Zinc status, dietary zinc intake and metabolic risk in Australian children and adolescents; Nepean Longitudinal Study.

PURPOSE: Zinc is essential for normal growth and metabolism. We aimed to characterise the total and bioavailable dietary zinc intake and plasma zinc concentrations in healthy children, longitudinally, and to examine the association between plasma zinc concentrations, dietary zinc intake and cardiometabolic markers in the same cohort. METHODS: A secondary data analysis of a prospective cohort study, the Nepean Longitudinal Study, which followed an Australian birth cohort at ages 8 (n = 436) and 15 years (n = 290) collecting dietary, anthropometry and biochemistry data (plasma zinc, fasting glucose, insulin and lipid profile). Diet was assessed by a 3-day food record and a food frequency questionnaire at 8 and 15 years, respectively. Zinc bioavailability was determined by the phytate/zinc molar ratio. RESULTS: At 8 years, the median zinc intake was 7.84 mg (interquartile range 6.57-9.35) for boys and 7.06 mg (5.98-8.30) for girls. Three of 345 children reported inadequate absorbable zinc intake, and none reported inadequate total zinc intake. At 15 years, median zinc intake was 11.8 mg (9.41-14.8) for boys and 8.54 mg (6.76-10.7) for girls. The prevalence of inadequate intakes of absorbable zinc and total zinc was 19 and 29 %, respectively. Plasma zinc concentration was not correlated with dietary zinc intake, adiposity nor lipids at either time point, but it was inversely correlated with fasting glucose at 8 year and with insulin at 15 years. CONCLUSIONS: Australian children had an overall adequate zinc status. However, adolescents who reported suboptimal dietary zinc intakes were more likely to have raised insulin concentrations.

Stepped-wedge cluster randomised controlled trial to assess the effectiveness of an electronic medication management system to reduce medication errors, adverse drug events and average length of stay at two paediatric hospitals: a study protocol.

INTRODUCTION: Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS). The study will also investigate system impact on clinical work processes. METHODS AND ANALYSIS: A stepped-wedge cluster randomised controlled trial (SWCRCT) will measure changes pre-eMM and post-eMM system implementation in prescribing and medication administration error (MAE) rates, potential and actual ADEs, and average LOS. In stage 1, 8 wards within the first paediatric hospital will be randomised to receive the eMM system 1 week apart. In stage 2, the second paediatric hospital will randomise implementation of a modified eMM and outcomes will be assessed. Prescribing errors will be identified through record reviews, and MAEs through direct observation of nurses and record reviews. Actual and potential severity will be assigned. Outcomes will be assessed at the patient-level using mixed models, taking into account correlation of admissions within wards and multiple admissions for the same patient, with adjustment for potential confounders. Interviews and direct observation of clinicians will investigate the effects of the system on workflow. Data from site 1 will be used to develop improvements in the eMM and implemented at site 2, where the SWCRCT design will be repeated (stage 2). ETHICS AND DISSEMINATION: The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospitals Network and Macquarie University. Results will be reported through academic journals and seminar and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) 370325.

Liquid versus solid energy intake in relation to body composition among Australian children.

BACKGROUND: The debate about whether energy consumed in liquid form is more obesogenic than energy consumed in solid form remains equivocal. We aimed to evaluate the effects of liquid versus solid energy intake and different beverage types on changes in childhood adiposity. METHODS: Our analyses included 8-year-old Australian children (n = 158) participating in the Childhood Asthma Prevention Study. Dietary information was collected using three 24-h recalls at age 9 years. Multivariate linear regression was used to evaluate the effects of liquid versus solid energy intake and different beverage types on changes in body mass index (BMI) Z-score from ages 8 to 11.5 years (△BMIz(8-11.5y)) and percentage body fat (%BF) at age 11.5 years (%BF(11.5y)). Substitution models were used to evaluate the effects of substituting other beverage types for sugar-sweetened beverages (SSB). RESULTS: Liquid energy intake (1 MJ day(-1)) was more closely associated with both △BMIz(8-11.5y) (ß = 0.23, P = 0.02) and %BF(11.5y) (ß = 2.31%, P = 0.01) than solid energy intake (△BMIz(8-11.5y): ß = 0.12, P = 0.01 and %BF(11.5y): ß = 0.80%, P = 0.07). SSB consumption (100 g day(-1)) was directly associated with △BMIz(8-11.5y) (ß = 0.08, P = 0.02) and %BF(11.5y) (ß = 0.92%, P = 0.004),whereas diet drinks (100 g day(-1) ) were inversely associated with △BMIz(8-11.5y) (ß = 0.18, P = 0.02). Substitution of 100 g of SSB by 100 g of water or diet drink, but not other beverages, was inversely associated with both △BMIz(8-11.5y) and %BF(11.5y) (P < 0.01). CONCLUSIONS: Our findings indicate that liquid energy is more obesogenic than solid energy. In particular, SSB, but not other beverage types, are a significant predictor of childhood adiposity and replacing SSB with water can have long-term beneficial effects on childhood adiposity.

