Twelve years of growth hormone (GH) therapy of short children born small for gestational age (SGA) have demonstrated that GH is an effective and well-tolerated therapy. Most children will reach a normal adult height (AH). AH of 55 SGA adolescents was comparable for those treated with a GH dose of 1 or 2 mg/m2 (∼0.033 or 0.066 mg/kg) per day, mean (SD) AH SDS being –1.2 (0.7) and –0.8 (0.7), respectively. GH therapy had no influence on the age at onset, the progression of puberty, duration of puberty and pubertal height gain. GH therapy induced higher fasting and glucose-stimulated insulin levels after 1 and 6 years, but 6 months after GH stop, all levels returned to normal. At baseline mean systolic blood pressure was significantly increased, but both systolic and diastolic blood pressure decreased significantly during 6 years of GH and remained so after GH stop. GH therapy demonstrated a beneficial effect on serum lipid profiles, body composition, bone mineral density and head growth. Treatment with 2 mg GH/m2 per day induced mean serum IGF-I levels of +2 SDS, whereas IGF-I levels remained within the normal range with 1 mg GH/m2 per day. In conclusion, long-term GH therapy of short SGA children with 1 mg/m2 per day appears to be effective and safe. Since the future consequences of high serum IGF-I levels during long-term GH therapy with 2 mg/m2 per day are as yet unknown, it seems safer to treat short prepubertal SGA children with a GH dose of 1 mg/m2 per day when children are to be treated continuously for many years.

1.
Albertsson-Wikland K, Karlberg J: Natural catch-up growth in children born small for gestational age with and without catch-up growth. Acta Paediatr Scand 1994;399(suppl):64–70.
2.
Hokken-Koelega ACS, De Ridder MAJ, Lemmen RJ, den Hartog H, de Muinck Keizer-Schrama S, Drop S: Children born small for gestational age: Do they catch-up? Pediatr Res 1995;38:267–271.
3.
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.
4.
Albertsson-Wikland K: Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand 1989;349(suppl):35–41.
5.
Stanhope R, Ackland F, Hamill G, Clayton J, Jones J, Preece MA: Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intra-uterine growth retardation. Acta Paediatr Scand 1989;349(suppl):47–52.
6.
de Waal WJ, Hokken-Koelega ACS, Stijnen T: 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. Clin Endocrinol 1994;41:621–630.
7.
Boguszewski M, Rosberg S, Albertsson-Wikland K: Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children. J Clin Endocrinol Metab 1995;80:2599–2606.
8.
Boguszewski M, Jansson C, Rosberg S, Carlsson LMS, Albertsson-Wikland K: Changes in serum insulin-like growth factor I and IGF-binding protein-3 levels during growth hormone treatment in prepubertal short children born small for gestational age. J Clin Endocrinol Metab 1996;81:3902–3908.
9.
Arends NJT, Hokken-Koelega ACS: Body composition and daily food intake in children with short stature after intrauterine growth retardation (IUGR). Horm Res 1998;50:47–48.
10.
Persson I, Ahlsson F, Ewald U, Tuvemo T, Qingyuan M, Van Rosen D, Proos L: Influence of perinatal factors on the onset of puberty in boys and girls: Implication for interpretation of link with risk of long term diseases. Am J Epidemiol 1999;150:747–755.
11.
Léger J, Lévy-Marchal C, Boch J, Pinet A, Chevenne D, Porquet D, Collin D, Czernichow P: Reduced final height and indications for early development of insulin resistance in a 20 year old population born with intrauterine growth retardation. Br Med J 1997;315:341–347.
12.
Luo ZC, Albertsson-Wikland K, Karlberg J: Length and body mass index at birth and target height influences on patterns of postnatal growth in children born small for gestational age. Pediatrics 1998;102:E72.
13.
Tanaka T, Suwa S, Yokoya S, Hibi I: Analysis of linear growth during puberty. Acta Paediatr Scand Suppl 1988;347:25–29.
14.
Tanaka T, Komatsu K, Takada G, Miyashita M, Ohno T: Prediction of adult height in healthy Japanese children. Acta Paediatr Suppl 1996;417:57–60.
15.
Bourguignon JP: Linear growth as a function of age at onset of puberty and sex steroid dosage: Therapeutic implications. Endocr Rev 1988;9:467–488.
16.
van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A: Final height after long-term, continuous GH treatment in short children born small for gestational age (SGA): Results of a randomised, double-blind, dose-response GH trial. J Clin Endocrinol Metab 2003;88:3584–3590.
17.
Chaussain JL, Colle M, Landier F: Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation. Acta Paediatr Scand 1994;399(suppl):74–75.
18.
Sas TCJ, Mulder P, Houdijk EC, Jansen M, Reeser HM, Hokken-Koelega ACS: Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab 1999;84:3064–3070.
