The aim of this study was to investigate the relationship of insulin-like growth factor-1 (IGF-1) and mild subclinical hypothyroidism (MSH) in obese boys and to assess whether the presence of MSH exacerbates cardiovascular risk factors in obesity. This study collected cross-sectional dataset covering 141 obese boys and 47 healthy non-obese boys. The obese group was further subdivided into two groups based on their serum Thyroid Stimulating Hormone (TSH) levels: the MSH group (n = 47) and the non-MSH group (n = 94). The MSH group exhibited significantly lower IGF-1 standard deviation score (IGF-1 SDS) and significantly higher Body Mass Index standard deviation score (BMI SDS) compared to the non-MSH group. Additionally, the MSH group demonstrated elevated triglycerides (TG) and gamma-glutamyl transferase (GGT) levels relative to the non-MSH group, and the incidence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) were also higher in the MSH group than in the non-MSH group. The results of multivariable logistic regression analysis indicated that lower IGF-1 SDS and higher BMI SDS are strongly associated with MSH in obese boys, independently of systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), GGT and uric acid. These findings underscore the clinical utility of IGF-1 SDS and BMI SDS as potential biomarkers for identifying MSH-related cardiovascular risks in obese pediatric populations, warranting targeted screening and intervention strategies.

Short stature and thinness among adolescent girls continue to be a severe public health problem in Ethiopia, due mainly to inadequate dietary intake, which turn affected by several factors. Evidence shows that in low and middle-income countries, the factors related to culture and belief play a pivotal role in making a difference in eating, negatively affecting girls. In Ethiopia, the roles of these factors in influencing the eating behavior of adolescent girls have not been well investigated.

This qualitative study was conducted to explore the barriers of eating among adolescent girls in Ethiopia.

A qualitative study was employed in northwest Ethiopia from January to April 2021. A focus group discussion of adolescent girls and an in-depth interview of mothers and adolescent boys were separately conducted. A total of six focus group discussions involving a total of forty-three adolescent girls and an in-depth interview of twelve adolescent males and ten mothers were performed. The adolescent girls and boys were aged 15 to 19, attending grades 9-12. The participants were selected using a purposive sampling method. Content analysis was employed to identify the predominant themes. The analysis was conducted using Open Code.

Four themes emerged from the current study. These included religion, the culture of male dominancy, roles and responsibilities, and perception related to girls' body food requirements and the consequences of proper feeding of adolescent girls on their behavior. Specifically, girls start fasting at an early age due to religious reasons; girls do not eat before the males eat and outside the home out of respect for males; girls spend most of their time at home doing less energy-demanding work; girls' body food requirement is lower and girls better tolerate hunger than their counterpart boys; and if girls eat well, they would not be disciplined, were among the reasons mentioned by the study participants for girls' intake of lower quality and quantity food.

Religion, the culture of male dominancy, roles given to females and males and the perception that girls' bodies require a lower quantity of food and well-nourished girls will not be disciplined were common factors responsible for the poor dietary behavior of adolescent girls. Educating the community about the food requirements of girls, the consequences of their inadequate feeding, and the misconception existing in the community about girls' food requirements is crucial. Strengthening policies and strategies helpful for empowering women and balancing gender inequalities may be required.

The aim of the study was to investigate whether there are any gender-related differences in growth hormone stimulation test (GHST) in prepubertal short children, with a particular emphasis on body mass index (BMI). Prepubertal patients who had two unprimed GHST using clonidine and L-dopa were included in this retrospective study. The anthropometrics and laboratory parameters were evaluated. Patients were categorized based on their peak growth hormone (GH) levels (GH <7 versus ≥7 ng/mL), stimulant agent, and gender. A total of 125 children (Male:Female = 75:50) were included. The mean age of the patients was 7.1 ± 3.0 years. lg-peak clonidine stimulated GH was associated with BMI standard deviation score (SDS) (β [95% CI] = 1.903 [1.665-2.140], P = .003) in females, and with IGF-SDS in males (β [95% CI] = 1.124 [0.910-1.339], P = .026). lg-peak L-dopa stimulated GH was associated with BMI SDS and IGF1-SDS (β [95% CI] = 1.327 [0.968-1.686], P = .009) in females. The blunted effect of BMI showed gender-related differences in the prepubertal pediatric patients.

Maternal preconception obesity and adverse gestational metabolic health increase the risk of childhood obesity in offspring, but the preconception period may be an opportune time to intervene, given the motivation of the mother and the epigenetic changes that may be beneficial for the gametes during this period. However, there is a lack of studies evaluating children born to women who have had a preconception intervention. Our group has therefore designed an ancillary study to assess children born to women enrolled in the obesity-fertility randomised controlled trial (RCT), who were 6-12 years of age, with the objective of evaluating the effect of a lifestyle intervention delivered during preconception and pregnancy on adiposity and cardiometabolic parameters in the offspring. This manuscript details the study protocol.

