Years In Boys Research Articles

12427 MKRN3 Methylation Abnormalities In Patients With Pubertal Disorders

Abstract Disclosure: N.C. Grosek: None. T. Silva: None. J.C. Magnotto: None. A. Latronico: None. A.P. Canton: None. Y. Chan: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objectives: Central Precocious Puberty (CPP) is caused by early reactivation of pulsatile GnRH secretion before age 8 years in girls and 9 years in boys. Delayed puberty (DP) is defined by the absence or incomplete development of sexual characteristics by age 13 years in girls and 14 years in boys. Environmental cues affect the HPG axis and timing of puberty via epigenetic mechanisms such as DNA methylation (DNAm). Inactivating mutations in the maternally imprinted Makorin Ring Finger 3 (MKRN3) gene are the most common genetic defect associated with CPP, representing ∼9% of patients with sporadic and familial CPP. Genomic imprinting occurs through differential methylation of CpG islands at a gene promoter or enhancer region. Differentially methylated regions (DMRs) regulate genetic imprinting. We hypothesized that transcription factor binding sites (TFBS) for ZFP57 (CpG57) andNRF1 (CpGs54+55) within the islet 3.7kb upstream of MKRN3 (MRKN3 islet) may impact expression. This study aimed to analyze if aberrant MKRN3 islet DNAm changes are associated with disorders of pubertal timing. Methods and Results: Germline DNA from 2 control patients was used to analyze the MKRN3 promoter region and islet DNAm profile. Bisulfite-treated DNA was amplified by PCR with primers targeting MKRN3 promoter and islet and submitted to Sanger sequencing. All CpG islands in the promoter region were 100% methylated, but those in the MKRN3 islet were differentially methylated with ∼50-60% methylated. DNA from our CPP cohort (n=71) underwent Next-Generation Sequencing analysis of bisulfite-treated DNA of these regions to identify the DMR potentially associated with MKRN3 imprinting. The MKRN3 islet covered CpG59-CpG49. Next, samples from our CPP cohort and patients with DP (n=44) and normal pubertal timing (n=33; 45% prepubertal, 55% pubertal) underwent pyrosequencing analyses of MKRN3islet. To compare DNAm levels between controls and our cohorts at each CpG island, T-tests were used: reported as mean±SEM. In the CPP cohort, 4/11 CpGs were significantly hypomethylated compared to controls (CpGs 54, 53, 51, 50). Specifically, the NRF1 TFBS was hypomethylated compared to controls (37.8 vs 41.6 ± 1.1, p<0.001) and DP (41.4 vs 43.8 ± 0.83, p=0.044). In the DP group, we found no significant difference in DNAm compared to controls. But they had hypermethylation of 4/11 CpGs compared to the CPP group, including the NRF1 TFBS (CpGs 55, 53, 51,50). Neither the CPP nor DP cohorts had significant DNAm differences at the ZFP57 TFBS compared to controls. Conclusion: Our study showed hypomethylation of 4 out of 11 CpGs in MKRN3 islet, including the NRF1 TFBS, in CPP compared to control and DP groups. On the other hand, NRF1 TFBS was hypermethylated in DPP compared to CPP. Further studies are needed to determine if these alternations in methylation are associated with MKRN3 expression levels and pubertal initiation. Presentation: 6/1/2024