19.
de Zegher F, Du Caju MV, Heinrichs C, Maes M, De Schepper J, Craen M, Vanwerser K, Malvaux P, Rosenfeld RG: Early, discontinuous, high-dose growth hormone treatment to normalize height and weight of short children born small for gestational age. J Clin Endocrinol Metab 1999;84:1558–1561.
20.
Job JC, Chaussain JL, Job B: Follow-up of three years off 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.
21.
Boguszewski M, Albertsson-Wikland K, Aronsen S, Gustafsson J, Hagenas L, Westgren U, Westphal O, Lipsanen-Nyman M, Sipila I, Gellert P, Muller J, Madsen B: Growth hormone treatment of short children born small-for-gestational-age: The Nordic Multicentre Trial. Acta Paediatr 1998;87:257–263.
22.
de Zegher F, Albertsson-Wikland K, Wilton P: Growth hormone treatment of short children born small for gestational age: A meta-analysis of four independent, randomized, controlled, multicentre studies. Acta Paediatr 1996;417 (suppl):27–31.
23.
de Zegher F, Butenandt O, Châtelain PG, Albertsson-WiklandK, Jonsson B, Lofstrom A, Chaussain JL: Growth hormone treatment of short children born small for gestational age: Reappraisal of the rate of bone maturation over 2 years and meta-analysis of height gain over 4 years. Acta Paediatr Scand 1997;423(suppl):207–212.
24.
Fjellestad-Paulsen A, Czernichow P, Brauner 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 Scand 1998;87:511–517.
25.
de Zegher F, François I, van Helvoirt M, Beckers D, Ibáñez L, Châtelain P: Growth hormone treatment of short children born small for gestational age. Trends Endocrinol Metab 1998;9:233–237.
26.
Ibáñez L, Potau N, Marcos MV, de Zegher F: Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 1999;84:4739–4741.
27.
Ibáñez L, Potau N, Marcos MV, de Zegher F: Adrenal hyperandrogenism in adolescent girls with a history of low birthweight and precocious pubarche. Clin Endocrinol (Oxf) 2000;53:523–527.
28.
Boonstra VH, Mulder PG, de Jong FH, Hokken-Koelega ACS: Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment. J Clin Endocrinol Metab 2004;89:712–717.
29.
Boonstra V, van Pareren Y, Mulder P, Hokken-Koelega ACS: Puberty in growth hormone-treated children born small for gestational age (SGA). J Clin Endocrinol Metab 2003;88:5753–5758.
30.
Hofman L, Cutfield WS, Robinson EM, Bergman RN, Menon RK, Sperling MA, Gluckman PD: Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402–406.
31.
Sas TCJ, Mulder P, Hokken-Koelega ACS: Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. Clin Endocrinol 2001;54:243–251.
32.
van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega ACS: Effect of discontinuation of GH treatment on risk factors for cardiovascular disease in adolescents born small for gestational age. J Clin Endocrinol Metab 2003;88:347–353.
33.
Barker DJP, Gluckman PD, Godrey KM, Harding JE, Owens JA, Robinson JS: Fetal nutrition and cardiovascular disease in adult life. Lancet 1993;341:938–941.
34.
Barker DJP, Hales CN, Osmond C, Phipps K, Clark PMS: Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36:62–67.
35.
Sas TCJ, 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.
36.
Léger J, Carel C, Legand I, Paulsen A, Hassan M, Czernichow P: Magnetic resonance imaging evaluation of adipose tissue and muscle mass in children with growth hormone deficiency, Turner’s syndrome, and intrauterine growth retardation during the first year of treatment with GH. J Clin Endocrinol Metab 1994;78:904–909.
37.
Arends NJ, Stijnen T, Hokken-Koelega ACS: Body composition by dual energy x-ray absorptiometry (DXA) in short children born small for gestational age (SGA) before and during growth hormone (GH) treatment: results of a randomized, controlled GH treatment study. J Clin Endocrinol Metab 2004, in press.
38.
Arends NJ, Boonstra VH, Mulder PG, Odink RJ, Stokvis-Brantsma WH, Rongen-Westerlaken C, Mulder JC, Delemarre-Van de Waal H, Reeser HM, Jansen M, Waelkens JJ, Hokken-Koelega ACS: GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial. Clin Endocrinol (Oxf) 2003;59:779–787.
39.
Sas TCJ, Mulder P, Hokken-Koelega ACS: Body proportions during six years of growth hormone treatment in children with short stature born small for gestational age participating in a randomized, double-blind, dose-response trial. Clin Endocrinol 2000;53:675–681.
40.
Arends NJ, Boonstra VH, Hokken-Koelega ACS: Head circumference and body proportions before and during GH treatment in short children born small for gestational age (SGA). Pediatrics 2004.
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