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Context Hormone reference intervals in pediatric endocrinology are traditionally partitioned by age and lack the framework for benchmarking individual blood test results as normalized z-scores and plotting sequential measurements onto a chart. Reference curve modeling is applicable to endocrine variables and represents a standardized method to account for variation with gender and age. Objective We aimed to establish gender-specific biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI). Methods Using cross-sectional population sample data from 2139 healthy Norwegian children and adolescents, we analyzed the pubertal status, ultrasound measures of glandular breast tissue (girls) and testicular volume (boys), BMI, and laboratory measurements of 17 clinical biomarkers modeled using the established “LMS” growth chart algorithm in R. Results Reference curves for puberty hormones and pertinent biomarkers were modeled to adjust for age and gender. Z-score equivalents of biomarker levels and anthropometric measurements were compiled in a comprehensive beta coefficient matrix for each gender. Excerpted from this analysis and independently of age, BMI was positively associated with female glandular breast volume (β = 0.5, P Conclusion Biomarker reference curves and corresponding z-scores provide an intuitive framework for clinical implementation in pediatric endocrinology and facilitate the application of machine learning classification and covariate precision medicine for pediatric patients.

Aim: To examine the effect of a family-oriented multidisciplinary intervention pro-gramme to curtail weight increase in young children with obesity.Methods: Children who weighed more than one kilogram above the 97th percentile for height at the preschool assessment in Oppland County, Norway, were identified. Parents residing in one part of the county were invited to participate in a group-based three-year intervention programme while the rest had no interventions. Body mass index (BMI) and family characteristics at entry and measurements at birth were explanatory variables, and change in BMI standard deviation score (SDS) the outcome measure. For the intervention group, outcome was also related to skinfold thicknesses, waist-to-height ratio and physical ability.Results: The programme was completed by 31 families in the intervention and 33 in the control group. At entry, the respective median (interquartile) age was 5.83 (0.36) and 5.74 (0.66) years, and the BMI SDS 2.35 (1.06) and 1.95 (0.49), P = .012. The median decrease in BMI SDS was 0.19 in both groups. The decline increased with increasing BMI SDS at entry, but irrespective of group. Social or behavioural factor or other anthropometric measures were not associated with outcome.Conclusion: The intervention programme had no effect on BMI SDS. The South-Eastern Norway Regional Health Authority (Helse Sør Øst) Innlandet Hospital Trust

BACKGROUND: Previous studies investigating the association between weight status and onset of puberty in boys have been equivocal. It is currently unclear to what extent weight class influences puberty onset and progression. OBJECTIVES: To explore the relationship between degree of sexual maturation and anthropometric measures in Norwegian boys. METHODS: The following endpoints were collected in a Norwegian cross-sectional study of 324 healthy boys aged 9-16: ultrasound-determined testicular volume (USTV), total serum testosterone, Tanner pubic hair stage, height, weight, waist circumference (WC), subscapular skinfolds (SSF), and body fat percentage (%BF). Testicular volume-for-age z-scores were used to classify "early," "average," or "late" maturing boys. Ordinal logistic regression analyses with a proportional odds model were applied to analyze the association between anthropometric variables and age-adjusted degree of pubertal development, with results expressed as age-adjusted odds ratios (AOR). Cumulative incidence curves for reaching pubertal milestones were stratified by BMI. RESULTS: Boys with a low BMI for age (BMIz 1) exhibited a comparable timing as normal weight boys. The same was found for WC. Pubertal markers were not associated with SSF or %BF. CONCLUSION: By examining the association between puberty and weight status classified as low, average, or high, we found that a low BMI or WC for age were associated with a less advanced pubertal development and delayed timing of puberty in boys. No significant association was observed for a high BMI or WC. Moreover, no significant effects of SSF or %BF were observed. A low weight status should also be considered when assessing pubertal development in boys. ispartof: ANDROLOGY vol:9 issue:3 pages:837-845 ispartof: location:England status: published

