Retrospective Examination of Peripubertal Return for Patients of Western Australia's Gender Diversity Service.

Purpose: Children far in advance of pubertal development may be deferred from further assessment for gender-affirming medical treatment until nearer puberty. It is vital that returning peripubertal patients are seen promptly to ensure time-sensitive assessment and provision of puberty suppression treatment where appropriate. This study investigates (1) how many referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital are deferred due to prepubertal status; and (2) how many deferred patients return peripubertally. Methods: A retrospective review of all closed referrals to the service was conducted to determine the frequency of prepubertal deferral and peripubertal re-referral. Results: Of 995 referrals received (2014 to 2020), 552 were closed. The reason for closure was determined for 548 referrals (99.3%). Prepubertal status was the second-most frequent reason for closure, and the most frequent for birth-registered males. Twenty-five percent of all deferred prepubertal patients returned peripubertally, before audit closure. A greater return frequency (55.6%) was estimated for those older than 13 years at audit closure. Conclusion: High rates of prepubertal referral indicate the importance of pediatric gender services in providing information, advice, and reassurance to concerned families. With increasing service demand, high rates of return peripubertally have implications for service planning to ensure that returning peripubertal patients are seen promptly for time-sensitive care. Frequency of peripubertal re-referral cannot, however, speak to the stability of trans identity or gender incongruence from childhood to adolescence. Clinics advising prepubertal deferral must proactively plan to ensure that sufficient clinical resources are reserved for this purpose.

Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort.

Importance: Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking. Objective: To determine the frequency of reidentification and explore associated characteristics in a pediatric gender clinic setting. Design, Setting, and Participants: This retrospective cohort study examined all referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital between January 1, 2014, and December 31, 2020. The Gender Diversity Service is the sole statewide specialist service in Western Australia that provides children and adolescents up to age 18 years with multidisciplinary assessment, information, support, and gender-affirming medical care. All closed referrals for this study were audited between May 1, 2021, and August 8, 2022. Exposure: Reidentification with birth-registered sex. Main Outcomes and Measures: The number of referrals closed due to reported reidentification with birth-registered sex was determined, as well as descriptives and frequencies of patient demographics (age, birth-registered sex), informant source, International Statistical Classification of Diseases, Tenth Revision gender-related diagnoses, pubertal status, any gender-affirming medical treatment received, and whether subsequent re-referrals were received. Results: Of 552 closed referrals during the study period, a reason for closure could be determined for 548 patients, including 211 birth-registered males (mean [SD] age, 13.88 [2.00] years) and 337 birth-registered females (mean [SD] age, 15.81 [2.22] years). Patients who reidentified with their birth-registered sex comprised 5.3% (29 of 548; 95% CI, 3.6%-7.5%) of all referral closures. Except for 2 patients, reidentification occurred before or during early stages of assessment (93.1%; 95% CI, 77.2%-99.2%). Two patients who reidentified with their birth-registered sex did so following initiation of puberty suppression or gender-affirming hormone treatment (1.0% of 196 patients who initiated any gender-affirming medical treatment; 95% CI, 0.1%-3.6%). Conclusions and Relevance: These findings from a pediatric gender clinic audit indicate that a small proportion of patients, and a very small proportion of those who initiated medical gender-affirming treatment, reidentified with their birth-registered sex during the study period. Longitudinal follow-up studies, including qualitative self-report, are required to understand different pathways of gender identity experience.

The Natural History of Symptomatic Fractures in Children and Adolescents with Osteogenesis Imperfecta Type 1: A Cohort Study from Western Australia.

The fracture experience of children and adolescents with osteogenesis imperfecta (OI) type 1 is not well described in the literature. We present data on symptomatic long bones and axial skeleton fractures of all patients aged 0 to 18 years with OI type 1 seen at a specialized bone clinic in Western Australia in the period 2008 to 2020 using a retrospective chart review method. The cohort consisted of 44 patients (21 males, 23 females). Median (interquartile range [IQR]) age was 11.3 (6.2 to 17) years, giving a total of 520 patient-years in the study during which 197 fractures were experienced. The mean fracture rate was 379 fractures per 1000 patient-years (95% confidence interval [CI]: 310 to 440); however, the experience for fractures varied from ≤1 fracture in 23% (n = 10) to two to 20 in 77% (n = 34) of the cohort. Twenty-one patients (48.5%) received bisphosphonates during the study period. In logistic regression, age, but not sex or family history of OI, was a significant predictor of fracture risk. The highest total fracture rate was observed in the age group 0 to <3 years at 469 fractures/1000 patient-years, which declined to 140 fractures/1000 patient-years in the age group 15 to 18 years. The lower limbs were the site of 49.7% of all fractures. The highest rate for lower limb fracture was in the age group 0 to <3 years at 331 fractures/1000 patient-years, decreasing to 0 fractures/1000 patient-years in the age group 15 to 18 years. Upper limb fracture rates increased from 100 fractures/1000 patient-years in the 0 to <3 years age group to 307 fractures/1000 patient-years in the 9 to <12 years age group and then declining to 70 fractures/1000 years in the 15 to 18 years age group. In pediatric patients with OI type 1, fracture risk is highest in early life, especially in the lower limbs. Multidisciplinary care of children with OI should have a particular focus on strategies to prevent these fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Prevalence and characteristics of paediatric X-linked hypophosphataemia in Australia and New Zealand: Results from the Australian and the New Zealand Paediatric Surveillance Units survey.

