Skip to main content
SpringerLink
Log in

Growth Impairment in Pediatric Inflammatory Bowel Disease

  • Chapter
  • First Online:
Pediatric Inflammatory Bowel Disease

  • 1563 Accesses

Abstract

The clinical course and severity of inflammatory bowel disease (IBD) vary widely in children and in adults. Unique to pediatric patient populations, however, is the potential for linear growth impairment as a complication of chronic intestinal inflammation. The challenge in treating each child or adolescent is to employ pharmacologic, nutritional, and where appropriate surgical interventions, to not only decrease mucosal inflammation and thereby alleviate symptoms, but also to optimize growth and normalize associated pubertal and social development. Indeed, normal growth is a marker of therapeutic success. This chapter reviews the prevalence of growth impairment in pediatric IBD, discusses its pathophysiology, and outlines strategies for its prevention and management.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 199.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 259.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM. Growth and clinical course of children with Crohn’s disease. Gut. 1993;34:939–43.

    Article  PubMed  CAS  Google Scholar 

  2. Hyams JS, Davis P, Grancher K, Lerer T, Justinich CJ, Markowitz J. Clinical outcome of ulcerative colitis in children. J Pediatr. 1996;129:81–8.

    Article  PubMed  CAS  Google Scholar 

  3. Karlberg J, Jalil F, Lam B, Low L, Yeung CY. Linear growth retardation in relation to the three phases of growth. Eur J Clin Nutr. 1994;48 Suppl 1:S25–43. discussion S-4.

    PubMed  Google Scholar 

  4. Rogol AD, Roemmich JN, Clark PA. Growth at puberty. J Adolesc Health. 2002;31:192–200.

    Article  PubMed  Google Scholar 

  5. Salmon Jr WD, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. 1956. J Lab Clin Med. 1990;116:408–19.

    PubMed  Google Scholar 

  6. Daughaday WH. A personal history of the origin of the somatomedin hypothesis and recent challenges to its validity. Perspect Biol Med. 1989;32:194–211.

    PubMed  CAS  Google Scholar 

  7. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978;253:2769–76.

    PubMed  CAS  Google Scholar 

  8. Isaksson OG, Jansson JO, Gause IA. Growth hormone stimulates longitudinal bone growth directly. Science. 1982;216:1237–9.

    Article  PubMed  CAS  Google Scholar 

  9. Isaksson OG, Lindahl A, Nilsson A, Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev. 1987;8:426–38.

    Article  PubMed  CAS  Google Scholar 

  10. Green H, Morikawa M, Nixon T. A dual effector theory of growth-hormone action. Differentiation. 1985;29:195–8.

    Article  PubMed  CAS  Google Scholar 

  11. Frank SJ, Messina JL, Baumann G, Black RA, Bertics PJ. Insights into modulation of (and by) growth hormone signaling. J Lab Clin Med. 2000;136:14–20.

    Article  PubMed  CAS  Google Scholar 

  12. Teglund S, McKay C, Schuetz E, et al. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998;93:841–50.

    Article  PubMed  CAS  Google Scholar 

  13. Bergad PL, Schwarzenberg SJ, Humbert JT, et al. Inhibition of growth hormone action in models of inflammation. Am J Physiol Cell Physiol. 2000;279:C1906–17.

    PubMed  CAS  Google Scholar 

  14. Denson LA, Held MA, Menon RK, Frank SJ, Parlow AF, Arnold DL. Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3. Am J Physiol Gastrointest Liver Physiol. 2003;284:G646–54.

    PubMed  CAS  Google Scholar 

  15. Ram PA, Waxman DJ. SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms. J Biol Chem. 1999;274:35553–61.

    Article  PubMed  CAS  Google Scholar 

  16. Asplin CM, Faria AC, Carlsen EC, et al. Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1989;69:239–45.

    Article  PubMed  CAS  Google Scholar 

  17. Herrington J, Smit LS, Schwartz J, Carter-Su C. The role of STAT proteins in growth hormone signaling. Oncogene. 2000;19:2585–97.

    Article  PubMed  CAS  Google Scholar 

  18. Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc Natl Acad Sci U S A. 1995;92:8831–5.

    Article  PubMed  CAS  Google Scholar 

  19. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3–34.

    PubMed  CAS  Google Scholar 

  20. Govoni KE, Baylink DJ, Mohan S. The multi-functional role of insulin-like growth factor binding proteins in bone. Pediatr Nephrol. 2005;20:261–8.

    Article  PubMed  Google Scholar 

  21. Rechler MM. Insulin-like growth factor binding proteins. Vitam Horm. 1993;47:1–114.

    Article  PubMed  CAS  Google Scholar 

  22. Miyakoshi N, Richman C, Qin X, Baylink DJ, Mohan S. Effects of recombinant insulin-like growth factor-binding protein-4 on bone formation parameters in mice. Endocrinology. 1999;140: 5719–28.