12672 MKRN3 Methylation Abnormalities In Patients With Pubertal Disorders

Abstract Disclosure: N.C. Grosek: None. T. Silva: None. J.C. Magnotto: None. A. Latronico: None. A.P. Canton: None. Y. Chan: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objectives: Central Precocious Puberty (CPP) is caused by early reactivation of pulsatile GnRH secretion before age 8 years in girls and 9 years in boys. Delayed puberty (DP) is defined by the absence or incomplete development of sexual characteristics by age 13 years in girls and 14 years in boys. Environmental cues affect the HPG axis and timing of puberty via epigenetic mechanisms such as DNA methylation (DNAm). Inactivating mutations in the maternally imprinted Makorin Ring Finger 3 (MKRN3) gene are the most common genetic defect associated with CPP, representing ∼9% of patients with sporadic and familial CPP. Genomic imprinting occurs through differential methylation of CpG islands at a gene promoter or enhancer region. Differentially methylated regions (DMRs) regulate genetic imprinting. We hypothesized that transcription factor binding sites (TFBS) for ZFP57 (CpG57) andNRF1 (CpGs54+55) within the islet 3.7kb upstream of MKRN3 (MRKN3 islet) may impact expression. This study aimed to analyze if aberrant MKRN3 islet DNAm changes are associated with disorders of pubertal timing. Methods and Results: Germline DNA from 2 control patients was used to analyze the MKRN3 promoter region and islet DNAm profile. Bisulfite-treated DNA was amplified by PCR with primers targeting MKRN3 promoter and islet and submitted to Sanger sequencing. All CpG islands in the promoter region were 100% methylated, but those in the MKRN3 islet were differentially methylated with ∼50-60% methylated. DNA from our CPP cohort (n=71) underwent Next-Generation Sequencing analysis of bisulfite-treated DNA of these regions to identify the DMR potentially associated with MKRN3 imprinting. The MKRN3 islet covered CpG59-CpG49. Next, samples from our CPP cohort and patients with DP (n=44) and normal pubertal timing (n=33; 45% prepubertal, 55% pubertal) underwent pyrosequencing analyses of MKRN3islet. To compare DNAm levels between controls and our cohorts at each CpG island, T-tests were used: reported as mean±SEM. In the CPP cohort, 4/11 CpGs were significantly hypomethylated compared to controls (CpGs 54, 53, 51, 50). Specifically, the NRF1 TFBS was hypomethylated compared to controls (37.8 vs 41.6 ± 1.1, p<0.001) and DP (41.4 vs 43.8 ± 0.83, p=0.044). In the DP group, we found no significant difference in DNAm compared to controls. But they had hypermethylation of 4/11 CpGs compared to the CPP group, including the NRF1 TFBS (CpGs 55, 53, 51,50). Neither the CPP nor DP cohorts had significant DNAm differences at the ZFP57 TFBS compared to controls. Conclusion: Our study showed hypomethylation of 4 out of 11 CpGs in MKRN3 islet, including the NRF1 TFBS, in CPP compared to control and DP groups. On the other hand, NRF1 TFBS was hypermethylated in DPP compared to CPP. Further studies are needed to determine if these alternations in methylation are associated with MKRN3 expression levels and pubertal initiation. Presentation: 6/1/2024

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 < 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 < 0.05 for all). Serum 11KA4 levels increased during 4-6 years in boys and 6-8 years in girls (p < 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 < 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 < 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 < 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 < 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

7128 Efficacy and Safety of Leuprolide Acetate 3M Depot in Chinese Children with Central Precocious Puberty: Interim Analysis of Multicenter, Single-Arm, Prospective Study

