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Aim: This study examined whether the parents of children who were overweight at two and five years of age perceived their children as being too heavy and related the findings to sociodemographic factors., Methods: The data collection included parental questionnaires and anthropometric data from a longitudinal birth cohort of 2666 children born in the south-west region of Sweden in 2007-2008., Results: We found that 14.9 and 11.8% of the children were considered overweight or obese at the age of two and five, but 96.4 and 87.1% of their parents perceived their weight to be just about right at these ages. The difference was statistically significant (p < 0.001). Parents who were overweight themselves and had a low educational level were associated with a higher probability of misperception: at two years of age, the odds ratio was 2.75 (95% confidence interval 1.80-4.21), and at the age of five, it was 1.92 (1.24-2.97)., Conclusion: Most parents did not perceive that their overweight children weighed too much, but their judgement improved as the child got older. Parents who were overweight or had a low educational level were more likely to misperceive their child's weight. Health Care professionals need to be aware of this gap in perception., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy., Methods: Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores)., Results: At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age., Conclusions: Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.

Lifestyle factors and behaviours are adopted very early in life and tend to persist throughout life. Considering that the parents are the primary gatekeepers for their child's health, there is a need to gain more knowledge and deeper understanding about what causes parents to act and react in order for early preventive efforts to have any effect. The aim was to explore the parental views and considerations concerning 'child health' among parents with infants 8-10 months old. The sample was strategic and 16 parents (aged 23-41) were recruited from three child health centres in Sweden. Open-ended interviews were conducted and a qualitative, manifest content analysis approach was utilized. The parents described the subject 'child health' as a large, multifaceted concept. Three categories emerged during data analysis: developing a sixth sense, being affected by perceptions and believing health and ill health as a continuum. The parents perceived food and feeding issues as one of the most worrying aspects and a significant indicator of 'child health'. In order to meet the parents on their turf, the 'healthy health message' conveyed needs to take the parental perspective into consideration rather than attempting to educate the parents from predetermined assumption, belief and values.

Intense droughts combined with increased temperatures are one of the major threats to forest persistence in the 21st century. Despite the direct impact of climate change on forest growth and shifts in species abundance, the effect of altered demography on changes in the composition of functional traits is not well known. We sought to (1) quantify the recent changes in functional composition of European forests; (2) identify the relative importance of climate change, mean climate and forest development for changes in functional composition; and (3) analyse the roles of tree mortality and growth underlying any functional changes in different forest types. We quantified changes in functional composition from the 1980s to the 2000s across Europe by two dimensions of functional trait variation: the first dimension was mainly related to changes in leaf mass per area and wood density (partially related to the trait differences between angiosperms and gymnosperms), and the second dimension was related to changes in maximum tree height. Our results indicate that climate change and mean climatic effects strongly interacted with forest development and it was not possible to completely disentangle their effects. Where recent climate change was not too extreme, the patterns of functional change generally followed the expected patterns under secondary succession (e.g. towards late-successional short-statured hardwoods in Mediterranean forests and taller gymnosperms in boreal forests) and latitudinal gradients (e.g. larger proportion of gymnosperm-like strategies at low water availability in forests formerly dominated by broad-leaved deciduous species). Recent climate change generally favoured the dominance of angiosperm-like related traits under increased temperature and intense droughts. Our results show functional composition changes over relatively short time scales in European forests. These changes are largely determined by tree mortality, which should be further investigated and modelled to adequately predict the impacts of climate change on forest function., (© 2017 John Wiley & Sons Ltd.)

