Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience.

BACKGROUND/AIMS: We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. METHODS: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. RESULTS: Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). CONCLUSION: Safety and effectiveness data on use of rhIGF-1 in a 'real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia

Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring

<div><h3>Aim/Hypothesis</h3><p>Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.</p> <h3>Results</h3><p>Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass.</p> <p>Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected.</p> <h3>Conclusions</h3><p>Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes <em>in-utero</em>, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.</p> </div

Long-term Surveillance of Children with Congenital Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE Hypo Dok)

Background: The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software (Hypo Dok) for the documentation of longitudinal data of patients with congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines. Methods/Patients: Anonymised data of 1 080 patients from 46 centres were statistically analysed. Results: Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 mu g/kg/day or 186.0 mu g/m(2)/day. Weight-, BMI-and height-SDS did not differ significantly from the normal population. Only 25 % of the patients (n = 262) underwent formal EQ/IQ-testing. Their average IQ was 98.8 +/- 13.2 points. Discussion: In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological long-term outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care. Conclusion: Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are - according to the recommendations. However standardised IQ testing requires improvement

Frequency of child maltreatment in a representative sample of the German population

Iffland B, Brähler E, Neuner F, Häuser W, Glaesmer H. Frequency of child maltreatment in a representative sample of the German population. BMC Public Health. 2013;13(1): 980.Background Representative data about the frequency of child maltreatment is needed in order to estimate the extent of the problem in the wider population as well as to provide the basis for interpretation of frequency rates in clinical samples. However, previous representative studies on the frequency of child maltreatment in Germany and other countries were limited as they focused on the assessment of physical and sexual abuse whilst emotional forms of maltreatment were ignored. In addition, previous studies applied scales that had not been validated against external criteria. Methods In a cross-sectional study, standardized questionnaires were administered to a representative sample of the German population. Maltreatment in childhood and adolescence was assessed using the German version of the Childhood Trauma Questionnaire. Empirically derived threshold values for the five different types of child maltreatment including emotional maltreatment were applied to determine presence of abuse and neglect. Results Complete data was available from N = 2,500 subjects. Prevalence rates were 13.9% for emotional neglect, 10.2% for emotional abuse, 12.0% for physical abuse, 48.4% for physical neglect, and 6.2% for sexual abuse. Differences between sexes were found for the frequency of sexual abuse. Conclusions Although our analysis has found lower rates of child maltreatment than previous reports that used less well validated criteria, the results of this study confirm that child abuse, with its many different facets, is a significant problem in Germany