Waist-to-height ratio and cardiometabolic risk factors in adolescence: findings from a prospective birth cohort.

OBJECTIVE: To examine the associations between body mass index (BMI) and waist-to-height ratio (WHtR) measured in childhood and adolescence and cardiometabolic risk factors in adolescence. METHODS: Secondary data analysis of the Avon Longitudinal Study of Parents and Children, a population based cohort. Data from 2858 adolescents aged 15.5 (standard deviation 0.4) years and 2710 of these participants as children aged 7-9 years were used in this analysis. Outcome measures were cardiometabolic risk factors, including triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol, insulin, glucose and blood pressure at 15 years of age. RESULTS: Both BMI and WHtR measured at ages 7-9 years and at age 15 years were associated with cardiometabolic risk factors in adolescents. A WHtR ≥0.5 at 7-9 years increased the odds by 4.6 [95% confidence interval 2.6 to 8.1] for males and 1.6 [0.7 to 3.9] for females of having three or more cardiometabolic risk factors in adolescence. Cross-sectional analysis indicated that adolescents who had a WHtR ≥0.5, the odds ratio of having three or more cardiometabolic risk factors was 6.8 [4.4 to 10.6] for males and 3.8 [2.3 to 6.3] for females. The WHtR cut-point was highly specific in identifying cardiometabolic risk co-occurrence in male children and adolescents as well as female children (90 to 95%), but had poor sensitivity (17 to 53%). Similar associations were observed when BMI was used to define excess adiposity. CONCLUSIONS: WHtR is a simple alternative to age and sex adjusted BMI for assessing cardiometabolic risk in adolescents.

Functional characterization of a heterozygous GLI2 missense mutation in patients with multiple pituitary hormone deficiency.

CONTEXT: The GLI2 transcription factor is a major effector protein of the sonic hedgehog pathway and suggested to play a key role in pituitary development. Genomic GLI2 aberrations that mainly result in truncated proteins have been reported to cause holoprosencephaly or holoprosencephaly-like features, sometimes associated with hypopituitarism. OBJECTIVE: Our objective was to determine the frequency of GLI2 mutations in patients with multiple pituitary hormone deficiency (MPHD). DESIGN: Patients were selected from participants in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) program. Patients with mutations within established candidate genes were excluded. PATIENTS: A total of 165 patients with MPHD defined as GH deficiency and at least 1 additional pituitary hormone deficiency were studied regardless of the presence of extrapituitary clinical manifestations. MAIN OUTCOME MEASURES: Prevalence of GLI2 variations in MPHD patients was assessed and detailed phenotypic characterization is given. Transcriptional activity of identified GLI2 variants was evaluated by functional reporter assays. RESULTS: In 5 subjects, 4 heterozygous missense variants were identified, of which 2 are unpublished so far. One variant, p.R516P, results in vitro in a complete loss of protein function. In addition to GH deficiency, the carrier of the mutation demonstrates deficiency of thyrotrope and gonadotrope function, a maldescended posterior pituitary lobe, and polydactyly, but no midline defects. CONCLUSIONS: For the first time, we show that heterozygous amino acid substitutions within GLI2 may lead to MPHD with mild extrapituitary findings. The phenotype of GLI2 mutations is variable, and penetrance is incomplete. GLI2 mutations are associated with anterior pituitary hypoplasia, and frequently, ectopy of the posterior lobe occurs.

The prevalence of increased central adiposity in Australian school children 1985 to 2007.