Aim: To study the electrophysiological changes in relation to fundus morphology in moderate-to-late preterm (MLP) children with no previous history of retinopathy of prematurity., Methods: Visual acuity (VA), refraction and fundus variables measured by optical coherence tomography, pattern reversal visual evoked potentials and full-field electroretinography (ff-ERG) were obtained from 22 twelve-year-old MLP children (11 male, 11 female) and 21 full-term controls., Results: There were no significant differences between the MLP and control groups in VA, refraction or optic disc parameters. There was a trend for thinner papillary retinal nerve fibre layer in the MLP group. Visual evoked potential amplitudes (P100) were lower in the MLP group than in controls, that is, right eye p=0.0027, left eye p=0.0037. No differences in latencies were found. After Bonferroni adjustment for multiple testing, no ff-ERG differences were noted between MLP and controls. Lower gestational age was correlated with smaller light-adapted 3.0 b-wave amplitudes (p=0.0076, r=0.565)., Conclusions: Our results indicate that moderate premature birth may affect visual evoked potential amplitudes without clear retinal structural changes in MLP children at 12 years of age., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Severe obesity in adolescence is associated with reduced life expectancy and impaired quality of life. Long-term benefits of conservative treatments in adolescents are known to be modest, whereas short-term outcomes of adolescent bariatric surgery are promising. We aimed to compare 5-year outcomes of adolescent surgical patients after Roux-en-Y gastric bypass with those of conservatively treated adolescents and of adults undergoing Roux-en-Y gastric bypass, in the Adolescent Morbid Obesity Surgery (AMOS) study., Methods: We did a nationwide, prospective, non-randomised controlled study of adolescents (aged 13-18 years) with severe obesity undergoing Roux-en-Y gastric bypass at three specialised paediatric obesity treatment centres in Sweden. We compared clinical outcomes in adolescent surgical patients with those of matched adolescent controls undergoing conservative treatment and of adult controls undergoing Roux-en-Y gastric bypass. The primary outcome measure was change in BMI over 5 years. We used multilevel mixed-effect regression models to assess longitudinal changes. This trial is registered with ClinicalTrials.gov, number NCT00289705., Findings: Between April, 2006, and May, 2009, 100 adolescents were recruited to the study, of whom 81 underwent Roux-en-Y gastric bypass (mean age 16·5 years [SD 1·2], bodyweight 132·8 kg [22·1], and BMI 45·5 kg/m 2 [SD 6·1]). 80 matched adolescent controls and 81 matched adult controls were enrolled for comparison of outcomes. The change in bodyweight in adolescent surgical patients over 5 years was -36·8 kg (95% CI -40·9 to -32·8), resulting in a reduction in BMI of -13·1 kg/m 2 (95% CI -14·5 to -11·8), although weight loss less than 10% occurred in nine (11%). Mean BMI rose in adolescent controls (3·3 kg/m 2 , 95% CI 1·1-4·8) over the 5-year study period, whereas the BMI change in adult controls was similar to that in adolescent surgical patients (mean change -12·3 kg/m 2 , 95% CI -13·7 to -10·9). Comorbidities and cardiovascular risk factors in adolescent surgical patients showed improvement over 5 years and compared favourably with those in adolescent controls. 20 (25%) of 81 adolescent surgical patients underwent additional abdominal surgery for complications of surgery or rapid weight loss and 58 (72%) showed some type of nutritional deficiency; health-care consumption (hospital attendances and admissions) was higher in adolescent surgical patients compared with adolescent controls. 20 (25%) of 81 adolescent controls underwent bariatric surgery during the 5-year follow-up., Interpretation: Adolescents with severe obesity undergoing Roux-en-Y gastric bypass had substantial weight loss over 5 years, alongside improvements in comorbidities and risk factors. However, gastric bypass was associated with additional surgical interventions and nutritional deficiencies. Conventional non-surgical treatment was associated with weight gain and a quarter of patients had bariatric surgery within 5 years., Funding: Swedish Research Council; Swedish Governmental Agency for Innovation Systems; National Board of Health and Welfare; Swedish Heart and Lung Foundation; Swedish Childhood Diabetes Foundation; Swedish Order of Freemasons Children's Foundation; Stockholm County Council; Västra Götaland Region; Mrs Mary von Sydow Foundation; Stiftelsen Göteborgs Barnhus; Stiftelsen Allmänna Barnhuset; and the US National Institute of Diabetes, Digestive, and Kidney Diseases (National Institutes of Health)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To investigate prevalence of neurodevelopmental disorders in children with obesity and to compare body mass index (BMI) and metabolic profile in the children., Methods: Seventy-six children (37 girls, 39 boys) were consecutively recruited from a university outpatient clinic specialized in severe obesity. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD) were assessed using interviews and questionnaires. Neurodevelopmental diagnoses were collected retrospectively in medical records., Results: BMI ranged between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4% ASD and ADHD was assigned, respectively. In addition, 25% screened positive for DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than girls without neurodevelopmental disorder (P = 0.006)., Conclusions: One third of children with obesity referred to specialist centers have a neurodevelopmental disorder including deviant motor skills, and these problems may deteriorate weight status. One fifth of the parents exhibit ADHD symptomatology which could partly explain the poor adherence by some families in obesity units. Future obesity therapy could benefit from incorporating a neurodevelopmental treatment approach., (© 2016 The Obesity Society.)

Purpose: To study ocular morphology and visual function in relation to general growth in moderate-to-late preterm (MLP) children., Methods: Visual acuity (VA), refraction, optic disc parameters, biometric values and anthropometric measures were obtained from 50 eight-year-old MLP and 43 full-term children. Macular parameters were examined by optical coherence tomography. Serum insulin-like growth factor I (IGF-I) levels were analysed at birth and at assessment and delta IGF-I was calculated., Results: Total macular volume was significantly less in MLP than in controls (both eyes p < 0.01). Macular volume correlated with head circumference (HCF) at assessment [right eye (RE) p = 0.002, r = 0.67; left eyes (LE) p = 0.01, r = 0.54] and refraction (both eyes p < 0.05, r = 0.4) in the MLP children. Furthermore, central retinal thickness correlated significantly with delta IGF-I (RE p = 0.03, r = -0.51, LE p = 0.006, r = -0.59) and refraction (both eyes p < 0.01, r = 0.5) and optic disc areas correlated with weight and height at assessment (all p < 0.05, r = 0.4). Total axial length correlated with HCF at assessment (both eyes p < 0.01, r = 0.5) and VA logMAR (both eyes p < 0.02, r = -0.4)., Conclusions: Macular volume was significantly less in MLP children than in controls examined at 8 years of age. General growth of children and IGF-I levels seem to be involved in development of ocular growth and morphology., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Neglecting tree size and stand structure dynamics might bias the interpretation of the diversity-productivity relationship in forests. Here we show evidence that complementarity is contingent on tree size across large-scale climatic gradients in Europe. We compiled growth data of the 14 most dominant tree species in 32,628 permanent plots covering boreal, temperate and Mediterranean forest biomes. Niche complementarity is expected to result in significant growth increments of trees surrounded by a larger proportion of functionally dissimilar neighbours. Functional dissimilarity at the tree level was assessed using four functional types: i.e. broad-leaved deciduous, broad-leaved evergreen, needle-leaved deciduous and needle-leaved evergreen. Using Linear Mixed Models we show that, complementarity effects depend on tree size along an energy availability gradient across Europe. Specifically: (i) complementarity effects at low and intermediate positions of the gradient (coldest-temperate areas) were stronger for small than for large trees; (ii) in contrast, at the upper end of the gradient (warmer regions), complementarity is more widespread in larger than smaller trees, which in turn showed negative growth responses to increased functional dissimilarity. Our findings suggest that the outcome of species mixing on stand productivity might critically depend on individual size distribution structure along gradients of environmental variation.

