Decreased vitamin D levels in the pediatric population after COVID-19 lockdown.

BACKGROUD: SARS-Cov2 infection began to spread worldwide since December 2019; on March 2020, the World Health Organization characterized its related disease, named COVID-19, as a pandemic. In Italy, to contain the spread of infection a severe lockdown in the spring 2020 was instituted. Other less severe restrictions were imposed in the winter 2020-2021 and in the spring 2021. The containment measures caused a series of consequences for the population and, in particular, for children and adolescents that presented psychophysical problems. The aim of this manuscript is to investigate the serum levels of vitamin D in children and adolescents before, during and after the lockdown consequent to COVID-19 pandemic. METHODS: This is a retrospective cross-sectional study, including all children and adolescents between 1 to 18 years referring to the Pediatric Endocrinology Service of the University Hospital of Verona, Italy, between January 2019 and December 2021. All patients affected by clinical conditions that involve vitamin D metabolism or assuming vitamin D supplementation were excluded. RESULTS: In total, 491 children (36.7% males and 63.3% females) were enrolled in this study. The vitamin D levels decreased over time: 28.3 ± 10.2 ng/mL in 2019; 28.2 ± 11.4 ng/mL in 2020 and 24.9 ± 10.1 ng/mL in 2021 (p < 0.05). The vitamin D levels are significant higher in summer and in autumn in comparison with the levels of winter and spring, regardless of the examined years. CONCLUSIONS: The measures adopted to contain the COVID-19 pandemic led to a reduction of serum levels of vitamin D in pediatric population, probably due to the reduced solar exposure. This may have severe consequences on the bone metabolism of those children who did not present optimal vitamin D levels even before the lockdown. Therefore, an adequate supplementation of vitamin D is necessary from the end of fall to the beginning of spring (November-April) in all children and adolescents living in Northern Italy.

The Impact of Growth Hormone Therapy on Sleep-Related Health Outcomes in Children with Prader-Willi Syndrome: A Review and Clinical Analysis.

This literature review of growth hormone (GH) therapy and sleep-related health outcomes in children diagnosed with Prader-Willi syndrome (PWS) assembles evidence for the consequences of sleep deprivation and poor sleep quality: difficulty concentrating and learning at school, behavioral problems, diminished quality of life, and growth impairment. Sleep-disordered breathing (SDB) is another factor that impacts a child's well-being. We searched the electronic databases Medline PubMed Advanced Search Builder, Scopus, and Web of Science using MeSH terms and text words to retrieve articles on GH deficiency, recombinant human growth hormone (rhGH) therapy, sleep quality, SDB, and PWS in children. The censor date was April 2023. The initial search yielded 351 articles, 23 of which were analyzed for this review. The study findings suggest that while GH may have a role in regulating sleep, the relationship between GH treatment and sleep in patients with PWS is complex and influenced by GH dosage, patient age, and type and severity of respiratory disorders, among other factors. GH therapy can improve lung function, linear growth, and body composition in children with PWS; however, it can also trigger or worsen obstructive sleep apnea or hypoventilation in some. Long-term GH therapy may contribute to adenotonsillar hypertrophy and exacerbate sleep apnea in children with PWS. Finally, GH therapy can improve sleep quality in some patients but it can also cause or worsen SDB in others, leading to diminished sleep quality and overall quality of life. The current evidence suggests that the initial risk of worsening SDB may improve with long-term therapy. In conclusion, rhGH is the standard for managing patients with PWS. Nonetheless, its impact on respiratory function during sleep needs to be thoroughly evaluated. Polysomnography is advisable to assess the need for adenotonsillectomy before initiating rhGH therapy. Close monitoring of sleep disorders in patients with PWS receiving GH therapy is essential to ensure effective and safe treatment.

Vitamin D and Osteogenesis Imperfecta in Pediatrics.

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.

The influence of growth hormone on pediatric body composition: A systematic review.

Background: Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD. Methods: The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM. Results: Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy. Conclusion: Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.

Complex relationship between growth hormone and sleep in children: insights, discrepancies, and implications.

Growth hormone (GH) is crucial to growth and development. GH secretion is regulated by a complex feedback system involving the pituitary gland, hypothalamus, and other organs, and predominantly occurs during deep sleep. Isolated and idiopathic growth hormone deficiency (GHD) is a condition characterized by GHD without any other signs or symptoms associated with a specific syndrome or disease. The aim of this narrative review was to evaluate the relationship between GH and sleep in children using published data. Various databases (Medline/PubMed, Scopus, and Web of Science) were systematically searched for relevant English language articles published up to April 2023. Search strategies included the terms 'children/pediatric', 'growth hormone', 'growth hormone deficiency' and 'sleep'. Data were extracted by two independent reviewers; 185 papers were identified of which 58 were duplicates and 118 were excluded (unrelated n=83, syndromic/genetic GHD n=17, non-English n=13, abstract n=1, case report n=1). Overall, nine studies (six clinical studies, two case series, and one survey) were included. GHD appears to have an adverse effect on sleep in children, and GH therapy has only been shown to have a beneficial effect on sleep parameters in some individuals. Notably, identified data were limited, old/poor quality, and heterogenous/inconsistent. Further research of GHD in pediatric populations is necessary to improve the understanding of GHD impact on sleep and its underlying mechanisms, and to determine the specific impacts of GH therapy on sleep in children.