The epidemic of obesity as measured by body mass index (BMI) maybe plateauing. However, studies using skin-fold and waist circumference measurements suggest that BMI may underestimate changes in fatness in children. In this study we examine changes in waist circumference and waist-to-height ratio (WHtR) in Australian children between 1985 and 2007, by undertaking secondary data analysis of three national data sets. The mean waist circumference z-score for boys increased from -0.02 (95% CI -0.05 to 0.01) in 1985, to 0.33 (0.26 to 0.40) in 1995 and 0.41 (0.35 to 0.47) in 2007 and was greater (P<0.001) than the increase in BMI z-score. The increase in mean waist circumference z-score for girls was greater (P<0.001) than boys and increased from -0.02 (0.05 to 0.01) in 1985, to 0.33 (0.26 to 0.41) in 1995 and to 0.57 (0.51 to 0.63) in 2007. The number of children with a WHtR ≥ 0.5 increased from 8.6% in 1985, to 13.6% in 1995 and 18.3% in 2007. Between 1985 and 2007 central adiposity increased at a faster rate than total adiposity, particularly in girls. The secular increase in waist circumference and WHtR is concerning as measures of central adiposity are associated with metabolic and cardiovascular risk.

Treatment of clinical insulin resistance in children: a systematic review.

The objective of this study was to evaluate the effectiveness of interventions aimed at improving clinical insulin resistance and/or pre-diabetes in children. This study is a systematic review and meta-analysis. Five electronic databases were searched for randomized controlled trials of at least 2-months' duration. The outcomes were fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI) and adverse outcomes. Four randomized controlled trials were identified. All compared the effect of 6 months of metformin plus or minus lifestyle intervention with placebo plus or minus lifestyle intervention. After pooling results from three trials, the mean difference after 6 months favoured the intervention with a statistically significant mean decrease in fasting insulin, HOMA-IR and BMI of 9.6 µU mL(-1) (95% confidence interval [CI]: 6.3, 13.0 µU mL(-1) ; I(2) = 76%), 2.7 (95% CI: 1.7, 3.6; I(2) = 74%) and 1.7 kg m(-2) (95% CI: 1.1, 2.3 kg m(-2) ; I(2) = 75) respectively. Mild gastrointestinal symptoms were reported in 19% (2-29%; median and range) of participants taking metformin. Metformin improves markers of insulin sensitivity and reduces BMI in children and adolescents with clinical insulin resistance or pre-diabetes. Stronger evidence from high-quality studies of longer duration and larger sample size are required before clinical conclusions about the optimal treatment protocol in this population can be drawn.

Clinical research in adolescents: challenges and opportunities using obesity as a model.

Adolescent medicine is relatively young, compared to paediatric or adult medicine. Descriptive and observational studies have dominated the adolescent literature, including those studies published in the International Journal of Obesity. In addition, many studies have combined child and adolescent age groups, making it difficult to determine adolescent-specific outcomes. It is important that high quality intervention studies in adolescents occur. Adolescence is a time of extraordinary plasticity. Habits, attitudes and physical morbidity that develop during adolescence set up trajectories that have a profound influence on health and wellbeing for the long term. Overweight and obesity are an excellent example of the need for high quality intervention studies and yet in the last two decades there have been very few randomized, controlled trials of overweight and obesity management in adolescents. There are a number of complexities in adolescent research that create additional challenges to those that accompany any clinical research. These include recruitment and retention, issues around consent and confidentiality and the central role that parents play in supporting the research protocol. Pubertal stage is a potential confounder and needs to be accurately measured. This is certainly true for studies in overweight and obesity where excess adiposity influences pubertal and other hormones. The opportunities to undertake quality research in adolescents are likely to be enhanced by the use of novel approaches which acknowledge the unique features of adolescents and their world.

Waist-to-height ratio: a simple option for determining excess central adiposity in young people.

