Background: Central precocious puberty (CPP) results from premature activation of the hypothalamic–pituitary–gonadal axis and may affect psychological well-being in patients and families. Although GnRH agonist (GnRHa) therapy slows pubertal progression, its impact on quality of life (QoL) and emotional perception is unclear. This study evaluated QoL and treatment-related stress in girlswith CPP and their families during and after GnRHa therapy. Methods: In this cross-sectional study, 56 females with ongoing or previous CPP (aged 4–18 years) and 30 healthy matched controls were enrolled. Patients were grouped by age (A1:4–7; A2:8–12; A3:13–18; A4:>18 years). QoL was assessed using PedsQL™ 4.0, while emotional perception and treatment-related stress were evaluated with a disease-specific Self-Perception Questionnaire (SPQ). Group comparisons and correlations with therapy duration were performed. Results: PedsQL scores did not differ significantly across CPP age groups or between patients and controls, except for lower Physical Functioning in A2 versus controls (p=0.02). No correlation was found between therapy duration and QoL. SPQ scores showed no significant differences between children and parents or across age groups, although therapy-related emotional stress tended to increase with age. In A4, longer therapy duration correlated with lower treatment-related stress (r=0.47, p=0.021), while reduced self-esteem persisted during treatment and at follow-up. Conclusion: QoL in CPP patients appears comparable to healthy peers, but emotional responses to treatment vary with age and are not captured by generic QoL tools. Disease-specific assessment highlighted age-related emotional stress and long-term self-esteem reduction, supporting psychological evaluation in CPP management.

Objective: Maternal pre-pregnancy overweight may contribute to a pro-inflammatory intrauterine environment potentially affecting early brain development. This study examined the association between maternal body mass index (BMI) and Motor Optimality Score–Revised (MOS-R) at 3–5 months in a cohort of healthy full-term infants.Methods: One hundred twenty-eight mother–infant dyads from uncomplicated pregnancies were enrolled from a sigle italian tertiary center. Maternal socio-demographic characteristics and pre-pregnancy BMI were collected. Infants underwent MOS-R assessment at 9–18 weeks post-term age (median 13 weeks, IQR 12–14). Group comparisons and multivariate regression analyses were performed. BMI was categorized as <25 or ≥25 kg/m².Results: Fifteen percent of mothers were overweight and 6.3% obese before pregnancy. The median MOS-R score was 26 (IQR 26–28), with 94.5% of infants scoring within the optimal range (≥25). Within the MOS-R subcategories, the ‘age adequate motor repertoire’ resulted the more variable category. Infants born to mothers with BMI ≥25 kg/m² had significantly lower MOS-R scores compared to those with BMI <25. Although maternal employment status showed an association in univariate analyses, pre-pregnancy BMI ≥25 kg/m² remained independently associated with lower MOS-R scores in multivariate analysis (p <0.05).Conclusion: Our sample of healthy infants showed a typical range of spontaneous movements reflecting neural integrity. However, lower MOS-R scores were associated with pre-pregnancy overweight. These findings support the importance to continue investigating the relationship between pre-pregnancy BMI and neurodevelopmental outcomes and of promoting healthy maternal weight before conception as protecting factor for offsprings’ health.

BackgroundPhthalates (PAEs) are ubiquitous endocrine-disrupting chemicals (EDCs) with well-documented prenatal effects, while their impact during early postnatal life remains less understood. Minipuberty, a transient activation of the hypothalamic-pituitary-gonadal (HPG) axis in early infancy, represents a critical window of endocrine programming. This study aimed to investigate the association between early-life exposure to PAEs and urinary reproductive hormone levels during minipuberty in healthy term-born infants.MethodsThis longitudinal study included infants from the Modena birth cohort with repeated urine sampling at birth (T0), 3 (T3), and 6 months (T6). Urinary concentrations of PAE metabolites (MMP, MEP, MnBP, MBzP, ΣDEHPm) and urine reproductive hormones (uLH, uFSH, uT and uE) were measured. Associations were assessed using sex-stratified Spearman correlations, single-pollutant linear regression models, and mixture approaches, including Weighted Quantile Sum (WQS) regression and quantile g-computation (qgcomp).ResultsPAE metabolites were evaluated in 162 infants and detected in nearly all samples, confirming widespread exposure. Consistent positive associations emerged between PAE exposure and urinary hormone levels. In males, increasing levels of metabolites were significantly associated particularly with increased uFSH and uT, at all timepoints. In females, associations were more evident at T3 and T6, mainly involving uFSH and uE. Mixture analyses confirmed these findings and identified MnBP, MBzP, and ΣDEHPm as the main contributors. Results were consistent across methods, highlighting a mixture association beside an isolated compound-specific findings.ConclusionEarly-life exposure to PAE mixtures is associated with sex-specific alterations in reproductive hormone levels during minipuberty. These findings highlight minipuberty as a sensitive window for endocrine disruption and underscore the importance of considering chemical mixtures in environmental health research. However, further studies are needed to determine whether these early hormonal perturbations may have implications for long-term reproductive development and health.