Background: A number of child/parental factors have been shown to be significant predictors of childhood overweight, although a better understanding of possible contextual influences of neighbourhood-level characteristics might provide new insights leading to tailored, targeted interventions. The aim of this study was to explore the impact of neighbourhood purchasing power and its relationship with other known risk factors related to childhood overweight in a prospective birth cohort., Methods: A prospective, population-based, birth-cohort study was conducted in south-western Sweden, comprising 2,666 infants born in 2007-2008. Childhood overweight was assessed by body mass index (BMI) data from follow-up examinations at four years of age (n = 2,026) and overweight defined according to the International Obesity Task Force. Using logistic regression analysis, the influential child/parental predictors were identified from the candidate predictors, viz. child's gender, as well as birth weight adjusted for gestational age and parental factors at recruitment, including maternal smoking status, maternal BMI (before pregnancy), paternal BMI and parental educational level. The children's residential parishes at follow-up were stratified by parish-level household purchasing power (<10 %, 10-19.9 %, 20-29.9 % and ≥30 % of all resident families with low purchasing power) and the "contextual" influence was analysed. In each such neighbourhood stratum, the adjusted overweight ratio (AOR), i.e. the ratio between the observed number of overweight children and the expected number, taking account of the influential child/parental predictors, was estimated., Results: The prevalence of overweight at four years of age was 11.9 %. In the economically strongest neighbourhoods (i.e. <10 % of resident families with low purchasing power), the AOR was 0.60 (95 % confidence interval (CI): 0.34-0.98). The corresponding empirically Bayes-adjusted AOR was 0.73 (95 % CI: 0.46-1.02; 97 % posterior probability of AOR <1). In the other neighbourhood strata, the statistical evidence of a deviant AOR was weaker., Conclusion: The economically strongest neighbourhoods had a lower prevalence than expected of overweight at four years of age. This finding should prompt studies to acquire more knowledge of potentially modifiable factors that differ between neighbourhoods and are related to childhood overweight, providing a basis for tailored, targeted interventions.

Background: About 20% of adolescents experience substantial mental health problems after bariatric surgery., Objectives: The aim of this study was to explore differences between adolescents with poor mental health (PMH) 2 years after surgery and those with average/good mental health., Setting: Three university hospitals in Sweden., Methods: Mental health and health-related quality of life were assessed in 82 of 88 adolescents (mean age: 16.8 yr, 67% female) at baseline and 1 and 2 years after laparoscopic gastric bypass. Possible associations among mental health, weight, and biochemical outcomes were explored., Results: Two years after surgery 16 (20%) adolescents were identified as having PMH. More symptoms of anxiety and depression and worse mental health at baseline significantly predicted PMH 2 years later. The decline in mental health for the PMH group happened mainly during the second year after surgery. Suicidal ideation was reported in 14% of the total sample 2 years postsurgery and was more frequent in the PMH group. Weight outcomes between groups were comparable at all time points, and physical health was equally improved 2 years after surgery., Conclusions: Although adolescents with PMH after surgery lose as much weight and have similar improvements in physical health compared with other adolescents, special attention should be given to adolescents who report mental health problems at baseline and follow-up, especially during the second year after gastric bypass. The high prevalence of suicidal ideation in adolescents 2 years after bariatric surgery is another indication that longer follow-up is necessary., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment., Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (ISS) or born small for gestational age (SGA)., Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982)., Main Outcome Measures: Death., Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001)., Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

Background: Previous cross-sectional studies have suggested that the mode of delivery can influence the composition of oral microflora. The aim of this prospective study was to compare the salivary colonization in vaginally delivered children with children delivered by Caesarian section (C-section) during their first 6 months of life., Methods: The study group consisted of 149 consecutively enrolled infants, delivered either vaginally (n = 96) or by C-section (n = 53) that volunteered after consent of their parents. Saliva samples were collected within 2 days after birth and then after 1, 3, and 6 months. A saliva sample from the mothers was obtained 6 months after delivery. The parents were asked to complete a questionnaire on socioeconomic factors, lifestyle, and hygiene at baseline and throughout the study period. All samples were analyzed with 13 pre-determined bacterial probes using checkerboard DNA-DNA hybridization., Results: The groups were balanced at baseline concerning all relevant background factors. Gram-positive streptococci (S. mitis, S. salivarius) displayed the highest counts in both groups but a greater diversity was observed in the vaginally delivered group. A. naeslundi, A. odontolytics, F. nucleatum and L. salivarius were only detected among the vaginally delivered infants. The prevalence of S. sanguinis, S. gordoni, R. denticariosa, and B. dentinum increased by age in both groups but the prevalence was significantly lower in the C-section group (p < 0.05). There was a link between the mothers and their offspring's concerning the salivary microbial profile., Conclusion: The microbial composition in saliva differs by the mode of delivery during the first six months of life.