This is an ancillary nested cohort study of the obesity-fertility RCT. Women with obesity and infertility were recruited at an academic fertility clinic and randomised to the control group, which followed usual care, or to the intervention group, which received a lifestyle intervention alone for the first 6 months and then in combination with fertility treatments for up to 18 months or until the end of pregnancy. Those who have given birth to a single child are invited to participate in this follow-up study with their child aged 6-12 years. This study started in November 2023 and is expected to end in May 2025. The primary outcome is age-adjusted and sex-adjusted body mass index z-scores in children. Secondary outcomes are anthropometry, body composition, lifestyle, physical fitness level and blood or saliva markers of cardiometabolic health in both mothers and children. Of the 130 women who participated in the obesity-fertility RCT, 52 mother-child dyads (24 in the control group; 28 in the intervention group) were potentially eligible for this follow-up study. Comparisons between groups will be performed using unpaired tests and adjusted for potential confounders using multivariable regression models. This study will provide important new data on the impact of a preconception lifestyle intervention, maintained throughout pregnancy, on the health trajectory of children and mothers 6-12 years after delivery.

The study has been approved by the institutional research ethics review boards of the Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke. The results will be widely disseminated to the scientific community, relevant health professionals and general public.

ClinicalTrials.gov (NCT06402825).

Low levels of Insulin-like Growth Factor 1 (IGF-1) are known risk factors for cardiovascular diseases. Left Ventricular Mass Index (LVMI) serves as an early predictor of adverse cardiovascular events. Obese children have relatively low concentrations of IGF-1 in their blood. To date, there is no research on whether there is a correlation between IGF-1 levels and LVMI in obese children. This study aims to investigate the potential correlation between IGF-1 and LVMI in obese children at a single center.

A total of 104 obese children were selected as the case group, while 61 healthy children undergoing physical examinations served as the normal control group. Anthropometric measurements, assessments of IGF-1, and cardiovascular metabolic factors were conducted. Echocardiographic examinations were also performed to calculate the LVMI.

Compared to the control group, the obese group had significantly higher LVMI and significantly lower standard deviation scores for Insulin-like Growth Factor 1 (IGF-1 SDS). After controlling for confounding factors including total cholesterol (TC), triglycerides (TG), and uric acid (UA), there was a significant linear negative correlation between IGF-1 SDS and LVMI, and a significant linear positive correlation between homeostasis model of assessment for insulin resistance (HOMA-IR) and LVMI. Each unit increase in IGF-1 SDS resulted in a 16.1% decrease in LVMI (β = -0.161; p = 0.046), and each unit increase in HOMA-IR resulted in a 24.1% increase in LVMI (β = 0.241; p = 0.007).

IGF-1 and LVMI exhibit an independent negative correlation. Monitoring IGF-1 levels might provide valuable insights into the cardiovascular health of obese children, facilitating early identification and management of cardiovascular risk factors.

Not applicable.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, commonly caused by 21-hydroxylase mutations, that converts 17-hydroxyprogesterone (17-OHP) into 11-deoxycortisol in the adrenal cortex. Elevated morning serum levels of 17-OHP identify suspected CAH, and the diagnosis is confirmed by CYP21 A2 gene analysis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) has become the recommended method for 17-OHP measurement; however, diagnostic 17-OHP thresholds measured with LC-MS/MS are not yet defined. We aimed to identify optimal cut-offs for basal and peak 17-OHP levels after ACTH stimulation test, measured by LC-MS/MS, to distinguish non-classical CAH (NC-CAH) and heterozygous carriers (HC) from wild type subjects (WT) in children.

We retrospectively analyzed the records of 198 children referred for suspected NC-CAH.

The ideal basal 17-OHP cut-off to differentiate NC-CAH from WT subjects was 0.94 ng/mL (2.82 nmol/L) with AUC 0.988 (95% CI 0.972-1.000; sensitivity 100%, specificity 90%). The optimal peak 17-OHP cut-off was 7.81 ng/mL (23.43 nmol/L) with AUC 0.998 (95% CI 0.994-1.000; sensitivity 100%, specificity 97%). The ideal basal 17-OHP cut-off to distinguish HC from WT subjects was 0.81 ng/mL (2.43 nmol/L), with AUC 0.727 (95% CI 0.645-0.809; sensitivity 54%, specificity 83%); while the optimal peak 17-OHP cut-off was 3.79 ng/mL (11.37 nmol/L) with AUC 0.932 (95% CI 0.894-0.971; sensitivity 96%, specificity 87%).

The ideal cut-offs of peak 17OHP able to distinguish NC-CAH and HC individuals from WT subjects were significantly lower to using LC-MS/MS. These new thresholds demonstrate high sensitivity and specificity, making them effective in distinguishing individuals with suspected NC-CAH.

There are limited number of studies in the literature reporting the effect of subclinical hypothyroidism (SH) on insulin resistance and glucose metabolism in children. This study compared insulin, glucose and Homeostasis Model Assessment (HOMA-IR) values in 50 patients with SH and 50 healthy subjects. However, no significant difference was found between the groups. In addition, no significant correlation was observed between the TSH and fT4 levels and blood glucose, insulin and HOMA-IR values in patients with SH. Our study showed that SH does not lead to insulin resistance. Weight gain may be higher than normal in patients with SH. More comprehensive studies are needed for the long-term metabolic and cardiovascular effects of SH.