    Article  PubMed  CAS  Google Scholar 

  23. Rajaram S, Baylink DJ, Mohan S. Insulin-like growth factor-­binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev. 1997;18:801–31.

    Article  PubMed  CAS  Google Scholar 

  24. Thissen JP, Davenport ML, Pucilowska JB, Miles MV, Underwood LE. Increased serum clearance and degradation of 125I-labeled IGF-I in protein-restricted rats. Am J Physiol. 1992;262:E406–11.

    PubMed  CAS  Google Scholar 

  25. Underwood LE, Thissen JP, Lemozy S, Ketelslegers JM, Clemmons DR. Hormonal and nutritional regulation of IGF-I and its binding proteins. Horm Res. 1994;42:145–51.

    Article  PubMed  CAS  Google Scholar 

  26. Nilsson O, Baron J. Impact of growth plate senescence on catch-up growth and epiphyseal fusion. Pediatr Nephrol. 2005;20:319–22.

    Article  PubMed  Google Scholar 

  27. Walker KV, Kember NF. Cell kinetics of growth cartilage in the rat tibia. II. Measurements during ageing. Cell Tissue Kinet. 1972;5:409–19.

    PubMed  CAS  Google Scholar 

  28. Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J. Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci U S A. 2001;98:6871–6.

    Article  PubMed  CAS  Google Scholar 

  29. Gafni RI, Weise M, Robrecht DT, et al. Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res. 2001;50:618–23.

    Article  PubMed  CAS  Google Scholar 

  30. Baron J, Klein KO, Colli MJ, et al. Catch-up growth after glucocorticoid excess: a mechanism intrinsic to the growth plate. Endocrinology. 1994;135:1367–71.

    Article  PubMed  CAS  Google Scholar 

  31. Wei W, Sedivy JM. Differentiation between senescence (M1) and crisis (M2) in human fibroblast cultures. Exp Cell Res. 1999;253:519–22.

    Article  PubMed  CAS  Google Scholar 

  32. Prader A, Tanner JM, von Harnack GA. Catch-up growth following illness or starvation. An example of developmental canalization in man. J Pediatr. 1963;62:646–59.

    Article  PubMed  CAS  Google Scholar 

  33. Cutler Jr GB. The role of estrogen in bone growth and maturation during childhood and adolescence. J Steroid Biochem Mol Biol. 1997;61:141–4.

    Article  PubMed  CAS  Google Scholar 

  34. Veldhuis JD, Bowers CY. Three-peptide control of pulsatile and entropic feedback-sensitive modes of growth hormone secretion: modulation by estrogen and aromatizable androgen. J Pediatr Endocrinol Metab. 2003;16 Suppl 3:587–605.

    PubMed  CAS  Google Scholar 

  35. Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER. Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab. 1993;76:996–1001.

    Article  PubMed  CAS  Google Scholar 

  36. Nilsson KO, Albertsson-Wikland K, Alm J, et al. Improved final height in girls with Turner’s syndrome treated with growth hormone and oxandrolone. J Clin Endocrinol Metab. 1996;81:635–40.

    Article  PubMed  CAS  Google Scholar 

  37. Stanhope R, Buchanan CR, Fenn GC, Preece MA. Double blind placebo controlled trial of low dose oxandrolone in the treatment of boys with constitutional delay of growth and puberty. Arch Dis Child. 1988;63:501–5.

    Article  PubMed  CAS  Google Scholar 

  38. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976;51:170–9.

    Article  PubMed  CAS  Google Scholar 

  39. Centers for Disease Control and Prevention NCfHS. CDC growth charts: United States. http://www.cdc.gov/growthcharts/.30-5-2000.

  40. Freeman JV, Cole TJ, Chinn S, Jones PR, White EM, Preece MA. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child. 1995;73:17–24.

    Article  PubMed  CAS  Google Scholar 

  41. Zeferino AM, Barros Filho AA, Bettiol H, Barbieri MA. [Monitoring growth]. J Pediatr (Rio J). 2003;79 Suppl 1:S23–32.

    Article  Google Scholar 

  42. Mason A, Malik S, Russell RK, Bishop J, McGrogan P, Ahmed SF. Impact of inflammatory bowel disease on pubertal growth. Horm Res Paediatr. 2011;76:293–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kirschner BS. Growth and development in chronic inflammatory bowel disease. Acta Paediatr Scand Suppl. 1990;366:98–104. discussion 5.

    Article  PubMed  CAS  Google Scholar 

  44. Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology. 1988;95:1523–7.

    PubMed  CAS  Google Scholar 

  45. Hildebrand H, Karlberg J, Kristiansson B. Longitudinal growth in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1994;18:165–73.