ObjectiveTo examine if underweight (UW), overweight (OW) or obesity (OB), or body mass index (BMI) expressed as its SD score (BMI SDS), were associated with psychological difficulties in preschool children.DesignRegional cohort study.SettingOppland County, Norway.MethodsAt the routine school entry health assessment at 5–6 years of age, parents were invited to participate by local public health nurses. The parents completed questionnaires on sociodemographic, health and lifestyle factors of the child and the family, and on the child’s neurocognitive development. They assessed psychological health with the Strengths and Difficulties Questionnaire (SDQ). Public health nurses measured weight and height on all eligible children and reported age, sex, height and weight anonymously for the children who declined to participate.ParticipantsWe obtained information on 1088 of 1895 (57%) eligible children. The proportion of UW, OW and OB was slightly higher among the children who declined.Main outcome measuresSDQ subscale and Total Difficulties Scores.ResultsThe mean SDQ scores and proportion of scores ≥the 90th percentile had a curvilinear pattern from UW through normal weight (NW), OW and OB with NW as nadir, but the pattern was only significant for the mean Emotional problems, Peer problems and Total SDQ Scales, and for the Total SDQ Score ≥the 90th percentile (TDS90). After adjusting for relevant social, developmental, health and behavioural characteristics, TDS90 was only significantly associated with UW in multiple logistic regression analyses, and only with the lowest quartile of BMI SDS in a linear spline regression analysis.ConclusionsThe study suggests that UW and low BMI, but not OW, OB or higher BMI, are independent risk factors for having psychological symptoms in preschool children.

Context Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset. Objective To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche. Design Setting and Participants Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years. Main Outcome Measures Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range. Results References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P Conclusions We provide the first hormone references for use with US breast staging and demonstrate the application of endocrine profiling to improve detection of female puberty onset.

Context Discriminating adipose and glandular tissue is challenging when clinically assessing breast development. Ultrasound facilitates staging of pubertal breast maturation (US B), but has not been systematically compared to Tanner breast (Tanner B) staging, and no normative data have been reported. Objective To present normative references for US B along with references for Tanner B, pubic hair (PH), and menarche. Design, Setting, and Participants A cross-sectional sample of 703 healthy girls aged 6 to 16 years were examined. Main Outcome Measures Breast development was determined with US B and Tanner B staging. Tanner PH and menarcheal status were recorded. The age distributions of entry in US B, Tanner B, and PH stages and menarche were estimated with generalized linear and generalized additive models with a probit link. Method agreement was tested with weighted Cohen’s kappa. Results The median (±2SD) ages for thelarche, US B2 and Tanner B2, were 10.2 (7.7, 12.8) and 10.4 (8.0, 12.7) years. The median (±2SD) ages at Tanner PH2 and menarche were 10.9 (8.5, 13.3) and 12.7 (11.0, 16.2) years. Cohen’s kappa of agreement (95% confidence interval) between US B and Tanner B was 0.87 (0.85–0.88). When the methods disagreed, US B was usually more advanced. Conclusion Thelarche occurred at a slightly younger age when assessed with ultrasound compared to clinical Tanner staging, although the 2 methods had a very good agreement when determining pubertal breast maturation. A significant decrease of 2.8 months in age at menarche was observed during the past decade in Norwegian girls.

Context Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals. Objective The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound. Design, Setting, and Participants Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional “Bergen Growth Study 2.” Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem–mass spectrometry and immunoassays. Main Outcome Measures We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin in relation to TV, chronological age, and Tanner pubic hair stages. Results In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P Conclusions Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty.

AIM: To estimate references for testicular volume measured with ultrasound and Tanner stages of pubic hair in Norwegian boys, and to compare the timing of puberty with data from similar populations. METHODS: Testicular volume was derived from ultrasound measurements of testicular volume in a cross-sectional study of 514 healthy boys. A continuous testicular volume for age reference curve was estimated with the LMS method. Tanner stages for pubic hair were clinically assessed in 452 boys. Age references for pubertal milestones were estimated with probit regression. RESULTS: Puberty onset, defined by an ultrasound testicular volume of 2.7 mL, equivalent to an orchidometer volume of 4 mL, occurred at a mean (SD) age of 11.7 (1.1) years. The reference range was 9.7 (3rd) to 13.7 years (97th percentile). Pubic hair (Tanner stage 2) appeared on average at 11.8 (1.2) years with a corresponding reference range of 9.5-14.1 years. CONCLUSION: The references for testicular volume measured with ultrasound are continuous in age and allow for the quantification of pubertal development. The age distribution of reaching pubertal milestones was comparable with data from other Northern European countries. ispartof: ACTA PAEDIATRICA vol:109 issue:8 pages:1612-1619 ispartof: location:Norway status: published

