Causes, patterns and severity of androgen excess in 487 consecutively recruited pre- and post-pubertal children

Objective Androgen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum DHEAS, androstenedione (A4) and testosterone in childhood androgen excess. Design Retrospective review of all children undergoing serum androgen measurement at a single center over 5 years. Methods Serum A4 and testosterone were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased androgen underwent phenotyping by clinical notes review. Results In 487 children with simultaneous DHEAS, A4 and testosterone measurements, we identified 199 with androgen excess (140 pre- and 59 post-pubertal). Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively. PCOS was diagnosed in 40% of post-pubertal subjects, presenting equally frequent with isolated excess of DHEAS (29%) or testosterone (25%) or increases in both A4 and testosterone (25%). CAH patients (6%) predominantly had A4 excess (86%); testosterone and DHEAS were increased in 50 and 33% respectively. Concentrations increased above the two-fold upper limit of normal were mostly observed in PA for serum DHEAS (&gt;20-fold in the single case of adrenocortical carcinoma) and in CAH for serum androstenedione. Conclusions Patterns and severity of childhood androgen excess provide pointers to the underlying diagnosis and can be used to guide further investigations.</p

Guidance to bone morbidity in children and adolescents undergoing allogeneic hematopoietic stem cell transplantation

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is widely performed in children and adolescents with hematologic diseases, including very high-risk leukemia. With increasing success and survival rates, the long-term sequelae of HSCT have become important. Here, we provide guidance to the prevention and treatment of the most common bone morbidities—osteoporosis and osteonecrosis—emerging in the context of HSCT in children and adolescents. We give an overview on definitions, symptoms, and diagnostics and propose an algorithm for clinical practice based on discussions within the International Berlin Frankfurt Münster (BFM) Stem Cell Transplantation Committee and the Pediatric Disease Working Party of the European Society for Blood and Marrow Transplantation, our expert knowledge, and a literature review

Breastfeeding behavior is not associated with health literacy: evidence from the German KUNO-Kids birth cohort study

Purpose!#!Despite the health benefits of full breastfeeding for both infants and mothers, less than 50% of mothers in Germany practice this method for at least 4 months after childbirth. Because of the growing importance of health literacy to improve public health, we investigated the role of maternal health literacy in breastfeeding behavior.!##!Methods!#!We analyzed the data of 1172 mother-child dyads of the KUNO-Kids health study of the University Children's and Maternity Hospital Regensburg. Maternal health literacy was assessed with the HLS-EU-Q47 questionnaire (sub-index health care) up to 48 h after childbirth. Outcome was analyzed 6 months after childbirth and categorized into full breastfeeding for less than 4 months or for at least 4 months. The association between breastfeeding and maternal health literacy was calculated with univariable and multivariable logistic regression analyses.!##!Results!#!38.8% of mothers showed inadequate or limited health literacy. 75.9% of mothers had fully breastfed their child for at least 4 months. Univariable logistic regression analysis showed that health literacy and full breastfeeding for at least 4 months were not associated (OR = 0.995 [CI 0.977-1.015], p = 0.60). After adjusting for all potentially confounding variables with a significant association (p ≤ 0.05) on both health literacy and breastfeeding, the multivariable model showed no association between health literacy and breastfeeding (OR = 0.984 [CI 0.963-1.007], p = 0.170).!##!Conclusion!#!Surprisingly, we found no association between health literacy and breastfeeding behavior in our study. Therefore, future research with comparable measurements of health literacy and breastfeeding is required to validate this result and to identify reasons for early breastfeeding cessation

PPIB Mutations Cause Severe Osteogenesis Imperfecta

Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the α1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the α1 chains of collagen type I