Growth Impairment in Pediatric Inflammatory Bowel Disease

  • Thomas D. Walters
  • Anne M. Griffiths


Inflammatory Bowel Disease Ulcerative Colitis Enteral Nutrition Standard Deviation Score Crohn Disease 
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  1. 1.
    Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM. Growth and clinical course of children with Crohn disease. Gut 1993; 34:939–43.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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 S43–4.PubMedGoogle Scholar
  4. 4.
    Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA. Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol 2004; 180:247–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Rogol AD, Roemmich JN, Clark PA. Growth at puberty. J Adolesc Health 2002; 31:192–200.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    Centers for Disease Control and Prevention NCfHS. CDC growth charts:United States,–5-2000.Google Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    Zeferino AM, Barros Filho AA, Bettiol H, Barbieri MA. [Monitoring growth]. J Pediatr (Rio J) 2003; 79 Suppl 1:S23–32.Google Scholar
  10. 10.
    Kirschner BS. Growth and development in chronic inflammatory bowel disease. Acta Paediatr Scand Suppl 1990; 366:98–104; discussion 105.PubMedGoogle Scholar
  11. 11.
    Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn disease. Gastroenterology 1988; 95:1523–7.PubMedGoogle Scholar
  12. 12.
    Hildebrand H, Karlberg J, Kristiansson B. Longitudinal growth in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1994; 18:165–73.PubMedGoogle Scholar
  13. 13.
    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.PubMedGoogle Scholar
  14. 14.
    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.PubMedGoogle Scholar
  15. 15.
    Kundhal P, Critch J, Hack C, Griffiths A. Clinical course and growth of children with Crohn disease. Can J Gastroenterol 2002.Google Scholar
  16. 16.
    Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child 2003; 88:995–1000.PubMedCrossRefGoogle Scholar
  17. 17.
    Wine E, Reif SS, Leshinsky-Silver E, et al. Pediatric Crohn disease and growth retardation:the role of genotype, phenotype, and disease severity. Pediatrics 2004; 114:1281–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Sawczenko A, Ballinger AB, Croft NM, Sanderson IR, Savage MO. Adult height in patients with early onset of Crohn disease. Gut 2003; 52:454–5; author reply 455.PubMedCrossRefGoogle Scholar
  19. 19.
    Alemzadeh N, Rekers-Mombarg LT, Mearin ML, Wit JM, Lamers CB, van Hogezand RA. Adult height in patients with early onset of Crohn disease. Gut 2002; 51:26–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Ferguson A, Sedgwick DM. Juvenile onset inflammatory bowel disease:height and body mass index in adult life. BMJ 1994; 308:1259–63.PubMedGoogle Scholar
  21. 21.
    Ballinger A. Fundamental mechanisms of growth failure in inflammatory bowel disease. Horm Res 2002; 58 Suppl 1:7–10.PubMedCrossRefGoogle Scholar
  22. 22.
    Kelts DG, Grand RJ, Shen G, Watkins JB, Werlin SL, Boehme C. Nutritional basis of growth failure in children and adolescents with Crohn disease. Gastroenterology 1979; 76:720–7.PubMedGoogle Scholar
  23. 23.
    Kirschner BS, Klich JR, Kalman SS, deFavaro MV, Rosenberg IH. Reversal of growth retardation in Crohn disease with therapy emphasizing oral nutritional restitution. Gastroenterology 1981; 80:10–5.PubMedGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Filipsson S, Hulten L, Lindstedt G. Malabsorption of fat and vitamin B12 before and after intestinal resection for Crohn disease. Scand J Gastroenterol 1978; 13:529–36.PubMedCrossRefGoogle Scholar
  26. 26.
    Griffiths AM, Drobnies A, Soldin SJ, Hamilton JR. Enteric protein loss measured by fecal alpha 1-antitrypsin clearance in the assessment of Crohn disease activity:a study of children and adolescents. J Pediatr Gastroenterol Nutr 1986; 5:907–11.PubMedGoogle Scholar
  27. 27.
    Azcue M, Rashid M, Griffiths A, Pencharz PB. Energy expenditure and body composition in children with Crohn disease:effect of enteral nutrition and treatment with prednisolone. Gut 1997; 41:203–8.PubMedCrossRefGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    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.PubMedCrossRefGoogle Scholar
  33. 33.