AIM: To study how sociodemographic factors and family structure associate with baseline BMI z-scores (BMIz) and BMIz change in 767 Norwegian children aged 6-15 years. METHODS: Baseline BMIz and 1-year BMIz increments in children from the Bergen Growth Study were analysed with linear and logistic regression, according to sociodemographic factors and family structure. A blended family was defined as including a step-parent and/or half-sibling. RESULTS: In a fully adjusted regression model, baseline BMIz were only significantly associated with maternal BMI (b = 0.087, 95%CI 0.067, 0.107). Body Mass Index z-scores increments were larger in children living in a blended family (b = 0.060, 95%CI 0.006, 0.115), with a lower parental education (b = 0.127, 95%CI 0.029, 0.226) and with a higher maternal BMI (b = 0.008, 95%CI 0.001, 0.014). The odds for a large BMIz increment (>1 SD) were higher in children living in blended families (OR 1.82, 95%CI 1.16, 2.88) and with higher maternal BMI (OR 1.07, 95%CI 1.01, 1.13) and lower in 9-11-year-old children (OR 0.44, 95%CI 0.26, 0.77) compared with 12-15-year-olds. CONCLUSION: Body Mass Index z-scores increments were more strongly associated with sociodemographic factors and living in a blended family than baseline BMIz values. BMI z-scores increments could be useful for identifying children at risk of becoming overweight or obese. ispartof: ACTA PAEDIATRICA vol:109 issue:3 pages:587-594 ispartof: location:Norway status: published

Prader orchidometry has been the standard method for evaluating testicular size. As this technique is subjective and tends to overestimate the testicular volume, ultrasound (US) has been proposed as more reliable. To evaluate the intra- and interobserver agreement of US measurements of testicular volume and to compare US with the Prader orchidometer. Dimensions of the right testicle were measured using US in 57 boys ages 6.5 to 16.4 years (mean: 12.0 years). The measurements were performed twice by one main observer and once by a second observer. A third observer estimated testicular volume using a Prader orchidometer. Agreement was investigated with Bland-Altman plots, summarized as the mean and standard deviation (SD) of differences, 95% limits of agreement and technical error of measurement. Mean intra-observer difference of testicular volume was 2.2%, SD=9.2% (limits of agreement: -20.3 to 15.9%) and technical error of measurement 6.5%. The mean interobserver difference was 4.8%, SD=20.7% (limits of agreement: -35.7 to 45.3%) and technical error of measurement 14.6%. Comparing US and orchidometer volumes required conversion that was nonlinear and volume dependent, estimated as VolOM = 1.96×VolUS0.71. The mean difference after transformation was 0.7% with an SD of 18.0% (limits of agreement: -34.5 to 35.9%). Our results showed a small mean intra- and interobserver difference that indicates the potential of US for measurement of testicular volume at group level. The intra-observer error was limited, which justifies its use in longitudinal follow-up of testicular development in an individual child, but the larger interobserver variability indicates the need for good standardization of methods. Agreement between the two methods requires a power transformation.

Clinical assessment of pubertal breast development using Tanner staging is subjective. This has led to the introduction of ultrasound (US), aiming for a more objective analysis. However, information regarding its reliability is lacking. To examine intra- and interobserver agreement of breast maturity staging using US and to examine the precision of direct measurements of the gland. Fifty-seven healthy girls (mean age: 10.9 years, range: 6.1 to 15.9 years) were examined independently by two observers using US of the left breast to score the glandular maturity stage on a 0-5 scale, and to measure the depth and diameter. One observer repeated the examination after 20 to 35 min to assess intra-observer agreement. Cohen’s kappa with linear weights was used to examine intra- and interobserver agreement of the US staging, while the measurement precision was analyzed using Bland-Altman plots and 95% limits of agreement. The agreement of US staging on a 0-5 scale was very good (kappa 0.84; 95% confidence interval [CI] 0.78-0.91) for intra-observer observation and good (kappa 0.71; 95% CI 0.62-0.80) for interobserver observation. Measurements of glandular depth and diameter were unbiased for a single observer, but the variances were large both within and between observers. US using a scale from 0 to 5 is a reliable method to stage the development of glandular breast tissue during puberty in healthy girls. Measurements of glandular depth and diameter were found to be imprecise.

