Growth in achondroplasia: Development of height, weight, head circumference, and body mass index in a European cohort.

As growth references for achondroplasia are limited to reports from United States, Japan, Argentina, and Australia, the aim of this study was to construct growth references for height, weight, head circumference, and body mass index (BMI) from a European cohort of children with achondroplasia and to discuss the development of these anthropometric variables. A mix of cross-sectional and longitudinal, retrospective, and prospective data from 466 children with achondroplasia and 4,375 measuring occasions were modeled with generalized additive model for location, scale and shape (GAMLSS) to sex-specific references for ages 0 to 20 years. Loss in height position, that is, reduction in height standard deviation scores, occurred mainly during first 2 years of life while pubertal growth seemed normal if related to adult height. Adult height was 132 cm in boys and 124 cm in girls with a variability comparable to that of the general population and seems to be remarkably similar in most studies of children with achondroplasia. BMI had a syndrome-specific development that was not comparable to BMI development in the general population. Weight and BMI might be misleading when evaluating, for example, metabolic health in achondroplasia. Head circumference reached adult head size earlier than in the general population. Increased tempo of head circumference growth necessitates thus close clinical follow-up during first postnatal years.

Development of body proportions in achondroplasia: Sitting height, leg length, arm span, and foot length.

The aims of this study was to construct references for sitting height, leg length, arm span, relative sitting height (sitting height/height), and foot length and to discuss the development for these anthropometric variables in achondroplasia. Sex-specific references covering ±2 SD are presented for ages 2-20 years. Legs and arms in achondroplasia are already at 2 years of age considerably shorter than in the general population and this deviation increases with age. At adult ages, legs are almost 50% shorter than in the general population and arm span roughly 35% shorter. As sitting height is only mildly affected, relative sitting height position develops far beyond normal ranges. Foot length is also not as affected as limbs.

A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype.

Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.

Early intervention for childhood overweight: A randomized trial in general practice.

OBJECTIVE: To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice. DESIGN: Prospective randomized controlled trial. SETTING: A total of 60 general practices in the former County of Funen, Denmark. SUBJECTS: Overweight children, identified by International Obesity Task Force criteria, aged 5-9 years. INTERVENTION: Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations. MAIN OUTCOME MEASURES: Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time. RESULTS: A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI -0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.09) in Model 2, respectively, was detected. The majority of the participants (2/3) continued in the study for more than one year in both models, with a mean of 12 consultations in general practice. CONCLUSION: In this particular setting the two intervention strategies against overweight and obesity did not differ significantly with regard to change in BMI z-scores.

Prevalence of overweight and obesity in Danish preschool children over a 10-year period: a study of two birth cohorts in general practice.

AIM: To determine change in the prevalence of overweight and obesity in preschool children, over a 10-year period and to identify possible predictors of overweight in 5-year-old children. METHODS: Anthropometric data from birth and routine child health examinations at 3 and 5 years of age performed in general practice were collected in 5580 children from two Funen birth cohorts (1992 and 2001, respectively) representing 48% of the total population at similar age. The prevalence of overweight and obesity was classified using the International Obesity Task Force definitions. RESULTS: In a Danish representative survey of preschool children, the average body mass index (BMI) and prevalence of overweight and obesity did not vary significantly during the 10-year period. No significant changes in mean birth weight were registered and mean BMI in the group of obese children did not increase. Overweight or obesity at 5 years was strongly associated with overweight and obesity at 3 years and with birth weight and gender. CONCLUSION: The prevalence of overweight and obesity was observed to be stable over a decade in Danish preschool children without changes in mean BMI in the group of obese children. A strong association between overweight and obesity at 3 and at 5 years of age was detected.

Identifying and prioritising technical procedures for simulation-based curriculum in paediatrics: a Delphi-based general needs assessment.

OBJECTIVES: To identify and prioritise technical procedures that should be integrated in a curriculum of simulation-based procedural training in paediatrics using the Delphi method. STUDY DESIGN: National general needs assessment using a Delphi process was completed among 93 key opinion leaders in paediatrics in Denmark. Delphi round 1 identified technical procedures. Round 2 explored frequency of procedures, number of paediatricians performing the procedures, risks and/or discomfort for patients and feasibility for simulation-based training. Round 3 included final elimination and reprioritisation. RESULTS: Response rates in the Delphi rounds were 73%, 71% and 72%. We identified 37 procedures in Delphi round 1, preprioritised in round 2, resulting in a final list of 19 procedures in round 3. Strong correlation between the prioritisation from the second and third Delphi rounds was identified, Spearman's r of 0.94 (p<0.0001). Top five on the final list were acute neonatal airway management, acute non-neonatal airway management, non-neonatal peripheral intravenous and intraosseous access, neonatal vascular access and advanced heart lung resuscitation. CONCLUSION: We identified and prioritised 19 technical procedures in paediatrics that are suitable for simulation and may be used as a guide for the development of simulation-based curriculum in paediatrics.

