Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
Abstract
Objective: The aim of this study was to examine height-gain response in relation to predicted good or poor response during first-year low or high growth hormone (GH) dose in short prepubertal children born small for gestational age.
Patients and methods: The OPTIMA (Optimization of GH Treatment in Short Children Born Small for Gestational Age Based on a Growth Prediction Model) randomised study evaluated 12-month height standard deviation score (SDS) changes in patients receiving GH dose: fixed high (FH; 0.067 mg/kg/day) or 0.035 mg/kg/day individually adjusted (IA) after 3 months according to the Cologne early growth prediction.
Results: Predicted 12-month height SDS gain was <0.75 for 21/89 FH-dose patients, considered poor responders; 11/21 reached a 12-month height SDS gain of ≥0.75. In IA-dose poor responders, increasing GH dose at 3 months maintained mean height velocity (HV), with 73.7% reaching a 12-month height SDS gain of ≥0.75 vs. 73.8% in IA-dose good responders who continued on low GH dose, where mean HV decreased after the initial 3-month period.
Conclusion: GH dose increase at 3 months in patients with predicted poor response maintained catch-up growth. Even when on FH dose, some patients did not achieve a good response.
Acknowledgments
The authors are very grateful for the cooperation of all of the investigators involved in the OPTIMA study. The authors also thank Dr. Peter Bates, Cambridge Medical Writing Services, UK, for his help in the preparation of the manuscript, and Claudia Nicolay, Lilly Deutschland, for her support in the statistical analysis.
Conflict of interest statement
Author’s conflict of interest disclosure: E.S. is a member of Medical Research advisory boards for, and E.S. and C.L. have received consulting fees and travel expenses from, Eli Lilly and Company. H.J. and W.F.B. are employees and stockholders of Eli Lilly and Company.
Funding source: The OPTIMA study was funded by Eli Lilly and Company, Indianapolis, IN, USA.
References
1. Mehls O, Lindberg A, Bettendorf M, Doerr H-G, Hauffa BP, et al., for the German KIGS Board. Is the response to growth hormone in children born small for gestational age dependent on genetic or environmental factors? Horm Res 2009;72:106–13.Search in Google Scholar
2. Maiorana A, Cianfarani S. Impact of growth hormone therapy on adult height of children born small for gestational age. Pediatrics 2009;124:e519–31.Search in Google Scholar
3. Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, et al. Management of the child born small for gestational age child (SGA) through to adulthood: a consensus statement of the International Societies of Paediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007;92:804–10.Search in Google Scholar
4. Eli Lilly and Company Limited. Humatrope US prescribing information. 2011. Available at: http://www.humatrope.com. Accessed March 15, 2013.Search in Google Scholar
5. Bang P, Bjerknes R, Dahlgren J, Dunkel L, Gustafsson J, et al. A comparison of different definitions of growth response in short prepubertal children treated with growth hormone. Horm Res Paediatr 2011;75:335–45.Search in Google Scholar
6. de Zegher F, Albertsson-Wikland K, Wollmann HA, Chatelain P, Chaussain J-L, et al. Growth hormone treatment of short children born small for gestational age: growth responses with continuous and discontinuous regimens over 6 years. J Clin Endocrinol Metab 2000;85:2816–21.Search in Google Scholar
7. Ranke MB. Clinical considerations in using growth hormone therapy in growth hormone deficiency. Endocr Dev 2010;18:83–91.Search in Google Scholar
8. Kriström B, Dahlgren J, Niklasson A, Nierop AF, Albertsson-Wikland K. The first-year growth response to growth hormone treatment predicts the long-term pubertal growth response in children. BMC Med Inform Decis Making 2009;9:1.Search in Google Scholar
9. de Ridder MA, Stijnen T. Hokken-Koelga AC. Prediction model for adult height of small for gestational age children at the start of growth hormone treatment. J Clin Endocrinol Metab 2008;93:477–83.Search in Google Scholar
10. Ranke MB, Lindberg A, Cowell CT, Albertsson-Wiland K, Reiter EO, et al. Prediction of response to growth hormone treatment in short children born small for gestational age: analysis of data from KIGS (Pharmacia International Growth Database). J Clin Endocrinol Metab 2003;88:125–31.Search in Google Scholar
11. Wit JM, Rekers-Mombarg LT, Cutler GB, Crowe B, Beck TJ, et al., for the European Idiopathic Short Stature Study Group. Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect. J Pediatr 2005;146:45–53.Search in Google Scholar
12. Dahlgren J, Kriström B, Niklasson A, Nierop AF, Rosberg S, et al. Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age. BMC Med Inform Decis Making 2007;7:40.Search in Google Scholar
13. Vosahlo J, Zidek T, Lebl J, Riedl S, Frisch H. Validation of a mathematical model predicting the response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency. Horm Res 2004;61:143–7.Search in Google Scholar
14. Ranke MB, Lindberg A, for the KIGS International Board. Prediction models for short children born small for gestational age (SGA) covering the total growth phase: analyses based on data from KIGS (Pfizer international growth database). BMC Med Inform Decis Making 2011;11:38.Search in Google Scholar
15. Hughes IP, Choong CS, Harris M, Ambler GR, Cutfield WS, et al., for the Australasian Paediatric Endocrine Group. Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response. Clin Endocrinol 2011;74:473–80.Search in Google Scholar
16. Schönau E, Westermann F, Rauch F, Stabrey A, Wassmer G, et al., for the German Lilly Growth Response Group. A new and accurate prediction model for growth response to growth hormone treatment in children with growth hormone deficiency. Eur J Endocrinol 2001;144:13–20.Search in Google Scholar
17. Land C, Blum WF, Shavrikova E, Kloeckner K, Stabrey A, et al. Predicting the growth response to growth hormone (GH) treatment in prepubertal and pubertal children with isolated GH deficiency – model validation in an observational setting (GeNeSIS). J Pediatr Endocrinol Metab 2007;20:685–93.Search in Google Scholar
18. Land C, Blum WF, Klöckner K, Stabrey A, Schoenau E. Validation of a growth prediction model in various patient groups. Monatsschr Kinderheilkd 2003;151:1128.Search in Google Scholar
19. Land C, Stabrey A, Blum WF, Schoenau E. A new growth response prediction model to growth hormone (GH) therapy in children with Turner Syndrome. Growth Hormone IGF Res 2002;12:233–4.Search in Google Scholar
20. Ranke MB, Lindberg A, Price DA, Darendeliler F, Albertsson-Wikland K, et al., for the KIGS International Board. Age at growth hormone therapy start and first-year responsiveness to growth hormone are major determinants of height outcome in idiopathic short stature. Horm Res 2007;68:53–62.Search in Google Scholar
21. Jung H, Land C, Nicolay C, De Schepper J, Blum WF, et al. Growth response to an individualized versus fixed dose GH treatment in short children born small for gestational age: the OPTIMA study. Eur J Endocrinol 2009;160:149–56.Search in Google Scholar
22. Brandt I, Reinken L. The growth of healthy children in the first 16 years. Bonn-Dortmund Longitudinal Development Study. Klinische Pädiatrie 1988;200:451–6.Search in Google Scholar
23. Ranke MB, Lindberg A, for the KIGS International Board. Observed and predicted growth responses in prepubertal children with growth disorders: guidance of growth hormone treatment by empirical variables. J Clin Endocrinol Metab 2010;95:1229–37.Search in Google Scholar
24. Cabrol S, Perin L, Colle M, Coutant R, Jesuran-Perelroizen M, et al. Evolution of IGF-1 in children born small for gestational age and with growth retardation, treated by growth hormone adapted to IGF-1 levels after 1 year. Horm Res Paediatr 2011;76:419–27.Search in Google Scholar
25. Tanaka T, Yokoya S, Seino Y, Togari H, Mishina J, et al. Long-term efficacy and safety of two doses of growth hormone in short Japanese children born small for gestational age. Horm Res Paediatr 2011;76:411–8.Search in Google Scholar
26. Carel J-C, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab 2012;97:416–25.Search in Google Scholar
27. Schönau E, Rauch F, Blum WF. Prediction of growth response to GH treatment: a reference guide. Oxfordshire: TMG Healthcare Communications Ltd., 2001.Search in Google Scholar
28. Carrascosa A, Audí L, Fernandez-Cancio M, Yeste D, Gussinye M, et al. Growth hormone secretory status evaluated by growth hormone peak after two pharmacological growth hormone release stimuli did not significantly influence the two-year catch-up growth induced by growth hormone therapy in 318 prepubertal short children with idiopathic growth retardation. Horm Res Paediatr 2011;75:106–14.Search in Google Scholar
29. Jung H, Rosilio M, Blum WF, Drop SL. Growth hormone treatment for short stature in children born short for gestational age. Adv Ther 2008;25:951–78.Search in Google Scholar
30. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;327:307–10.Search in Google Scholar
31. Anderson TW, Finn JD. The new statistical analysis of data. New York: Springer, 1996.Search in Google Scholar
©2014 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Images in pediatric endocrinology
- Leprechaunism (Donohue syndrome): report of a case in a newborn
- Original articles
- Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
- Age of onset of pubertal maturation of Thai boys
- Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
- Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
- Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
- Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
- Insulin resistance in young adults born small for gestational age (SGA)
- The effect of childhood obesity on cardiac functions
- Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
- Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
- Health-related quality of life in Turner syndrome and the influence of key features
- Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
- The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
- Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
- Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
- The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
- A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
- Heterozygous GHR gene mutation in a child with idiopathic short stature
- A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
- A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
- Patient reports
- Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
- Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
- Pituitary stalk lesion in a 13-year-old female
- Radiologic manifestation of a BCS1L-mutated patient
- Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
- NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
- A teenage boy with hypocalcemia after radioablation for Graves’ disease
- Short communication
- A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
- Letter to the Editor
- Endometriosis and migraine: what is there behind the scenes?
- 10.1515/jpem-2014-0999
Articles in the same Issue
- Masthead
- Masthead
- Images in pediatric endocrinology
- Leprechaunism (Donohue syndrome): report of a case in a newborn
- Original articles
- Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
- Age of onset of pubertal maturation of Thai boys
- Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
- Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
- Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
- Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
- Insulin resistance in young adults born small for gestational age (SGA)
- The effect of childhood obesity on cardiac functions
- Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
- Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
- Health-related quality of life in Turner syndrome and the influence of key features
- Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
- The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
- Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
- Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
- The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
- A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
- Heterozygous GHR gene mutation in a child with idiopathic short stature
- A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
- A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
- Patient reports
- Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
- Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
- Pituitary stalk lesion in a 13-year-old female
- Radiologic manifestation of a BCS1L-mutated patient
- Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
- NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
- A teenage boy with hypocalcemia after radioablation for Graves’ disease
- Short communication
- A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
- Letter to the Editor
- Endometriosis and migraine: what is there behind the scenes?
- 10.1515/jpem-2014-0999