Anthropometry is the general tool for defining overweight and obesity with body mass index (BMI; kg/m2) as the most common variable, using sex and age-adjusted cut-offs for children (Cole et al., 2000). We rely on BMI in identifying overweight, but the accuracy of BMI in predicting overweight and obesity varies with degree of fatness, with a high accuracy in fat children, less so in thin children (Freedman and Sherry, 2009). Annual increases in BMI during childhood have been shown to be attributed to increases in lean mass more than increases in fat mass, but varied according to sex and age (Maynard et al., 2001). Hence, changes in BMI percentile do not necessarily reflect changes in adiposity in children over time, especially not in children with lower BMI values (Demerath et al., 2006). Waist circumference (WC) as well as waist to height ratio (WHtR), have been shown to correlate with amount of abdominal fat, as well as cardiovascular and metabolic risk factors (Bluher et al., 2013; Grober-Gratz et al., 2013). Skinfolds in various combinations have proven to correlate with adverse health risk, as well as being able to predict % body fat better than BMI (Brambilla et al., 2013; Nooyens et al., 2007). During childhood and adolescence, the ratio between the upper and the lower body segment changes considerably, and especially during adolescence growth of the lower segment tends to precede the growth of the upper segment by several months. Sitting height excludes the growth of lower extremities, but little is known about the impact of sitting height on BMI during childhood. In spite of available BMI definitions, a major concern regarding the overweight epidemic among children is the inability of parents, as well as healthcare workers, to recognize that a child is overweight. Several studies have demonstrated that parents in general underestimate their child's weight, and that the age and sex of the child affect their judgments. This is especially evident among the youngest children (He and Evans, 2007; Juliusson et al., 2010b). The same applies to healthcare workers (Isma et al., 2012; Turner et al., 2009). This is serious, as obesity tracking throughout childhood represents a consistent predictor of adult metabolic risk (Janssen et al., 2005). We wonder whether differences in anthropometric measurements related to weight could contribute to this discrepancy between parental perception and weight status, observed particularly in young children. In this work, we have studied a cohort of Norwegian children 4–16 years of age from the Bergen Growth Study with the purpose of analyzing how BMI and other variables of weight status in children associate during different ages. The main research questions were: how does BMI correlate to WC, WHtR, subscapular skinfold (SSF), triceps skinfolds (TSF), and waist to sitting height ratio (WSHtR) during different ages in childhood, and which of these anthropometric variables contribute most to variation in BMI during childhood?

Fibroblast growth factor 23 (FGF23) plays a crucial role in renal phosphate regulation, exemplified by the causal role of PHEX and DMP1 mutations in X-linked hypophosphatemic rickets and autosomal recessive rickets type 1, respectively. Using whole exome sequencing we identified compound heterozygous mutations in family with sequence similarity 20, member C (FAM20C) in two siblings referred for hypophosphatemia and severe dental demineralization disease. FAM20C mutations were not found in other undiagnosed probands of a national Norwegian population of familial hypophosphatemia. Our results demonstrate that mutations in FAM20C provide a putative new mechanism in human subjects leading to dysregulated FGF23 levels, hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis of the long bones in the absence of rickets.

Previous growth references for Norwegian children were based on measurements from the 1970s and 1980s. New reference data, collected through the Bergen Growth Study and the Medical Birth Registry of Norway, are presented as LMS values.A cross-sectional sample of children aged 0-19 years in stratified randomized design measured in 2003-2006 as a part of the Bergen Growth Study (n = 7291) and birth data of children born in 1999-2003 from the Medical Birth Registry of Norway (n = 12 576) was used to estimate the new references by the means of the LMS method. Measurement reliability was assessed by test-rest studies.New references were constructed for length/height, weight, body mass index (BMI) and head circumference. Length/height and weight for children aged 0-4 years were similar to previous Norwegian references, but mean height increased up to a maximum of 3.4 cm in boys and 2.5 cm in girls during the pubertal years. Mean height was similar to (or slightly higher) in comparison with other recent European references. Reliability of the measurements compared well with published estimates.Because of the observed secular trends in growth, it is advised to use the new references, which have been endorsed by the Norwegian Department of Health.

Aim To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6–15-year-old Norwegian children. Methods Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study. Results More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34(+) progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte - colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34(+) cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation. After 7 days of cytokine-dependent proliferation the total number of viable cells increased 1.6-8.2 times, and subsets of cells expressing the granulocyte marker CD15, the myelomonocytic marker CD64 and the erythrocyte phenotype CD71(high) /CD64(-) were detected among the in vitro cultured cells. Addition of G-CSF together with SCF + IL-3 + GM-CSF increased the number of CD15(+) and CD64(+) cells, but without altering the number of erythroid cells. IGF-1 caused a dose-dependent increase in the number of CD15(+), CD64(+) and CD71(high) /CD64(-) cells, and this increase was detected when cells were cultured in both SCF + IL-3 + GM-CSF alone and G-CSF + SCF + IL-3 + GM-CSF. A minor subset of CD34(+) cells could still be detected among in vitro cultured cells and the number of CD34(+) cells was not altered by adding G-CSF and/or IGF-1. Morphologically recognizable mature granulocytes or erythroid cells could not be detected for any of the combinations investigated. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from apheresis CD34(+) cells.