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) due to early activation of the hypothalamic-pituitary-gonadal axis leads to early puberty. CPP has a negative impact on adult height. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist (GnRHa) is the standard treatment for CPP. As CPP requires prolonged treatment, a 3-month (3M) depot formulation would increase patient compliance and reduce the injection burden. This interim analysis presents the effect of LA 3M depot on the gonadotropic axis and assesses safety in children with CPP. Methods: In this open-label, multicenter, single-arm, and prospective study, 31 children with CPP were included. Key inclusion criteria were the appearance of secondary sexual characteristics below the age of eight years in girls and nine years in boys with a confirmed diagnosis of CPP. Children treated with prior GnRHa and/or having underlying medical conditions were excluded. Eligible children were treated with LA 11.25 mg subcutaneously every 12 weeks. The primary endpoint of this interim analysis was the proportion of children achieving inhibition of peak LH defined as peak LH ≤ 3.0 IU/L in the GnRH stimulation test at weeks 24. The secondary endpoint was safety analysis in the children receiving at least one dose of LA 3M depot. Results: At baseline, 30 girls and one boy were enrolled. The median (95% CI) chronological age (CA) of the girls was 8.0 (7.0, 9.0) years and the boy was 10 years old. Girls had a median height of 136.95 (131.5, 139.7) cm, weight of 30 (27, 34) kg, and BMI of 16.4 (15.1, 17.9) kg/m2. Baseline bone (BA) age was 11 (10, 11) years, and BA/CA was 1.24 (1.2, 1.3). Boy’s characteristics at baseline differed in CA (10 years), height (144 cm), and BMI (17.4 kg/m2) from girls of this cohort. Due to the data collection time points for the interim analysis, 8 out of the 31 enrolled subjects had a visit at week 24, and 30 subjects reached the week 12 visit time point and had a visit at week 12. The percentage of children achieving inhibition of peak LH (≤ 3.0 IU/L) in the GnRH stimulation test at week 12 was 100 (88.4, 100) %. At week 24, all of them achieved inhibition of LH in the GnRH stimulation test 100 (63, 100) %. Decreases in BA/CA from baseline at weeks 12 and 24 are 93 (77.9, 99.2) % and 50 (15.7, 84.3) % respectively. No progression of the Tanner stage was observed in 96.7 (82.8, 99.9) % and 100 (63, 100) % at weeks 12 and 24. At the data cut-off, 4 (13.33%) patients experienced a total of 5 treatment-emergent adverse events (TEAEs) in the safety population of 30 subjects. No grade ≥3 AE or serious AE was reported. The incidence of injection site reaction was 3.33%. Conclusion: LA at 11.25mg/3M depot effectively suppresses the gonadotropic axis at weeks 12 and 24, normalizing growth and reversibly slowing the early onset of puberty in children with CPP. LA in a 3-month injecting frequency is a safe and convenient treatment option to improve patient compliance. Presentation: 6/3/2024

The estimation of pubertal growth spurt parameters using the superimposition by translation and rotation model in Korean children and adolescents: a longitudinal cohort study.

Understanding the characteristics of the pubertal growth spurt in Korean children and adolescents can serve as crucial foundational data for researching puberty and growth-related disorders. This study aims to estimate the key parameters of pubertal growth, specifically the age and magnitude of the pubertal growth spurt, utilizing longitudinal data from a cohort of Korean children and adolescents. This study used mixed longitudinal height data from a cohort of Korean elementary, middle, and high school students aged 7-18 years. The Superimposition by Translation and Rotation (SITAR) model, a shape-invariant growth curve model, was utilized to estimate a reference height velocity curve for the entire dataset and individual curves via random effects to evaluate pubertal growth parameters. Altogether, 3,339 height measurements (1,519 for boys and 1,820 for girls) from 270 individuals (123 boys and 147 girls) were analyzed. The average age of growth spurt onset in Korean boys was 10.17 ± 0.61 years (mean ± SE), with peak height velocity occurring at 12.46 ± 0.69 years of age (9.61 ± 1.26 cm/year). Korean girls, contrarily, experience their growth spurt at an earlier age (8.57 ± 0.68 years), with peak height velocity occurring at 10.99 ± 0.74 years of age (8.32 ± 1.09 cm/year). An earlier onset of puberty in both sexes is associated with a shorter growth spurt duration (0.63 years for boys and 0.58 years for girls) and a higher peak height velocity (1.82 cm/year for boys and 1.39 cm/year for girls). These associations were statistically significant for both sexes (all p < 0.0001). This study is the first to use the height velocity curve from the SITAR model to examine the pubertal growth spurt of Korean children and adolescents. The estimated timing and magnitude of the pubertal growth spurt, and their relationships can be useful data for clinicians and researchers.

Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.

Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls? In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood. AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome. In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years. AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and SD scores (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (r) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve. In boys, AGD/body size-index SD score correlated significantly between infancy and 9 years, strongest for AGDas (r = 0.540 P > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (P > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low. The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys. In boys, AGDas, relative to body size, correlated from infancy to 9 years, suggesting that AGD in infancy can be considered a non-invasive marker of later reproductive health. Further follow-up studies are needed to evaluate long-term individual tracking of AGD as well as assessment of childhood AGD as early marker of adult reproductive health. This study was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, the Municipality of Odense, Denmark, the University of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, the Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), Sygeforsikring Danmark (journalnr. 2021-0173), the Collaborative Foundation between Odense University Hospital and Rigshospitalet, and Helsefonden. There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported. N/A.

A comparison of two artificial intelligence-based methods for assessing bone age in Turkish children: BoneXpert and VUNO Med-Bone Age.

This study aimed to evaluate the validity of two artificial intelligence (AI)-based bone age assessment programs, BoneXpert and VUNO Med-Bone Age (VUNO), compared with manual assessments using the Greulich-Pyle method in Turkish children. This study included a cohort of 292 pediatric cases, ranging in age from 1 to 15 years with an equal gender and number distribution in each age group. Two radiologists, who were unaware of the bone age determined by AI, independently evaluated the bone age. The statistical study involved using the intraclass correlation coefficient (ICC) to measure the level of agreement between the manual and AI-based assessments. The ICC coefficients for the agreement between the manual measurements of two radiologists indicate almost perfect agreement. When all cases, regardless of gender and age group, were analyzed, a nearly perfect positive agreement was observed between the manual and software measurements. When bone age calculations were separated and analyzed separately for girls and boys, there was no statistically significant difference between the two AI-based methods for boys; however, ICC coefficients of 0.990 and 0.982 were calculated for VUNO and BoneXpert, respectively, and this difference of 0.008 was significant (z = 2.528, P = 0.012) for girls. Accordingly, VUNO showed higher agreement with manual measurements compared with BoneXpert. The difference between the agreements demonstrated by the two software packages with manual measurements in the prepubescent group was much more pronounced in girls compared with boys. After the age of 8 years for girls and 9 years for boys, the agreement between manual measurements and both AI software packages was equal. Both BoneXpert and VUNO showed high validity in assessing bone age. Furthermore, VUNO has a statistically higher correlation with manual assessment in prepubertal girls. These results suggest that VUNO may be slightly more effective in determining bone age, indicating its potential as a highly reliable tool for bone age assessment in Turkish children. Investigating the most suitable AI program for the Turkish population could be clinically significant.

Community Awareness and Knowledge About Precocious Puberty in Riyadh City, Saudi Arabia.

Background Puberty is the process of physical maturation where an adolescent reaches sexual maturity and becomes capable of reproduction. On average, puberty typically begins between 8 and 13 years old in females and 9 and 14 years oldin males. The traditional definition of precocious puberty is the development of secondary sexual characteristics before eight years of age in girls and nine years in boys. In this study, we aimed to assess the knowledge and awareness of Riyadh residents in Saudi Arabia about precocious puberty and its complications. Methodology A cross-sectional study was conducted to estimate the awareness and knowledge among Riyadh residents about precocious puberty and its complications; 426 participants were included in this study. Participants completed a pretested self-administered questionnaire that included sociodemographic data, knowledge about precocious puberty definition, risk factors, complications, and treatment. Results This study enrolled 426 participants. Overall, 10.1% were correct about the precocious puberty age for girls, and 8.5% knew about the precocious puberty age for boys. The overall mean knowledge score among the study sample was 5.56 (SD = 2.79), with poor knowledge being prominent and constituting 68.8%, while fair and good knowledge were 30% and 1.2%, respectively. Working in a non-medical field was the sole independent significant predictor of incorrect answers of knowledge about precocious puberty. Conclusions Awareness strategies are needed to increase awareness among the community to encourage prevention and treatment for precocious puberty as the awareness and knowledge of Riyadh residents in Saudi Arabia about precocious puberty and its complications are low.

Association between bone age maturity and childhood adiposity.