Waist circumference is recommended as a means of identifying people at risk of morbidity associated with central adiposity. Yet, there are no universally agreed cut-points to determine when a waist circumference is too large in young people. In this study we examined the relation between sex- and age-specific waist circumference cut-points, the waist-to-height ratio (WHtR) cut-point of <0.5 and cardiovascular disease (CVD) risk clustering in 164 young people, mean age 14.9+/-0.2 years (mean+/-s.d.). In total 19 (11.6%) of the sample were identified as having CVD risk clustering. These young people were significantly (P<0.001) heavier and had higher body mass index (BMI) and waist circumference z-scores compared to those without CVD risk clustering. The WHtR cut-point of 0.5 estimated CVD risk clustering to a similar extent to sex- and age-adjusted cut-points for waist circumference and BMI. Young people with excess central adiposity (WHtR> or =0.5) were 11 times (OR 11.4, P<0.001), more likely to have CVD risk clustering compared to those who did not have excess central adiposity. The WHtR has several advantages; it is easy to calculate, does not require sex- and age-specific centiles and as has been previously suggested, it is a simple message, easily understood by clinicians and families, to 'keep your waist circumference to less than half your height'.

Sex-specific developmental changes in muscle size and bone geometry at the femoral shaft.

INTRODUCTION: When expressed as a percentage of the average result in young adults, bone mineral content lags behind bone length before puberty. Even though this observation has led to speculation about bone fragility in children, such relationships could simply be due to scaling effects when measures with different geometrical dimensions are compared. METHODS: The study population comprised 145 healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to determine femur length, bone mineral content, cortical bone mineral density, cross-sectional bone geometry (bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index) and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. Sex-differences were also assessed before and after functionally adjusting variables for femur length and weight or muscle size. RESULTS: In prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area

Growth hormone for children with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is an uncommon but important condition. Growth retardation, one of the complications of CKD, is of concern to families. Recombinant human growth hormone (rhGH) treatment has been used to help short children with CKD attain a height more in keeping with their age group. However, there are concerns that rhGH may have an adverse effect on the preservation of native kidney function, predispose to acute rejection in kidney transplant recipients, and cause benign intracranial hypertension and slipped capital femoral epiphysis. OBJECTIVES: To evaluate the benefits and harms of rhGH treatment in children with CKD. SEARCH STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, article reference lists and through contact with local and international experts in the field. Date of most recent search: July 2005 SELECTION CRITERIA: RCTs were included if they were carried out in children aged 0-18 years, diagnosed with CKD, who were pre-dialysis, on dialysis or post-transplant; if they compared rhGH treatment with placebo/no treatment or two doses of rhGH treatments; and if they included height outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for methodological quality and extracted data from eligible trials. Data was pooled using a random effects model with calculation of weighted mean difference (MD) for continuous outcomes and relative risk (RR) for categorical outcomes with 95% confidence intervals (CI). MAIN RESULTS: Fifteen RCTs (629 children) were identified. Treatment with rhGH (28 IU/m(2)/wk) resulted in a significant increase in height standard deviation score (SDS) at one year (MD 0.78 SDS, 95% CI 0.52 to 1.04), and a significant increase in height velocity at six months (MD 2.85 cm/6 mo, 95%CI 2.22 to 3.48) and one year (MD 3.80 cm/y, 95%CI 3.20 to 4.39). Compared to the 14 IU/m(2)/wk group, there was a 1.34 cm/y (0.55 to 2.13) increase in height velocity in the 28 IU/m(2)/wk group. The frequency of reported side effects of rhGH were similar to that of the control group. AUTHORS' CONCLUSIONS: One year of 28 IU/m(2)/wk rhGH in children with CKD resulted in a 3.80 cm/y increase in height velocity above that of untreated patients. Trials were too short to determine if continuing treatment resulted in an increase in final adult height.

Soft drink consumption and excess weight gain in Australian school students: results from the Nepean study.

We studied the relation between soft drink/cordial (a sweet, flavoured, concentrated syrup that is mixed with water to taste), fruit juice/drink and milk consumption in mid-childhood, and body mass index (BMI) status in early adolescence in a contemporary Australian cohort. In 1996/7, 268 children (136 males) were recruited from western Sydney at baseline (mean+/-s.d.: 7.7+/-0.6 years), and at follow-up 5 years later (13.0+/-0.2 years). Height and weight were measured at both time periods and overweight and obesity defined using the International Obesity TaskForce criteria. Beverage consumption was calculated from a 3-day food record at baseline. Median carbohydrate intake from soft drink/cordial was 10 g higher (P=0.002) per day in children who were overweight/obese at follow-up compared to those who had an acceptable BMI at both baseline and follow-up. Intakes of soft drink/cordial in mid-childhood, but not fruit juice/fruit drink and milk, were associated with excess weight gain in early adolescence.