BACKGROUND: X-linked hypophosphataemia (XLH) is the most common heritable form of rickets. Prevalence data varies across the literature between 1 in 20,000 and 1 in 200,000 per population. METHODS: Australian and New Zealand Paediatric Surveillance Units collected cross-sectional data from paediatricians on existing cases to estimate prevalence and characteristics of paediatric XLH in Australia and New Zealand. RESULTS: Seventy-five cases in Australia and 18 cases in New Zealand were identified. Estimated minimum prevalence based on these cases was 1.33 (1.04-1.66) per 100,000 and 1.60 per 100,000 (95%CI 0.97-2.58) in Australia and New Zealand respectively, with actual prevalence likely higher due to incomplete ascertainment. Despite a family history in most cases, delayed diagnosis was common, with 49 % diagnosed after 2 years of age. Delayed diagnosis was more common in sporadic versus familial cases. Most common clinical characteristics included leg bowing (89 %), bone and joint pain (68 %), abnormal gait (57 %) and short stature (49 %). There was a significant burden of orthopaedic disease and surgeries and a high rate of complications of nephrocalcinosis and hyperparathyroidism (32 % and 20 % respectively). Additionally, while guidelines stress the importance of multidisciplinary care, many did not have access to recommended health professionals, with only 3 % seeing a psychologist and 68 % seeing a dentist. This is despite the high psychological burden of XLH and a significant proportion (41 %) of this cohort having dental issues (tooth abscess, dental capping, tooth extraction). There were two cases from NZ without data available. Of the 91 cases with data collected, 46 % were on burosumab therapy. Consistent with clinical trials, those on burosumab had a higher serum phosphate levels (p < 0.001) at most recent follow-up. Three cases reported cancellation of orthopaedic surgery due to improvement in lower limb deformity after commencement of burosumab. CONCLUSION: These data describe the multisystem burden of disease for children with XLH with care impacted by delayed diagnosis and a lack of access to many health professionals, especially psychological support.

Potential immunological effects of gender-affirming hormone therapy in transgender people - an unexplored area of research.

There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19). Oestrogen and testosterone have immune-modulatory properties, and it is likely that these contribute to the sexual dimorphism of the immune system. There are also important immune-related genes located on the X chromosome, such as toll-like receptor (TLR) 7/8; and the mosaic bi-allelic expression of such genes may contribute to the state of immune hyperactivation in cis females. The scientific literature strongly suggests that sex-based differences in the functioning of the immune system are related to both X-linked genes and immune modulation by sex hormones. However, it is currently not clear how this impacts transgender (trans) people receiving gender-affirming hormonal therapy. Moreover, it is estimated that in Australia, at least 2.3% of adolescents identify as trans and/or gender diverse, and referrals to specialist gender-affirming care are increasing each year. Despite the improving social awareness of trans people, they remain chronically underrepresented in the scientific literature. In addition, a small number of case studies describe new onset autoimmune disorders in adult trans females following oestrogen use. However, there is currently minimal long-term research with an immunological focus on trans people. Therefore, to ensure the positive health outcomes of trans people, it is crucial that the role of sex hormones in immune modulation is investigated further.

Pre- and Postnatal Vitamin D Status and Allergy Outcomes in Early Childhood.

The dramatic increase in the prevalence of allergic disease in recent decades reflects environmental and behavioural changes that have altered patterns of early immune development. The very early onset of allergic diseases points to the specific vulnerability of the developing immune system to environmental changes and the development of primary intervention strategies is crucial to address this unparalleled burden. Vitamin D is known to have immunomodulatory functions. While allergic disease is multifactorial, associations with reduced sunlight exposure have led to the hypothesis that suboptimal vitamin D levels during critical early periods may be one possible explanation. Interventions to improve vitamin D status, especially in early life, may be the key to allergic disease prevention.

Ten year analysis of the clinic profile of the tertiary paediatric endocrine service in Western Australia.