Diabetic peripheral neuropathy (DN) is a major complication of type 1 diabetes (T1D), frequently subclinical in youth. Although international pediatric guidelines recommend annual screening, adherence in pediatric care is uncertain. This study aimed to assess DN screening practices in Italian pediatric diabetes centers and identify barriers to implementation. Between December 2024 and May 2025, we conducted a nationwide, cross-sectional survey among Italian centers affiliated with the ISPED Diabetes Study Group. One respondent per center completed a 27-item questionnaire exploring organizational features, DN screening practices, and professional training. Forty-eight centers responded to the survey. Written internal protocols for DN screening were available in 22.9

CONTEXT:Anti-transglutaminase antibodies (anti-TTG IgA) titer is associated with mucosal damage in celiac disease (CD). OBJECTIVE:The primary focus was to correlate anti-TTG IgA titer, HbA1c when CD occurs (HbA1cCD), and Marsh grade in children and adolescents with type 1 diabetes (T1D) at the time of CD diagnosis. As secondary outcomes, we assessed the optimal anti-TTG IgA upper limit of normal (ULN) cutoff for sparing biopsy, and personal and familial autoimmunity history in the individuals with T1D and CD (T1D-CD) compared with T1D-only. METHODS:In this retrospective observational study, among 6933 individuals with T1D onset (2010-2019), 556 were grouped according to CD onset: before (CD_FIRST), concomitant (CD_CONCOMITANT), or after T1D (T1D_FIRST), and compared with 141 T1D without CD. Measures included HbA1cCD, fold-anti-TTG IgA, anti-TTG IgA cutoff, and autoimmunity history of both groups, as well as Marsh grade in T1D-CD. RESULTS:In youths with T1D, HbA1cCD was associated with increased fold-anti-TTG IgA (Spearman r = 0.14, P = .0047). The optimal anti-TTG IgA cutoff for sparing biopsy was 11 ULN. Autoimmunity was prevalent in T1D-CD individuals, who showed more comorbidities than controls (χ2 25.4, P < .001), particularly the CD_FIRST (P < .001). CONCLUSION:In children with T1D-CD, worse glucometabolic control is associated with an increase in fold anti-TTG IgA and with worse Marsh grade. A slightly higher anti-TTG IgA cutoff may be necessary for sparing biopsy compared to children in the general population. Higher prevalence of autoimmune comorbidities in CD_FIRST suggests that screening for T1D in the CD population should be mandatory.

Over the past century, female pubertal timing has progressively advanced and this trend cannot be fully explained by genetic factors, childhood obesity, endocrine-disrupting chemicals, air pollution or other established risk factors alone, thereby providing a rationale for investigating additional environmental exposures. As climate change increases the frequency and intensity of heat waves worldwide, chronic thermal stress may represent a potential contributor to earlier pubertal timing that warrants further investigation. This narrative review integrates current evidence on heat exposure and neuroendocrine regulation to propose a biological framework linking prolonged heat-wave exposure to earlier female pubertal timing. Available evidence suggests that thermal stress may influence pubertal timing through multiple converging pathways, including activation of the hypothalamic–pituitary–adrenal axis, metabolic alterations involving insulin and IGF-1, sleep disruption with reduced melatonin secretion and, more speculatively, modulation of hypothalamic KNDy neurons involved in both thermoregulation and reproductive control. To date, it is important to note that the proposed relationship between heat exposure and earlier pubertal timing remains a biologically plausible hypothesis supported primarily by indirect epidemiological and mechanistic evidence, as direct evidence of causality in humans is lacking. Because children living in socioeconomically disadvantaged environments often experience greater exposure to extreme heat, climate-related endocrine effects may also contribute to widening health inequalities. Clarifying this relationship could expand current understanding of climate-sensitive pediatric endocrine health and inform future epidemiological research as well as public health strategies aimed at protecting children from the long-term consequences of rising global temperatures