    Article  PubMed  CAS  Google Scholar 

  46. Markowitz J, Grancher K, Rosa J, Aiges H, Daum F. Growth failure in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1993;16:373–80.

    Article  PubMed  CAS  Google Scholar 

  47. Motil KJ, Grand RJ, Davis-Kraft L, Ferlic LL, Smith EO. Growth failure in children with inflammatory bowel disease: a prospective study. Gastroenterology. 1993;105:681–91.

    PubMed  CAS  Google Scholar 

  48. Kundhal P, Critch J, Hack C, Griffiths A. Clinical course and growth of children with Crohn’s disease. Can J Gastroenterol 2002;16: Suppl SA, A118.

    Google Scholar 

  49. Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child. 2003;88:995–1000.

    Article  PubMed  CAS  Google Scholar 

  50. Wine E, Reif SS, Leshinsky-Silver E, et al. Pediatric Crohn’s disease and growth retardation: the role of genotype, phenotype, and disease severity. Pediatrics. 2004;114:1281–6.

    Article  PubMed  Google Scholar 

  51. Sawczenko A, Ballinger AB, Croft NM, Sanderson IR, Savage MO. Adult height in patients with early onset of Crohn’s disease. Gut. 2003;52:454–5. author reply 5.

    Article  PubMed  CAS  Google Scholar 

  52. Alemzadeh N, Rekers-Mombarg LT, Mearin ML, Wit JM, Lamers CB, van Hogezand RA. Adult height in patients with early onset of Crohn’s disease. Gut. 2002;51:26–9.

    Article  PubMed  CAS  Google Scholar 

  53. Vasseur F, Gower-Rousseau C, Vernier-Massouille G, et al. Nutritional status and growth in pediatric Crohn’s disease: a population-based study. Am J Gastroenterol. 2010;105:1893–900.

    Article  PubMed  Google Scholar 

  54. Gupta N, Lustig RH, Kohn MA, McCracken M, Vittinghoff E. Sex differences in statural growth impairment in Crohn’s disease: role of IGF-1. Inflamm Bowel Dis. 2011;17:2318–25.

    Article  PubMed  Google Scholar 

  55. Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS. Growth, body composition, and nutritional status in children and adolescents with Crohn’s disease. J Pediatr Gastroenterol Nutr. 2000;31:33–40.

    Article  PubMed  CAS  Google Scholar 

  56. Pigneur B, Seksik P, Viola S, et al. Natural history of Crohn’s disease: comparison between childhood- and adult-onset disease. Inflamm Bowel Dis. 2010;16:953–61.

    PubMed  Google Scholar 

  57. Gupta N, Bostrom AG, Kirschner BS, et al. Gender differences in presentation and course of disease in pediatric patients with Crohn disease. Pediatrics. 2007;120:e1418–25.

    Article  PubMed  Google Scholar 

  58. Shono T, Kato M, Aoyagi Y, et al. Assessment of growth disturbance in Japanese children with IBD. Int J Pediatr. 2010;2010:958915.

    PubMed  Google Scholar 

  59. Kim BJ, Song SM, Kim KM, et al. Characteristics and trends in the incidence of inflammatory bowel disease in Korean children: a single-center experience. Dig Dis Sci. 2010;55:1989–95.

    Article  PubMed  Google Scholar 

  60. Ferguson A, Sedgwick DM. Juvenile onset inflammatory bowel disease: height and body mass index in adult life. BMJ. 1994;308:1259–63.

    Article  PubMed  CAS  Google Scholar 

  61. Walters TD, Griffiths AM. Mechanisms of growth impairment in pediatric Crohn’s disease. Nat Rev Gastroenterol Hepatol. 2009;6:513–23.

    Article  PubMed  CAS  Google Scholar 

  62. Kelts DG, Grand RJ, Shen G, Watkins JB, Werlin SL, Boehme C. Nutritional basis of growth failure in children and adolescents with Crohn’s disease. Gastroenterology. 1979;76:720–7.

    PubMed  CAS  Google Scholar 

  63. Kirschner BS, Klich JR, Kalman SS, deFavaro MV, Rosenberg IH. Reversal of growth retardation in Crohn’s disease with therapy emphasizing oral nutritional restitution. Gastroenterology. 1981;80:10–5.

    PubMed  CAS  Google Scholar 

  64. Ballinger A, El-Haj T, Perrett D, et al. The role of medial hypothalamic serotonin in the suppression of feeding in a rat model of colitis. Gastroenterology. 2000;118:544–53.

    Article  PubMed  CAS  Google Scholar 

  65. Filipsson S, Hulten L, Lindstedt G. Malabsorption of fat and vitamin B12 before and after intestinal resection for Crohn’s disease. Scand J Gastroenterol. 1978;13:529–36.