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.

Clinical practice guidelines for paediatric X-linked hypophosphataemia in the era of burosumab.

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.

Physical activity estimated by osteogenic potential and energy expenditure has differing associations with bone mass in young adults: the raine study.

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 (ß = 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 (ß = 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.

The Benefits to Bone Health in Children and Pre-School Children with Additional Exercise Interventions: A Systematic Review and Meta-Analysis.

OBJECTIVE: Determine if exercise interventions, beyond what is already provided to children and preschool children, improve bone health and reduce fracture incidence. DESIGN: Systematic review and meta-analysis reported using the PRISMA guidelines. Certainty of evidence was assessed using GRADE recommendations. DATA SOURCES: Five electronic databases were searched for records: PUBMED; CINAHL; CENTRAL; SPORTDiscus; Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised, quasi-randomised and non-randomised controlled trials (including cluster-randomised) assessing the impact of additional exercise interventions (e.g., increased physical education classes or specific jumping programs) on bone health in children (6-12 years) and pre-school children (2-5 years) without dietary intervention. RESULTS: Thirty-one records representing 16 distinct clinical trials were included. Dual-energy X-ray Absorptiometry (DXA) and/or peripheral Quantitative Computed Tomography (pQCT) were used to quantify bone health. Increased femoral neck bone mineral content in children with additional exercise interventions (n = 790, SMD = 0.55, 95% CI = 0.01 to 1.09) was reported, however this was not significant following sensitivity analysis. Other DXA and pQCT measures, as well as fracture incidence, did not appear to significantly differ over time between intervention and control groups. No studies reported adverse events. Studies failed to report all domains within the TIDieR checklist. All studies were at high risk of bias using the Cochrane RoB Tool 2.0. The certainty of the evidence was very low. CONCLUSIONS: The addition of exercise interventions, beyond what is provided to children, does not appear to improve DXA and pQCT measures of bone health. The effect of additional exercise interventions on bone health in pre-school children is largely unknown. Future trials should ensure adherence is clearly reported and controlled for within analysis as well as including reports of adverse events (e.g., apophysitis) that occur due to increased exercise interventions.

Peri-operative steroid management in the paediatric population.

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.

The Influence of Sunlight Exposure and Sun Protecting Behaviours on Allergic Outcomes in Early Childhood.

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.

Randomized Controlled Trial Evaluating the Use of Zoledronic Acid in Duchenne Muscular Dystrophy.

CONTEXT: Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss. OBJECTIVE: To investigate use of zoledronic acid (ZA) in DMD in improving BMD. METHODS: Two 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. RESULTS: At 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. CONCLUSION: ZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.

Impact of a multimodal exercise program on tibial bone health in adolescents with Development Coordination Disorder: an examination of feasibility and potential efficacy.

OBJECTIVES: Developmental coordination disorder (DCD) compromises bone health purportedly due to lower levels of physical activity. The potential of an exercise intervention to improve bone health parameters in adolescents with DCD has not previously been studied. This study thus aimed to determine the impact of a multimodal exercise intervention on bone health in this population at-risk of secondary osteoporosis. METHODS: Twenty-eight adolescents (17 male, 11 female) aged between 12-17 years (Mage=14.1) with DCD participated in a twice weekly, 13-week generalised multimodal exercise intervention. Peripheral quantitative computed tomography scans of the tibia (4% and 66%) were performed over a six month period. Generalised estimating equations were used to examine the impact of fitness measures on bone parameters over time. RESULTS: An overall improvement trend was observed for bone health, with significant increases at the 66% tibial site for bone mass (4.12% increase, dcohen=0.23, p=0.010) and cortical area (5.42% increase, η2 =12.09, p=0.014). Lower body fitness measures were significantly associated with improvements in bone health parameters, tempered by the degree of motor impairment. CONCLUSION: A multimodal exercise intervention may be effective in improving bone health of adolescents with DCD. Given the impact of motor impairments, gains may be greater over an extended period of study.

Biological basis of bone strength: anatomy, physiology and measurement.

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.

Benefits of powered standing wheelchair devices for adolescents with Duchenne muscular dystrophy in the first year of use.

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.

In "High-Risk" Infants with Sufficient Vitamin D Status at Birth, Infant Vitamin D Supplementation Had No Effect on Allergy Outcomes: A Randomized Controlled Trial.

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 "hereditary risk" 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 "high-risk" infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36-40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥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 "allergy high-risk" 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.

Global consensus on nutritional rickets: Implications for Australia.

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.

In infants with sufficient vitamin D status at birth, vitamin D supplementation does not impact immune development.

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 naïve 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 (FcεR1) 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.