Abstract
Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9-32.0 wk), median (range) birth weight 970 g (610-2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) −1 and −3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 μg/L (6-28.4 μg/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 μg/L (1.7-11.9 μg/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p < 0.01, p < 0.01, and p < 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p < 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found.
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Abbreviations
- DEXA:
-
dexamethasone
- BPD:
-
bronchopulmonary dysplasia
- IGFBP-1:
-
IGF-binding protein-1
- IGFBP-3:
-
IGF-binding protein-3
REFERENCES
DeRegnier RO, Guilbert TW, Mills MM, Georgieff MK 1996 Growth failure and altered body composition are established by one month of age in infants with bronchopulmonary dysplasia. J Nutr 126: 168–175
Ehrenkranz RA, Younes N, Lemons JA, Fanaroff AA, Donovan EF, Wright LL, Katsikiotis V, Tyson JE, Oh W, Shankaran S, Bauer CR, Korones SB, Stoll BJ, Stevenson DK, Papile LA 1999 Longitudinal growth of hospitalized very low birth weight infants. Pediatrics 104: 280–289
Gibson AT, Pearse RG, Wales JKH 1993 Growth retardation after dexamethasone administration: assessment by knemometry. Arch Dis Child 69: 505–509
Bloomfield FH, Knight DB, Harding JE 1998 Side effects of 2 different dexamethasone courses for preterm infants at risk of chronic lung disease: a randomized trial. J Pediatr 133: 395–400
Ward WE, Atkinson SA, Donovan SM, Paes B 1999 Bone metabolism and circulating IGF-I and IGFBPs in dexamethasone-treated preterm infants. Early Hum Dev 65: 127–141
Brownlee KG, Ng PC, Henderson MJ, Smith M, Green JH, Dear PRF 1992 Catabolic effect of dexamethasone in the preterm baby. Arch Dis Child 67: 1–4
Van Goudoever JB, Wattimena JDL, Carnielli VP, Sulkers EJ, Degenhart HJ, Sauer PJJ 1994 Effect of dexamethasone on protein metabolism in infants with bronchopulmonary dysplasia. J Pediatr 124: 112–118
Crofton PM, Shrivastava A, Wade JC, Stephen R, Kelnar CJH, McIntosh N, Lyon AJ 2000 Effects of dexamethasone treatment on bone and collagen turnover in preterm infants with chronic lung disease. Pediatr Res 48: 155–162
Frantz AG, Rabkin MT 1964 Human growth hormone. N Engl J Med 271: 1375–1381
Krieger DT, Glick SM 1972 Growth hormone and cortisone responsiveness in Cushing's syndrome: a relation to a possible central nervous system etiology. Am J Med 52: 25–40
Takahashi H, Bando H, Zhang C, Yamasaki R, Saito S 1992 Mechanism of impaired growth hormone secretion in patients with Cushing's disease. Acta Endocrinol 127: 13–17
Jux C, Leiber K, Hügel U, Blum W, Ohlsson C, Klaus G, Mehls O 1998 Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I receptor in cultured rat chondrocytes. Endocrinology 139: 3296–3305
Gluckman PD, Gunn AJ, Wray A, Cutfield W, Chatelain PG, Guilbaud O, Ambler GR, Wilton P, Albertsson-Wikland K 1992 Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure: The International Board of the Kabi Pharmacia International Growth Study. J Pediatr 121: 920–923
Ogilvy-Stuart AL, Hands SJ, Adcock CJ, Holly JMP, Matthews DR, Mohamed-Ali V, Yudkin JS, Wilkinson AR, Dunger DB 1998 Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn. J Clin Endocrinol Metab 83: 3550–3557
Baker J, Liu JP, Robertson EJ, Efstratiadis A 1993 Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75: 73–82
Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A 1993 Mice carrying null mutation of the genes encoding IGF (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75: 59–72
Usher R, McLean F 1969 Intrauterine growth of liveborn Caucasian infants at sea level: standard obtained from measurements of infants born between 25 and 44 weeks of gestation. J Pediatr 74: 901–910
Daughaday WH, Mariz IK, Blethen SL 1980 Inhibition of access bound somatomedin to membrane receptor and immunobinding sites—a comparison of radioceptor and radioimmunoassay of somatomedin in native and acid-ethanol extracted serum. J Clin Endocrinol Metab 51: 781
Merriam GR, Wachter KW 1984 Measurement and analysis of episodic hormone secretion. In: Rodbard D, Forti G (eds) Computers in Endocrinology. Raven Press, New York, pp 325–346
Skinner AM, Battin M, Solimano A, Daaboul J, Kitson HF 1997 Growth and growth factors in premature infants receiving dexamethasone for bronchopulmonary dysplasia. Am J Perinatol 14: 539–546
Shrivastava A, Lyon AJ, McIntosh N 1998 Effect of dexamethasone on mineral balance and bone mineralisation in preterm infants with chronic lung disease. Early Hum Dev 51: 82A–83A
Bloomfield FH, Knight DB, Breier BH, Harding JE 2001 Growth restriction in dexamethasone-treated preterm infants may be mediated by reduced IGF-I and IGFBP-3 plasma concentrations. Clin Endocrinol 54: 235–242