Hypocalcemia following Neridronate Administration in Pediatric Patients with Osteogenesis Imperfecta: A Prospective Observational Study.

The use of intravenous bisphosphonates has been linked to hypocalcemia both in children and adults with osteogenesis imperfecta (OI). The aims of this study were: (1) to investigate the incidence of hypocalcemia in the first 48 hours (T48) after neridronate infusion in a pediatric population with OI and (2) to assess any correlation between the baseline values of calcium, vitamin D (25-hydroxyvitamin D) and bone turnover markers, and the postinfusion calcium values. We conducted a prospective observational study on 37 pediatric patients. All patients were treated with a single infusion of neridronate at a dose of 1 to 2 mg/kg. The study provided two postinfusion reassessments: 24 hours (T24) and T48 after neridronate administration. Hypocalcemia was observed in 11% of patients at T24 and in 50% of patients at T48 from neridronate infusion. We observed a positive linear correlation between the baseline vitamin D values and postinfusion calcium values, both at baseline and at T24 and T48. Hypocalcemia was mild and asymptomatic in all cases. Postinfusion calcium levels were related to baseline vitamin D levels. Consequently, low vitamin D levels should be considered a significant risk factor for hypocalcemia and should be carefully investigated and treated before neridronate infusion.

Growth hormone retesting during puberty: a cohort study.

OBJECTIVES: To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty. DESIGN: Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. METHODS: The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 µg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. RESULTS: GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. CONCLUSIONS: GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.

Sympatho-adrenergic activation by endurance exercise: Effect on metanephrines spillover and its role in predicting athlete's performance.

BACKGROUND: The sympatho-adrenergic activation during exercise is implicated in many cardiovascular respiratory and metabolic adaptations which have been thought to partially explain the different levels of performance observed between trained and untrained subjects. To date, no evidence exists about the association between competition performance and markers of "acute stress response". We designed this study to investigate; (i) the acute sympatho-adrenergic activation during endurance exercise in recreational runners by measuring plasma levels of free metanephrine (MN) and normethanephrine (NMN) before and after a half-marathon run; (ii) the association between the metanephrines levels and the running time. METHODS: 26 amateur runners (15 males, 11 females) aged 30 to 63 years were enrolled. The quantification of MN and NMN was performed by LC-MS/MS. Anthropometric ergonomic and routine laboratory data were recorded. Statistical analyses included paired T-test, univariate and multivariate regressions. RESULTS: The post-run values of MN and NMN displayed a nearly 3.5 and 7 fold increase respectively compared to the baseline values (p < 0.0001 for both). NMN pre-run values and pre/post run delta values showed a significant direct and inverse association (p = 0.021 and p = 0.033, respectively) with running performance. No correlations were found for MN values. CONCLUSION: NMN is a reliable marker of sympatho-adrenergic activation by exercise and can predict endurance performance in the individual athlete. Adaptation phenomenon occurring not only in the adrenal medulla might represent the biological mechanism underlying this association. Further studies on sympatho-adrenergic activation, competition performance and training status should contemplate the measurement of these metabolites instead of their unstable precursors.

Urinary free cortisol assessment by liquid chromatography tandem mass spectrometry: a case study of ion suppression due to unacquainted administration of piperacillin.

INTRODUCTION: Liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-ESI-MS/MS) is currently considered the reference method for quantitative determination of urinary free cortisol (UFC). One of the major drawbacks of this measurement is a particular form of matrix effect, conventionally known as ion suppression. MATERIALS AND METHODS: We describe here the case of a 66-year-old-patient referred to the daily service of general medicine for intravenous antibiotic administration due to a generalized Staphylococcus aureus infection and for routine 24 hours UFC monitoring in the setting of glucocorticoid replacement therapy. RESULTS: The observation of 10-fold decrease of internal standard of cortisol signal led us to hypothesize the presence of an ion suppression effect due to a co-eluting endogenous compound. Screening analysis of tandem mass spectrometry (MS/MS) spectra of the interfering molecule, along with in vitro confirmation analyses, were suggestive of the presence of high concentration of piperacillin. The problem was then easily solved with minor modifications of the chromatographic technique. CONCLUSIONS: According to our findings, antibiotic therapy with piperacillin/tazobactam should be regarded as an important interference in UFC assessment, which may potentially affect detection capability, precision and accuracy of this measurement. This case report emphasizes that accurate anamnesis and standardization of all phases of urine collection are essential aspects for preventing potential interference in laboratory testing.