ObjectiveHereditary hypophosphatemias (HH) are rare monogenic conditions characterized by decreased renal tubular phosphate reabsorption. The aim of this study was to explore the prevalence, genotypes, phenotypic spectrum, treatment response, and complications of treatment in the Norwegian population of children with HH.DesignRetrospective national cohort study.MethodsSanger sequencing and multiplex ligand-dependent probe amplification analysis ofPHEXand Sanger sequencing ofFGF23,DMP1,ENPP1KL, andFAM20Cwere performed to assess genotype in patients with HH with or without rickets in all pediatric hospital departments across Norway. Patients with hypercalcuria were screened forSLC34A3mutations. In one family, exome sequencing was performed. Information from the patients' medical records was collected for the evaluation of phenotype.ResultsTwety-eight patients with HH (18 females and ten males) from 19 different families were identified. X-linked dominant hypophosphatemic rickets (XLHR) was confirmed in 21 children from 13 families. The total number of inhabitants in Norway aged 18 or below by 1st January 2010 was 1 109 156, giving an XLHR prevalence of ∼1 in 60 000 Norwegian children.FAM20Cmutations were found in two brothers andSLC34A3mutations in one patient. In XLHR, growth was compromised in spite of treatment with oral phosphate and active vitamin D compounds, with males tending to be more affected than females. Nephrocalcinosis tended to be slightly more common in patients starting treatment before 1 year of age, and was associated with higher average treatment doses of phosphate. However, none of these differences reached statistical significance.ConclusionsWe present the first national cohort of HH in children. The prevalence of XLHR seems to be lower in Norwegian children than reported earlier.

Aim: To establish reference values for waist circumference and waist-to-height ratio of Norwegian children. Material: Data were collected in 2003–2006 as part of a cross-sectional study, including 5725 children 4–18 years of age. Reference curves were fitted with the LMS method; appropriate cut-offs were selected using receiver operating characteristic analysis. Results: Reference values for waist circumference and waist-to-height ratio are presented. Mean waist circumference increased with age for both genders. Boys had a higher waist circumference at almost all ages. Mean waist-to-height ratio decreased until early adolescence and thereafter increased slightly towards adult age. There was a strong positive correlation between waist circumference and BMI (r = 0.907, p

Background The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed. Material and methods The paper is based on four case reports and provides a short review of the condition. Results Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many. Interpretation In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.

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. Only IGHD patients with peak stimulated growth hormone level Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

Objectives The purpose of this study was to investigate the association between weight-related anthropometric measures and children's eating habits, physical activity and sedentary lifestyle at a population level. Methods Data from the Bergen Growth Study were used to study the association of z-scores of waist circumference (WC), weight-to-height ratio (WHtR), subscapularis (SSF) and triceps (TSF) skinfolds and BMI, with lifestyle factors in 3063 Norwegian children (1543 boys) aged 4-15 years, using linear regression analysis. Each sex was analyzed separately. Results In a fully adjusted model with additional correction for BMI z-scores, the consumption of vegetables was associated with higher WC (b = 0.03) and TSF (b = 0.05) z-scores in girls. Sedentary behavior was not associated with any of the anthropometric measures. Physical activity was negatively associated with SSF (b = -0.07) and TSF (b = -0.07) z-scores in boys, while a significant negative association was observed with WC (b = -0.02), WHtR (b = -0.03), SSF (b = -0.04) and TSF (b = -0.06) in girls. Conclusion Physical activity was negatively associated with skinfolds in both sexes. The BMI was not related to the level of physical activity, and should be complemented with direct measures of fat tissue, like skinfolds, when studying the effect of physical activity on body composition in children.

Aims: To compare the parental perception of overweight and underweight in their children to objective criteria, based on body mass index (BMI), waist circumference and triceps skinfold thickness, and to explore the effects of potential determinants. Methods: Logistic regression of anthropometric measurements, socio-demographic characteristics and self-reported parental height and weight on the parental perception of their child’s weight status in 3770 children aged 2–19. Results: Seventy per cent of overweight/obese children and 40.8% of underweight children were perceived having normal weight by parents. In 2- to 5-year-old overweight children, 91.2% were considered to have normal weight. For a given BMI, primary school age children, adolescents and girls had a higher probability to be assigned as overweight, whereas adolescents and girls had a lower probability to be assigned as underweight. Overweight parents more readily assigned their children as underweight, but there was no effect of parental educational level or parental underweight. Conclusion: Parental ability to recognize overweight or underweight in their offspring was generally poor. The findings emphasize the need for objective criteria based on physical measurements in the routine follow up of children, as parental ability to recognize weight problems in their children is nonreliable.