    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.PubMedGoogle Scholar
  34. 34.
    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.PubMedGoogle Scholar
  35. 35.
    Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins:biological actions. Endocr Rev 1995; 16:3–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Kirschner BS, Sutton MM. Somatomedin-C levels in growth-impaired children and adolescents with chronic inflammatory bowel disease. Gastroenterology 1986; 91:830–6.PubMedGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    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.PubMedGoogle Scholar
  39. 39.
    Ram PA, Waxman DJ. SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms. J Biol Chem 1999; 274:35553–61.PubMedCrossRefGoogle Scholar
  40. 40.
    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.PubMedCrossRefGoogle Scholar
  41. 41.
    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.PubMedGoogle Scholar
  42. 42.
    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.PubMedCrossRefGoogle Scholar
  43. 43.
    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.PubMedCrossRefGoogle Scholar
  44. 44.
    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-6 G/C polymorphism in children. Proc Natl Acad Sci U S A 2005; 102:13260–5.PubMedCrossRefGoogle Scholar
  45. 45.
    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.PubMedCrossRefGoogle Scholar
  46. 46.
    Mauras N. Growth hormone therapy in the glucocorticosteroid-dependent child:metabolic and linear growth effects. Horm Res 2001; 56 Suppl 1:13–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Ballinger AB, Savage MO, Sanderson IR. Delayed puberty associated with inflammatory bowel disease. Pediatr Res 2003; 53:205–10.PubMedGoogle Scholar
  48. 48.
    Russell RK, Drummond HE, Nimmo EE, et al. Genotype-phenotype analysis in childhood-onset Crohn disease:NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease. Inflamm Bowel Dis 2005; 11:955–64.PubMedCrossRefGoogle Scholar
  49. 49.
    Tomer G, Ceballos C, Concepcion E, Benkov KJ. NOD2/CARD15 variants are associated with lower weight at diagnosis in children with Crohn disease. Am J Gastroenterol 2003; 98:2479–84.PubMedCrossRefGoogle Scholar
  50. 50.
    Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP. Differential effects of NOD2 variants on Crohn disease risk and phenotype in diverse populations:a metaanalysis. Am J Gastroenterol 2004; 99:2393–404.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Levine A, Shamir R, Wine E, et al. TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn disease. Am J Gastroenterol 2005; 100:1598–604.PubMedCrossRefGoogle Scholar
  53. 53.
    Griffiths AM, Otley AR, Hyams J, et al. A review of activity indices and end points for clinical trials in children with Crohn disease. Inflamm Bowel Dis 2005; 11:185–96.PubMedCrossRefGoogle Scholar
  54. 54.
    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.PubMedCrossRefGoogle Scholar
  55. 55.
    Aiges H, Markowitz J, Rosa J, Daum F. Home nocturnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn disease. Gastroenterology 1989; 97:905–10.PubMedGoogle Scholar
  56. 56.
    Belli DC, Seidman E, Bouthillier L, et al. Chronic intermittent elemental diet improves growth failure in children with Crohn disease. Gastroenterology 1988; 94:603–10.PubMedGoogle Scholar
  57. 57.
    Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, Griffiths A. Supplementary enteral nutrition maintains remission in paediatric Crohn disease. Gut 1996; 38:543–8.PubMedCrossRefGoogle Scholar
  58. 58.
    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.PubMedCrossRefGoogle Scholar
  59. 59.
    Walker-Smith JA. Management of growth failure in Crohn disease. Arch Dis Child 1996; 75:351–4.PubMedGoogle Scholar
  60. 60.
    Gassull MA, Stange EF. Nutrition and diet in inflammatory bowel disease. In:Satsangi J, Sutherland LR, eds. Inflammatory Bowel Diseases. London, UK:Elsevier, 2003:461–74.Google Scholar
  61. 61.
    Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for inducing remission of Crohn disease. Cochrane Database Syst Rev 2001:CD000542.Google Scholar
  62. 62.