Purpose: To evaluate ophthalmological findings in preschool children born moderate-to- late preterm (MLP) and relate the findings to auxological data at birth and at 5.5 years of age., Methods: Seventy-eight MLP children [gestational age (GA) 32-36 weeks; 34 girls; mean age 5.7 years] were investigated. Gestational age, weight, length and head circumference at birth and at the time of assessment were registered. Visual acuity (VA), refraction, orthoptic evaluation, slit-lamp examination and ophthalmoscopy were conducted, and a history of visuoperceptual problems was recorded. The data were compared with age- and sex-matched controls born full term (n = 35)., Results: Ophthalmological abnormalities were noted in 82% of MLP children and 47% of controls (p = 0.0004). There was a significant difference with regard to impaired motility (p = 0.03), heterophoria at distance (p = 0.006) and refraction expressed as spherical equivalent dioptre (p = 0.01). Amongst auxological data at birth, birthweight (BW) was the strongest predictor to ophthalmological abnormalities (p = 0.0003). In a stepwise logistic regression, GA was the strongest predictor of VA outcome at time of assessment (p = 0.0036). Moderate-to-late preterm birth showed a 2.4-fold increased risk of refractive errors compared with full-term children (RR 2.39: 95% CI 1.10-5.20; p = 0.02)., Conclusion: Based on our findings, MLP birth may be associated with increased ocular morbidity compared with their full-term counterparts. Auxological data at birth, especially BW, seems to be an important factor when conducting an ophthalmological diagnosis in preschool MLP children, and an increased VA was correlated to a higher GA., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Noonan syndrome (NS), a heterogeneous developmental disorder associated with variable clinical expression including short stature, congenital heart defect, unusual pectus deformity and typical facial features, is caused by activating mutations in genes involved in the RAS-MAPK signaling pathway., Case Presentation: Here, we present a clinical and molecular characterization of a small family with Noonan syndrome. Comprehensive mutation analysis of NF1, PTPN11, SOS1, CBL, BRAF, RAF1, SHOC2, MAP2K2, MAP2K1, SPRED1, NRAS, HRAS and KRAS was performed using targeted next-generation sequencing. The result revealed a recurrent mutation in NRAS, c.179G > A (p.G60E), in the index patient. This mutation was inherited from the index patient's father, who also showed signs of NS., Conclusions: We describe clinical features in this family and review the literature for genotype-phenotype correlations for NS patients with mutations in NRAS. Neither of affected individuals in this family presented with juvenile myelomonocytic leukemia (JMML), which together with previously published results suggest that the risk for NS individuals with a germline NRAS mutation developing JMML is not different from the proportion seen in other NS cases. Interestingly, 50% of NS individuals with an NRAS mutation (including our family) present with lentigines and/or Café-au-lait spots. This demonstrates a predisposition to hyperpigmented lesions in NRAS-positive NS individuals. In addition, the affected father in our family presented with a hearing deficit since birth, which together with lentigines are two characteristics of NS with multiple lentigines (previously LEOPARD syndrome), supporting the difficulties in diagnosing individuals with RASopathies correctly. The clinical and genetic heterogeneity observed in RASopathies is a challenge for genetic testing. However, next-generation sequencing technology, which allows screening of a large number of genes simultaneously, will facilitate an early and accurate diagnosis of patients with RASopathies.

Objective: This study aimed to evaluate changes in mental health over 2 years in adolescents undergoing gastric bypass., Methods: Eighty-eight adolescents (65% girls) aged 13 to 18 years were assessed at baseline and 1 and 2 years after surgery. Generic and obesity-specific questionnaires were used to evaluate outcomes in mental health, also in relation to age- and gender-specific norms., Results: Symptoms of anxiety (P = 0.001), depression (P = 0.001), anger (P = 0.001), and disruptive behavior (P = 0.022) were significantly reduced at 2 years after surgery, as were obesity-related problems (P < 0.001). Self-esteem (P < 0.001), self-concept (P < 0.001), and overall mood (P = 0.025) improved significantly. Improvements were mainly observed during the first year after surgery. The second year was characterized by stabilization. Symptoms of anxiety, depression, anger, disruptive behavior, and self-concept were at normative levels after surgery. However, 19% of the adolescents had depressive symptoms in the clinical range., Conclusions: A substantial improvement in mental health in adolescents over the first 2 years after gastric bypass was found. Most adolescents had a level of mental health and self-concept similar to norms, but a marked subgroup showed substantial depressive symptoms 2 years after surgery., (© 2015 The Obesity Society.)

Background: The relationship between mesothelioma and exposure to asbestos is well established. As a result, the use of asbestos in buildings, construction sites, and mines, as well as the implications of disease for the workers has received considerable attention. However, asbestos was also used in household equipment and consumer products, including hairdryers., Purpose: To examine one case of peritoneal mesothelioma in a hairdresser and review the relevant literature on asbestos exposure from hairdryers., Methods: The subject's medical and occupational records were obtained and reviewed and a physical examination was performed., Results: The results indicate that the subject developed peritoneal mesothelioma from her occupational exposure to asbestos containing hairdryers in accordance with the literature., Conclusion: Hairdryers are possible sources of asbestos exposure in patients with mesothelioma, and the asbestos exposure risk is higher for those who use hairdryers occupationally.

Aim: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome., Patients: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years., Results: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged., Conclusions: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues., (© 2015 S. Karger AG, Basel.)

Purpose: Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA., Patients and Methods: In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20)., Results: For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer., Conclusion: These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer., (© 2014 by American Society of Clinical Oncology.)

Background: Little is known about the development of excess skin and requests for body-contouring surgery after bariatric surgery in adolescents., Methods: Forty-seven of 86 adolescents that had undergone gastric bypass surgery answered two questionnaires regarding excess skin and requests for and performed body-contouring surgery. An objective assessment of the amount of excess skin was also performed. The results were compared to earlier results from postbariatric adults., Results: The most common overall problem in adolescents was the feeling of having an unattractive body (91 percent). The most common locations for developing excess skin were the upper arms and thighs according to the measurements. Five of 47 adolescents had undergone body-contouring surgery, and 88 percent of the others desired one or more body-contouring operations. Correlations were found between the objectively measured excess skin and the subjectively experienced amount of excess skin. Correlations were also found between the measured excess skin and the experienced discomfort of excess skin for the abdomen, breast/chest, upper arms, and chin., Conclusions: The authors' results indicate that bariatric surgery in adolescents often leads to severe problems associated with excess skin in both sexes. Thus, the commonly held belief that young people do not develop excess skin to the same extent as adults is strongly questioned. Health care professionals must address the current imbalance between requests for and the performance of body-contouring surgery in adolescents., Clinical Question/level of Evidence: Therapeutic, IV.

Context: Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals., Objective: The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays., Setting: This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe., Participants: A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study., Main Outcome Measures: Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured., Results: Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males., Conclusions: We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.

Context: Measurement of IGF-I is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-I assays and for establishment of normative data., Objectives: Our objectives were development and validation of a novel automated IGF-I immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness., Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15 014 subjects (6697 males and 8317 females, 0-94 years of age)., Main Outcome Measures: We measured concentrations of IGF-I as determined by the IDS iSYS IGF-I assay., Results: A new IGF-I assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-I secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-I concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals., Conclusions: Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-I assay. The strict adherence to recent consensus criteria for IGF-I assays might facilitate clinical application of the results.

In this paper, we address surgical aspects on bariatric surgery in adolescents from a nationwide Swedish study. Laparoscopic gastric bypass surgery was performed for 81 adolescents with morbid obesity (13-18 years), while 81 adolescents with obesity-matched by age, sex, and BMI received conventional care. Another comparison group was adults undergoing gastric bypass at the same institution during the same time period. This report addresses the 2-year clinical outcome and five-year surgical adverse event rate. Body weight decreased from 133 kg (SD = 22) at inclusion to 92 kg (SD = 17) after 1 year and was 89 (SD = 18) after 2 years (p < 0·001) representing a 32% (-35 to -30) weight loss after 2 years, corresponding to 76% (-81 to -71) excess weight loss. Weight loss was similar in the adult gastric bypass patients (-31%) while weight gain (+3%) was seen in the conventionally treated obese adolescents. Significant improvement in cardiovascular and metabolic risk factors and inflammation was seen after surgery. The treatment was generally well tolerated and quality of life improved significantly. The surgical adverse events included cholecystectomies (10%) and operations for internal hernia (9%) but no postoperative mortality. Adolescents undergoing laparoscopic gastric bypass surgery achieve similar weight loss to adults. Improvements in risk factors and quality of life were substantial. There were surgical complications similar to the adult group, which may be preventable., (© 2013 Published by Elsevier Inc.)

We report seven cases of acute myeloid leukemia (AML) with occupational exposure to a toluene-based hydrocarbon solvent. The cases were employed at a facility, which manufactured rubber belts and hoses, between 1950 and 2005 for periods ranging from 21 to 37 total years. Detailed histories were obtained for three workers who were diagnosed with AML within a 3-year period (2003-2005). Death certificates, medical records, and accounts by workers were reviewed. Benzene, a known cause of AML, is typically a contaminant of toluene. Benzene contamination in toluene and other widely used solvents and the potential for concurrent benzene exposure during usage of these solvents in occupational settings are discussed.

Aim: Infant feeding affects growth, obesity and life-long health. This study examined the impact of dietary patterns on body mass index (BMI) at 12 and 18 months., Methods: We followed a cohort of 2666 children recruited in 2007-2008. Feeding practices were obtained from parental questionnaires and anthropometric data collected by child health nurses., Results: At 6 months, 58.3% of the infant were breastfed, but only 1.6% exclusively. Many had begun eating solids (91.8%), porridge (87.7%) or milk cereal drink (46.6%). Bottle-feeding at 4 months was not a risk factor for a high BMI (>1 SD) at 12 or 18 months. Milk cereal drink at six months increased the risk of a high BMI at 12 and 18 months, respectively (OR 1.58, 95% CI 1.12-2.22, and 1.52, 1.07-2.17). Milk cereal drink use was increased by low parental education and maternal obesity and reduced by troubled sleep and parental group participation., Conclusion: Formula at 4 months did not predict a high BMI at 12 or 18 months. Milk cereal drink use at 6 months was a risk factor for a high BMI at 12 and 18 months. The choice of milk cereal drink was influenced by parental factors, especially educational levels., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Parental socioeconomic status (SES) is an important determinant in child health, influencing beneficial factors such as breastfeeding. A better understanding of the influence of neighbourhood-level SES measures, relating to spatial determinants, might lead to targeted actions to promote breastfeeding during infancy., Methods: A cross-sectional study analysis the association between breastfeeding at four months of age and neighbourhood purchasing power, taking account of individual-level variables including maternal age, smoking and parental level of education. Data were obtained from a prospective population- based cohort study recruited from birth in 2007-2008 in the Halland region, southwestern Sweden. Questionnaire data on the individual-level variables and the outcome variable of breastfeeding at four months (yes/no) were used (n=2,407). Each mother was geo-coded with respect to her residential parish (there are 61 parishes in the region) and then stratified by parish-level household purchasing power. It emerged that four neighbourhood characteristics were reasonable to use, viz. <10%, 10-19%, 20-29% and ≥ 30% of the resident families with low purchasing power., Results: The proportion of mothers not breastfeeding at four months of age showed a highly significant trend across the neighbourhood strata (p=0.00004): from 16.3% (< 10% with low purchasing power) to 29.4% (≥ 30% with low purchasing power), yielding an OR of 2.24 (95% confidence interval: 1.45-3.16). After adjusting for the individual-level variables, the corresponding OR=1.63 (1.07-2.56) was significant and the trend across the strata was still evident (p=0.05). A multi-level analysis estimated that, in the neighbourhoods with ≥ 30% of the families with low purchasing power, 20% more mothers than expected, taking account of the individual-level factors, reported no breastfeeding at four months of age (≥ 95% posterior probability of an elevated observed-to-expected ratio)., Conclusion: The neighbourhood purchasing power provided a spatial determinant of low numbers of mothers breastfeeding at four months of age, which could be relevant to consider for targeted actions. The elevated observed-to-expected ratio in the neighbourhoods with the lowest purchasing power points toward a possible contextual influence.

Objective: A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment., Design, Patients and Measurements: The study population consisted of 128 prepubertal children receiving GH treatment. Thirty-nine were short as a result of GH deficiency, and 89 had idiopathic short stature (ISS). Serum protein expression profiles at study start and after 1 year of GH treatment were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Body composition was analysed by dual-energy X-ray absorptiometry (DXA), reliably estimating muscle mass from appendicular (arms and legs) lean soft tissue mass (LST). DXA was also used to estimate appendicular bone mineral content (BMC) and fat mass for the total body., Results: Specific protein expression patterns associated with GH response in different body compartments were identified. Among identified proteins, different isoforms of nutrition markers such as apolipoproteins (Apo) were recognized: Apo C-I, Apo A-II, serum amyloid A4 (SAA4) and transthyretin (TTR). In addition, unidentified peaks were associated with GH effects on specific body compartments., Conclusions: Our results suggest that unique protein markers are associated with remodelling of different body compartments during GH treatment, which in the future might be useful to optimize GH treatment not only with regard to longitudinal growth., (© 2013 John Wiley & Sons Ltd.)

Objective: There are clear sex differences in the distribution of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in adults, with males having more VAT and less SAT than females. This study assessed whether these differences between the sexes were already present in preschool children. It also evaluated which measures of body composition were most appropriate for assessing abdominal obesity in this age group., Design and Methods: One-hundred and five children (57 boys and 48 girls) participated in the study. Body composition was measured using dual-energy X-ray absorptiometry (DXA). Weight, height, and waist circumference (WC) were also recorded. Magnetic resonance imaging (MRI) of the entire abdomen using sixteen 10-mm-thick T1 -weighted slices was performed in a subgroup of 48 children (30 boys and 18 girls); SAT and VAT volumes were measured using semiautomated segmentation., Results: Boys had significantly more VAT than girls (0.17 versus 0.10 l, P < 0.001). Results showed that VAT correlated significantly with all measurements of anthropometry (P < 0.01) after adjusting for SAT and for total fat mass measured with DXA. The mean limits of agreement between DXA and MRI regarding truncal FM were calculated to be -11.4 (range -17.8 to -3.6), using a Bland-Altman plot., Conclusion: Sex differences in adipose tissue distribution are apparent at an early age. MRI is the best method with which to study abdominal fat distribution in young children., (Copyright © 2013 The Obesity Society.)

Background: The mission of the National Cancer Institute's Early Detection Research Network (EDRN) is to identify and validate cancer biomarkers for clinical use. Since its inception, EDRN investigators have learned a great deal about the process of validating biomarkers for clinical use. Translational research requires a broad spectrum of research expertise, and coordinating collaborative activities can be challenging. The EDRN has developed a robust triage and validation system that serves the roles of both "facilitator" and "brake.", Content: The system consists of (a) establishing a reference set of specimens collected under PRoBE (Prospective Specimen Collection Retrospective Blinded Evaluation) design criteria; (b) using the reference set to prevalidate candidate biomarkers before committing to full-scale validation; (c) performing full-scale validation for those markers that pass prevalidation testing; and (d) ensuring that the reference set is sufficiently large in numbers and volumes of sample that it can also be used to study future candidate biomarkers. This system provides rigorous and efficient evaluation of candidate biomarkers and biomarker panels. Reference sets should also be constructed to enable high-quality biomarker-discovery research., Summary: We describe the process of establishing our system in the hope that it will serve as an example of how to validate biomarkers for clinical application. We also hope that this description of the biospecimen reference sets available from the EDRN will encourage the biomarker research community--from academia or industry--to use this resource to advance biomarkers into clinical use., (© 2012 American Association for Clinical Chemistry)

Background: Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers., Objectives: We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types., Conclusions: Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.

Objective: Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period., Design: Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17-100 μg/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental height(SDS) , children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID, n = 28) or an unchanged individualized dose (UID, n = 37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 μg/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX., Results: We observed less variation in fasting insulin levels (-50%), insulin sensitivity as assessed by homoeostasis model assessment (-55·1%), lean soft tissue (-27·8%) and bone mineral content (-31·3%) in RID compared with UID (all P < 0·05), but no differences compared with FIX., Conclusions: Continued reduced individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired height(SDS) is achieved to avoid overtreatment in terms of metabolic outcome., (© 2012 Blackwell Publishing Ltd.)

Aim: To present data on body size, lifestyle and health status in students in their final year in high schools in Gothenburg area, Sweden, with specific attention to origin and gender., Methods: Weight, height and waist circumference were measured by standardized procedures. Self-administered questionnaires described dietary habits, sleep, physical activity, body image, country of origin and general health., Results: Eighty-six percent of participants, (2600 girls, 2714 boys, mean age 18.6 years) were of Nordic origin, 86% reported no chronic health problems and 14%/19% of girls/boys were overweight or obese. Girls consumed more vegetables and fruits and fewer sweet drinks than boys, while breakfast consumption was most common in Nordic groups. Boys reported more positive answers than girls regarding body image. Nordic girls had more negative body image and higher morbidity compared with other groups., Conclusion: Within this generally healthy cohort, boys were more likely to be overweight/obese than girls, although paradoxically boys were more satisfied with their appearance. Nordic girls constitute a group with particularly high risk of reporting low body self-esteem and chronic morbidity. In the longer term, the current cross-sectional data on body size, lifestyle and health will provide important baseline information for future follow-up studies of health outcomes in later life., (©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.)

Obese adolescents have high concentrations of saturated fatty acids and low omega-3 long-chain polyunsaturated fatty acids (LCUFAs) in plasma phospholipids. We aimed to investigate effects of omega-3 LCPUFA supplementation to obese adolescents on skeletal muscle lipids and glucose and insulin homeostasis. Twenty-five obese adolescents (14-17 years old, 14 females) completed a randomized double-blind crossover study supplying capsules containing either 1.2 g omega-3 LCPUFAs or placebo, for 3 months each with a six-week washout period. Fasting blood glucose, insulin, leptin, adiponectin, and lipids were measured. Intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp were performed, and skeletal muscle biopsies were obtained at the end of each period. The concentrations of EPA, DHA, and total omega-3 PUFA in muscle phospholipids increased in both sexes. In the females, omega-3 LCPUFA supplementation improved glucose tolerance by 39% (P = 0.04) and restored insulin concentration by 34% (P = 0.02) during IVGTT. Insulin sensitivity improved 17% (P = 0.07). In males, none of these parameters was influenced by omega-3 supplementation. Thus, three months of supplementation of omega-3 LCPUFA improved glucose and insulin homeostasis in obese girls without influencing body weight.

Background: Breastfeeding is associated with many benefits for both mother and child. Initiation rates are high in Sweden. Recently a slight decline is seen., Aim: The aim of this study was to assess factors associated with discontinuation of breastfeeding during the first 4 weeks., Method: A population-based longitudinal birth cohort study recruiting from 2007 to 2008 in south-western Sweden. At the first visit to the child health centre, parents were asked to complete a questionnaire. Also, the infants' height, weight, head and waist circumference were collected. Response rate was 69.2%., Results: Twenty-seven per cent of mothers had breastfeeding problems. In a multivariate analysis, there was a negative correlation between breastfeeding and use of pacifier (OR 3.72; CI 2.09-6.63), maternal smoking (OR 2.09; CI 1.08-4.05) and breastfeeding problems (OR 2.54; CI 1.73-3.71). Breastfeeding problems were correlated with poor sucking technique (OR 2.96; CI 2.14-4.07), support from maternity ward (OR 2.56; CI 2.05-3.19) and perceived poor weight gain (OR 1.37; CI 1.00-1.86)., Conclusion: Many mothers reported breastfeeding problems that are associated with an early cessation. This is preventable with support, but the timing is crucial. To promote breastfeeding, the support from the child health centres must be tailored with the maternal perspective in mind., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children., Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children's and parents' responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height., Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother's height, parental sense of the child's tallness and age explained more variance in children's sense of tallness (34%) than measured height (0%)., Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short., (Copyright © 2012 S. Karger AG, Basel.)

Aim: Previous studies have shown visual evoked potential (VEP) abnormalities in infants and animals born small for gestational age (SGA) compared with controls. The current exploratory study aims to investigate whether VEP abnormalities persist in older ages., Methods: Pattern VEP latencies were obtained in 21 children (11 girls, 10 boys), born SGA and moderately preterm, at an average age of 5 years and 8 months. Fifty-one children (24 girls, 27 boys, mean age of 5 years and 7 months), also born moderately preterm but with normal height and weight at birth, served as controls, Results: Visual evoked potential results showed no significant differences in latency between children born SGA and controls born appropriate for gestational age (AGA) for either binocular stimulation, right eye or left eye stimulation., Conclusions: Our findings do not indicate any differences in VEP latency at preschool age for children born SGA compared with children born AGA. The results may support previous studies, suggesting that children born SGA show accelerated neurophysiologic maturation during their first year of life and that previously delayed VEP latencies after catch-up stay unchanged compared with controls., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS)., Design: In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population., Methods: Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer., Results: Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E(2)) concentrations started to increase during puberty and inhibin B and anti-Müllerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P<0.01), FSH (7.1 vs 2.5 U/l, P<0.001), testosterone (18.7 vs 15.6  nmol/l, P<0.01) and E(2) (66 vs 46  pmol/l, P<0.001) levels and lower AMH (33 vs 65  pmol/l, P<0.01) and inhibin B (median 108 vs 187  pg/ml, P<0.01) levels than the reference population., Conclusions: In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.

Context: Children born prematurely with growth failure might benefit from GH treatment., Objectives: The aim was to evaluate the first year growth response to GH treatment in short children born prematurely and to identify predictors of the growth response., Design/patients: A total of 3215 prepubertal children born prematurely who were on GH treatment were selected from KIGS (The Pfizer International Growth Database), a large observational database. They were classified according to gestational age as preterm (PT; 33 to no more than 37 wk) and very preterm (VPT; <33 wk), and according to birth weight as appropriate for gestational age [AGA; between -2 and +2 sd score (SDS)] and small for gestational age (SGA; -2 SDS or below)., Results: Four groups were identified: PT AGA (n = 1928), VPT AGA (n = 629), PT SGA (n = 519), and VPT SGA (n = 139). GH treatment was started at a median age of 7.5, 7.2, 6.7, and 6.0 yr, respectively. After the first year of GH treatment, all four groups presented a significant increase in weight gain and height velocity, with a median increase in height SDS higher than 0.6. Using multiple stepwise regression analysis, 27% of the variation in height velocity could be explained by the GH dose, GH peak during provocative test, weight and age at GH start, adjusted parental height, and birth weight SDS. The first year growth response of the children born PT and SGA could be estimated by the SGA model published previously., Conclusion: Short children born prematurely respond well to the first year of GH treatment. Long-term follow-up is needed.

