Recent reports have shown that high-dose growth hormone (GH) treatment in short children born with small for gestational age (SGA) resulted in a pronounced acceleration of linear growth. We describe the results of multicenter trials of recombinant human GH (rhGH) treatment in short SGA children in Japan. Two clinical studies were performed and the results were combined. Study 1 comprised 104 SGA children and study 2 comprised 61 SGA children. The patients were divided into three groups: group 1 consisted of 20 patients (13 boys and 7 girls) who received rhGH 25 µg/kg per day six or seven times per week in the first year and 50 µg/kg per day in the second year and thereafter; group 2 consisted of 48 patients (28 boys, 20 girls) who received rhGH 45/50 µg/kg per day; group 3 consisted of 44 patients (28 boys, 16 girls) who received 90/100 µg/kg per day. The mean increments in height SDS were 0.46, 0.67 and 0.94 SD in boys and 0.49, 0.79 and 0.93 SD in girls in groups 1, 2 and 3, respectively. The mean increment in height SDS at 2 years in group 3 was significantly greater than that in group 1, but it was not significantly different from that in group 2 in boys and girls. Our data demonstrated that high-dose GH administration significantly improved height velocity and height SDS in short SGA children. Additional studies are necessary to optimize a long-term GH treatment regimen and combined luteinizing hormone releasing hormone analog treatment for final height. Careful observation is also necessary to assess the metabolic effects of high-dose GH, especially on carbohydrate metabolism.

1.
Albertsson-Wikland K, Karlberg J: Natural growth in children born small for gestational age with and without catch-up growth. Acta Paediatr Suppl 1994;399:64–70.
2.
Karlberg J, Albertsson-Wikland K: Growth in full-term small-for-gestational age infants: from birth to final height. Pediatr Res 1995;38:733–739.
3.
Fitzhardinge PM, Inwood S: Long-term growth in small-for-date children. Acta Paediatr Scand Suppl 1989;349:27–33.
4.
Westwood M, Kramer MS, Nunz D, Lovett JM, Watters GV: Growth and development of full term nonasphyxiated small-for-gestational-age newborns: follow-up through adolescence. Pediatrics 1983;71:376–382.
5.
Albertsson-Wikland K, Karlberg J: Growth in children born small for gestational age. Clin Pediatr Endocrinol 1994;3(suppl 5):35–41.
6.
Tanner JM, Whitehouse RH, Hughes PCR, Vinve FP: Effect of human growth hormone for one to seven years on growth of 100 children, with growth hormone deficiency, low birth weight, inherited smallness, Turner syndrome and other complaints. Arch Dis Child 1971;46:745–782.
7.
Grunt JA, Enriquesz AR, Daughaday WH, Budd S: Acute and long-term responses to hGH in children with idiopathic small-for-dates dwarfism. J Clin Endocrinol Metab 1972;35:157–168.
8.
Albertsson-Wikland K: Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand Suppl 1989;349:35–41.
9.
Foley TP Jr, Thompson RG, Shaw M, Baghadassavian A, Nissley SP, Blizzard RM: Growth responses to human growth hormone in patients with intrauterine growth retardation. J Pediatr 1974;84:635–641.
10.
Lanes R, Plotnick LP, Lee PA: Sustained effect of human growth hormone therapy on children with intra-uterine growth retardation. Pediatrics 1979;63:731–735.
11.
Châtelain P, Job JC, Blanchard J, Ducret JP, Olivier M, Sagnard L, Vanderschueren-Lodeweyckx M: Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. J Clin Endocrinol Metab 1994;78:1454–1460.
12.
Stanhope R, Preece MA, Hamill F: Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation? Arch Dis Child 1991;66:4480–4483.
13.
De Zegher F, Maes M, Gargosky SE, Heinrichs C, Du Caju MV, Thiry G, De Schepper J, Craen M, Breysem L, Lofstrom A, Jonsson P, Bourguignon JP, Malvaux P, Rosenfeld RG: High-dose growth hormone treatment of short children born small for gestational age. J Clin Endocrinol Metab 1996;81:1887–1892.
