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BACKGROUND Patients with adrenal insufficiency are at risk of adrenal crisis, a potentially life-threatening emergency in the peri-operative period due to their attenuated ability to mount a cortisol response. There is a lack of standardization regarding peri-operative stress-dose glucocorticoids in paediatric clinical practice with the absence of agreed protocols. For the individual patient, the risk of adrenal crisis must be weighed against the potential adverse clinical outcomes associated with unnecessary or supra-physiologic glucocorticoid dosing in susceptible patients. Specific clinical concerns in the paediatric population include osteopenia, growth restriction and increased risk of cardiovascular disease in adulthood. This review aimed to identify and evaluate available literature in the field of peri-operative stress-dose glucocorticoids. METHODS A comprehensive literature search was conducted to construct a narrative review. RESULTS The outcome of this review identified that paediatric patients, unlike adults, do not show a graded response to surgical stress with implications for glucocorticoid stress dose regimens for general anaesthesia and less invasive surgical procedures. The studies highlight a lack of information on physiological steroid responses to stress situations and differences in the approach to glucocorticoid replacement strategies in the paediatric population. CONCLUSION The review identified there is a lack of high-quality paediatric-specific studies evaluating appropriate stress-dose glucocorticoid regimens in paediatric patients with or at risk of adrenal insufficiency. Further research is needed to establish clear evidence-based clinical guidelines for paediatric peri-operative practice regarding steroid stress dosing in adrenal insufficiency. Current knowledge would suggest that a balanced view of risks and benefits should be taken appropriate to the clinical context, to dictate peri-operative stress-dose glucocorticoids use that permits safe perioperative management.

Summary Ground impacts during physical activity may be important for peak bone mass. We found differences in how energy expenditure and impact scores estimated from a physical activity questionnaire related to bone health in young adults. Using both estimate types can improve our understanding of the skeletal benefits of physical activity. Purpose It is unclear whether mechanical loading during physical activity, estimated from physical activity questionnaires which assess metabolic equivalents of task (METs), is associated with skeletal health. This longitudinal study investigated how physical activity loading scores, assessed at ages 17 and 20 years, (a) compares with physical activity measured in METs, and (b) is associated with bone mass at age 20 years. Methods A total of 826 participants from the Raine Study Gen2 were assessed for physical activity energy expenditure via the International Physical Activity Questionnaire (IPAQ) at age 17 and 20 years. Loading scores (the product of peak force and application rate) per week were subsequently estimated from the IPAQ. Whole-body and appendicular bone mineral density (BMD) at age 20 years were assessed by dual-energy X-ray absorptiometry. Results Bland–Altman minimal detectable difference for physical activity Z- scores at age 17 and 20 years were 1.59 standard deviations (SDs) and 1.33 SDs, respectively, greater than the a priori minimal clinically important change of 0.5 SDs. Loading score, but not IPAQ score, had significant positive associations with whole-body and leg BMD after adjustment for covariates (β = 0.008 and 0.012 g/cm2, respectively, for age 17 and 20 years loading scores). IPAQ score at age 20 years, but not loading score, had a significant positive association with arm BMD (β = 0.007 g/cm2). Conclusion This study revealed disagreement in associations of self-reported METs and loading score estimates with bone health in young adults. Coupling traditional energy expenditure questionnaire outcomes with bone-loading estimates may improve understanding of the location-specific skeletal benefits of physical activity in young adults.

X-linked hypophosphataemia (XLH), the most common inherited form of rickets, is caused by a PHEX gene mutation that leads to excessive serum levels of fibroblast growth factor 23 (FGF23). This leads to clinical manifestations such as rickets, osteomalacia, pain, lower limb deformity and overall diminished quality of life. The overarching aims in the management of children with XLH are to improve quality of life by reducing overall burden of disease, optimise an individual's participation in daily activities and promote normal physical and psychological development. Burosumab, a monoclonal antibody targeting FGF23, has been shown to improve biochemistry, pain, function and radiological features of rickets in children with XLH and has transformed management of XLH around the world. Burosumab has been recently approved for clinical use in children with XLH in Australia. This manuscript outlines a clinical practice guideline for the use of burosumab in children with XLH to assist local clinicians, encourage consistency of management across Australia and suggest future directions for management and research. This guideline also strongly advocates for all patients with XLH to have multidisciplinary team involvement to ensure optimal care outcomes and highlights the need to consider other aspects of care for XLH in the era of burosumab, including transition to adult care and the effective coordination of care between local health-care providers and specialist services.