Evidence shows that overweight and obesity are associated with advanced bone age (BA). To analyse the effect of adiposity on BA among Mexican children. This cross-sectional study included 902 children (5-18 years old). Anthropometric measurements, dual-energy X-ray absorptiometry (DXA) and automated hand X-ray-based BA measurements were obtained. BA curves of children stratified by sex and age were created based on nutritional status. We also calculated odds ratios for advanced BA associated with the body mass index (BMI), waist/height ratio and adiposity estimated using DXA (total and truncal fat mass). Participants with overweight/obesity by BMI (SDS ≥1) advanced earlier in BA than did normal weight participants (6.0 vs. 12.0 years in boys and 6.0 vs. 10.3 in girls, p < 0.01); similarly, participants with a greater body fat percentage (SDS ≥1) exhibited earlier advanced BA (7.5 vs. 10.0 years in boys and 6.0 vs. 9.6 in girls, p < 0.01). Differences were also observed according to the waist/height ratio and truncal fat. Children with a BMI or DXA SDS ≥1 had greater odds of presenting an advanced BA of more than 1 year (OR 1.79-3.55, p < 0.05). Increased adiposity in children, mainly in boys, is associated with advanced BA at earlier ages.

Pubertal, Auxological, and Adult Height Outcomes in Children Treated for Adrenocortical Tumors: Half a Century Experience.

Most children with adrenocortical tumors (ACTs) present with accelerated growth and skeletal maturation at diagnosis, which potentially compromises their adult heights (AHs). Knowledge about growth and pubertal patterns after ACT resection is scarce. This study presents the pubertal and auxological development of patients treated for ACT and followed up at a single pediatric endocrinology service in Brazil. Retrospective cohort study including 63 patients (47 girls) followed up between 1966 and 2021. Pubertal and auxological data from ACT diagnosis to AH were analyzed. At diagnosis, the patients had median values of bone age (BA) more advanced than chronological age (CA), height standard deviation score greater than target height (TH-SDS), and predicted adult height (PAH-SDS) lower than TH-SDS. The difference between BA and CA decreased gradually during follow-up and the PAH-SDS moved closer to the TH-SDS 7 years after tumor resection. Puberty started at a median CA of 9.3 (8.3-11.3) years in girls and 9.9 (9.2-13.6) years in boys. Nine patients (6 girls) developed central precocious puberty (CPP), which was influenced by a CA &gt;4 years at diagnosis. The difference between AH-SDS and TH-SDS was not significant (p = 0.3). The factors independently associated with AH below TH were CA &gt;4 years at diagnosis, time between clinical manifestation and diagnosis &gt;1 year, and development of CPP. Most patients treated for ACT during childhood attained AH within the TH despite presenting with advanced skeletal maturation at diagnosis. Development of CPP was not infrequent.

Acceleration of skeletal maturation in Central Europe over the last two decades: insights from two cohorts of healthy children

BackgroundDeviations between the determination of bone age (BA) according to Greulich and Pyle (G&P) and chronological age (CA) are common in Caucasians. Assessing these discrepancies in a population over time requires analysis of large samples and low intra-observer variability in BA estimation, both can be achieved with artificial intelligence-based software. The latest software-based reference curve contrasting the BA determined by G&P to the CA of Central European children dates back over two decades.ObjectiveTo examine whether the reference curve from a historical cohort from the Netherlands (Rotterdam cohort) between BA determined by G&P and CA still applies to a current Central European cohort and derive a current reference curve.Materials and methodsThis retrospective single-center study included 1,653 children and adolescents (aged 3–17 years) who had received a radiograph of the hand following trauma. The G&P BA estimated using artificial intelligence-based software was contrasted with the CA, and the deviations were compared with the Rotterdam cohort.ResultsAmong the participants, the mean absolute error between BA and CA was 0.92 years for girls and 0.97 years for boys. For the ages of 8 years (boys) and 11 years (girls) and upward, the mean deviation was significantly greater in the current cohort than in the Rotterdam cohort. The reference curves of both cohorts also differed significantly from each other (P < 0.001 for both boys and girls).ConclusionThe BA of the current Central European population and that of the curve from the Rotterdam cohort from over two decades ago differ. Whether this effect can be attributed to accelerated bone maturation needs further evaluation.