    Article  PubMed  CAS  Google Scholar 

  66. Griffiths AM, Drobnies A, Soldin SJ, Hamilton JR. Enteric protein loss measured by fecal alpha 1-antitrypsin clearance in the assessment of Crohn’s disease activity: a study of children and adolescents. J Pediatr Gastroenterol Nutr. 1986;5:907–11.

    Article  PubMed  CAS  Google Scholar 

  67. Azcue M, Rashid M, Griffiths A, Pencharz PB. Energy expenditure and body composition in children with Crohn’s disease: effect of enteral nutrition and treatment with prednisolone. Gut. 1997;41:203–8.

    Article  PubMed  CAS  Google Scholar 

  68. De Benedetti F, Alonzi T, Moretta A, et al. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest. 1997;99:643–50.

    Article  PubMed  Google Scholar 

  69. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJ. Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Gut. 2000;46:694–700.

    Article  PubMed  CAS  Google Scholar 

  70. Martensson K, Chrysis D, Savendahl L. Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones. J Bone Miner Res. 2004;19:1805–12.

    Article  PubMed  CAS  Google Scholar 

  71. Varghese S, Wyzga N, Griffiths AM, Sylvester FA. Effects of serum from children with newly diagnosed Crohn disease on primary cultures of rat osteoblasts. J Pediatr Gastroenterol Nutr. 2002;35:641–8.

    Article  PubMed  CAS  Google Scholar 

  72. Kirschner BS, Sutton MM. Somatomedin-C levels in growth-impaired children and adolescents with chronic inflammatory bowel disease. Gastroenterology. 1986;91:830–6.

    PubMed  CAS  Google Scholar 

  73. Tenore A, Berman WF, Parks JS, Bongiovanni AM. Basal and stimulated serum growth hormone concentrations in inflammatory bowel disease. J Clin Endocrinol Metab. 1977;44:622–8.

    Article  PubMed  CAS  Google Scholar 

  74. Wang X, Jiang J, Warram J, et al. Endotoxin-induced proteolytic reduction in hepatic growth hormone (GH) receptor: a novel mechanism for GH insensitivity. Mol Endocrinol. 2008;22:1427–37.

    Article  PubMed  CAS  Google Scholar 

  75. Denson LA, Menon RK, Shaufl A, Bajwa HS, Williams CR, Karpen SJ. TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding. J Clin Invest. 2001;107:1451–8.

    Article  PubMed  CAS  Google Scholar 

  76. Dejkhamron P, Thimmarayappa J, Kotlyarevska K, et al. Lipopolysaccharide (LPS) directly suppresses growth hormone receptor (GHR) expression through MyD88-dependent and -independent Toll-like receptor-4/MD2 complex signaling pathways. Mol Cell Endocrinol. 2007;274:35–42.

    Article  PubMed  CAS  Google Scholar 

  77. Colson A, Le Cam A, Maiter D, Edery M, Thissen JP. Potentiation of growth hormone-induced liver suppressors of cytokine signaling messenger ribonucleic acid by cytokines. Endocrinology. 2000;141:3687–95.

    Article  PubMed  CAS  Google Scholar 

  78. Cohney SJ, Sanden D, Cacalano NA, et al. SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol Cell Biol. 1999;19:4980–8.

    PubMed  CAS  Google Scholar 

  79. Ram PA, Waxman DJ. Role of the cytokine-inducible SH2 protein CIS in desensitization of STAT5b signaling by continuous growth hormone. J Biol Chem. 2000;275:39487–96.

    Article  PubMed  CAS  Google Scholar 

  80. Shumate ML, Yumet G, Ahmed TA, Cooney RN. Interleukin-1 inhibits the induction of insulin-like growth factor-I by growth hormone in CWSV-1 hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2005;289:G227–39.

    Article  PubMed  CAS  Google Scholar 

  81. De Benedetti F, Meazza C, Oliveri M, et al. Effect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis. Endocrinology. 2001;142:4818–26.

    Article  PubMed  Google Scholar 

  82. Mauras N. Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. Horm Res. 2001;56 Suppl 1:13–8.

    Article  PubMed  CAS  Google Scholar 

  83. De Benedetti F, Rucci N, Del Fattore A, et al. Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis Rheum. 2006;54:3551–63.

    Article  PubMed  CAS  Google Scholar 

  84. Kamimura D, Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol. 2003;149:1–38.

    Article  PubMed  CAS  Google Scholar 

  85. Tamura T, Udagawa N, Takahashi N, et al. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci U S A. 1993;90:11924–8.

    Article  PubMed  CAS  Google Scholar 

  86. Franchimont N, Wertz S, Malaise M. Interleukin-6: an osteotropic factor influencing bone formation? Bone. 2005;37:601–6.