Aim Poorer physical and mental health often accompany loss of walking in Duchenne muscular dystrophy. This study assessed the impacts of powered wheelchair standing device (PWSD) use on muscle and joint pain, joint angles when standing and mental health in adolescents with Duchenne muscular dystrophy. Methods Fourteen adolescents and parents participated in a stepped wedge design study over 12 months. During a baseline and intervention period, adolescents described pain and mental health, and parents reported their child's mental health. Video data were collected to measure hip, knee and ankle joint angles in the preferred standing position. Results Compared with baseline and adjusting for covariates, standing wheelchair use was associated with no change in muscle or joint pain or videoed joint angles in standing. Child-reported Strengths and Difficulties total scores decreased (coefficient -3.1, 95% confidence interval -4.6, -1.5); and parent-reported Personal Adjustment and Role Skills Scale total scores increased (coefficient 7.9, 95% confidence interval 3.3-12.5). Conclusions PWSD use was associated with maintenance of musculoskeletal status and advantages to mental health. Long-term observations are necessary to improve understanding of how to support wellbeing in adolescents with Duchenne muscular dystrophy.

Objectives There is a paucity of information regarding the profile of entire paediatric endocrine clinics and how they are changing. This study aimed to analyse the clinic profile of the Western Australian tertiary paediatric endocrine outpatient service over 10 years and compare to national and international data. Methods Retrospective analysis of the Western Australian Paediatric Endocrine Database (WAPED) between 2007 and 2017 looking at the frequency, proportion and longitudinal change of diagnosis categories, specific diagnoses, and gender breakdown. Results In total, 2,791 endocrine diagnoses were recorded for 2,312 patients. The most frequent reason for referral (22.1% of patients), was for evaluation of abnormalities in thyroid function. The most common diagnosis being hypothyroidism (76.7%). Evaluation of short stature was the reason for referral in 19.2% of patients, 14.6% of whom were diagnosed with growth hormone deficiency. Evaluation of puberty disorders, syndromes with endocrine features and disorders of calcium and phosphate metabolism were other common reasons for clinic referral, seen in 11.3, 9.8 and 8.2% of patients respectively. Between 2007 and 2017, the odds ratio of a thyroid diagnosis increased by 1.07 per year (95% CI: 1.02–1.12), whilst the odds ratio of a short stature diagnosis decreased by 0.91 per year (95% CI: 0.87–0.95). Conclusions The profile of the WAPED is similar to previously published national and international data. The analysis of the profile of diagnoses and its longitudinal change over a ten-year period offer a unique opportunity to guide clinic planning, resource allocation and future research.

Duchenne muscular dystrophy is a common neuromuscular disorder involving progressive muscle weakness. A powered wheelchair standing device provides capacity to stand despite increasing muscle weakness. This study used qualitative methods to explore how adolescents with Duchenne muscular dystrophy used a powered wheelchair standing device in their daily lives. Semi-structured interviews were conducted with 12 adolescents, 11 parents and 11 teachers. Qualitative thematic analysis using a grounded theory framework was conducted to identify emerging domains. "Capacity to be able" was the central theme that emerged across the dataset: the introduction of the powered wheelchair standing device at a time when motor skills were declining enabled the adolescent to maintain and sometimes extend his independence. There were four underlying themes including (1) Independence, (2) Health, (3) Comfort, and (4) Community belonging and involvement. Each theme was illustrated in data collected from adolescents, parents and teachers. The device appeared to mitigate some of the challenges of progressive muscle weakness by providing the option for the individual with Duchenne muscular dystrophy to choose when and where to stand for participation in a range of activities, beyond what would be possible with existing therapeutic regimes involving standing frames.