Perkembangan Masa Puber

This research explores and evaluates Puberty, which is a time when a child experiences physical and emotional changes that indicate sexual and reproductive maturity. Puberty usually lasts around 9-14 years for girls and 12-16 years for boys. Hormonal changes during puberty cause various physical changes, such as breast growth, the appearance of acne, pubic hair, and height. Hormonal changes also cause emotional development, identity, and reproductive abilities. Deviant maturity can be caused by various factors, such as genetics, hormonal disorders, problems with the pituitary or thyroid gland, chromosomal disorders, eating disorders and so on. Early puberty can increase the risk of disease. Teenagers can experience the development of different characteristics, such as changes in body posture, height, and bone growth.

Growth charts for children aged 6–17 years in Shanxi, China: comparison with other cities of China and WHO

BackgroundGrowth charts are an important method for evaluating a child’s health, growth, and nutritional status. It is essential to monitor the growth of children and adolescents using growth charts.ObjectivesTo present body mass index (BMI)-for-age references reflecting children’s growth in Shanxi. We also compare our new data with growth references of other cities of China and World Health Organization (WHO) growth standards.MethodsA stratified cluster random sampling method was used to recruit 5461 children and adolescents aged 6–17 years. Height and weight were measured and BMI was calculated. The LMS method was used to calculate the percentile values of body mass index by sex and age. Smoothed BMI-for-age growth curves were presented for both sexes and compared with reference data from other cities of China and WHO.ResultsBMI centiles increased with age but with different patterns in both boys and girls. The centile curves from the 3rd to the 50th had a slight increase, while a sharp increase was seen from 11 to 17 years in boys and from 6 to 14 years in girls in the higher centiles. In comparison with other cities of China, the values for the 50th percentile are higher than those reported for children from China 2009, Shanghai, Changsha and China 2010 in both sexes. In comparison with WHO growth references, Chinese girls and boys had higher values in all percentiles, whereas curves of girls look roughly the same. The medians for BMI in Shanxi increase linearly from 6 to 17 years in boys.ConclusionsThe BMI percentiles of children aged 6–17 years in Shanxi differed significantly from the growth reference curves of other cities of China and WHO. Recommending the provision of BMI reference curves for local children and adolescents to assess their growth and development and monitor their nutritional status.Early detection of overweight and obesity in children provides a scientific basis for the prevention and control of overweight and obesity in children.

Normative value of hyperopia reserve and myopic shift in Chinese children and adolescents aged 3–16 years

BackgroundThis research aims to generate normative values of hyperopia reserve and refractive progression as effective tools to estimate the risk of myopia.MethodsA 1-year follow-up study was conducted among Chinese children...

The Study of Marriage Postponement Process in the Youth: A Phenomenological Study

Aim: The purpose of this study was to study the phenomenological process of postponing marriage in young people in order to understand different aspects of this phenomenon and how young people perceive it. Methods: To achieve the research goal, a qualitative approach and a descriptive phenomenological method were utilized. The research population included single and never-married girls and boys living in Tehran between the ages of 28 to 34 years for girls, and 32 to 38 years for boys. Purposeful sampling was used with the convenient sampling and 13 individuals including 7 girls and 6 boys were selected as the sample.y. Data were collected through semi-structured interviews and analyzed by Colaizzi method. Finding: Finally, the research findings reported falls into 12 main themes and 61 sub-themes. The main themes are: economic concerns, idealism, fear of future marriage, the impact of premarital relationships, motivational processes, immaturity and readiness for marriage, the role of family barriers, socio-cultural factors, selection constraints, preconceived notions of marriage, positive consequences and negative consequences. Conclusions: The results showed that postponing marriage is a complex phenomenon which is affected by objective constraints, limiting mental perceptions and insufficient maturity and has many negative consequences for young people. It seems that the efforts of the counseling and psychological community to produce content in the fields of creating a culture of easy marriage process, reviving the values of marriage, correcting the misconceptions of young people, and dissemination of successful marriages in the social media and networks, is an effective step to remove mental barriers of marriage.