Obesity represents a major global public-health problem during childhood and adolescence. The genetic contribution to obesity and its consequences is well-established. Variation in glucocorticoid (GC)-sensitivity can be partly explained by polymorphisms in GC receptor (GR) gene where NR3C1; Bcl1 rs41423247 and NR3C1 rs6198 single nucleotide polymorphisms (SNPs) have been linked to higher and lower GC sensitivity, respectively. We aimed to explore the potential association between the GR gene SNPs and risk of obesity in a cohort of Egyptian children. We included 100 pre-pubertal children; 60 obese children and 40 age-and sex-matched normal-weight controls. Bcl1 rs41423247 SNP was genotyped using PCR-restriction fragment length polymorphism technique and NR3C1 rs6198 SNP was genotyped using Real-time-PCR.In Bcl1 rs41423247, obese children had more frequent CG, GG genotypes and G allele compared to healthy controls (P = 0.039, 0.019 and 0.007 respectively). Moreover, insulin resistance was significantly higher in combined CG + GG group compared to CC group. On the contrary, no significant differences were found in genotypes, alleles frequencies or insulin resistance between obese and non-obese children in NR3C1 rs6198. GR Bcl1 rs41423247 gene polymorphism may play a role in genetic susceptibility to obesity that can be a future targeted therapy for obesity.

Background/Objectives: This study sought to identify key barriers to treatment adherence in children and adolescents with type 1 diabetes (T1D) using the Adherence Starts with Knowledge-12 (ASK-12) questionnaire and to evaluate its impact on metabolic control, providing insights for optimizing T1D management. Methods: A total of 160 children and adolescents with T1D aged 5-18 years who sought treatment from a pediatric endocrinology outpatient clinic between June and August in 2022 were prospectively examined. The patients' low treatment adherence (LTA) or high treatment adherence (HTA) was determined based on their ASK-12 questionnaire scores. Two pediatric endocrinologists reviewed the participants' medical records and then classified them into two groups: tight metabolic control and poor metabolic control. Results: LTA, which was determined based on the participants' ASK-12 scores, was significantly associated with puberty, presence of diabetic ketoacidosis, and daily self-management (p < 0.001, p < 0.001, and p < 0.001, respectively). Those whose ASK-12 scores indicated LTA were older and had a longer duration of T1D, higher hemoglobin A1c levels, and lower BMI-SDS values than those with HTA) (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). A total of 94 (59%) participants were indicated to have HTA, but 24 (25.5%) of them were found by the clinicians to have poor metabolic control. Conclusions: The ASK-12 questionnaire scores can identify pediatric patients with T1D who exhibit LTA and thus may be beneficial for early recognition of low adherence. Approximately 25% of the patients with ASK-12 scores indicating HTA were at risk of poor metabolic control. Puberty, duration of T1D, BMI-SDS, HbA1C, and parental involvement alongside ASK-12 score may be considered to improve treatment compliance. Integrating these variables into adherence assessments may enhance treatment compliance and improve long-term outcomes in pediatric T1D management.

Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene.

We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay.

Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis.

The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles.

This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP.

Osteogenesis with impact-loading exercise is often assessed by the extra bone growth induced in the loaded arm of tennis players. We used PRISMA to explore % bone mineral content (BMC) and area (BA) asymmetry in players 8-30 years according to weekly training hours, age, sex, maturity, and bone segment. Proper statistics for 70 groups were extracted by two reviewers from 18 eligible studies of low risk of bias (< 35, STROBE) and good quality (> 70%). The quality of the review was high (AMSTAR, 81%). Using "random effects" we tested moderation-specific meta-comparisons and meta-regressions. The loaded bones % hypertrophy was higher in BMC (19%) than BA (10%), and, with BMC and BA merged, in boys (17%) than girls (13%), in humerus (19%) than radius-ulna (14%), and in pubertal (19%) players. Weekly training hours were more important (43%) than sex (17%), puberty (14%) and bone (15%) in BMC, and puberty (48%) was more important than weekly training hours (19%), sex (12%), and radius-ulna (5%) in BA. The loaded bones % hypertrophy correlated with weekly training hours highly (> 0.60) in all maturity groups for BMC and BA, and moderately (0.41) in early adults for BA; it also correlated with age (≥ 0.60) in children and peripubertal players, but not (0.037) with starting age. Impact loading exercise favors mineralization twice than bone expansion, while puberty favors bone expansion about three times more than mineralization. The bone gains are higher for boys than girls, and for peripubertal than older players. The bone growth implications are discussed considering limitations and future research.

To assess the relationship between body composition indicators and inflammatory biomarkers in children and adolescents of the GENOBOX study.

Anthropometry data from 264 subjects from the subsample of Zaragoza (Spain) included: weight, height, waist circumference, body mass index and triponderal index. Body composition was determined by Dual-energy X-ray Absorptiometry (DXA), obtaining visceral adipose tissue, fat mass index and lean mass index. Age and sex specific z-scores were computed. Simple linear regression models were performed with inflammatory biomarkers (hsCRP, IL8, TNF-α, adiponectin, leptin and resistin) as dependent variables, and each of the body composition indices as independent variables. Prepubertal boys had higher IL8 and resistin values and pubertal girls had higher HOMA-IR and leptin values. hsCPR and leptin were associated with fat mass, both in prepubertals and pubertals, independently of lean mass, and regardless of how body composition was measured. All body composition indices were inversely associated with adiponectin, except for fat mass index in pubertals, but none of them were statistically significant.

A positive association between hsCRP and leptin with all body fat composition parameters, measured by standard nutritional indicators and DXA, was observed in both sexual stages.

To examine whether the children's superiority, over adults, to resist fatigue during repeated maximal-efforts depends on their often-cited oxidative advantage, attributed to greater muscle blood flow and O2-delivery. We also investigated the mechanisms underlying child-adult differences in muscle-oxygenation (due to O2-supply or O2-utilization) and examined if there are age-differences in cerebral-oxygenation response (a brain-activation index).