Cushing's syndrome in children and adolescents: a Danish nationwide population-based cohort study.

OBJECTIVE: Cushing's syndrome (CS) affects all age groups, but epidemiologic data in young patients are very limited. We therefore examined the incidence, prevalence and hospital morbidity of CS in children and adolescents. DESIGN: In a nationwide cohort study, we included all Danish citizens aged 0-20 years from 1977 to 2012. Data were obtained from the Danish National Patient Registry using the International Classification of Diseases (ICD) codes and the Danish Civil Registration System. The diagnosis and treatment were validated by means of individual patient charts. Incidence rate of CS patients aged 0-20 years at diagnosis were computed (standardized to the age and sex distribution of the Danish population). The patients were followed for a maximum of 36 years. Standardized incidence ratios (SIRs) of different hospital-recorded outcomes based on the ICD codes in patients with CS compared to the general population were assessed. RESULTS: We identified a total of 40 pediatric patients with CS, yielding an annual incidence of 0.89 cases/106 population (95% confidence interval (CI) = 0.63-1.16). The median age at the time of diagnosis was 13.8 years (interquartile range: 10.5-18.2 years), 58% were female and 70% had adrenocorticotropic hormone-producing pituitary adenomas. During follow-up, CS patients (excluding three malignant cases) were at increased risk of being diagnosed with infections (SIR: 3.24, 95% CI: 1.05-7.54) and infertility (SIR: 4.56, 95% CI: 1.48-10.63). The three patients with an adrenocortical carcinoma died shortly after diagnosis, but mortality was not increased in the remaining patients. CONCLUSIONS: CS is rare in the pediatric population. The risk of morbidity related to infections and infertility is elevated and merits further attention.

Danish Registry of Childhood and Adolescent Diabetes.

AIM: The aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes. STUDY POPULATION: The study population consists of all children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (<18 years of age) will be included. MAIN VARIABLES: The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. DESCRIPTIVE DATA: The number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients <15 years of age were diagnosed in 2014). The disease management has changed dramatically with more children treated intensively with multiple daily injections, insulin pumps, and increased number of self-monitored blood glucose values per day. These initiatives have resulted in a significant improvement in HbA1c over the years and a decrease in the number of children experiencing severe hypoglycemia, diabetic nephropathy, and retinopathy. CONCLUSION: The systematic collection of data in DanDiabKids documents improved quality of care over the last 12 years, despite a substantial increase in the number of patients cared for by pediatric departments in Denmark, fulfilling the purpose of the registry.

Recombinant human growth hormone treatment, using two dose regimens in children with chronic renal failure--a report on linear growth and adverse effects.

The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.

[Severe vitamin D deficiency causing hypocalcaemic seizures in an ethnic Danish teenager].

We describe an ethnic Danish teenage boy presenting with repeated non-febrile generalized hypocalcaemic seizures. During the previous two years he experienced fatigue, painful legs, increasing social isolation and failure to attend school. Severe hypocalcaemia was recognized at his second seizure. After treatment with vitamin D his symptoms resolved and he became increasingly social and outgoing. This case describes possible non-skeletal effects of severe vitamin D deficiency and underlines the necessity of measuring ionized calcium at the presentation of non-febrile seizures.

Serious disease - serious game.

Teenagers with diabetes often experience their disease as a heavy burden, feeling estranged from their peers. Traditional aids to monitoring and controlling the illness are often not used by this group, because they seem to enhance this feeling. Preliminary interviews with a focus group indicate that teenagers will be motivated by competing to maintain a certain level of blood glucose, regular measurements and assessment of the glucose level in their diet as well as insulin dosing at mealtimes. By the use of serious gaming and taking a user oriented approach for the development process, the DiaApp project will develop a smartphone app that will incorporate disease monitoring and maintenance into a game, thus encouraging the teenagers to manage their disease better and educating them about it as well.

Semi-structured interview is a reliable and feasible tool for selection of doctors for general practice specialist training.

INTRODUCTION: In order to optimise the selection process for admission to specialist training in family medicine, we developed a new design for structured applications and selection interviews. The design contains semi-structured interviews, which combine individualised elements from the applications with standardised behaviour-based questions. This paper describes the design of the tool, and offers reflections concerning its acceptability, reliability and feasibility. MATERIAL AND METHODS: We used a combined quantitative and qualitative evaluation method. Ratings obtained by the applicants in two selection rounds were analysed for reliability and generalisability using the GENOVA programme. Applicants and assessors were randomly selected for individual semi-structured in-depth interviews. The qualitative data were analysed in accordance with the grounded theory method. RESULTS: Quantitative analysis yielded a high Cronbach's alpha of 0.97 for the first round and 0.90 for the second round, and a G coefficient of the first round of 0.74 and of the second round of 0.40. Qualitative analysis demonstrated high acceptability and fairness and it improved the assessors' judgment. Applicants reported concerns about loss of personality and some anxiety. The applicants' ability to reflect on their competences was important. CONCLUSION: The developed selection tool demonstrated an acceptable level of reliability, but only moderate generalisability. The users found that the tool provided a high degree of acceptability; it is a feasible and useful tool for -selection of doctors for specialist training if combined with work-based assessment. Studies on the benefits and drawbacks of this tool compared with other selection models are relevant. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Video recordings can be used for easier and faster evaluations of the performances of postgraduate trainees]. / Videooptagelse kan bruges til nemmere og hurtigere evalueringer i uddannelsen af læger i klinisk basisuddannelse.