Pubertal Delay Secondary to Hashimoto's Disease in the Hypothyroid Phase: About a Case in the Internal Medicine Department of the Gabriel Touré University Hospital in Bamako, Mali

Introduction: Pubertal delay is defined by the absence of development of secondary sexual characteristics beyond the age of 13 in girls or 14 years in boys. In children of puberty age, delayed puberty is common in long-standing, untreated hypothyroidism. We report a case of delayed puberty revealed by Hashimoto's disease in the hypothyroid phase diagnosed in the Internal Medicine department of the Gabriel Touré University Hospital in Bamako, Mali. Observation: This was a female patient, aged 20 years old, without any particular medico-surgical ATCD or notion of taking medication, who had consulted at the end of 2021, in the Internal Medicine department of the University Hospital Gabriel Touré from Bamako for primary amenorrhea and delayed puberty. At the end of the clinical and paraclinical examination, a hypometabolism syndrome and pubertal delay were noted. On an evolutionary level, development of secondary sexual characteristics (From T1 to T3, and appearance of menstruation) after one year of treatment. Conclusion: Delayed puberty may be the consequence of hypothyroidism. Opotherapy with L Thyroxine helps restore normal pubertal development.

Associations of Serum Mineral levels of Copper, Magnesium and Calcium with Skeletal Muscle mass and Strength in Chinese children, aged 6-11: A Cross-Sectional Study

Background: Skeletal Muscle Mass (SMM) and strength are crucial for children's health, and low SMM can lead to adverse health outcomes. A deficiency of essential minerals can cause poor growth, fractures or osteoporosis. The study aimed to explore the relationship between serum Calcium (Ca), Copper (Cu), and Magnesium (Mg) levels and SMM in Chinese children. Methods: 466 primary school children were recruited for a cross-section study aged 6-11 in Guangzhou City, South of China, from December 2015 to February 2017. The study conducted whole-body dual-energy x-ray absorptiometry (DXA) scans using the Hologic discovery W to obtain the Total skeletal mass (TSM) and appendicular skeletal mass (ASM) were calculated, which were used as parameters to calculate variables of Skeletal muscle mass (SMM). Results: Of the 466 primary school children, 266 were boys and 200 girls with mean ages of 8.00±1.00 years for boys and 8.08±0.97 years for girls. An increase in mean Cu serum concentration between the T1 and T3 in girls resulted in 3.19% (P- trend =0.034, P-diff =0.083), 3.57% (P- trend =0.037, P-diff=0.083), 2.44% (P- trend =0.018, P=diff=0.060) and 2.25% (P- trend =0.024, P-diff= 0.072) for ASM/Height, ASH/ Weight, TSM/ Height and TSM/ Weight respectively, No significant mean difference was observed between serum Cu and ASM, TSM, ASM/ AFM and TSM/TFM (P- trend &gt;0.05). A significant mean difference in serum Mg levels and ASM/ AFM for the total and boys' group was observed, with 6.68% and 9.44% (P- trend =0.042 and 0.041) respectively. No significant mean differences were seen between all the variables of serum Ca levels and all the variables of skeletal muscle mass and strength. Conclusions: Serum copper levels influence the development of SMM in girls, but not in boys. Serum Ca and Mg level in girls and boys do not influence SMM development among children aged 6-11.

Thyroid Absorbed Dose from Brain CT Examinations in Different Age Groups of Pediatric Based on Monte Carlo Simulation