    Article  PubMed  CAS  Google Scholar 

  87. Bross DA, Leichtner AM, Zurakowski D, Law T, Bousvaros A. Elevation of serum interleukin-6 but not serum-soluble interleukin-2 receptor in children with Crohn’s disease. J Pediatr Gastroenterol Nutr. 1996;23:164–71.

    Article  PubMed  CAS  Google Scholar 

  88. Suzuki A, Hanada T, Mitsuyama K, et al. CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J Exp Med. 2001;193:471–81.

    Article  PubMed  CAS  Google Scholar 

  89. Tebbutt NC, Giraud AS, Inglese M, et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med. 2002;8:1089–97.

    Article  PubMed  CAS  Google Scholar 

  90. Nicholson SE, De Souza D, Fabri LJ, et al. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130. Proc Natl Acad Sci U S A. 2000;97:6493–8.

    Article  PubMed  CAS  Google Scholar 

  91. Carey R, Jurickova I, Ballard E, et al. Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:446–57.

    Article  PubMed  Google Scholar 

  92. Mudter J, Weigmann B, Bartsch B, et al. Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases. Am J Gastroenterol. 2005;100:64–72.

    Article  PubMed  CAS  Google Scholar 

  93. Cassidy JT, Hillman LS. Abnormalities in skeletal growth in children with juvenile rheumatoid arthritis. Rheum Dis Clin North Am. 1997;23:499–522.

    Article  PubMed  CAS  Google Scholar 

  94. MacRae VE, Farquharson C, Ahmed SF. The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology (Oxford). 2006;45:11–9.

    Article  CAS  Google Scholar 

  95. Sawczenko A, Azooz O, Paraszczuk J, et al. Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the −174 IL-6G/C polymorphism in children. Proc Natl Acad Sci U S A. 2005;102:13260–5.

    Article  PubMed  CAS  Google Scholar 

  96. Cezard JP, Touati G, Alberti C, Hugot JP, Brinon C, Czernichow P. Growth in pediatric Crohn’s disease. Horm Res. 2002;58 Suppl 1:11–5.

    Article  PubMed  CAS  Google Scholar 

  97. Bernstein CN, Leslie WD. The pathophysiology of bone disease in gastrointestinal disease. Eur J Gastroenterol Hepatol. 2003;15:857–64.

    Article  PubMed  CAS  Google Scholar 

  98. Lien G, Selvaag AM, Flato B, et al. A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Arthritis Rheum. 2005;52:833–40.

    Article  PubMed  Google Scholar 

  99. Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology. 2004;126:989–96. discussion 47.

    Article  PubMed  CAS  Google Scholar 

  100. Nishimoto N, Kishimoto T. Inhibition of IL-6 for the treatment of inflammatory diseases. Curr Opin Pharmacol. 2004;4:386–91.

    Article  PubMed  CAS  Google Scholar 

  101. Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50:1761–9.

    Article  PubMed  CAS  Google Scholar 

  102. Yokota S, Miyamae T, Imagawa T, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2005;52:818–25.

    Article  PubMed  CAS  Google Scholar 

  103. Wolk K, Witte E, Hoffmann U, et al. IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL-22 in Crohn’s disease. J Immunol. 2007;178:5973–81.

    PubMed  CAS  Google Scholar 

  104. Allen DB. Influence of inhaled corticosteroids on growth: a pediatric endocrinologist’s perspective. Acta Paediatr. 1998;87: 123–9.

    Article  PubMed  CAS  Google Scholar 

  105. Ballinger AB, Savage MO, Sanderson IR. Delayed puberty associated with inflammatory bowel disease. Pediatr Res. 2003;53:205–10.

    Article  PubMed  Google Scholar 

  106. Brain CE, Savage MO. Growth and puberty in chronic inflammatory bowel disease. Baillieres Clin Gastroenterol. 1994;8:83–100.

    Article  PubMed  CAS  Google Scholar 

  107. Mizokami A, Gotoh A, Yamada H, Keller ET, Matsumoto T. Tumor necrosis factor-alpha represses androgen sensitivity in the LNCaP prostate cancer cell line. J Urol. 2000;164:800–5.

    Article  PubMed  CAS  Google Scholar 

  108. Zadik Z, Cooper M, Chen M, Stern N. Cushing’s disease presenting as pubertal arrest. J Pediatr Endocrinol. 1993;6:201–4.

    PubMed  CAS  Google Scholar 

  109. Russell RK, Drummond HE, Nimmo EE, et al. Genotype-phenotype analysis in childhood-onset Crohn’s disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease. Inflamm Bowel Dis. 2005;11:955–64.

    Article  PubMed  Google Scholar 

  110. Tomer G, Ceballos C, Concepcion E, Benkov KJ. NOD2/CARD15 variants are associated with lower weight at diagnosis in children with Crohn’s disease. Am J Gastroenterol. 2003;98:2479–84.

