Aris Siafarikas

Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement.

The recommended level for serum 25‐hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10–20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. Vitamin D deficiency can be treated with daily low‐dose vitamin D supplements, although barriers to adherence have been identified. High‐dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D3 daily for at least the first year of life. There is increasing evidence of an association between low vitamin D and a range of non‐bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.

Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes

OBJECTIVE To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. RESULTS Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2–19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8–18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01–9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62–74) vs. 96 (87–115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = −0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA1c. Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. CONCLUSIONS The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

Clinical guidelines for management of bone health in Rett syndrome based on expert consensus and available evidence

Objectives We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. Results Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. Conclusion A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.

Factors associated with the performance of a blood-based interferon-γ release assay in diagnosing tuberculosis

Background Indeterminate results are a recognised limitation of interferon-γ release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common co-morbidities were associated with IGRA performance in an unselected cohort of resettled refugees. Methods A retrospective cross-sectional study of refugees presenting for their post-resettlement health assessment during 2006 and 2007. Refugees were investigated for prevalent infectious diseases, including TB, and for common nutritional deficiencies and haematological abnormalities as part of standard clinical screening protocols. Tuberculosis screening was performed by IGRA; QuantiFERON-TB Gold in 2006 and QuantiFERON-TBGold In-Tube in 2007. Results Complete data were available on 1130 refugees, of whom 573 (51%) were children less than 17 years and 1041 (92%) were from sub-Saharan Africa. All individuals were HIV negative. A definitive IGRA result was obtained in 1004 (89%) refugees, 264 (26%) of which were positive; 256 (97%) had LTBI and 8 (3%) had TB disease. An indeterminate IGRA result was obtained in 126 (11%) refugees (all failed positive mitogen control). In multivariate analysis, younger age (linear OR  = 0.93 [95% CI 0.91–0.95], P<0.001), iron deficiency anaemia (2.69 [1.51–4.80], P = 0.001), malaria infection (3.04 [1.51–6.09], P = 0.002), and helminth infection (2.26 [1.48–3.46], P<0.001), but not vitamin D deficiency or insufficiency, were associated with an indeterminate IGRA result. Conclusions Younger age and a number of common co-morbidities are significantly and independently associated with indeterminate IGRA results in resettled predominantly African refugees.

Symptoms of depression and anxiety in youth with type 1 diabetes: A systematic review and meta-analysis

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.

Randomised controlled trial analysing supplementation with 250 versus 500 units of vitamin D3, sun exposure and surrounding factors in breastfed infants

Background The rate of non-compliance with vitamin D supplementation is as high as 45%. This is why randomised controlled trials are needed to analyse the response to low doses of vitamin D3. Objective (1) To compare supplementation with 250 versus 500 units of vitamin D3 and (2) to analyse sun exposure time/ultraviolet B (UVB) exposure during the first 6 weeks of life. Design 40 breastfed infants (skin photo-types I, II) were recruited in Berlin, Germany (52.5°N), during summer (n=20) and winter (n=20) and randomised into equal groups on either 250 or 500 units of vitamin D3 per day. Outcome measures were: parameters of vitamin D and bone metabolism at delivery and 6 weeks later, sun exposure time, UVB dosimetry and surrounding factors including maternal diet. Results At delivery 25-hydroxy vitamin D levels were insufficient: 68 (53–83) nmol/l in each group. 6 weeks later levels were sufficient: 139 (114–164) nmol/l on 250 units of vitamin D3 per day and 151 (126–176) nmol/l on 500 units/day. There was no seasonal variation. Daily sun exposure time was 0.4–3.5 h and higher in summer. UVB exposure was 0.01–0.08 minimal erythema dose/day. Calcium levels were within normal. Conclusions In Berlin, Germany, supplementation with 250 units of vitamin D3 is sufficient for breastfed infants during their first 6 weeks of life in summer and winter. UVB exposure is very low throughout the year.

Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0+/-1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA(1c) (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4+/-1.7 mmol/l) and 120 (5.0+/-1.1 mmol/l) min increased significantly relative to baseline (4.1+/-0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1+/-21.3 m-units/l) and 120 (34.9+/-23.6 m-units/l) min compared with baseline (4.7+/-4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.

Sterile abscess formation associated with depot leuprorelin acetate therapy for central precocious puberty

We describe a case of an 8 year old girl with central precocious puberty. She was commenced on 3 monthly intramuscular depot Leuprorelin acetate therapy, as a result of which she developed sterile abscesses. She was converted to daily subcutaneous Leuprorelin acetate therapy with no recurrence of the abscesses. The possible mechanisms for this reaction are described in the article.

In utero and postnatal vitamin D exposure and allergy risk.

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Pubertal trajectory in females with Rett syndrome: A population-based study

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.