A critical comparative study of the performance of three AI-assisted programs for bone age determination.

Objectives: To date, AI-supported programs for bone age (BA) determination for medical use in Europe have almost only been validated separately, according to Greulich and Pyle (G&P). Therefore, the current study aimed to compare the performance of three programs, namely BoneXpert, PANDA, and BoneView, on a single Central European population.

Materials And Methods: For this retrospective study, hand radiographs of 306 children aged 1-18 years, stratified by gender and age, were included.

Acceleration of skeletal maturation in Central Europe over the last two decades: insights from two cohorts of healthy children.

Background: Deviations between the determination of bone age (BA) according to Greulich and Pyle (G&P) and chronological age (CA) are common in Caucasians. Assessing these discrepancies in a population over time requires analysis of large samples and low intra-observer variability in BA estimation, both can be achieved with artificial intelligence-based software. The latest software-based reference curve contrasting the BA determined by G&P to the CA of Central European children dates back over two decades.

Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency, Small for Gestational Age, and Turner Syndrome in Germany: Data from the PATRO® Children Study.

Introduction: Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment.

Methods: German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018.

Automated bone age assessment in a German pediatric cohort: agreement between an artificial intelligence software and the manual Greulich and Pyle method.

Objectives: This study aimed to evaluate the performance of artificial intelligence (AI) software in bone age (BA) assessment, according to the Greulich and Pyle (G&P) method in a German pediatric cohort.

Materials And Methods: Hand radiographs of 306 pediatric patients aged 1-18 years (153 boys, 153 girls, 18 patients per year of life)-including a subgroup of patients in the age group for which the software is declared (243 patients)-were analyzed retrospectively. Two pediatric radiologists and one endocrinologist made independent blinded BA reads.

Deeplasia: deep learning for bone age assessment validated on skeletal dysplasias.

Background: Skeletal dysplasias collectively affect a large number of patients worldwide. Most of these disorders cause growth anomalies. Hence, evaluating skeletal maturity via the determination of bone age (BA) is a useful tool.

Growth Patterns of Children With Short Stature in Adulthood According to Auxological Status and Maturity at Birth.

Context: Prematurity carries a risk for impaired postnatal growth and long-term growth restriction. Especially children born SGA seem vulnerable for poor growth, as a persistent short stature can be observed in app 10-15% of these children.

Objective: In this study we aimed to recognize differences in growth patterns of children according to sex, maturity, and auxological status at birth facilitating earlier identification of small-for-gestational-age (SGA) children with adult short stature.

The Influence of Body Mass Index on the Growth Hormone Peak Response regarding Growth Hormone Stimulation Tests in Children.

Introduction: Several studies have analyzed the association between the maximal growth hormone serum level obtained during a growth hormone stimulation test (GHMax) and the body mass index-standard deviation score (BMI-SDS). However, as sample sizes were quite small, our study aimed to analyze the association between GHMax and BMI-SDS within a large cohort of 991 children. Further, we investigated other influencing factors, like test type, age, sex, puberty, and preterm birth.

BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span.

Context: Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described.

Objective: We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels.

Design And Setting: Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study.

Age- and weight group-specific weight gain patterns in children and adolescents during the 15 years before and during the COVID-19 pandemic.

Background/objectives: There is a concern that measures aiming to limit a further spread of COVID-19, e.g., school closures and social distancing, cause an aggravation of the childhood obesity epidemic.

Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values.

Background: Obesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes.

Methods: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020).

Safety and Effectiveness of Recombinant Human Growth Hormone in Children with Turner Syndrome: Data from the PATRO Children Study.

Introduction: PATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope®; Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).

Methods: The study population included infants, children, and adolescents with TS who received Omnitrope® treatment according to standard clinical practice.

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts' consensus.

Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus.

Important Tools for Use by Pediatric Endocrinologists in the Assessment of Short Stature.

Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions.

Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years' Experience from the PATRO Children Study.

Introduction: Omnitrope® was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006.

Objective: The purpose of this work was to evaluate the long-term safety and effectiveness of Omnitrope® in PATRO Children - an ongoing, international, longitudinal, non-interventional study in children who require rhGH treatment.

Methods: The study population includes infants, children, and adolescents receiving Omnitrope®.

GH and IGF-1 Replacement in Children.

In this chapter, we want to give an overview on what we have learned from more than 30 years ago on the use of recombinant human growth hormone (rhGH) and later recombinant human IGF-1 which was introduced for the treatment of short children and what are the safety issues concerned with this treatment. However, rhGH is used not solely in conditions where short stature is the consequence of GH deficiency but also in various disorders without a proven GH deficiency. In clinical studies, growth responses to various forms of rhGH therapy were analyzed, adding to our concept about the physiology of growth.

GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice.

Introduction: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure.

A Comprehensive Cohort Analysis Comparing Growth and GH Therapy Response in IGF1R Mutation Carriers and SGA Children.

Context: IGF1 receptor mutations (IGF1RM) are rare; however, patients exhibit pronounced growth retardation without catch-up. Although several case reports exist, a comprehensive statistical analysis investigating growth profile and benefit of recombinant human growth hormone (rhGH) treatment is still missing.

Objective And Methods: Here, we compared IGF1RM carriers (n = 23) retrospectively regarding birth parameters, growth response to rhGH therapy, near final height, and glucose/insulin homeostasis to treated children born small for gestational age (SGA) (n = 34).

Genetics of Growth Disorders-Which Patients Require Genetic Testing?

The second 360° European Meeting on Growth Hormone Disorders, held in Barcelona, Spain, in June 2017, included a session entitled vs. , which examined current concepts of genetics and growth in the clinical setting, in terms of both growth failure and overgrowth. For patients with short stature, multiple genes have been identified that result in GH deficiency, which may be isolated or associated with additional pituitary hormone deficiencies, or in growth hormone resistance, primary insulin-like growth factor (IGF) acid-labile subunit deficiency, IGF-I deficiency, IGF-II deficiency, IGF-I resistance, and primary PAPP-A2 deficiency.

Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration.

Introduction: Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family.

Case Report: We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.

Needle-Free and Needle-Based Growth Hormone Therapy in Children: A Pooled Analysis of Three Long-Term Observational Studies.

Background: Treatment with growth hormone (GH) is standard clinical practice in children with GH deficiency (GHD) or Turner syndrome (TS). Hitherto, no long-term data on auxological outcome and safety of Zomacton® have been published. Data comparing needle-free administration (NF) and needle injection (NI) of GH are very sparse.

Gene Alterations in Children Born Small for Gestitional Age (SGA).

Background: Small for gestational age (SGA)-born children are a heterogeneous group with few genetic causes reported. Genetic alterations in the IGF1 receptor (IGF1R) are found in some SGA children.

Aim: To investigate whether alterations in gene are present in SGA born children.