    Article  PubMed  CAS  Google Scholar 

  111. Russell RK, Drummond HE, Nimmo ER, et al. Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut. 2006;55:1114–23.

    Article  PubMed  CAS  Google Scholar 

  112. Lee JJ, Essers JB, Kugathasan S, et al. Association of linear growth impairment in pediatric Crohn’s disease and a known height locus: a pilot study. Ann Hum Genet. 2010;74:489–97.

    Article  PubMed  CAS  Google Scholar 

  113. Levine A, Shamir R, Wine E, et al. TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn’s disease. Am J Gastroenterol. 2005;100:1598–604.

    Article  PubMed  CAS  Google Scholar 

  114. Lee JJ, Escher JC, Shuman MJ, et al. Final adult height of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score. Inflamm Bowel Dis. 2010;16:1669–77.

    Article  PubMed  Google Scholar 

  115. Griffiths AM, Otley AR, Hyams J, et al. A review of activity indices and end points for clinical trials in children with Crohn’s disease. Inflamm Bowel Dis. 2005;11:185–96.

    Article  PubMed  Google Scholar 

  116. Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008;153:484–90.

    Article  PubMed  CAS  Google Scholar 

  117. Thayu M, Leonard MB, Hyams JS, et al. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH study. Clin Gastroenterol Hepatol. 2008;6:1378–84.

    Article  PubMed  CAS  Google Scholar 

  118. Wong SC, Smyth A, McNeill E, et al. The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation. Clin Endocrinol (Oxf). 2010;73:220–8.

    CAS  Google Scholar 

  119. Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:839–49.

    Article  PubMed  Google Scholar 

  120. Griffiths AM, Nicholas D, Smith C, et al. Development of a quality-of-life index for pediatric inflammatory bowel disease: dealing with differences related to age and IBD type. J Pediatr Gastroenterol Nutr. 1999;28:S46–52.

    Article  PubMed  CAS  Google Scholar 

  121. Aiges H, Markowitz J, Rosa J, Daum F. Home nocturnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn’s disease. Gastroenterology. 1989;97:905–10.

    PubMed  CAS  Google Scholar 

  122. Belli DC, Seidman E, Bouthillier L, et al. Chronic intermittent elemental diet improves growth failure in children with Crohn’s disease. Gastroenterology. 1988;94:603–10.

    PubMed  CAS  Google Scholar 

  123. Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, Griffiths A. Supplementary enteral nutrition maintains remission in pediatric Crohn’s disease. Gut. 1996;38:543–8.

    Article  PubMed  CAS  Google Scholar 

  124. Bannerjee K, Camacho-Hubner C, Babinska K, et al. Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease. J Pediatr Gastroenterol Nutr. 2004;38:270–5.

    Article  PubMed  CAS  Google Scholar 

  125. Gassull MA, Stange EF. Nutrition and diet in inflammatory bowel disease. In: Satsangi J, Sutherland LR, editors. Inflammatory bowel diseases. London: Elsevier; 2003. p. 461–74.

    Google Scholar 

  126. Walker-Smith JA. Management of growth failure in Crohn’s disease. Arch Dis Child. 1996;75:351–4.

    Article  PubMed  CAS  Google Scholar 

  127. Newby E, Sawczenko A, Thomas A, Wilson D. Interventions for growth failure in childhood Crohn’s disease. Cochrane Database Syst Rev 2005;CD003873.

    Google Scholar 

  128. Fell JM, Paintin M, Arnaud-Battandier F, et al. Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in pediatric Crohn’s disease. Aliment Pharmacol Ther. 2000;14:281–9.

    Article  PubMed  CAS  Google Scholar 

  129. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for inducing remission of Crohn’s disease. Cochrane Database Syst Rev 2001;CD000542.

    Google Scholar 

  130. Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr. 2000;31:8–15.

    Article  PubMed  CAS  Google Scholar 

  131. Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology. 1995;108:1056–67.

    Article  PubMed  CAS  Google Scholar 

  132. Seidman E, Griffiths AM, Jones A. Semi-elemntal diet versus prednisone in the treatment of acute Crohn’s disease in children and adolescents. Gastroenterology. 1993;104:A778.

    Google Scholar 

  133. Griffiths AM. Enteral nutrition: the neglected primary therapy of active Crohn’s disease. J Pediatr Gastroenterol Nutr. 2000;31:3–5.

    Article  PubMed  CAS  Google Scholar 

  134. Rigaud D, Cosnes J, Le Quintrec Y, Rene E, Gendre JP, Mignon M. Controlled trial comparing two types of enteral nutrition in treatment of active Crohn’s disease: elemental versus polymeric diet. Gut. 1991;32:1492–7.

