Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n = 18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n = 13). Final height SDS was > 122 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model

Purpose We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. Methods We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. Results We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R-2 87.2%). Conclusion This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies

Whole-exome sequencing identification of non-synonymous SNP variants of 10 CHI patients.

*<p>Mutation reported in Human Genome Mutation Database( HGMD).</p><p>PolyPhen/SIFT: (−) benign or tolerated; (+) possibly damaging/DAMAGING Low confidence;</p><p>(++) probably damaging/DAMAGING.</p><p>In bold known causative genes.</p

Functional annotation of novel variants.

<p>Functional annotation of novel variants.</p

Exome coverage and target coverage statistics of ten CHI probands.

<p>Exome coverage and target coverage statistics of ten CHI probands.</p

MODELLO DI PREVISIONE DELLA STATURA FINALE IN PAZIENTI PEDIATRICI ITALIANI AFFETTI DA DEFICIT DI GH TRATTATI CON SOMATROPINA

Obiettivi: elaborare un modello di previsione della statura finale in pazienti pediatrici con deficit di GH trattati con somatropina ricombinante, valutando quali siano le variabili più importanti nel determinismo della statura finale. Metodi: 1043 pazienti trattati per deficit di GH (picco di GH &lt;10 ng/dl a 2 test di stimolo) giunti ad altezza finale. Mediana età a inizio trattamento 11 (IQR 8.7/12.8) anni; mediana altezza a inizio trattamento -2.43 (IQR -2.80/-2.01) SDS; mediana altezza bersaglio -1.09 (IQR -1.63/-0.48) SDS; dose iniziale di somatropina mediana altezza finale -1.08 SDS (IQR -1.64/-0.50 SDS, vs altezza a inizio trattamento p &lt;0.001, vs altezza bersaglio p=ns). Analisi statistica con metodica RELIMPO. Risultati: 2 modelli sono risultati migliori rispetto ad altri. Il primo modello (488 pazienti) ha testato l’effetto di genere, altezza bersaglio, età alla pubertà, altezza alla pubertà ed età a fine trattamento sull’altezza finale in cm con r-quadro di 87.2%. Le variabili più importanti nel determinismo dell’altezza finale sono risultate: altezza bersaglio (18.8%), altezza alla pubertà (16.3%) ed età a fine terapia (circa 35% considerando le variabili polinomiali). Il secondo modello ha valutato su 543 pazienti l’effetto di genere, durata della terapia, età a inizio terapia, altezza SDS alla pubertà, altezza bersaglio SDS e altezza dopo 12 mesi di terapia sull’altezza finale SDS con r-quadro di 59%. Altezza a 12 mesi di terapia e altezza SDS alla pubertà sono state le variabili più importanti nel determinismo dell’altezza finale SDS (rispettivamente 23% e 10%). Conclusioni: La metodica RELIMPO (Relative Importance of Regressors in Linear Models) estrae casualmente dal database i pazienti con dataset completo, elabora il modello di previsione e lo valida su altri pazienti estratti sempre casualmente. In questo modo abbiamo ottenuto 2 modelli di previsione staturale, il primo dell’altezza finale in cm e in SDS. La previsione della statura in cm è più precisa. Mostriamo per la prima volta un modello di previsione solo su dati italiani, con una casistica molto ampia e con un r-quadro elevato

Pianeta Nutrizione kids: international pediatric conference on food, physical activity, growth and well-being : Milan, Italy. 25-27 June 2015

A1 Preterm and low birth weight nutrition in the first month life: implications for the outcome Massimo Agosti A2 Behind human milk and breastfeeding: not only food, not only growth Carlo Agostoni A3 To prevent obesity: importance and issues of cultural adaptation from weaning to 3 years of age Serge Chalons A4 Diet before and during pregnancy and child health: lessons from animal models Pascale Chavatte-Palmer A5 Infant nutrition: an opportunity to optimize future health José Manuel Moreno Villares A6 Complementary feeding strategies to facilitate acceptance of fruits and vegetables Sophie Nicklaus A7 Diet of young children in the Mediterranean region Luís Pereira-da-Silva A8 Proposal of 10 good practices to help prevent obesity in the first 1,000 days Angelo Pietrobelli, the MeNu Group A9 Macronutrient intakes in early life and subsequent risk of obesity Marie Françoise Rolland-Cachera A10 The burden of childhood obesity in Italy and the results of Nutrintake study Gian Vincenzo Zuccotti A11 Growth body composition and growth hormone therapy: linear growth Marco Cappa A12 Early nutrition pattern and late metabolic consequences Manuela Caruso-Nicoletti A13 Nutrition and Insulin-like Growth Factor (IGF) System Elena Inzaghi, Stefano Cianfarani A14 Nutrition of preterm infants Mario De Curtis A15 Early nutrition patterns and later metabolic outcomes- I part: Genetic and metabolic mechanisms Laura Guazzarotti A16 Diagnosis of metabolic disease by imaging techniques Lorenzo Iughetti A17 Nutrition, growth and cardiovascular diseases Francesco Chiarelli, Laura Comegna, Simone Franchini A18 Body fat mass and gender Laura Perrone, Giuseppina Rosaria Umano A19 Lifestyle interventions for an appropriate birth weight Elisabetta Petrella, Raffaele Bruno, Valentina Bertarini, Giulia Pedrielli, Isabella Neri, Fabio Facchinetti A20 Nutrition, growth and body composition Flavia Prodam A21 Nation-specific reference growth charts in the daily practice Alessandro Sartorio, John M. H. Buckler, Nicoletta Marazzi A22 Growth patterns in inflammatory bowel diseases (IBD) and in cystic fibrosis (CF) Maria E. Street, Viviana D. Patianna, Paola Accorsi, Sara Lo Scocco, Sergio Amarri A23 Newborn in the digital era and their body feeling: physical exercise to counteract hyperphagia Alberto Pellai A24 Nutrition, young athletes and effects of exercise. Practical suggestions Giampiero Merati A25 Physical exercise as a way to prevent criminality in minors and teenagers Isabella Merzagora A26 The measurement of daily energy expenditure in children. Evaluation of a new wrist portable device vs breath-by-breath metabolimeter Susanna Rampichini, Arsenio Veicsteinas A27 Probiotic and inflammasomes Mario Clerici A28 Probiotics and newborns Paolo Manzoni, Elena Tavella, Elena Boano, Daniele Farina A29 Relationship between gut microbiota and obesity Fabio Pac