Eleven men (23.3 ± 1.8yrs) and eleven boys (11.6 ± 1.1 yrs) performed 15 maximal-effort handgrips (3-s contraction/3-s rest) under two conditions: free-flow circulation (FF) and arterial-occlusion (OCC). Force, muscle-oxygenation (TSImuscle) and cerebral-oxygenation (oxyhemoglobin-O2Hbcerebral; total hemoglobin-tHbcerebral; deoxyhemoglobin-HHbcerebral) were assessed.

In boys, force declined less (- 26.3 ± 2.6 vs. - 34.4 ± 2.4%) and at slower rate (- 1.56 ± 0.16 vs. - 2.24 ± 0.17%·rep-1) vs. men in FF (p < 0.01-0.05; d = 0.60-1.24). However, in OCC there were no age-differences in the magnitude (- 38.3 ± 3.0 vs. - 37.8 ± 3.0%) and rate (- 2.44 ± 0.26 vs. - 2.54 ± 0.26%·rep-1) of force decline. Boys compared to men, exhibited less TSImuscle decline in both protocols, and lower muscle VO2 (p < 0.05). Boys, also, presented a smaller O2Hbcerebral and tHbcerebral rise than men in FF; exercising with OCC increased the O2Hbcerebral and tHbcerebral response in boys. Using MVIC as a covariate in FF condition, abolished boys-men differences in force and TSImuscle decline and O2Hbcerebral rise.

During repeated maximal-efforts: (i) blood flow is a significant contributor to children's superiority over adults to resist fatigue; (ii) age-difference in muscle hypoxia/deoxygenation is rather attributed to men's greater metabolic demand than to lower muscle-perfusion; and (iii) cerebral oxygenation/blood volume increase more in men than boys under free circulation, implying greater brain activation.

To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome.

A prospective cohort study as a follow-up of OTC in a research setting (the TurnerFertility trial, NCT03381300).

A total of 28 girls with Turner syndrome with follicles in their cryopreserved ovarian cortex tissue, aged 5-19 years. Of the 28 girls, 21 had a 45,X/46,XX mosaic karyotype; 5 had structural aberrations of the X chromosome; 1 had a 45,X monosomy; and 1 had a 45,X/47,XXX karyotype.

Girls were monitored annually after OTC for pubertal development and levels of antimüllerian hormone (AMH), follicle-stimulating hormone, luteinizing hormone, estradiol, and inhibin B.

Thelarche, menarche, and onset of premature ovarian insufficiency.

The girls were monitored for a median duration of 3.4 years (maximum 6.6 years). The pubertal development of five prepubertal girls is still unknown; all were aged <10 years and had low gonadotropin and estradiol levels at the end of the follow-up. Seven of the eight girls of approximately pubertal age (10-12 years) experienced spontaneous thelarche, although one received medication to induce puberty. Eleven of the 14 girls between the ages of 14-17 years experienced spontaneous menarche; three other girls with thelarche still had ongoing puberty at the end of follow-up with normal gonadotropins and AMH levels above the detection limit. Approximately 6-12 months after OTC, a decline in AMH concentration was observed in 57% (16/28) of girls, followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy because of symptoms of premature ovarian insufficiency, and all had AMH levels <0.50 μg/L before OTC.

Pubertal development progressed after unilateral ovariectomy for OTC in most girls with Turner syndrome. Hormone replacement therapy was required within a few years for girls with unfavorable parameters before OTC, such as AMH levels <0.50 μg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics.

NCT03381300.

The efficacy of growth hormone (GH) treatment in short, healthy children diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS) suggests an overlap between these 2 conditions. Although imperfect and inconsistent, GH stimulation testing (GHST) remains the primary diagnostic tool for differentiating GHD and ISS, influencing GH treatment eligibility and dosing. This study aims to assess the clinical significance of GHST by comparing the response to GH treatment in children diagnosed with GHD or ISS based on their GHST results.

A retrospective study in an endocrine clinic at a tertiary pediatric referral center comparing the response to GH treatment over 3 years in children diagnosed with GHD or ISS.

Two hundred ninty-one children treated with GH, 97 children diagnosed with GHD, and 194 with ISS are included in the analysis. Height significantly improved, and insulin-like growth factor-1 levels increased independent of the GHST results, gender, or pubertal status (P < .001). When adjusting for dosage, height gain was not associated with the treatment indication, GHD or ISS, or GHST peak levels.

Our findings indicate similar responses to GH treatment in children classified as GHD or ISS based on GHST. These results suggest that the pivotal role of GHST in diagnosing and treating short children should be reconsidered.