14.
De Zegher F, Albertsson-Wikland K, Wilton P, Châtelain P, Jonsson B, Loefstroem A, Butenandt O, Chaussain J-L: Growth hormone treatment of short children born small for gestational age: meta-analysis of four independent, randomized, controlled, multicentre studies. Acta Paediatr Scand Suppl 1996;417:27–31.
15.
Ranke MB, Lindberg A: Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS, including the first report on final height. Acta Paediatr 1996;417(suppl):18–26.
16.
Sas T, de Waal W, Mulder P, Jansen M, Reeser M, Hokken-Koelega A: Growth hormone treatment in children with short stature born small for gestational age: Five-year results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab 1999;84:3064–3070.
17.
Chernausek SD, Breen TJ, Frank GR: Linear growth in response to growth hormone treatment in children with short stature associated with intrauterine growth retardation: the National Cooperative Growth study experience. J Pediatr 1996;128:S22–S27.
18.
Ogawa M, Kohno H, Nishi Y, for the Clinical Study Group of IUGR: A two-year study of the growth-promoting effect and safety of human growth hormone for short stature due to intrauterine growth retardation. Clin Pediatr Endocrinol 1999;8:67–75.
19.
Tanaka T, Matsuo N, Seino Y, Fujieda K, Yokoya S, Tachibana K, for the Study Group of GH treatment in IUGR: Growth-promoting and psychological effects of high-dose growth hormone treatment in children with intrauterine growth retardation. Clin Pediatr Endocrinol 2000;9:7–17.
20.
Tanaka T: Growth-promoting effect of growth hormone treatment at various doses in children with intrauterine growth retardation. Clin Pediatr Endocrinol 2001;10(suppl 15):15–23.
21.
Tanae A, Horikawa R, Hibi I, Satoh M, Katsumata N, Tanaka T: An attempt to improve final height with cyproterone acetate in children with non-endocrine short stature. Clin Endocrinol (Tokyo) 1998;46(suppl 33):13–17.
22.
Iinuma K: Growth of subjects born small for gestational age [in Japanese]. J Japan Soc Pediatr 1989;102:451–459.
23.
Carel JC, Châtelain P, Rochiccioli P, Chaussain JL: Improvement in adult height after growth hormone treatment in adolescents with short stature born small for gestational age: results of a randomized controlled study. J Clin Endocrinol Metab 2003;88:1587–1593.
24.
Van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A: Adult height after long-term continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab 2003;88:3584–3590.
25.
Gutbrod T, Wolke D, Soehne B, Ohrt B, Riegel K: Effects of gestation and birth weight on the growth and development of very low birthweight small for gestational age infants: A matched group comparison. Arch Dis Child Fetal Neonatol 2000;82:F208–F214.
26.
Lundgren EM, Cnattingious S, Jonsson B, Tuvemo T: Intellectual and psychological performance in males born small for gestational age with and without catch-up growth. Pediatr Res 2001;50:91–96.
27.
Frisk V, Amsel R, Whyte HE: The importance of head growth patterns in predicting the cognitive abilities and literacy skills of small-for-gestational-age children. Dev Neuropsychol 2002;22:565–593.
28.
van der Reijden-Lakeman EA, Slijper FME, van Dongen-Melman JE, de Waal WJ, Verhulst FC: Self-concept before and after two years of growth hormone treatment in intrauterine growth-retarded children. Horm Res 1996;46:88–94.
29.
Barker DJ, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PM: Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36:62–67.
30.
Sas T, Mulder P, Aanstoot HJ, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A: Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. Clin Endocrinol 2001;54:243–251.
31.
Sas T, Mulder P, Hokken-Koelega A: Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab 2000;85:3786–3792.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.