Background Australian adolescents with low motor competence (LMC) have higher fracture rates and poorer bone health compared to European normative data, but currently no normative data exists for Australians. Aims To examine whether there were bone health differences in Australian adolescents with LMC or Developmental Coordination Disorder (DCD) when compared to typically developing age-matched Australian adolescents. Methods and Procedures Australian adolescents aged 12–18 years with LMC/DCD (n = 39; male = 27; female = 12) and an Australian comparison sample (n = 188; boys = 101; girls = 87) undertook radial and tibial peripheral Quantitative Computed Tomography (pQCT) scans. Stress Strain Index (SSI (mm3)), Total Bone Area (TBA (mm2)), Muscle Density (MuD [mgcm3]), Muscle Area (MuA [cm2]), Subcutaneous Fat Area (ScFA [cm2]), Cortical Density (CoD [mgcm3]), Cortical Area (CoD [mm2]), cortical concentric ring volumetric densities, Functional Muscle Bone Unit Index (FMBU: (SSI/bone length)) and Robustness Index (SSI/bone length^3), group and sex differences were examined. Outcome and Results The main finding was a significant sex-x-group interaction for Tibial FMBU (p = .021), Radial MuD (p = .036), and radial ScFA (p = .002). Boys with LMC/DCD had lower tibial FMBU scores, radial MuD and higher ScFA than the typically developing age-matched sample. Conclusion and Implications Comparisons of bone measures with Australian comparative data are similar to European findings however sex differences were found in the present study. Australian adolescent boys with LMC/DCD had less robust bones compared to their well-coordinated Australian peers, whereas there were no differences between groups for girls. These differences may be due to lower levels of habitual weight–bearing physical activity, which may be more distinct in adolescent boys with LMC/DCD compared to girls.

The dramatic rise in allergic disease has occurred in tandem with recent environmental changes and increasing indoor lifestyle culture. While multifactorial, one consistent allergy risk factor has been reduced sunlight exposure. However, vitamin D supplementation studies have been disappointing in preventing allergy, raising possible independent effects of ultraviolet (UV) light exposure. The aim of this study was to examine whether UV light exposure influences the development of allergic disease in early childhood. Direct sunlight exposure (290–380 nm) in early infancy was measured via UV dosimeters. Outdoor exposure, sun protective behaviours, and allergy outcomes were assessed over the first 2.5 years of life with clinical assessment appointments at 3, 6, 12 and 30 months of age. Children with eczema had less (p = 0.038) direct UV light exposure between 0-3 months of age (median (IQR) 747 (473–1439) J/m2) than children without eczema (median (IQR) 1204 (1717–1843) J/m2), and less outdoor exposure time (7 min/day) between 11 a.m. and 3 p.m. compared to children without eczema (20 min/day, p = 0.011). These associations were seen independent of vitamin D status, and after adjusting for other potential confounders. Whilst we could not find any associations between direct UV light exposure and other allergic disease outcomes, exposure to UV light appears to be beneficial in reducing the risk of eczema development in early childhood. Further research is required to determine optimal levels of UV light exposure while balancing the potential risks.

ContextPatients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss.ObjectiveTo investigate use of zoledronic acid (ZA) in DMD in improving BMD.MethodsTwo arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores.ResultsAt 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia.ConclusionZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.

Summary The Endocrine Society Clinical Practice Guidelines on the treatment of gender incongruent people recommend the use of gender-affirming cross-sex hormone (CSH) interventions in transgender children and adolescents who request this treatment, who have undergone psychiatric assessment, and have maintained a persistent transgender identity. The intervention can help to affirm gender identity by inducing masculine or feminine physical characteristics that are congruent with an individual's gender expression, while aiming to improve mental health and quality-of-life outcomes. Some transgender individuals might also wish to access gender-affirming surgeries during adolescence; however, research to inform best clinical practice for surgeons and other medical professionals is scarce. This Review explores the available published evidence on gender-affirming CSH and surgical interventions in transgender children and adolescents, amalgamating findings on mental health outcomes, cognitive and physical effects, side-effects, and safety variables. The small amount of available data suggest that when clearly indicated in accordance with international guidelines, gender-affirming CSHs and chest wall masculinisation in transgender males are associated with improvements in mental health and quality of life. Evidence regarding surgical vaginoplasty in transgender females younger than age 18 years remains extremely scarce and conclusions cannot yet be drawn regarding its risks and benefits in this age group. Further research on an international scale is urgently warranted to clarify long-term outcomes on psychological functioning and safety.