BMD, an important marker of bone health, is regulated by a complex interaction of proteins. Plasma proteomic analyses can contribute to identification of proteins associated with changes in BMD. This may be especially informative in stages of bone accrual and peak BMD achievement (ie, adolescence and young adulthood), but existing research has focused on older adults. This analysis in the Study of Latino Adolescents at Risk for Type 2 Diabetes (SOLAR; n = 304; baseline age 8-13, 100% Hispanic) explored associations between baseline proteins (n = 653 proteins) measured with Olink plasma protein profiling and repeated annual DXA measures of BMD (average of 3.2 visits per participant). Covariate-adjusted linear mixed effect regression models were applied to estimate longitudinal protein-BMD associations using an adjusted p value cutoff (p < .00068). Identified proteins were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to determine significantly enriched protein pathways. Forty-four proteins, many of which are involved in inflammatory processes, were associated with longitudinal changes in total body BMD, including several proteins previously linked to bone health such as osteopontin (SPP1) and microfibrillar-associated protein 5 (MFAP5; both p < .00068). These 44 proteins were associated with enrichment of pathways including PI3K-Akt signaling pathway and cytokine-cytokine receptor interaction, supporting results from existing proteomics analyses in older adults. To evaluate whether protein associations were consistent into young adulthood, linear mixed effect models were repeated in a young adult cohort (n = 169; baseline age 17-22; 62.1% Hispanic) with 346 available overlapping Olink protein measures. While there were no significant overlapping longitudinal protein associations between the cohorts, these findings suggest differences in protein regulation at different ages and provide novel insight on longitudinal protein associations with BMD in overweight/obese adolescents and young adults of primarily Hispanic origin, which may inform the development of biomarkers for bone health in youth.

Contemporary longitudinal data on dietary patterns (DP) during adolescence are scarce. This study aimed to identify trajectories of adherence to an obesogenic DP and changes in diet quality (DQ), related food consumption, and adiposity markers during adolescence.

A cohort of 600 adolescents (293 girls, 48.8%) attending 24 secondary schools enrolled on the SI! Program for Secondary Schools trial in Spain was assessed when participants were approximately 12, 14, and 16 years old. An energy-dense, high-fat, and low-fiber (obesogenic) DP was derived at each time point by reduced rank regression (RRR) using the percentage energy intake from fat, fiber density, and dietary energy density as intermediate variables. Based on each participant's resulting scores, trajectories of adherence to the obesogenic DP were identified by latent class trajectory modeling. Adjusted associations between trajectories, DQ and food consumption changes, and adiposity markers during adolescence were analyzed with generalized linear models.

Based on adherence to the obesogenic DP during adolescence, four stable trajectory groups (from lowest to highest adherence) were identified: trajectory 1 (44 participants [7.3%]), trajectory 2 (180 participants [30.0%]), trajectory 3 (292 participants [48.7%]), and trajectory 4 (84 participants [14.0%]). Overall DQ was moderate, but showed a gradient across trajectories, with trajectory 1 having the best quality. Although the identified trajectories were stable, individuals in the group with the lowest adherence to the obesogenic DP (trajectory 1) significantly improved their overall DQ over time, whereas those with the highest adherence (trajectory 4) showed the opposite trend. The group of adolescents in trajectory 4 had the least healthy central adiposity profile when ∼16 years old.

Four stable trajectories of adherence to an obesogenic DP were identified in a large cohort of adolescents, with DQ decreasing as adherence to the DP increased. Although adherence to the DP was stable, differences in food intake between trajectories widened over time, resulting in increased central adiposity in participants with the highest adherence to the pattern at the end of the study. Further research is needed to explore the determinants of adherence to obesogenic DPs in adolescence and to evaluate their effects on adiposity and overall health later in life.

ClinicalTrials.gov NCT03504059.

Recombinant growth hormone (rhGH) treatment plays an important role in the transition phase in those subjects diagnosed as having persistent growth hormone deficiency (GHD). We aimed to identify the main predictors of persistent GHD in a large cohort of subjects with childhood-onset GHD who underwent retesting and their correlation with height gain and mid-parental height (MPH).

Anthropometric data, such as growth rate; bone age (BA); IGF-1 SDS at the start, at 1 year, and at the end of rhGH therapy; GH peak at diagnosis and at retesting; brain Magnetic Resonance Imaging (MRI) at diagnosis; and height gain upon reaching final height (FH) and compared to MPH, were obtained from medical records of GHD patients.

Persistent GHD was detected in 37 out of 91 (40.7%) GHD subjects. In univariate analysis, persistent GHD was associated with growth rate at 1 year (p = 0.0117) and with the first test GH peak (p = 0.0290). In the regression analysis, persistent GHD was positively associated with growth rate at 1 year (p = 0.0294) and negatively with female gender (p = 0.0424). Height gain was positively associated with growth rate (p = 0.0010) and with age at onset (p = 0.0021), while an inverse association with BA at baseline (p = 0.0002) and IGF-1 SDS (p = 0.0321) was found.

Our study confirmed that the most important predictor of persistent GHD is the growth rate in the first year of therapy. Furthermore, growth rate in the first year, female gender, and lower BA at diagnosis are predictors of rhGH efficacy both in terms of height gain and target height achievement.

Klinefelter syndrome (KS) is a common genetic condition in males associated with an extra X chromosome (i.e., 47,XXY). Individuals with KS often experience androgen insufficiency and tall stature and are at increased risk for depression, anxiety, and social challenges. This cross-sectional study investigates social and emotional functions in 52 boys with KS and 62 typically developing (TD) boys, aged 8 to 13 years.

Self-report measures of anxiety, depression, and behavior and parent-report measures of social functioning and behavior were completed. In primary analyses, linear regression was used to test the effect of group (KS, TD) on standardized scores derived from widely used rating scales. In secondary analyses, we explored the influence of pubertal status on these scores and concordance between self- and parent ratings.

Our results indicate that boys with KS exhibit significantly increased anxiety, depression, and social difficulties relative to TD peers. Among participants with KS, peripubertal boys generally experienced more difficulties in aspects of social and emotional functioning as compared to prepubertal boys. Concordance analyses revealed differences between parent- and child-reports.