    Article  PubMed  CAS  Google Scholar 

  135. Escher JC. Budesonide versus prednisolone for the treatment of active Crohn’s disease in children: a randomized, double-blind, controlled, multicentre trial. Eur J Gastroenterol Hepatol. 2004;16:47–54.

    Article  PubMed  CAS  Google Scholar 

  136. Papi C, Luchetti R, Gili L, Montanti S, Koch M, Capurso L. Budesonide in the treatment of Crohn’s disease: a meta-analysis. Aliment Pharmacol Ther. 2000;14:1419–28.

    Article  PubMed  CAS  Google Scholar 

  137. Kundhal P, Zachos M, Holmes JL, Griffiths AM. Controlled ileal release budesonide in pediatric Crohn disease: efficacy and effect on growth. J Pediatr Gastroenterol Nutr. 2001;33:75–80.

    Article  PubMed  CAS  Google Scholar 

  138. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119:895–902.

    Article  PubMed  CAS  Google Scholar 

  139. Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol. 2007;102:2804–12. quiz 3, 13.

    Article  PubMed  CAS  Google Scholar 

  140. Thayu M, Denson LA, Shults J, et al. Determinants of changes in linear growth and body composition in incident pediatric Crohn’s disease. Gastroenterology. 2010;139:430–8.

    Article  PubMed  Google Scholar 

  141. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132:863–73. quiz 1165–6.

    Article  PubMed  CAS  Google Scholar 

  142. Walters TD, Gilman AR, Griffiths A. Infliximab therapy restores normal growth in children with chronically active severe Crohn disease refractory to immunomodulatory therapy. Gastroenterology. 2005;128 Suppl 2:A27.

    Google Scholar 

  143. de Ridder L, Escher JC, Bouquet J, et al. Infliximab therapy in 30 patients with refractory pediatric Crohn disease with and without fistulas in The Netherlands. J Pediatr Gastroenterol Nutr. 2004;39:46–52.

    Article  PubMed  Google Scholar 

  144. Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Dig Liver Dis. 2004;36:342–7.

    Article  PubMed  CAS  Google Scholar 

  145. Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2003;36:632–6.

    Article  PubMed  CAS  Google Scholar 

  146. Wanty C, Stephenne X, Sokal E, Smets F. [Long-term outcome of infliximab therapy in pediatric Crohn disease]. Arch Pediatr. 2011;18:863–9.

    Article  PubMed  CAS  Google Scholar 

  147. Malik S, Wong SC, Bishop J, et al. Improvement in growth of children with Crohn disease following anti-TNF-alpha therapy can be independent of pubertal progress and glucocorticoid reduction. J Pediatr Gastroenterol Nutr. 2011;52:31–7.

    Article  PubMed  CAS  Google Scholar 

  148. Griffiths AM, Hyams JS, Crandall W. Height of children with active crohn’s disease improves during treatment with Infliximab. Gastroenterology. 2006;130 Suppl 2:A59.

    Google Scholar 

  149. Hyams J, Walters TD, Crandall W, et al. Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn’s disease in children: REACH open-label extension. Curr Med Res Opin. 2011;27:651–62.

    Article  PubMed  CAS  Google Scholar 

  150. DiFedele LM, He J, Bonkowski EL, et al. Tumor necrosis factor alpha blockade restores growth hormone signaling in murine colitis. Gastroenterology. 2005;128:1278–91.

    Article  PubMed  CAS  Google Scholar 

  151. Vespasiani Gentilucci U, Caviglia R, Picardi A, et al. Infliximab reverses growth hormone resistance associated with inflammatory bowel disease. Aliment Pharmacol Ther. 2005;21:1063–71.

    Article  PubMed  CAS  Google Scholar 

  152. Nicholls S, Vieira MC, Majrowski WH, Shand WS, Savage MO, Walker-Smith JA. Linear growth after colectomy for ulcerative colitis in childhood. J Pediatr Gastroenterol Nutr. 1995;21:82–6.

    Article  PubMed  CAS  Google Scholar 

  153. Griffiths AM, Wesson DE, Shandling B, Corey M, Sherman PM. Factors influencing postoperative recurrence of Crohn’s disease in childhood. Gut. 1991;32:491–5.

    Article  PubMed  CAS  Google Scholar 

  154. Davies G, Evans CM, Shand WS, Walker-Smith JA. Surgery for Crohn’s disease in childhood: influence of site of disease and operative procedure on outcome. Br J Surg. 1990;77:891–4.

    Article  PubMed  CAS  Google Scholar 

  155. Baldassano RN, Han PD, Jeshion WC, et al. Pediatric Crohn’s disease: risk factors for postoperative recurrence. Am J Gastroenterol. 2001;96:2169–76.