Wernicke-Korsakoff syndrome is a neurological disorder caused by thiamine (vitamin B1) deficiency. This encephalopathy is typically suspected in alcoholics adults, but it is important to remember that other less known and suspected causes can determine the development of the non-alcoholic Wernicke’s encephalopathy. In non-alcoholic patients, the primary causes of Wernicke’s encephalopathy include hyperemesis gravidarum, restrictive diets and malnutrition, cancer, post-operative complications following bariatric surgery. Few data are reported regarding non-alcoholic thiamine deficiency, especially within the paediatric population. We describe the case of an 11-year-old Caucasian male with obesity who experienced prolonged emesis after the beginning of a strictly hypocaloric dietary regimen. This resulted in biliary colic episodes and subsequent necessity for cholecystectomy. The day after surgery, the patient developed acute visual impairment, horizontal nystagmus and diplopia, which were attributed to thiamine deficiency. Wernicke’s encephalopathy was suspected, so a blood sample was immediately collected to assay thiamine levels and empiric thiamine supplementation was started. Already from the day after the beginning of the treatment, the patient showed a significant improvement in his clinical conditions. This case study delineates clinical presentation, diagnosis, and treatment of our patient and provides information regarding the red-flag risk factors of non-alcoholic Wernicke’s encephalopathy in children. The aim is to increase the likelihood of suspecting the diagnosis and to promptly start the therapy, which is both simple and lifesaving.

Background: Familial hypobetalipoproteinemia (FHBL) is the most frequent monogenic form of HBL with a dominant mode of inheritance. Heterozygous patients are often asymptomatic, but the genetic mutation causes a defect of exportation of VLDL from the hepatocytes that remain stuck in the liver causing steatosis. In childhood, the diagnosis of FHBL is often underestimated and guidelines are still lacking. The aim of the study is to describe the phenotypic features of a cohort of children and adolescents with a genetic confirmed FHBL attending our pediatric lipid clinic. Methods: This is a monocentric, observational study collecting anamnestic, anthropometric, biochemical and instrumental data (liver ultrasound and elastographic profile) in children and adolescents with a genetic confirmation of heterozygous FHBL. Results: 12 children and adolescents (4 females), aged 12.14 ± 1.80 years, were genetically diagnosed with heterozygous FHBL. Overweight and/or obesity were identified in 7/12 cases while failure to thrive was detected in 4/12 cases. Only one patient was fully asymptomatic. In 6/12 patients, steatosis was graded from moderate to severe, mainly when accompanied by overweight and/or obesity (p 0.05). Transient elastography was more elevated in FHBL patients if overweight and/or obese (5.65 ± 0.71 vs. 4.60 ± 0.28, p 0.06). Conclusions: Our data document an unexpectedly wide phenotype of FHBL in childhood and adolescence ranging from no symptoms to growth failure or, on the other side, to obesity. Moreover, we document a frequent precocious hepatic involvement in FHBL children, especially if obese and overweight with a potential rapid evolution in fibrosis.

INTRODUCTION:The introduction of long-acting formulations in recent years is changing the landscape of growth hormone (GH) therapy. Daily recombinant human GH (rhGH) has been the treatment of choice for children and adults with GH deficiency (GHD), since its approval in 1985. However, decreasing adherence to treatment over time has been identified as a cause of the decline in rhGH efficacy, leading to significant efforts to develop long-acting rhGH (LAGH) formulations. AREAS COVERED:A comprehensive analysis of the literature was conducted to evaluate their mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, safety profile, and administration route. The review focuses on the LAGH approved from both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of pediatric growth hormone deficiency (PGHD): Lonapegsomatropin, Somatrogon and Somapacitan. We aim to facilitate evidence-based clinical decisions by analyzing the available data on the three LAGH formulations. EXPERT OPINION:Even if current evidence suggests a non-inferiority of all the three LAGH formulations when compared to daily rhGH, long-term concerns persist regarding the non-physiological GH profile associated with LAGH, characterized by weekly instead of daily peaks. Further research and real-life studies are required to better define the long-term efficacy of these formulations.