These findings indicate that alterations in social, emotional, and behavioral functions are present in boys and adolescents with KS and may be influenced by puberty.

Omnitrope® (a somatropin biosimilar), used to treat growth disturbances, is considered to have a good safety profile in children. Here, we present the analysis of final data of the Italian cohort of the PAtients TReated with Omnitrope® (PATRO) Children study.

This multicenter, open-label, longitudinal, post-marketing surveillance study enrolled eligible children during 2010-2018. The primary objective was to assess the long-term safety of Omnitrope® by recording all adverse events (AEs), serious AEs, and adverse drug reactions (ADRs). A secondary objective was to evaluate the long-term effectiveness of Omnitrope® using height measurements.

A total of 375 patients were included in the Italian cohort of the PATRO Children study. After a mean ± standard deviation (SD) follow-up duration of 40.9 ± 24.6 months, 607 AEs were reported in 58.4% of patients, mostly of mild (52.5%) or moderate (15.7%) severity. The most common AEs were headache (11.7%), elevated insulin-like growth factor (IGF)-1 (4.8%), abdominal pain (4.3%), and pyrexia (3.7%). Sixty-seven ADRs occurred in 52 patients (13.9%); the most common ADRs were elevated IGF-1 (3.5%) and insulin resistance (2.9%). Mean ± SD height standard deviation scores in treatment-naïve patients increased from -2.5 ± 0.7 at baseline (n = 318) to -1.3 ± 0.7 at 5 years (n = 56) and to -0.8 ± 0.7 at 7.5 years (n = 13).

This final analysis extends the interim analysis findings from the PATRO Children study and confirms the long-term safety and effectiveness of Omnitrope® in Italian pediatric patients with growth disturbances.

Anterior cruciate ligament (ACL) injuries are common in pediatric and adolescent patients. Understanding this population's injury characteristics and treatment strategies is vital for managing this high-risk group.

To report the descriptive epidemiology and treatment strategies of a large cohort of skeletally immature patients with complete ACL tears.

Cross-sectional study; Level of evidence, 2.

Consecutive skeletally immature patients diagnosed with complete ACL tears were enrolled at 10 institutions across the United States. Treatment was provided by 1 of 23 participating orthopaedic surgeons. Patient characteristics (chronological and skeletal age, sex, race, and ethnicity) as well as anthropometric measures, mechanism of injury, and ACL treatment type were collected.

A total of 749 skeletally immature participants were included in the final cohort; the mean chronological age was 12.9 years, and 62% were male. The mean skeletal age (13.2 years) was a mean of 0.34 years (4 months) higher than the mean chronological age (P < .001). Tanner staging revealed that 18% of participants were Tanner stage 1, 20% were Tanner stage 2, 28% were Tanner stage 3, 30% were Tanner stage 4, and 4% were Tanner stage 5. Five percent of participants reported a previous ipsilateral knee injury, and 30% had a family history of ACL injuries. Sport was the predominant mechanism of injury (89%), with noncontact injuries the most common (64%). The most common sport resulting in an ACL tear among boys was American football (41%) and among girls was soccer (44%). Overall, 99.9% of skeletally immature patients were treated surgically by 1 of 4 reconstruction techniques: transphyseal (53%), partial transphyseal (7%), physeal-sparing all-epiphyseal (13%), and physeal-sparing iliotibial band (ITB) (27%). The most common surgical techniques for patients with a skeletal age <13 years were physeal sparing with ITB (56%) and all-epiphyseal (22%), while in patients with a skeletal age ≥13 years, transphyseal (71%) and physeal sparing with ITB (12%) were the most common. Overall, 57% of patients who underwent ACL reconstruction had arthroscopically documented meniscal tears, with high rates of meniscal repair (90% medial tears and 66% lateral tears).

Almost all skeletally immature patients with ACL tears were injured during sports, surgical treatment was overwhelmingly the treatment of choice, and preferred surgical techniques varied based on skeletal ages.

The management of adrenal insufficiency (AI) is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in patients with congenital adrenal hyperplasia (CAH), and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropin. To personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of AI include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present 3 illustrative cases of AI with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with an emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with AI.

Background/Objectives: Fructose consumption in children is increasing, as is the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite evidence linking added sugars to metabolic syndrome, fructose's impact on liver disease in youth remains unclear, especially in pediatrics. Our study aimed to evaluate the role of fructose intake in metabolic and liver dysfunction in a cohort of pre-school children and adolescents with obesity. Methods: We recruited 41 children and adolescents with obesity (age range: 2.5-16 years, BMI SDS 2.6 ± 0.5 kg/m2). Clinical and biochemical parameters were assessed. Through ultrasound (US), MASLD, hepatorenal index (HRI), subcutaneous adipose tissue (scAT), and visceral adipose tissue (vAT) were assessed. Dietary intake was evaluated using the IDEFICS FFQ and a fructose-specific questionnaire. Results: Pubertal subjects had more scAT and vAT, higher insulin resistance, and higher liver fibrosis parameters than those prepubertal. MASLD was detected in 12 subjects, associated with higher scAT and vAT. Pubertal subjects had lower weekly fructose intake than prepubertal subjects (p < 0.02). However, they consumed less fructose from fruits (p < 0.04) and more from other sugars (p < 0.04) than younger children. Patients with MASLD reported higher fructose intake (p < 0.01), primarily from fruits (p < 0.003), likely due to misreporting, alongside higher consumption of unhealthy food, mainly rich in saturated fats. Conclusions: Fructose intake and unhealthy dietary habits were associated with MASLD in pre-school and adolescents with obesity. Advice to pay attention to fructose intake and foods rich in saturated fats is mandatory to decrease both obesity and MASLD. Further high-powered studies in any pediatric age and different geographical areas are needed to better evaluate the MASLD history.