Evaluating post-graduate trainees under direct observation is troublesome, and there are concerns about rater-variability. The aim of this study was to explore if video recordings could be used for evaluation. The performances of five trainees were video recorded. The videos were assessed by six supervisors watching either the complete recording or approximately 20 min. Video recording was well tolerated by the patients and the supervisors, but not the trainees. Watching part of the videos was sufficient for assessment. Video recording seems to provide a feasible method of assessing postgraduate trainees.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual ß-cell function 1 year after diagnosis of type 1 diabetes.

The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual ß-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration of disease symptoms (P = 0.0004), and with risk alleles of WFS1, CDKN2A/2B and RNLS (P = 0.006). (2) A second pattern of high ZnT8 autoantibody levels and low postprandial glucagon levels associated with risk alleles of IFIH1, TCF2, TAF5L, IL2RA and PTPN2 and protective alleles of ERBB3 gene (P = 0.0005). These results demonstrate that Latent Factor Modelling can identify associating patterns in clinical prospective data--future functional studies will be needed to clarify the relevance of these patterns.

[Recommendation for identical growth curves in Denmark]. / Anbefaling af ens vaekstkurver i Danmark.

Growth monitoring is essential for the evaluation of health in children. Growth and final height have changed over time, the secular trend, and therefore updated growth curves are important. In this article the growth curves in use in Denmark are reviewed. In 2003 two different growth curves with older reference populations were used for growth evaluation after the neonatal period, and five different growth curves were in use for neonatal growth evaluation. To make growth evaluation more homogeneous we recommend one updated Scandinavian growth curve for child growth monitoring in Denmark.

[Vitamin D1alpha-hydroxylase deficiency as the cause of severe rickets in a 1-year-old-old boy]. / D-vitamin-1 alpha-hydroxylase-mangel som årsag til svaer rakitis hos en etårig dreng.

We describe a 15-month-old boy referred to the hospital because of delayed development of motor skills and growth retardation. Blood samples and X-rays of the wrists and knees revealed rickets. He was treated with oral calcium and vitamin D with modest clinical and biochemical effect. 1,25-dihydroxyvitamin D was undetectable in laboratory tests. Vitamin D1alpha-hydroxylase deficiency was suspected and confirmed by DNA analysis, which revealed a 7 bp duplication in exon 8 of the CYP27B1 gene. The treatment was changed to an activated formula of vitamin D, alphacalcidol, whereupon the clinical and biochemical symptoms rapidly improved.

[Growth hormone treatment of short children born small for gestational age]. / Vaeksthormonbehandling af korte børn født small for gestational age.

Short children born small for gestational age (SGA) are defined as having a birth weight below -2 SD for gestational age and a reduced height at four years of age (height < -2.5 SD). Growth hormone (GH) treatment significantly improves final height (mean height gain 12 centimetres) in such children. Consequently, GH therapy has been an approved indication in Europe since 2003 for SGA children who remain short at four years of age. The Danish consensus guidelines for diagnosis, treatment and control of short SGA children are described in this review.

Growth hormone treatment in 35 prepubertal children with achondroplasia: a five-year dose-response trial.

BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. METHODS: Patients were randomized to either 0.1 IU/kg (n = 18) or 0.2 IU/kg (n = 17) per day. GH treatment was interrupted for 12 mo after 2 y of treatment in prepubertal patients to study catch-down growth. Mean height SDS (HSDS) at start was -5.6 and -5.2 for the low- and high-dose groups, respectively, and mean age 7.3 and 6.6 y. RESULTS: Mean growth velocity (baseline 4.5/4.6 cm/y for the groups) increased significantly by 1.9/3.6 cm/y during the first year and by 0.5/1.5 cm/y during the second year. During the third year, a decrease of growth velocity was observed at 1.9/1.3 cm/y below baseline values. HSDS increased significantly by 0.6/0.8 during the first year of treatment and in total by 1.3/1.6 during the 5 y of study. Sitting height SDS improved significantly from -2.1/-1.7 to -0.8/0.2 during the study. Body proportion (sitting height/total height) or arm span did not show any significant change. CONCLUSION: GH treatment of children with achondroplasia improves height during 4 y of therapy without adverse effect on trunk-leg disproportion. The short-term effect is comparable to that reported in Turner and Noonan syndrome and in idiopathic short stature.