Background: This study was designed to assess the thyroid absorbed dose from brain computed tomography (CT) scans across various pediatric age groups, utilizing Monte-Carlo simulation and thermoluminescent dosimeters (TLDs). Methods: We used the Monte Carlo N-particle (MCNP) transport code to model the spiral CT scan of the brain and calculated the average thyroid dose for each pediatric age group. Techniques for variance reduction, such as Time cutoff, Energy cutoff, and Russian roulette, were implemented. Additionally, a cross-sectional study measured the average thyroid absorbed dose in 45 patients under 20 years using TLD dosimetry. The data were analyzed with SPSS software at a 95% confidence interval (CI). Results: The absorbed thyroid dose for an irradiation time of 1 second and 120 mA across the age groups 0 - 5, 6 - 10, 11 - 15, and 16 - 20 years for boys was 4.165 ± 0.028, 3.802 ± 0.036, 3.861 ± 0.031, and 3.021 ± 0.029 mGy, respectively, and for girls, it was 4.185 ± 0.024, 3.852 ± 0.044, 4.052 ± 0.028, and 4.072 ± 0.047 mGy, respectively. For a dose of 110 mAs, the results for boys were 3.711 ± 0.037, 3.660 ± 0.026, 3.251 ± 0.019, and 3.204 ± 0.031 mGy, respectively, and for girls were 3.882 ± 0.040, 3.842 ± 0.032, 3.412 ± 0.026, and 3.619 ± 0.029 mGy, respectively (P &lt; 0.001). Conclusions: Comparing these results with experimental studies indicates the feasibility of using less computationally intensive methods. The thyroid dose received by girls was higher than that for boys, aligning with findings from experimental studies and other research.

Морфометрические особенности сердца у детей 7–10 лет, проживающих на территории Архангельской области

The purpose of this paper was to determine the morphometric characteristics of the heart in 7–10-year-old children living in the Arkhangelsk Region in relation to their physical development parameters. Materials and methods. The research was performed in Vyzhletsov Arkhangelsk Regional Children’s Clinical Hospital. Using echocardiography, we studied the morphometric parameters of 990 children of both sexes aged between 7 and 10 years without cardiovascular pathologies and collected their anthropometric data. Results. With the relative stability of the processes of morphofunctional maturation at this stage of ontogenesis, both sexand age-related structural features of the heart were detected. The largest number of sex-related differences was found for children aged 8 years, and they were associated with greater values of cardiac parameters in boys compared to girls. Sеx-related differences in the width of the major vessels get levelled out by the age of 10. Parameters of physical development naturally increase with age, evenly over the years; sexual dimorphism is not pronounced. The total increase in anthropometric values from 7 to 10 years in boys and girls was: 12.67 % and 14.10 % for body length, 38.68 % and 40.66 % for body weight, and 24.21 % and 27.17 % for body surface area (BSA), respectively. The most consistent and unidirectional age-related changes concern BSA, which demonstrates a significant correlation with cardiac morphology, especially in late prepuberty. The greatest stability in reflecting the share of variation in echocardiogram parameters in all age and sex groups has BSA calculated by the Mosteller formula. The left heart in boys starts to enlarge from 8 to 10 years, while in girls, between 9 and 10 years. Factor analysis showed an increase in the contribution of physical development parameters to the dispersion of morphological characteristics of the heart with age.

Association of height, foot length, and pubertal development in children aged 3-18: a cross-sectional survey in China.

This study aimed to analyze the growth patterns of height and foot length (FL) among Chinese children aged 3-18 and examine their associations with puberty development. A cross-sectional survey was conducted in September 2022 in Beijing. Data were collected through questionnaires and on-site physical examinations. The growth patterns and velocity of height and FL in different age groups were described, and their associations with puberty development were analyzed. From an age perspective, the peak FL growth occurred between 9 and 11 years (boys were 11 years and girls were 9 years), while the peak height growth occurred at 11 ~ 13 years for boys and 9 ~ 11 years for girls. Additionally, boys and girls reached 99.0% of their final FL at the ages of 14 and 13, respectively, while they reached 99.0% of their final height at the ages of 16 and 15, respectively. From the perspective of Tanner stage, the age of peak FL growth in boys coincided with the age of the G2 stage, while in girls it occurred slightly earlier than the mean age of the B2 stage. The peak height growth for both boys and girls occurred between Tanner stages 2 and 3. Boys and girls reach their peak FL growth at 11 and 9 years old, respectively, which were both 2 years earlier than their peak height growth. The peak FL growth occurred around the onset of puberty, while the peak height growth occurred between Tanner stages 2 and 3.