The aim of this study was to examine whether attachment to each parent moderates the relationship between bullying victimisation and self-esteem. The sample consisted of 250 junior high school students (114 males, 136 females; mean age: 11.3 years). The administered scales were the Bully/Victim Questionnaire Revised, the Inventory of Parent and Peer Attachment for Children and the Rosenberg Self-Esteem Scale. Results showed that early adolescents subjected to bullying had lower self-esteem than non-bullied peers. For girls, attachment to mother also accounted for self-esteem over and above the effect of bullying. For boys, attachment with the father appeared as a pure moderator of the effect of bullying as the association with self-esteem was non-significant when attachment scores were high. The findings suggest that attachment to same sex parents may foster better self-esteem in the face of bullying. Parents' participation in preventive measures could be encouraged.

Acanthosis nigricans (AN) is a common finding often associated with hyperinsulinemia and childhood obesity. There has been a lack of studies evaluating the association of AN with underlying cardio-metabolic risk factors in children and adolescents. Our objective was to study the association between AN and cardio-metabolic risk factors in children with overweight/obesity.

This cross-sectional study included school-going children (6-16 years of age) with overweight/obesity. Physical examination, anthropometry, and blood pressure (BP) data were collected. Fasting blood samples were collected to measure insulin, glucose, homeostasis model assessment index (HOMAIR), and lipid profile.

Of 1930 children screened, 545 had overweight/obesity, and were included. Boys to girls ratio was 1.27. AN was present in 46.4% of children. Children with AN had higher body mass index [BMI] (P < 0.01), waist circumference [WC] (P < 0.01), systolic (P = 0.03), and diastolic BP (P = 0.02), hyperglycemia (P = 0.02), hyperinsulinemia (P < 0.01), and a higher HOMA-IR (P < 0.01) compared to those without AN. HDL level was lower in children with AN.

Children with overweight/obesity who have AN have significant elevations of BP, insulin level, and HOMA-IR. AN is a clinical marker that seems to be associated with cardio-metabolic risk factors in children with overweight/obesity in the given study population.

Previous research in adults has suggested that healthy dietary patterns could be an effective strategy for blood pressure (BP) control. However, during adolescence, the scientific literature examining this relationship is scarce and controversial since inverse and null associations have been reported. Thus, the aim of our study was to analyze the relationship between the level of adherence to the Mediterranean diet (MD) and consumption of fresh fruits and vegetables at baseline with changes in BP over a two-year period during adolescence.

The analyses included 197 adolescents (92 girls) aged 13.9 ± 0.3 years. Adherence to the MD and consumption of fresh fruits and vegetables were assessed using the KIDMED questionnaire and a food frequency questionnaire, respectively. BP values were measured using an automatic sphygmomanometer according to standardized procedures.

Adolescents with high adherence levels to the MD, and high consumption of vegetables (but not fruits) at baseline, showed smaller increases in diastolic BP changes over two years (percentage of reduction ranging from ~48% to ~88%, all p < 0.026). No significant relationships were identified in systolic BP over the two-year period.

Our findings underscore the importance of promoting MD and vegetable consumption to reduce diastolic BP during adolescence, contributing to lowering future cardiovascular risk.

The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase.

The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement.

Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies).

Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was -1.4 SD score (95% CI -1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population.

A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD.

This research aimed to examine the dynamics of changes in sprint and long jump performance and the age of gender divergence in well-trained young athletes specialising in athletics. Data were collected from 1249 male and 1497 female athletes aged 10 to 15 years who participated in the final round of the annual national athletics tournament "Shipovka Yunykh" from 2017 to 2019. The top 50 results in each age group for the 60-metre sprint and long jump were analysed. Boys showed significantly higher performance than girls in both events from ages 11 and 12. Significant performance improvements were noted between ages 12 and 13 for boys in the long jump and 10-11 in the sprint. Girls showed significant improvements between ages 12 and 13 in the long jump and 11-12 in the sprint. Gender divergence in sprint and long jump performance occurs around age 11. The dynamics of performance changes are influenced by the timing of the growth spurt, highlighting the need for age-specific competition categories in athletics.

Background/Objectives: The rising prevalence of pediatric obesity highlights the urgent need for effective lifestyle interventions that improve diet quality, in line with global health objectives. Tackling obesity through planetarian dietary practices not only enhances individual health but also mitigates the environmental impact of food systems. The EAT-Lancet Commission's plant-based dietary recommendations underscore the dual benefit of promoting human health while supporting environmental sustainability. This study aims to assess changes in adherence to a planetarian diet, measured through planetary environmental impact indices, following a lifestyle intervention in a pediatric population. Methods: In this randomized controlled trial, 107 participants with abdominal obesity were assigned to either a usual care group or an intensive intervention group, the latter following a moderately hypocaloric Mediterranean diet combined with nutritional education. Adherence to the EAT-Lancet diet was evaluated using both the EAT-Lancet Diet Score and the EAT-Lancet Diet Index. Results: The intensive lifestyle intervention significantly improved adherence to the EAT-Lancet diet, leading to notable reductions in body mass index (BMI), weight, and waist circumference, alongside improvements in both anthropometric and clinical outcomes. Conclusions: This study demonstrates that intensive lifestyle interventions in children and adolescents with abdominal obesity can reduce BMI-SDS (BMI-standard deviation score) and improve adherence to planetarian dietary patterns, leading to enhanced health outcomes. Further research is needed to evaluate the long-term effects of such interventions and to determine their broader applicability across diverse pediatric populations.