[No authors listed] 2002 Postnatal steroids to treat or prevent chronic lung disease in preterm infants. Pediatrics 109: 330–338
Haynes RC Jr 1990 Adrenocorticotropic hormone: adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Goodman Gillman A, Rall TW, Nies AS, Taylor P (eds) The Pharmacological Basis of Therapeutics. Pergamon Press, New York, pp 1431–1462
Casanueva FF, Burguera B, Tome MA, Lima L, Tresguerres JAF, Devesa J, Dieguez C 1988 Depending on the time of administration, dexamethasone potentiates or blocks growth hormone-releasing hormone-induced growth hormone release in man. Neuroendocrinology 47: 46–49
Burguera B, Muruais C, Penalva A, Dieguez C, Casanueva FF 1990 Dual and selective action of glucocorticoids upon basal and stimulated growth hormone release in man. Neuroendocrinology 51: 51–58
Wehrenberg WB, Janowski BA, Piering AW, Culler F, Jones KL 1990 Glucocorticoids: potent inhibitors and stimulators of growth hormone secretion. Endocrinology 126: 3200–3203
Kaufmann S, Jones KL, Wehrenberg WB, Culler FL 1988 Inhibition by prednisone of growth hormone (GH) response to GH-releasing hormone in normal men. J Clin Endocrinol Metab 67: 1258–1261
Hokken-Koelega ACS, Stijnen T, de Muinck Keizer-Schrama SMPF, Blum WF, Drop SLS 1993 Levels of growth hormone, IGF-I and -II, IGF-BP-1 and -3, and cortisol in prednisone treated children with growth retardation after renal transplantation. J Clin Endocrinol Metab 77: 932–939
Casanueva FF, Burguera B, Muruais C, Dieguez C 1990 Acute administration of corticoids: a new and peculiar stimulus of growth hormone secretion in man. J Clin Endocrinol Metab 70: 234–237
Martul P, Pineda J, Dieguez C, Casanueva FF 1992 Corticoid-induced growth hormone (GH) secretion in GH-deficient and normal children. J Clin Endocrinol Metab 75: 536–539
Pineda J, Martul P, Casanueva FF, Dieguez C, Rica I, Loridan LL 1994 Oral dexamethasone administration: new pharmacological test for the assessment of growth hormone secretion. Eur J Endocrinol 131: 598–601
Pellini C, De Angelis R, di Natale B, Lukezic M, Mora S, Chiumello G 1998 Dexamethasone in the diagnostic work-up of growth hormone deficiency. Clin Endocrinol 48: 223–228
Miell JP, Buchanan CR, Norman MR, Maheshwari HG, Blum WF 1994 The evolution of changes in immunoreactive serum insulin-like growth factors (IGFs), IGF-binding proteins, circulating growth hormone (GH) and GH-binding protein as a result of short-term dexamethasone treatment. J Endocrinol 142: 547–554
Smith JW, Underwood LE, Keyes L, Clemmons DR 1997 Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants. J Clin Endocrinol Metab 82: 3982–3988
De Groof F, Joosten KFM, Janssen JAMJL, de Kleijn ED, Hazelzet JA, Hop WCJ, Uitterlinden P, van Doorn J, Hokken-Koelega ACS 2002 Acute stress response in children with meningococcal sepsis: important endocrine, metabolic and immunologic differences between nonsurvivors and survivors. J Clin Endocrinol Metab 87: 3118–3124
Lee PDK, Conover CA, Powell DR 1993 Minireview: regulation and function of insulin-like growth factor-binding protein-1 (43630). Proc Soc Exp Biol Med 204: 4–29
Tapanainen PJ, Bang P, Wilson K, Unterman TG, Vreman HJ, Rosenfeld RG 1994 Maternal hypoxia as a model for intrauterine growth retardation: effect on insulin-like growth factors and their binding proteins. Pediatr Res 36: 152–158
Miell JP, Taylor AM, Jones J, Holly JMP, Gaillard RC, Pralong FP, Ross RJM, Blum WF 1993 The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers. J Endocrinol 136: 525–533
Holly JMP, Biddlecombe RA, Dunger DB, Edge JA, Amiel SA, Howell R, Chard T, Rees LH, Wass JAH 1988 Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin: a new role for insulin?. Clin Endocrinol 29: 667–675
Suikkari AM, Koivisto VA, Rutanen EM, Yki-Järvinen H, Karonen SL, Seppälä M 1988 Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab 66: 266–272
Unterman TG, Phillips LS 1985 Glucocorticoid effects on somatomedins and somatomedin inhibitors. J Clin Endocrinol Metab 61: 618–626
Luo J, Murphy LJ 1989 Dexamethasone inhibits growth hormone induction of insulin-like growth factor-I (IGF-I) messenger ribonucleic acid (mRNA) in hypophysectomized rats and reduces IGF-I mRNA abundance in the intact rat. Endocrinology 125: 165–171
Acknowledgements
The authors thank Dr. W. de Waal, pediatrician in Diakonessehuis Utrecht, The Netherlands, for his help in the analysis of the GH profiles.
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Huysman, M., Hokken-Koelega, A., Hop, W. et al. Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants. Pediatr Res 54, 37–43 (2003). https://doi.org/10.1203/01.PDR.0000065727.45195.69
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DOI: https://doi.org/10.1203/01.PDR.0000065727.45195.69