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.

Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy vitamin D supplementation on allergic disease outcomes in infants at &ldquo, hereditary risk&rdquo, of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of &ldquo, high-risk&rdquo, infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36&ndash, 40 weeks) maternal 25-hydroxyvitamin D levels needed to be &ge, 50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (n = 97) or a placebo (n = 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for &ldquo, allergy high-risk&rdquo, infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.

Objectives: To describe peripheral long bone material and structural differences in youth at risk of secondary osteoporosis across disease-specific profiles. Methods: Upper- and lower limbs of children and adolescents were scanned at 4% distal and 66% mid-shaft sites using peripheral Quantitative Computed Tomography sub-categorised as (1) increased risk of secondary osteoporosis (neuromuscular disorders; chronic diseases; endocrine diseases; inborn errors of metabolism; iatrogenic conditions), (2) low motor competence and (3) non-affected controls. Results: Children with disease-specific profiles showed a range of bone deficits compared to the control group with these predominantly indicated for neuromuscular disorders, chronic diseases and low motor competence. Deficits between upper arm and lower leg long bone parameters were different for disease-specific profiles compared to the control group. Endocortical radius, muscle area, and mid-cortical ring density were not significantly different for any disease-specific profile compared to the control group for any bone sites. Conclusions: Neuromuscular disorders, chronic diseases and low motor competence have a strong correlation to bone health for appendicular bone parameters in youth, suggesting a critical mechanical loading influence which may differ specific to disease profile. As mechanical loading effects are observed in regional bone analyses, targeted exercise interventions to improve bone strength should be implemented to examine if this is effective in reducing the risk of secondary osteoporosis in youth.

Background Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. Method A double‐blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. Results Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naive CD4‐ T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FceR1) on monocytes and dendritic cells with eczema at 6 months. Conclusions Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.

Summary The World Professional Association for Transgender Health's standards of care recommend suspending puberty, preferably with the use of gonadotropin-releasing hormone agonists, in certain gender non-conforming minors (aged under 18 years) who have undergone a psychiatric assessment and have reached at least Tanner stage II of puberty. This approach seeks to lessen the discordance between assigned natal sex and gender identity by temporarily halting the development of secondary sexual characteristics, essentially widening the temporal window for gender clarification. Despite promising preliminary evidence on the clinical utility of this approach, there is a dearth of research to inform evidence-based practice. In view of these challenges, we review the available empirical evidence on the cognitive, physical, and surgical implications of puberty suppression in gender-incongruent children and adolescents. We also explore the historical underpinnings and clinical impetus for suspending puberty in this population, and propose key research priorities.

Low carbohydrate diets for the management of type 1 diabetes have been popularised by social media. The promotion of a low carbohydrate diet in lay media is in contrast to published pediatric diabetes guidelines that endorse a balanced diet from a variety of foods for optimal growth and development in children with type 1 diabetes. This can be a source of conflict in clinical practice. We describe a series of 6 cases where adoption of a low carbohydrate diet in children impacted growth and cardiovascular risk factors with potential long-term sequelae. These cases support current clinical guidelines for children with diabetes that promote a diet where total energy intake is derived from balanced macronutrient sources.

In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.

Accurately detecting vitamin D deficiency (defined as concentration in blood of 25-hydroxyvitamin D (25(OH)D),20 ng/mL) is important for both clinicians and researchers. Drawing blood may be difficult in some populations, such as infants and children. We thus explored the development of a method to measure 25(OH)D concentrations in saliva, using a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. Using 25(OH)D