    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 paediatric Crohn disease. Aliment Pharmacol Ther 2000; 14:281–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn disease in children. J Pediatr Gastroenterol Nutr 2000; 31:8–15.PubMedCrossRefGoogle Scholar
  64. 64.
    Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn disease. Gastroenterology 1995; 108:1056–67.PubMedCrossRefGoogle Scholar
  65. 65.
    Seidman E, Griffiths AM, Jones A. Semi-elemntal diet versus prednisone in the treatment of acute Crohn disease in children and adolescents. Gastroenterology 1993; 104:A778.Google Scholar
  66. 66.
    Griffiths AM. Enteral nutrition:the neglected primary therapy of active Crohn disease. J Pediatr Gastroenterol Nutr 2000; 31:3–5.PubMedCrossRefGoogle Scholar
  67. 67.
    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 disease:elemental versus polymeric diet. Gut 1991; 32:1492–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Seidman E, Jones A, Issenman R. Cyclical exclusive enteral nutrition versus alternate day prednisone in maintaining remission of pediatric Crohn disease. J Pediatr Gastroenterol Nutr 1996; 23:A344.Google Scholar
  69. 69.
    Whittington PF, Barnes HV, Bayless TM. Medical management of Crohn disease in adolescence. Gastroenterology 1977; 72:1338–44.PubMedGoogle Scholar
  70. 70.
    Escher JC. Budesonide versus prednisolone for the treatment of active Crohn disease in children:a randomized, double-blind, controlled, multicentre trial. Eur J Gastroenterol Hepatol 2004; 16:47—54.PubMedCrossRefGoogle Scholar
  71. 71.
    Papi C, Luchetti R, Gili L, Montanti S, Koch M, Capurso L. Budesonide in the treatment of Crohn disease:a meta-analysis. Aliment Pharmacol Ther 2000; 14:1419–28.PubMedCrossRefGoogle Scholar
  72. 72.
    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.PubMedCrossRefGoogle Scholar
  73. 73.
    Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn disease. Gastroenterology 2000; 119:895–902.PubMedCrossRefGoogle Scholar
  74. 74.
    Sands BE. Immunosuppressive drugs in ulcerative colitis:twisting facts to suit theories? Gut 2006; 55:437–41.PubMedCrossRefGoogle Scholar
  75. 75.
    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.PubMedCrossRefGoogle Scholar
  76. 76.
    Griffiths AM, Wesson DE, Shandling B, Corey M, Sherman PM. Factors influencing postoperative recurrence of Crohn disease in childhood. Gut 1991; 32:491–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Davies G, Evans CM, Shand WS, Walker-Smith JA. Surgery for Crohn disease in childhood:influence of site of disease and operative procedure on outcome. Br J Surg 1990; 77:891–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Baldassano RN, Han PD, Jeshion WC, et al. Pediatric Crohn disease:risk factors for postoperative recurrence. Am J Gastroenterol 2001; 96:2169–76.PubMedCrossRefGoogle Scholar
  79. 79.
    Walters TD, Gilman AR, Griffiths AM. Linear growth improves during infliximab therapy in children with chronically active severe Crohn disease inflammatory bowel diseases April 2007, Vol 13(4):424–430.CrossRefGoogle Scholar
  80. 80.
    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.PubMedCrossRefGoogle Scholar
  81. 81.
    Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn disease. Dig Liver Dis 2004; 36:342–7.PubMedCrossRefGoogle Scholar
  82. 82.
    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.Google Scholar
  83. 83.
    Griffiths AM, Hyams JS, Crandall W. Height of children with Active Crohn Disease Improves During Treatment with Infliximab. Gastroenterology 2006; 130 Suppl2:A59.Google Scholar
  84. 84.
    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.PubMedCrossRefGoogle Scholar
  85. 85.
    Slonim AE, Bulone L, Damore MB, Goldberg T, Wingertzahn MA, McKinley MJ. A preliminary study of growth hormone therapy for Crohn disease. N Engl J Med 2000; 342:1633–7.PubMedCrossRefGoogle Scholar
  86. 86.
    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.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Thomas D. Walters
  • Anne M. Griffiths
    • 1
  1. 1.Division of Gastroenterology/NutritionThe Hospital for Sick ChildrenTorontoCanada

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