Aim: The aim of this study was to estimate the prevalence of childhood overweight and obesity and to identify socio-demographic risk factors in Norwegian children. Methods: The body mass index of 6386 children aged 2–19 years was compared with the International Obesity Task Force (IOTF) cut-off values to estimate the prevalence of overweight including obesity (OWOB) and obesity (OB). The effect of socio-demographic factors on this prevalence was analysed using multiple ordinal logistic regression analysis in a subsample of 3793 children. Results: The overall prevalence of OWOB was 13.8% (13.2% in boys and 14.5% in girls, p = 0.146), but the prevalence was higher in primary school children aged 6–11 years (17%, p

The production of serum opsonins and other antibodies to serogroup B serotype 15 meningococci was examined in 7 patients with serogroup B serotype 15 meningococcal disease and 7 volunteers immunized with a vaccine containing outer membrane proteins from serogroup B serotype 2b and 15 meningococcal strains complexed with polysaccharides from serogroups A, C, Y and W-135 meningococci. Serum opsonic activity was measured by a flow cytometric phagocytosis technique, using unfixed serogroup B Neisseria meningitidis labelled with fluorescein isothiocyanate. Serum antibodies to outer membrane complexes prepared from the meningococcal test strain, B:15:P1.16, were measured by an enzyme linked immunosorbent assay. The mean number of bacteria per phagocyte increased from 9.7 to 17.3 (mean difference 7.6, p

A synthetic analog of a hemoregulatory peptide associated with mature human granulocyte (HP5B) has been investigated for inhibitory effects on human myelopoietic stem cells in vitro. In addition, it has been tested for effects on phagocytosis by human granulocytes and monocytes by use of an automatic flow cytometric method. A dose-dependent inhibition of colony formation was found after preincubation of bone marrow cells for 1 h at 37 degrees C in the range 10(7) -10(-11) mol/l. Above or below these concentrations, no inhibitory effects were seen. The degree of inhibition varied from experiment to experiment, indicating variable responsiveness of the donor cells. Maximal effect was of magnitude 90% inhibition, and the optimal dose was 10(7) mol/l. The peptide had no effect on the kinetics of phagocytosis by measurements of the uptake of fluorescent Zymosan particles or Staphylococcus aureus. This may indicate a selective effect on the precursor cells, with no effect on the functional state of their progeny, the granulocytes and monocytes.

Background The growth charts currently used in Norway, are based on measurements from the 1970s and 80s. New data are available from the Bergen Growth Study collected in 2003 - 6. In 2006, WHO published international charts for 0-5 year-old children. Material and methods New growth charts based on data from the Bergen Growth Study and the Medical Birth Registry of Norway are presented for children aged 0-19 years. These were compared with existing references and with the WHO curves. Results Norwegian children aged 0-4 years have length, height and weight measurements that are only marginally different from those in the Norwegian growth charts in current use. In older children there has been an increase in the 50-percentile for height up to 3.4 cm in boys and 2.5 cm in girls. For children older than four years, weight for height has increased, especially for the upper percentiles. The percentile lines in the new Norwegian reference are generally positioned above the WHO standard for weight at birth, and for length/height, weight and head circumference in the age group 6 months to 5 years. Interpretation The secular trends in growth mirror the need for new charts. The fact that Norwegian children differ from the WHO standards may reflect population differences relating to environment or growth potential between the populations.

Aim: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. Methods: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. Recommendations: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery—to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

Undescended testis is a common finding in boys, and the majority of cases have no discernible aetiology. There are unexplained geographical differences and temporal trends in its prevalence. Cryptorchidism, especially bilateral, is associated with impaired spermatogenesis and endocrine function and increases the risk of testicular cancer. There is an urgent need to identify factors that adversely affect testicular development and optimize treatment. Conclusion: Cryptorchidism may reflect a primary testicular maldevelopment with long-term consequences.

Background and objectivesGrowth reference charts are usually based on measurements of children free from a medical condition that affects growth. However, samples collected during the past decades often contain a large proportion of overweight or obese children. Because obesity increases linear growth, the question arises to what extent the percentiles curves for length/height are affected by the presence of children with overweight or obesity.MethodsData from two cross-sectional samples of 2-year-old to 18-year-old children were analysed: 12 252 Belgian children, measured in 2002–2004, and 6159 Norwegian children, measured in 2003–2006. The LMS method was used to estimate height-for-age curves with and without children considered overweight or obese according to the International Obesity Task Force thresholds.ResultsThe prevalence of overweight (including obesity) and obesity was 13.0% and 2.8% in the Belgian and 13.8% and 2.3% in the Norwegian sample. Children were taller when overweight (+0.49 and 0.43 SD, in the Belgian and Norwegian sample, respectively) or obese (+0.73 and 0.72 SD in the Belgian and Norwegian sample, respectively). Effect sizes were smaller in younger and older children, which points to an advanced age of maturation as a possible cause. Excluding overweight and obese children had only a minor impact on the growth curves with largest difference in mean height SD scores −0.09 in the Belgian and −0.12 in the Norwegian sample with a corresponding increase of up to 0.5% and 1.2% in number of children >+2 SD.ConclusionsCurrent Belgian and Norwegian growth references for length/height were found to be largely unaffected by the current proportion of overweight and obese children. There is, therefore, no need for revised height charts that exclude overweight or obese children.