Introduction The interaction between psychosocial factors and type 1 diabetes is complex and screening for psychosocial risk factors from diagnosis of type 1 diabetes has been recommended. This is a systematic review and meta-analysis to address the following questions: (1) How prevalent are symptoms of depression and anxiety in children and adolescents with type 1 diabetes? (2) Is there an association of symptoms of depression and anxiety with diabetes management and glycemic control? Material and methods We searched EMBASE, MEDLINE, The Cochrane Library, and PsycINFO in April 2014 with an update in May 2015. When possible, data were pooled to estimate summary effects. Results 14 studies investigated symptoms of depression and anxiety in children and adolescents with type 1 diabetes. The pooled prevalence of depressive symptoms was 30.04%, 95% CI [16.33; 43.74]. There were correlations between symptom levels and glycemic control as well as three-way interactions between HbA1c, blood glucose monitoring frequency or diabetes-specific stress and depression. Symptoms of anxiety were reported for up to 32% of patients. A negative impact on glycemic control was demonstrated. Conclusions Our analyses confirmed a high prevalence of symptoms of depression and anxiety in youth with type 1 diabetes that potentially compromise diabetes management and glycemic control. In our opinion these findings support recommendations for early screening for psychological comorbidity and regular psychosocial assessment from diagnosis. Future prospective studies are warranted to further explore the interaction of symptoms of depression and anxiety with type 1 diabetes and develop evidence-based treatment models.

Hypovitaminosis D is prevalent worldwide, however, analytical bias in the measurement of circulating 25-hydroxyvitamin D (25(OH)D) concentrations may affect clinical treatment decisions and research. We performed parallel plasma 25(OH)D analyses using the Abbott Architect i2000 chemiluminescent immunoassay (CIA) and liquid chromatography&ndash, tandem mass spectrometry (LC&ndash, MS/MS) for paired samples from the same infants at 3 (n = 69), 6 (n = 79) and 12 months (n = 73) of age. To test agreement, we used Lin&rsquo, s concordance correlation coefficient and corresponding 95% confidence interval, Bland&ndash, Altman&rsquo, s limits of agreement, and Bradley&ndash, Blackwood (BB) test. Agreement was high at 3 months (coefficient between difference and mean &minus, 0.076, BB F = 0.825, p = 0.440), good at 12 months (&minus, 0.25, BB F = 2.41, p = 0.097) but missing at 6 months of age (&minus, 0.39, BB F = 12.30, p &lt, 0.001). Overall, 18 infants had disparate results based on the cut-off point for vitamin D deficiency (25(OH)D &lt, 50 nmol/L), particularly at three months, with seven (10%) infants deficient according to CIA but not LC&ndash, MS/MS, and four (6%) deficient by LC&ndash, MS/MS but not CIA. To our knowledge, this is the first study to show that the reported 25(OH)D concentration may be influenced by both age and assay type. Physicians and researchers should be aware of these pitfalls when measuring circulating 25(OH)D concentrations in infants and when developing treatment plans based on measured vitamin D status.

Summary : Fracture incidence data of Australian children and adolescents have not been reported in the literature. A 10-year case review of fracture presentations in Western Australia is provided. Between 2005 and 2015, fracture incidence increased relative to population growth. This is concerning, and interventions are required to reverse this trend. Purpose : Fracture incidence in 0–16-year-olds is high and varies between countries. Boys have a 1.5:1 ratio of fracture incidence compared to girls. There are no specific data for Australia. Western Australia is a state with unique geography and population distribution having only a single tertiary paediatric hospital (Princess Margaret Hospital, PMH, in Perth) managing the majority of children and adolescents with fractures in the Emergency Department (ED). The aims of this study were to characterise fracture presentations to PMH-ED and compare the incidence to population data. Methods : A database audit of fracture presentations between 2005 and 2015 for fracture rates with a sub-analysis for gender, fracture site and age and a comparison to Perth Metropolitan and Western Australian population data was performed. Results : Analysis included 31,340 presentations. Fracture incidence, adjusted for the annual population size, increased from 0.63% in 2005 to 0.85% in 2015 (p < 0.001). The month of May reported the highest fracture rate (p < 0.001) corresponding with the start of the winter sports season. Males had a 1.5 times higher fracture incidence than females (p < 0.001), with upper limb fractures three times more common than lower limb fractures (p < 0.001). Fracture incidence increased with age until the early teenage years (15 years for males; 12 years for females) when a decline occurred. Conclusions : Increased fracture incidence in Western Australia between 2005 and 2015 identifies a concerning trend for bone health in children and adolescents. Further research is needed to identify potential lifestyle factors that impact fracture incidence translating into evidence-based strategies to reverse these trends and improve bone health.

Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this study was to compare daily versus depot treatment and factors influencing the therapeutic outcome. Newly settled refugees (n = 151) with 25(OH)D levels less than 78 nmol/L were randomised to receive daily or depot vitamin D therapy with eight weekly interval follow up to 40 weeks. Biochemical and clinical parameters were collected at each visit. Generalized Linear Mixed Models (GLMM) examined the longitudinal changes over time controlling for confounders including age, gender, treatment arm, season, country of refuge/origin and sun exposure score. Participants were aged 5.5 months to 16.0 years (75 males, 83 females). Both treatment groups achieved vitamin D sufficiency. The daily treatment group had significantly higher 25(OH)D levels at each visit post baseline and a higher proportion of participants with levels above 50 nmol/L at all time points. Time, treatment group, calcium and sun exposure score were significant predictors of 25(OH)D serum levels. Depot vitamin D therapy is an alternative to daily treatment in this at-risk group of children and adolescents in whom treatment adherence is problematic.

Aim The prevalence of vitamin D deficiency has risen in countries with a high ultraviolet index and sunny environment such as Australia. There is lack of information on vitamin D status and best possible therapy in Australian Aboriginal children. We aim to (i) describe the vitamin D status in an opportunistic sample of Aboriginal children in Western Australia and (ii) compare the efficacy of oral daily vitamin D with oral stoss vitamin D therapy in this sample. Method Participants were recruited from a metropolitan area (31′ S) and a rural area (17′ S). Those with a 25(OH)D level less than 78 nmol/L were randomised to receive daily or stoss vitamin D therapy with follow-up at 4–6 months and 9–12 months. Biochemical and clinical parameters such as 25(OH)D, alkaline phosphatase, calcium and sun exposure were collected. Results Seventy-three participants were enrolled (61 from a metropolitan and 12 from a rural area). 25(OH)D levels were greater than 78 nmol/L in 9/12 (75%) participants in the rural group and 21/61 (34%) in the metropolitan group. 25(OH)D levels were less than 78 nmol/L in 43/73 (59%) participants. Of these, 34/43 (79%) were insufficient (50–78 nmol/L), 8/43 (19%) mildly deficient (27.5–50 nmol/L) and 1/43 (2%) deficient (

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.

Most imaging methods, including peripheral quantitative computed tomography (pQCT), are susceptible to motion artifacts particularly in fidgety pediatric populations. Methods currently used to address motion artifact include manual screening (visual inspection) and objective assessments of the scans. However, previously reported objective methods either cannot be applied on the reconstructed image or have not been tested for distal bone sites. Therefore, the purpose of the present study was to develop and validate motion artifact classifiers to quantify motion artifact in pQCT scans. Whether textural features could provide adequate motion artifact classification performance in 2 adolescent datasets with pQCT scans from tibial and radial diaphyses and epiphyses was tested. The first dataset was split into training (66% of sample) and validation (33% of sample) datasets. Visual classification was used as the ground truth. Moderate to substantial classification performance (J48 classifier, kappa coefficients from 0.57 to 0.80) was observed in the validation dataset with the novel texture-based classifier. In applying the same classifier to the second cross-sectional dataset, a slight-to-fair (κ = 0.01–0.39) classification performance was observed. Overall, this novel textural analysis-based classifier provided a moderate-to-substantial classification of motion artifact when the classifier was specifically trained for the measurement device and population. Classification based on textural features may be used to prescreen obviously acceptable and unacceptable scans, with a subsequent human-operated visual classification of any remaining scans.

Background:Universal vitamin D supplementation is controversial. Preventative examinations and public health initiatives in former East Germany that included vitamin D prophylaxis for children were regulated by official recommendations and guidelines. The aim of this study is to analyse the impact of a standardised nationwide guideline for universal supplementation with 400 International Units (IU) vitamin D3/day during the first year of life on clinical and biochemical parameters and the influence of surrounding factors.Methods:This is a cross-sectional analysis looking at data from a field study of 3481 term-born children during their first year of life that was conducted in 1989.Results:There were no significant clinical signs of rickets. 25 hydroxyvitamin D (25(OH)D) (mean and SEM, total analyses n=572) after birth (n=28) was 36(7) nmol/L, at 1 month 64(4) nmol/L (n=70, p1500 U/L (95th percentile) in 3.6%. Participants were on breastmilk or vitamin D-free formula, with solids added from 6 months of age. There were seasonal variations in 25(OH)D levels with a rise during spring and autumn. Thus this analysis is unique as sun exposure and supplementation can be considered as the only vitamin D sources.Conclusions:We conclude that universal supplementation with 400 IU of vitamin D3 during the first year of life is safe and provides sufficient 25(OH)D levels in Germany.