    Article  PubMed  CAS  Google Scholar 

  156. McCaffery Jr TD, Nasr K, Lawrence AM, Kirsner JB. Effect of administered human growth hormone on growth retardation in inflammatory bowel disease. Am J Dig Dis. 1974;19:411–6.

    Article  PubMed  Google Scholar 

  157. Henker J. Therapy with recombinant growth hormone in children with Crohn disease and growth failure. Eur J Pediatr. 1996;155:1066–7.

    Article  PubMed  CAS  Google Scholar 

  158. Henker J. Effect of growth hormone therapy in patients with Crohn disease. J Pediatr Gastroenterol Nutr. 2002;34:424–5.

    Article  PubMed  Google Scholar 

  159. Heyman MB, Garnett EA, Wojcicki J, et al. Growth hormone treatment for growth failure in pediatric patients with Crohn’s disease. J Pediatr 2008;153:651–8, 8 e1-3.

    Google Scholar 

  160. Calenda KA, Schornagel IL, Sadeghi-Nejad A, Grand RJ. Effect of recombinant growth hormone treatment on children with Crohn’s disease and short stature: a pilot study. Inflamm Bowel Dis. 2005;11:435–41.

    Article  PubMed  Google Scholar 

  161. Denson LA, Kim MO, Bezold R, et al. A randomized controlled trial of growth hormone in active pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2010;51:130–9.

    Article  PubMed  CAS  Google Scholar 

  162. Wong SC, Kumar P, Galloway PJ, et al. A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn’s disease. Clin Endocrinol (Oxf). 2011;74:599–607.

    Article  CAS  Google Scholar 

  163. Vortia E, Kay M, Wyllie R. The role of growth hormone and insulin-like growth factor-1 in Crohn’s disease: implications for therapeutic use of human growth hormone in pediatric patients. Curr Opin Pediatr. 2010;23:545–51.

    Article  CAS  Google Scholar 

  164. Bechtold S, Ripperger P, Dalla Pozza R, et al. Dynamics of body composition and bone in patients with juvenile idiopathic arthritis treated with growth hormone. J Clin Endocrinol Metab. 2010;95:178–85.

    Article  PubMed  CAS  Google Scholar 

  165. Phung OJ, Coleman CI, Baker EL, et al. Recombinant human growth hormone in the treatment of patients with cystic fibrosis. Pediatrics. 2010;126:e1211–26.

    Article  PubMed  Google Scholar 

  166. Mauras N, George D, Evans J, et al. Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. Metabolism. 2002;51:127–35.

    Article  PubMed  CAS  Google Scholar 

  167. Slonim AE, Bulone L, Damore MB, Goldberg T, Wingertzahn MA, McKinley MJ. A preliminary study of growth hormone therapy for Crohn’s disease. N Engl J Med. 2000;342:1633–7.

    Article  PubMed  CAS  Google Scholar 

  168. Han X, Sosnowska D, Bonkowski EL, Denson LA. Growth hormone inhibits signal transducer and activator of transcription 3 activation and reduces disease activity in murine colitis. Gastroenterology. 2005;129:185–203.

    Article  PubMed  CAS  Google Scholar 

  169. Mason A, Wong SC, McGrogan P, Ahmed SF. Effect of testosterone therapy for delayed growth and puberty in boys with inflammatory bowel disease. Horm Res Paediatr. 2011;75:8–13.

    Article  PubMed  CAS  Google Scholar 

  170. Leung DW, Spencer SA, Cachianes G, et al. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987;330:537–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, Canada, M5G 1X8

    Thomas D. Walters MBBS, MSc, FRACP & Anne M. Griffiths MD, FRCP(C)

Authors
  1. Thomas D. Walters MBBS, MSc, FRACP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne M. Griffiths MD, FRCP(C)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas D. Walters MBBS, MSc, FRACP .

Editor information

Editors and Affiliations

  1. Perelman School of Medicine, The Children’s Hospital of Philadelphia, University of Pennsylvania, 34th St. & Civic Ctr. Blvd., Philadelphia, 19104, Pennsylvania, USA

    Petar Mamula

  2. School of Medicine--Greenville, Pediatric Gastroenterology & Nutrition, University of South Carolina, 200 Patewood Drive, Suite A-140, Greenville, 29615, South Carolina, USA

    Jonathan E. Markowitz

  3. Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 34th St. & Civic Ctr. Blvd., Philadelphia, 19104, Pennsylvania, USA

    Robert N. Baldassano

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Walters, T.D., Griffiths, A.M. (2013). Growth Impairment in Pediatric Inflammatory Bowel Disease. In: Mamula, P., Markowitz, J., Baldassano, R. (eds) Pediatric Inflammatory Bowel Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5061-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-5061-0_12

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-5060-3

  • Online ISBN: 978-1-4614-5061-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation