Background: Optimal dosage for growth hormone (GH) therapy in short, prepubertal children born small for gestational age (SGA) is controversial. Methods: SGA OPTIMIS (NCT00249821) is a multicenter, open-label, parallel-group, pilot study of short children born SGA who had received recombinant human GH (r-hGH) (57 µg/kg/day) for 3 years. Children were randomized 1:1 to receive either 57 or 35 µg/kg/day r-hGH during year 4. The primary endpoint was height gain during year 4. Results: 22 children were randomized (57 µg/kg/day, n = 10; 35 µg/kg/day, n = 12) and 21 completed the fourth year of therapy; 22 were included in efficacy analyses. During year 4, mean [standard deviation (SD)] height velocity was 6.4 (1.4) and 4.4 (1.2) cm/year (p = 0.001) and height velocity SD score (SDS) was 0.3 (0.3) and –0.1 (0.2) (p = 0.002) in the 57 and 35 µg/kg/day groups, respectively. The 57 µg/kg/day group continued with catch-up growth, had a significantly higher mean weight gain (p = 0.015) and significantly higher insulin-like growth factor-I levels at 12 months (p = 0.038). Five treatment-emergent adverse events were reported; none was serious or caused study withdrawal. Conclusions: Children who continued receiving 57 µg/kg/day r-hGH in year 4 had significantly greater height gain than those receiving 35 µg/kg/day r-hGH.

Keywords:
Catch-up growth, Small for gestational age, Growth hormone, Pediatric growth hormone therapy
1.
Albanese A, Stanhope R: Growth and metabolic data following growth hormone treatment of children with intrauterine growth retardation. Horm Res 1993;39:8–12.
2.
Chatelain P, Job JC, Blanchard J, Ducret JP, Oliver M, Sagnard L, Vanderschueren-Lodeweyckx M: Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. Belgian and French Pediatric Clinics and Sanofi-Choay (France). J Clin Endocrinol Metab 1994;78:1454–1460.
3.
De Zegher F, Albertsson-Wikland K, Wilton P, Chatelain P, Jonsson B, Lofstrom A, Butenandt O, Chaussain JL: Growth hormone treatment of short children born small for gestational age: meta-analysis of four independent, randomized, controlled, multicentre studies. Acta Paediatr Suppl 1996;417:27–31.
4.
De Zegher F, Hokken-Koelega A: Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term. Pediatrics 2005;115:e458–e462.
5.
Fjellestad-Paulsen A, Czernichow P, Brauner R, Bost M, Colle M, Lebouc JY, Lecornu M, Leheup B, Limal JM, Raux MC, Toublanc JE, Rappaport R: Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation. Acta Paediatr 1998;87:511–517.
6.
Job JC, Chaussain JL, Job B, Ducret JP, Maes M, Olivier M, Ponte C, Rochiccioli P, Vanderschueren-Lodeweyckx M, Chatelain P: Follow-up of three years of treatment with growth hormone and of one post-treatment year, in children with severe growth retardation of intrauterine onset. Pediatr Res 1996;39:354–359.
7.
Maiorana A, Cianfarani S: Impact of growth hormone therapy on adult height of children born small for gestational age. Pediatrics 2009;124:e519–e531.
8.
Phillip M, Lebenthal Y, Lebl J, Zuckerman-Levin N, Korpal-Szczyrska M, Marques JS, Steensberg A, Jons K, Kappelgaard AM, Ibanez L: European multicentre study in children born small for gestational age with persistent short stature: comparison of continuous and discontinuous growth hormone treatment regimens. Horm Res 2009;71:52–59.
9.
Tanner JM, Lejarraga H, Cameron N: The natural history of the Silver-Russell syndrome: a longitudinal study of thirty-nine cases. Pediatr Res 1975;9:611–623.
10.
De Waal WJ, Hokken-Koelega AC, Stijnen T, de Muinck Keizer-Schrama SM, Drop SL: Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I and IGF-II levels in prepubertal children with short stature after intrauterine growth retardation. The Dutch Working Group on Growth Hormone. Clin Endocrinol (Oxf) 1994;41:621–630.
11.
Boonstra VH, Arends NJ, Stijnen T, Blum WF, Akkerman O, Hokken-Koelega AC: Food intake of children with short stature born small for gestational age before and during a randomized GH trial. Horm Res 2006;65:23–30.
12.
Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, Rogol A: Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007;92:804–810.
13.
Fjellestad-Paulsen A, Simon D, Czernichow P: Short children born small for gestational age and treated with growth hormone for three years have an important catch-down five years after discontinuation of treatment. J Clin Endocrinol Metab 2004;89:1234–1239.
14.
Edouard T, Oliver I, Jouret B, Lounis N, Moulin P, Pienkowski C, Elefterion M, Salles JP, Tauber M: Growth follow-up of SGA children after 3 years of GH treatment (in French). Arch Pediatr 2008;15:115–121.
15.
Hokken-Koelega AC, De Ridder MA, Lemmen RJ, Den Hartog H, de Muinck Keizer-Schrama SM, Drop SL: Children born small for gestational age: do they catch up? Pediatr Res 1995;38:267–271.
16.
Greulich WW, Pyle S: Radiographic Atlas of Skeletal Development of Hand and Wrist, ed 2. Palo Alto, Stanford University Press, 1959.
17.
Sassolas G, Chatelain P, Cohen R, Boissel JP, Laporte S, Galleyrand J, Claustrat B, Elmcharfi A, Chayvialle JA, Cohen H, Ferry S, Underwood L: Effects of human pancreatic tumor growth hormone-releasing hormone (hpGRH1–44-NH2) on immunoreactive and bioactive plasma growth hormone in normal young men. J Clin Endocrinol Metab 1984;59:705–709.
18.
Committee for Proprietary Medicinal Products (CPMP): Points to consider on adjustment for baseline covariates. Stat Med 2004;23:701–709.
19.
Cohen P, Rogol AD, Howard CP, Bright GM, Kappelgaard AM, Rosenfeld RG: Insulin growth factor-based dosing of growth hormone therapy in children: a randomized, controlled study. J Clin Endocrinol Metab 2007;92:2480–2486.
20.
Chatelain P, Carrascosa A, Bona G, Ferrandez-Longas A, Sippell W: Growth hormone therapy for short children born small for gestational age. Horm Res 2007;68:300–309.
21.
Labarta JI, Ruiz JA, Molina I, de Arriba A, Mayayo E, Longas AF: Growth and growth hormone treatment in short stature children born small for gestational age. Pediatr Endocrinol Rev 2009;6(suppl 3):350–357.
22.
Lee PA, Chernausek SD, Hokken-Koelega AC, Czernichow P: International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24–October 1, 2001. Pediatrics 2003;111:1253–1261.
23.
Gharib H, Cook DM, Saenger PH, Bengtsson BA, Feld S, Nippoldt TB, Rodbard HW, Seibel JA, Vance ML, Zimmerman D: American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children – 2003 update. Endocr Pract 2003;9:64–76.
24.
De Zegher F, Albertsson-Wikland K, Wollmann HA, Chatelain P, Chaussain JL, Lofstrom A, Jonsson B, Rosenfeld RG: 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;85:2816–2821.
25.
Van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A: Adult height after long-term, continuous growth hormone treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response growth hormone trial. J Clin Endocrinol Metab 2003;88:3584–3590.
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2012
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