The epidemic of allergic disease is a public health crisis, particularly for children in developed countries. Recognized effects of vitamin D in immune development have given credence to the hypothesis that changing patterns of human behavior associated with declining sunlight exposure may be linked to the rising immune and inflammatory diseases. Although data to support this are still limited and heterogeneous, vitamin D supplementation in early life is recommended to prevent vitamin D deficiency in many countries, raising important questions around safety and benefit for immune development and implications for allergic risk.This review article examines the evidence of the impact of in utero and postnatal vitamin D exposure on allergy risk in childhood. Evaluated are relevant studies from 2007 to June 2014.Information on the impact of vitamin D on rising rates of allergic diseases is largely based on observational studies with conflicting results. There is an urgent need to conduct well-designed randomized controlled trials to address the significant uncertainty in this field. Additionally, the effects of other potential immunomodulatory factors associated with sun exposure (such as UV light) need to be examined further.

Seasonality in glucose metabolism has been observed in adult populations, however, little is known of the associations between season and glucose metabolism in children. In this study, we examined whether markers of glucose metabolism (fasting glucose, insulin and HbA1c) varied by season in a paediatric population (6&ndash, 13 years of age) located in Perth (Western Australia, n = 262) with data categorised by weight. Linear regression was used to analyse the nature of the relationships between mean daily levels of terrestrial ultraviolet radiation (UVR) (prior to the day of the blood test) and measures of glucose metabolism. Fasting blood glucose was significantly lower in autumn compared to spring, for children in combined, normal and obese weight categories. Fasting insulin was significantly lower in autumn and summer compared to winter for individuals of normal weight. HbA1c was significantly higher in summer (compared with winter and spring) in overweight children, which was in the opposite direction to other published findings in adults. In children with obesity, a strong inverse relationship (r = &minus, 0.67, p = 0.002) was observed for fasting glucose, and daily terrestrial UVR levels measured in the previous 6 months. Increased safe sun exposure in winter therefore represents a plausible means of reducing fasting blood sugar in children with obesity. However, further studies, using larger paediatric cohorts are required to confirm these relationships.

Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher latitudes.We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development.By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age.At 3 (P .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D-supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/mThis study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.

Background: Rett syndrome is a severe genetic neurodevelopmental disorder mainly affecting females. The aim of this study was to describe pubertal development in a population-based cohort of females with Rett syndrome. Methods: To assess pubertal trajectory we used six waves of data provided by parents of girls and women, recruited through the Australian population-based Rett Syndrome Database. The age at which adrenarche, thelarche or menarche occurred was used as the parameter for time to event (survival) analysis. The relationships between BMI, mutation type and the trajectories were investigated, using Cox proportional hazards. Results: One quarter of girls reached adrenarche by 9.6 years, half by 11 years and three quarters by 12.6 years. Half reached menarche by 14 years (range 8–23). Being underweight was associated with later age at adrenarche, thelarche and menarche, while higher BMI (overweight) was associated with earlier onset. In general, girls with C-terminal deletions and early truncating mutations reached pubertal stages earlier and those with the p.R168X mutation reached them later. Conclusion: The pubertal course in Rett syndrome may be abnormal, sometimes with early adrenarche but delayed menarche. These features may be genotype dependent and may have varying relationships with growth and bone acquisition.

Previous research suggests prevalent vitamin D deficiency in pregnant women residing in South Australia and the Eastern Seaboard, however recent data from Perth, Western Australia (WA) is lacking. This cross-sectional study ofn=209 pregnant women (36–40 weeks of gestation, 84% white Caucasian) reports on the vitamin D (25[OH]D) status of a contemporary population of pregnant women in Perth, WA, with a focus on the relative contributions of supplemental vitamin D and ambient ultraviolet (UV) radiation to 25(OH)D levels. Mean (SD) season-adjusted 25(OH)D levels were 77.7 (24.6) nmol/l. The prevalence of vitamin D deficiency (25[OH]DPP