The aim was to examine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D).

We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short-term and long-term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin-like phospholipase domain-containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann-Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD.

The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040-2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009-1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013-1.078, p = 0.004) were independently associated with the presence of MASLD.

MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD.

The study aimed to investigate the correlation between insulin-like growth factor 1 (IGF-1) and ocular surface parameters in obese prepubertal boys. Thirty obese prepubertal boys and 30 age- and gender-matched healthy controls underwent physical measurements, laboratory tests, and ocular surface assessments. The obese group showed lower IGF-1 levels (P = 0.001), reduced Schirmer I tear test (SIT) (P <0.001), and higher meibomian gland scores (meiboscore) compared to controls (P = 0.015). Bivariate analysis revealed a positive association between IGF-1 and SIT (r = 0.677, P < 0.001), and a negative association with between IGF-1 and meiboscore (r =  - 0.487, P < 0.001). Multiple regression analysis indicated that IGF-1 (P < 0.001) and triglycerides (P = 0.028) independently influenced SIT. Logistic analysis showed a significant association between decreased IGF-1 and higher meiboscore values (OR 0.994, 95% confidence interval 0.988-1.000; P = 0.033).

The findings suggest that reduced IGF-1 in obese prepubertal boys is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. This implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on.

• Obese children exhibit decreased levels of IGF-1, and this reduction in IGF-1 is associated with cardiovascular metabolic complications related to obesity. • Ocular surface tissues might act as targets for hormones, might experience local effects of these hormone.

• In prepubertal obese boys, the decrease in IGF-1 is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. • This finding implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on.

Breastfeeding is the best source of nutrition for most babies and has been recognized as a means of optimizing health and wellbeing [...].

The 24-hour Movement Behaviour (24-h MovBeh) paradigm, encompassing physical activity (PA), sedentary behaviour (SB) and sleep patterns, is recognised as a holistic approach to adolescent health. It emphasises promoting PA, reducing SB and ensuring sufficient sleep, especially in school environments. Understanding the links between lifestyle factors and health outcomes is crucial for clinical and public health, informing interventions for lifestyle changes among adolescents. This study aims to assess adherence to 24-h MovBeh among Lithuanian adolescents, examining the patterns, inter-relationships and impacts on socio-demographic status, 24-h MovBeh, health-related fitness, blood pressure, body composition, dietary patterns, health-related quality of life, mental health, physical and exercise motivation, other lifestyles and health indicators, and academic performance. The 24-h MovBeh study is a prospective cohort study beginning in 2025 with baseline data collected in schools. It will recruit 500 primary and secondary school adolescents (11-14 years old) from Klaipeda and Kaunas, Lithuania. The study will evaluate 11 main categories: Socio-demographic status, 24-h MovBeh, health-related fitness, blood pressure, body composition, dietary patterns, health-related quality of life, mental health, physical and exercise motivation, other lifestyles and health indicators, and academic performance. Statistical analysis will estimate adherence to 24-h MovBeh and its inter-relationships with individual and environmental factors and health outcomes. The 24-h MovBeh study will be a crucial step towards establishing a monitoring system for health and lifestyle outcomes, benefiting researchers, policymakers, adolescents, and parents, while laying the groundwork for future intervention studies.

The aim of this study was to analyse whether the association between adherence to the Mediterranean diet and health-related quality of life (HRQoL) is mediated by physical fitness components (i.e., cardiorespiratory fitness, lower-limb strength, upper-limb strength and motor competence) in adolescents.

This is a cross-sectional study including mediation analyses. This study involved 181 adolescents (86 girls) aged 15.8 ± 0.3 years recruited from secondary schools and sport clubs located in Castellon (Spain). Adherence to the Mediterranean diet was evaluated using the KIDMED questionnaire. HRQoL was assessed with the KIDSCREEN-10 questionnaire. Cardiorespiratory fitness was assessed using the 20-m shuttle run test. Lower-limb strength was assessed through the standing broad jump test. Upper-limb strength was evaluated using a handgrip dynamometer. Motor competence was assessed using the 4 × 10 m shuttle run test. Mediation analyses were performed for each physical fitness component in order to assess its mediating effect on the association between adherence to the Mediterranean diet and HRQoL. Indirect effects (IE) with confidence intervals (CI) not including zero were interpreted as statistically significant.

Cardiorespiratory fitness and lower-limb strength had a mediating effect on the positive association between adherence to the Mediterranean diet and HRQoL (IE = 0.11, 95 % CI = 0.01; 0.27 and IE = 0.07, 95 % CI = 0.01; 0.19). Upper-limb strength and motor competence did not act as mediators in the association between adherence to the Mediterranean diet and HRQoL (IE = 0.00, 95 % CI = -0.04; 0.07 and IE = 0.01, 95 % CI = -0.03; 0.07, respectively).

Our findings showed that the positive association of adherence to the Mediterranean diet on adolescents' HRQoL was mediated by physical fitness. Educational and public health strategies aiming to improve Spanish adolescents' HRQoL should focus on diet and physical fitness.