Aim: To evaluate ophthalmological findings in children with Silver-Russell syndrome (SRS)., Methods: An ophthalmological evaluation including visual acuity (VA), refraction, strabismus, near point of convergence (NPC), slit-lamp examination, ophthalmoscopy, axial length measurements and full-field electroretinogram was performed on 18 children with SRS (8 girls, 10 boys; mean age 11.6 years). Fundus photographs were taken for digital image analysis. Data were compared with data on an age- and gender-matched reference group (ref) of school children (n=99)., Results: Seventeen out of 18 children with SRS had ophthalmological abnormalities. Best corrected VA of the best eye was <0.1 log of the minimal angle of resolution in 11 children (ref n=98) (p<0.0001), and 11 children had refractive errors (ref n=33) (p=0.05). Anisometropia (≥1 dioptre) was noted in three of the children (ref n=3) (p=0.046). Subnormal stereo acuity and NPC were found in 2/16 (ref=0) (p=0.02). The total axial length in both eyes was shorter compared with that in controls (p<0.006 and p<0.001). Small optic discs were found in 3/16, large cup in 3/16 and increased tortuosity of retinal vessels in 4/13 children with SRS., Conclusion: Children with SRS, who are severely intrauterine growth retarded, show significant ophthalmological abnormalities. Based on the present findings, ophthalmological examination is recommended in children with SRS.

The few studies that have evaluated the long-term height outcomes following growth hormone (GH) treatment in children with idiopathic short stature (ISS) have shown a growth response to GH treatment similar to that in GH-deficient children. A literature search of all randomized and nonrandomized studies of GH treatment in children with ISS from prepubertal years to adult height or near-adult height published over the last 10 years identified six publications (none was a classic meta-analysis). Several studies showed a dose-dependent response in height outcome. Overall, the younger the patient and the greater the difference in current height vs. parental height at start of treatment, the more substantial the gain in height. Height improvement ranged from 0.5 to 1.3 standard deviation score (SDS). The magnitude of height gain was substantial, even after adjustment for growth changes in control subjects (0.5 to 1 SDS), and it was comparable to that seen in other non-GH-deficient syndromes. Only two studies reported data from matched control subjects. Interestingly, there was no difference in height gain between familial short stature and non-familial short stature after adjusting for spontaneous height gain to adult age in non-GH-treated control subjects. To summarize, patients with ISS can benefit from GH treatment with respect to growth outcome, with results maintained into adulthood., (Copyright © 2011 S. Karger AG, Basel.)

The US Food and Drug Administration approved use of recombinant human growth hormone (GH) for the treatment of idiopathic short stature (ISS) in children; however, few studies have evaluated metabolic outcomes. This article addresses whether children with ISS treated with GH experience the same metabolic benefits as children with GH deficiency (GHD) treated with GH. A systematic review of all published studies of GH treatment in children with ISS that included data on metabolic outcomes identified five studies. No meta-analysis has been performed.Studies show a metabolic response to GH treatment in children with ISS similar to that observed in children with GHD; effects include a transient decrease in insulin sensitivity and a dose-dependent increase in insulin-like growth factor I. However, no increase in the risk of diabetes was found. Children with ISS seem to benefit from GH treatment in terms of height gain without any severe negative metabolic outcomes., (Copyright © 2011 S. Karger AG, Basel.)

In this 12-week open-label, uncontrolled study, patients (n = 85; mean [SD] age 11.2 [3.95] years) were trained to use an injection device with an automatic needle insertion accessory (NordiFlex/NordiFlex PenMate: Novo Nordisk A/S, Bagsvaerd, Denmark) for growth hormone (GH) injection. The opinions of patients and the physicians/nurses who trained patients on device were recorded by questionnaire. Most (88.4%) patients reported that the device was "very easy/easy" to use. The majority (82.4%) of patients were "very satisfied/satisfied" with the device and 64% wished to continue its use. Device training instructions were reported as "very easy/easy" by 96.1% of physicians/nurses, and 65.8% of participants could use the device after ≤10-minute training. In this study, NordiFlex PenMate was well accepted by patients and medical staff. Patients had a high opinion of the device and over half wished to continue its use. High patient acceptance may facilitate treatment adherence optimizing treatment outcomes.

Background/aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children., Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months., Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male., Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment., (Copyright © 2011 S. Karger AG, Basel.)

Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial., Aim: Assess various criteria of poor response., Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤-2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS -3.2., Results: Median [25-75 percentile] first-year gain in Ht SDS was 0.65 (0.40-0.90) and height velocity (HtV) 8.67 (7.51-9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 μg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5., Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients., (Copyright © 2011 S. Karger AG, Basel.)

Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. Because of the variability in presentation and the need for multidisciplinary care, it is essential that the condition be identified and managed comprehensively. The Noonan Syndrome Support Group (NSSG) is a nonprofit organization committed to providing support, current information, and understanding to those affected by NS. The NSSG convened a conference of health care providers, all involved in various aspects of NS, to develop these guidelines for use by pediatricians in the diagnosis and management of individuals with NS and to provide updated genetic findings.