ObjectiveTo identify associations between the weight groups underweight (UW), overweight (OW) and obesity (OB) at 5 years of age and exposures related to pregnancy, anthropometric measures at birth, sociodemographic factors, and family health, anthropometric measures and habits.DesignRegional cohort study.SettingOppland County, Norway.MethodsPregnancy data were obtained from a prospective perinatal register for children born in the county, and weight and height were measured by midwives at birth and by public health nurses at 5 years. Other information was obtained from questionnaires completed by parents.ParticipantsOf 1895 eligible children, current weight and height were obtained for all, weight and length at birth and information from parents for 1119 (59%) and pregnancy register data for 749 (40%) of the children. The significance of potential explanatory variables from descriptive statistics was tested in multinomial logistic regression analysis.ResultsThe prevalence of UW, OW and OB among participants was 7.8%, 10.6% and 3.5%, respectively. UW was associated with anthropometric measures at birth and those of parents, but not with sociodemographic or behavioural characteristics. OW and OB were associated with anthropometric measures of parents and siblings and with a variety of unfavourable social characteristics, lack of prolonged breast feeding, sedentary behaviour and dental caries, but not with current dietary habits. After adjustments, OW and OB were marginally related to birth parameters and diet and unrelated to physical activity, but significantly related to parental body mass index, low parental education and maternal smoking.ConclusionThe strong associations between sociodemographic and behavioural factors and OW and OB, but not with UW, may suggest that environmental factors are major contributing causes of OW and particularly OB at 5 years. These results may be helpful in targeting preventive measures against OW and OB.

Early identification of wheezing children with an increased risk of recurrent wheezing or subsequent asthma is important. The aim of the study was to determine the role of markers of eosinophil activation, along with other parameters, in the prediction of recurrent wheezing and allergic sensitization in children with early and severe wheezing. We examined 105 children without atopic dermatitis, hospitalized for wheezing during the first year of life. At a 20-mo follow-up, 101 of the children were assessed for the occurrence of recurrent wheezing (at least 3 episodes, including 1 in the previous 6 mo) and allergic sensitization (positive skin-prick test). By univariate analysis, levels of eosinophil counts at the time of hospitalization (p= 0.005, OR = 18.9), age in months (p < 0.0001, OR =1.5), respiratory syncytial virus (RSV)-negative disease (p

It has been suggested that urinary eosinophil protein X (U-EPX) can be used to monitor bronchial inflammation in childhood asthma. However, the influence of atopy and airway infections is not well elucidated. To determine the clinical value of measuring U-EPX in children with asthma and to evaluate the influence of atopy and airway infections, U-EPX was measured in 170 children with asthma (mean age 69 months, range 12-179 months), in 79 children with lower or upper respiratory tract infections (mean age 41 months, range 1-165 months), and in 64 controls. U-EPX was elevated in children with acute asthma (median 132 microg/mmol of creatinine, quartiles 77-195 microg/mmol of creatinine, n = 51, p

Background: Parameters of eosinophil inflammation have been suggested as markers of disease activity in atopic dermatitis (AD), but the value of urinary eosinophil protein X (U-EPX) in children with AD, as well as the influence of allergic sensitization, is not known. Methods: We measured U-EPX in 59 atopic and 29 nonatopic children with mild (n=32), moderate (n=34), and severe (n=22) AD, as well as in 64 controls. Results: U-EPX was increased in children with AD (110; 67–164 μg/mmol creatinine, median; quartiles) compared to controls (62; 41–95, P