The re-emerging burden of rickets: a decade of experience from Sydney.

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Prevention and treatment of osteoporosis in chronically ill children.

Osteoporosis secondary to chronic disease in children has emerged as a major health issue. As the severity of a child's illness increases, so too does the number of factors affecting their bone health. Determinants of bone health in children include level of mobility, exposure to osteotoxic medication, nutritional status, calcium and vitamin D intake, chronic inflammation and pubertal development.

Increasing central adiposity: the Nepean longitudinal study of young people aged 7-8 to 12-13 y.

BACKGROUND: Estimates of the prevalence of overweight and obesity in young people are typically based on body mass index (BMI). However, BMI may not indicate the level of central adiposity. Waist circumference has therefore been recommended to identify young people at risk of morbidity associated with central adiposity. OBJECTIVE: To investigate (a) change in total and central adiposity between 7-8 and 12-13 y (b) agreement between classifying young people as overweight or obese based on total adiposity and central adiposity, and (c) risk factors associated with the development of total and central adiposity. DESIGN: Anthropometric measurements were taken on 342 children in 1996/97 and 5 y later. Risk factors examined included birth weight, physical activity, TV viewing, pubertal status, parental adiposity, diet and socio-economic status. RESULTS: Between 7-8 and 12-13 y indices of central adiposity increased more than total adiposity; waist circumference z-score increased by (mean+/-s.d.) 0.74+/-0.92 and BMI z-score increased by 0.18+/-0.67. At 12-13 y there was moderate agreement between the two measures of adiposity (weighted kappa=0.64). However, waist circumference identified a greater number of young people as overweight or obese compared to BMI (41.2 vs 29.3%, P<0.001). Adiposity status at 7-8 y, maternal obesity, and pubertal stage were the strongest predictors of BMI status at 12-13 y. Risk factors associated with increased central adiposity were similar. CONCLUSIONS: Overweight and obesity, as measured by waist circumference, is a bigger problem than is currently assessed by BMI. Targeting known risk factors for total adiposity may be an appropriate strategy for preventing increased central adiposity.

Cyclic bisphosphonate therapy in osteogenesis imperfecta type V.

The clinical and radiographic features and management of a young person with recently delineated Osteogenesis Imperfecta Type V is described. A female aged 9 years presented with a history of multiple fractures since 3 years of age and bilateral dislocation of the elbows from infancy. She was commenced on a low dose frequent regimen of cyclic intravenous pamidronate, which resulted in progressive improvement in bone density, reduced fracture frequency and remission of symptoms of osteoporosis.

Features of the metabolic syndrome after childhood craniopharyngioma.

Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.

A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging.

In upper extremity bones, a sexual dimorphism exists in the development of periosteal and endocortical bone surfaces during growth. Little is known about developmental patterns of bone geometry at weight-bearing bones like the femur. Using MRI and dual energy X-ray absorptiometry (DXA), this study assessed the differences in mid-femoral total (TA), cortical (CA) and medullary areas (MA), cortical thickness, and cortical density (BMD(compartment)) between prepuberty and young adulthood in 145 healthy subjects (94 females) 6 to 25 years old. Additionally, agreement between mid-femoral total bone volume (TV) measurements by DXA and MRI were investigated. In both sexes, TA, CA, MA, and cortical thickness were significantly larger in adults compared to prepubertal subjects (P < 0.001), and males had greater values than females. This sex difference persisted for TA, CA, and cortical thickness (P < 0.05), but not MA, after adjusting for femur length and weight. Mean (SD) cortical BMD increased from 1.05 (0.07) and 1.09 (0.10) g/cm(3) in prepubertal children to 1.46 (0.14) and 1.42 (0.1) g/cm(3) in young adults, females and males, respectively (P < 0.001). TV measurements by DXA were significantly greater than by MRI (P < 0.001) in young adults. In conclusion, periosteal and endocortical expansion and increasing cortical BMD are the growth processes found at the mid-femur in both sexes. Our findings contrast to that in upper extremity bones, where MA is constant in females during growth. The difference in femoral bone development may be due to higher strains caused by weight bearing and genetic factors. DXA, in contrast to MRI, is inaccurate in the determination of mid-femoral TV measures.