. Additionally, our findings show that young children often only partly meet the Friedman criteria due to a lack of papilledema, emphasizing the need for pediatric-specific diagnostic criteria. Further large-scale studies are needed to confirm these findings and to explore the underlying reasons for this increase in venous pressure and potential new treatment avenues.

Factors affecting maximal oxygen uptake in prepubertal children: a systematic review and meta-analysis

In pre-pubertal children the factors affecting maximal oxygen uptake have yet to be fully understood. Therefore, the purpose of this analysis is to present cardiorespiratory fitness in prepubertal boys and girls and to determine if there are any differences based on sex, exercise testing modality or if maximal or peak oxygen consumption metrics are used. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. For statistical analysis, multilevel models grounded in Bayesian principles were used. Selected studies obtained: maximal effort during the test, peak or maximal oxygen consumption (V̇O2) values, boys and girls (sex specific groups only) age under 11, cycle ergometry or treadmill, pre-intervention or no intervention data. In boys using cycle ergometry, 118 studies were included in the analysis, in boys using treadmill 115, in girls using cycle ergometry 83 and in girls using treadmill testing 95 study entries were included. As children get older, their cardiorespiratory fitness increases (P ≈ 100%). Studies with participants having smaller body mass have higher V̇O2 relative to body mass values (P ≈ 100%). Boys have higher V̇O2 values than girls (P ≈ 100%). Studies using treadmill reported higher values than those using cycle ergometer (P ≈ 100%). Regarding the influence of measurement method (max vs. peak) on V̇O2 values we did not find significant differences. In conclusion, we present reference values for cardiorespiratory fitness in prepubertal boys and girls using cycle ergometry or treadmill. Prepubertal boys have higher cardiorespiratory fitness than girls and using treadmill testing might be a preferred method to cycle ergometry, especially in older children. Maximal or peak oxygen consumption metrics might be used interchangeably in prepubertal children.

The association between depressive symptoms and overweight or obesity in prepubertal children: Findings from the QUALITY cohort

BackgroundYouth obesity and depression are public health concerns. Although meta-analyses suggest a positive association between those conditions in adults and adolescents, evidence remains unclear in prepubertal children. We examined the bidirectional associations between levels of depressive symptoms and weight status in 8–10-year-old children with a parental history of obesity, over two years, and whether they differ by sex. Methods: Data were drawn from the QUebec Adipose and Lifestyle InvesTigation in Youth Cohort Study's baseline and first follow-up evaluations (n = 558). Depressive symptoms were assessed using the 12-item Center for Epidemiological Studies Depression scale and weight status using body mass index z-scores based on World Health Organization standards. Linear and logistic regression models were used to test the directionality and magnitude of the associations, adjusting for age, sex, physical activity, screen time, parental education, alcohol and cigarette use, and baseline outcome measure. Results: Children with higher levels of depressive symptoms at baseline were not more likely to have overweight/obesity at follow-up (odds ratio [95 % Coefficient Interval] = 0.95[0.88;1.02]). Baseline overweight/obesity was not associated with subsequent higher levels of depressive symptoms (beta coefficient [95 % Coefficient Interval] = 0.20 [−0.47;0.87]). No sex differences emerged. Limitations: Selection bias may have occurred due to loss at follow-up (10 % attrition) and exclusion of 6 participants taking mood disorder medication. Conclusions: Unlike in adults and adolescents, no association between weight status and depressive symptoms was observed in childhood over two years. Underlying mechanisms linking both conditions later in life may not apply as early as prepubertal childhood.