Extra-uterine growth restriction (EUGR) is a condition caused by the failure of very preterm infants to reach their potential growth during the NICU hospital stay. Despite improvements in nutritional supports, their growth pattern is still far from that expected. EUGR is now recognized as a major risk factor for long-term metabolic, anthropometric, and cognitive outcomes. Aim of our study was to evaluate anthropometric and metabolic outcome at peripubertal age in a population of ex-preterm VLBW infants and to detect the possible influence of EUGR on short stature. Retrospective cohort study of children born in a single centre between 2005 and 2009 with VLBW (birth weight < 1500 g). Families were recruited by telephone. During the clinical evaluation at peri-pubertal age, we measured height, head circumference, weight, and Body Mass Index (BMI), and clinical laboratory tests. Data were analyzed using SPSSv10.0 (SPSS Inc., Chicago, IL, USA). The Mann-Whitney U test was used for inter-group comparisons of continuous variables, and the Spearman test was used for correlations between variables. For intra-group comparisons, the paired t-test was used. Differences among three or more groups were assessed using the non-parametric Kruskal–Wallis test. We enrolled 78 patients, 21 (27

Background: Gender identity (GI) is the unified and persistent self-perception on the male-female spectrum, and its acquisition is a multifactorial process. GI is generally consolidated around ages 3–4 years. The gender identity questionnaire for children (GIQC) aims to assess GI in both clinical and non-clinical populations. The aim of the research is to evaluate GI in relation to social and biological factors. Methods: Single-center, prospective birth-cohort study enrolling those born at term, appropriate for gestational age. The GIQC was administered to the parents at age 3. The scoring was performed through the original coding scheme and the new coding scheme for the non-clinical group based on three scales: female typical behavior (FTB), male typical behavior (MTB), and cross-gender (CG). Anthropometrics, anogenital distances, and urinary hormone assessment were performed at birth, 3, 6 and 36 months. Results: 86 children (males 53) participated. FTB, MTB, and CG scores differed significantly according to sex: boys (3.28 ± 0.59) scored higher than girls (2.45 ± 0.44) on MTB, while girls (3.41 ± 0.75) scored higher than boys (1.92 ± 0.61) on FTB. Girls (4.14 ± 0.64) scored higher than boys (3.66 ± 0.88) on the CG scale. Within the whole sample, the FTB scale showed a moderate negative correlation with MTB (r: −0.464, P < 0.01) and a positive one with CG (r: 0.377, P < 0.001) in the female population. Correlations exist between MTB and ano-scrotal distance (AGD-AS) in males, and between MTB and ano-clitoral distance (AGD-AC) in females. Conclusion: Our findings confirm that by age 3, most children express differentiated sex-typed behavior according to the sex assigned at birth. In addition, androgenization appears to play a role in GI development in males.

Intranasal corticosteroids (INCS) are widely used to treat allergic rhinitis and nasal obstruction. While their safety profile is generally well established, both local and systemic side effects can occur. While it is well-known that a chronic exposure to systemic glucocorticoid treatment could determine Cushing's syndrome (CS) and suppression of the hypothalamic-pituitary-adrenal (HPA) axis, there is less awareness when the administration is topical or intranasal. We report the case of an 8-year-old Caucasian girl who developed Cushingoid features following prolonged INCS treatment-initially with betamethasone and subsequently with mometasone furoate. Endocrine testing revealed undetectable baseline and after stimulation cortisol levels, suggesting a condition of adrenal insufficiency secondary to the prolonged glucocorticoid exogenous administration. Temporary hydrocortisone replacement therapy was required. Even if extremely rare, pediatricians should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic CS, as well as systemic glucocorticoid treatment. Clinical features are characterized by the complications of glucocorticoid excess and by the potential life-threatening complications of adrenal insufficiency. Pediatric follow-up should be scheduled during the prolonged steroid treatment and at discontinuation, with prompt referral to a Pediatric Endocrinologist if signs and symptoms of CS (or adrenal insufficiency) are noticed.