The immunopathogenesis of human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased death by apoptosis of T cell subsets. In the present study, we have examined correlates of apoptosis of CD4+, CD8S+CD28+, and CD8+CD28- T cells in tonsillar lymphoid tissue in persons with HIV-1. Single-cell suspensions of tonsillar lymphocytes were analyzed by flow cytometry to determine the fraction of cells showing typical characteristics of apoptosis as well as the expression of activation markers within the live and the apoptotic cell populations. The proportion of cells carrying infectious provirus was quantified by limiting dilution analysis. Compared with uninfected controls, apoptosis of both CD4+ and CD8+ T cells was enhanced in HIV-1 infection and was higher among CD8+ than among CD4+ T cells. Apoptosis of CD28-cells was more prevalent than apoptosis of CD28+ cells for both CD4+ and CD8+ T cells. Occurrence of apoptosis of CD4+ T cells correlated with provirus levels and proportional expression of the activation marker HLA-DR. Apoptosis of CD8+CD28+ cells correlated with expression of the activation markers CD69 and HLA-DR while apoptosis within CD8+CD28- cells did not correlate with any of the studied parameters. Although apoptosis was much more prevalent among CD8+ than CD4+ T cells, CD8+ T cells still accumulated in tonsillar lymphoid tissue in persons with HIV-1. Our data may be interpreted to suggest that apoptosis of CD4+, CD8+CD28+, and CD8+CD28- cells in tonsillar tissue is regulated by different mechanisms and the results are of importance to our understanding of the immunopathogenesis of HIV-1 infection.

We describe two brothers of consanguineous Pakistani parents who lived in Norway and had disseminated infections due to nontuberculous mycobacteria. The first boy developed clinical signs of disseminated BCG infection after vaccination. He was successfully treated with antimycobacterial agents. Two and one-half years later, he developed disseminated Mycobacterium avium complex infection and died at 6 years of age. The second boy, born 5 years after the death of his brother, did not receive BCG vaccine. At 2 years of age, he developed disseminated M. avium complex infection. Because he responded only partly to specific chemotherapy, empirical interferon gamma treatment was added to the antimycobacterial regimen. After 2 years of combined therapy, his condition is stable. Studies of peripheral blood mononuclear cells from the second boy demonstrated reduced surface expression of the ligand binding chain of interferon gamma receptor 1. This defect explains the increased susceptibility to mycobacterial disease in the two brothers.

The object of the study was to assess the levels of circulating forms of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin, L-selectin and P-selectin in young children with asthma and acute bronchiolitis. Thirty-nine children aged 12 to 84 months with mild or moderate asthma were studied at admission for acute asthma (n = 15) or in a stable phase (n = 24). Ten of the children with acute asthma were seen again after one month. Twenty-two children aged 1 to 17 months with acute bronchiolitis and nine non-atopic controls were also included in the study. In children with acute asthma, the mean concentration of circulating soluble ICAM-1 (sICAM-1) was increased compared to children with stable asthma (mean 442 micrograms/l versus 363 micrograms/l; p < 0.001) and to controls (363 micrograms/l; p < 0.05). The levels of sICAM-1 remained high at follow up. In children with stable asthma, the mean serum concentration of soluble L-selectin (sL-selectin) (2080 micrograms) was significantly higher than in the controls (1664 micrograms/l; p < 0.05). The levels of circulating cellular adhesion molecules were similar in atopic and non-atopic asthmatics. Children with acute bronchiolitis had increased serum levels of soluble VCAM-1 (sVCAM-1) (1637 micrograms/l versus 1019 micrograms/l in the controls; p < 0.01) and sL-selectin (2041 micrograms/l versus 1664 micrograms/l in the controls; p < 0.05). There was no difference between the levels of circulating cellular adhesion molecules in children with respiratory syncytial virus (RSV) positive and RSV negative bronchiolitis. Soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) in serum were not significantly increased in any of the groups studied. In conclusion, our data suggest differential patterns of circulating cellular adhesion molecules in young children with acute asthma, stable asthma, and acute bronchiolitis, which may reflect differences in the underlying inflammatory processes in these obstructive pulmonary diseases.

SUMMARY Levels of HIV-1 have been reported to increase in peripheral blood after influenza vaccination of HIV+ individuals. In this study we have evaluated the dynamics of these changes. Ten HIV-1+ individuals classified in revised CDC clinical categories B and C as well as five seronegative healthy controls were vaccinated with the recommended influenza strains. HIV viral RNA and proviral DNA were sequentially quantified in serum and blood lymphocytes, respectively. Nine of the 10 HIV+ individuals had an increase in the frequency of infected CD4 cells 2 weeks after influenza vaccination. Individuals with low viral load had a rapid increase in viraemia and a small increase in frequency of infected cells in peripheral blood. In contrast, individuals with high viral load had a small drop in viraemia followed by a significant rise in the rate of infected cells. The observed changes may resemble those taking place during intercurrent infections in HIV+ individuals. The effects of the relative increases in infectious virus after the transient viraemic phase should be further investigated to evaluate potential risks of vaccination.