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Growth failure and poor weight gain in children with inflammatory bowel disease

Author
Jonathan E Teitelbaum, MD
Section Editors
Kathleen J Motil, MD, PhD
Melvin B Heyman, MD, MPH
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Growth failure is the most common extraintestinal manifestation of inflammatory bowel disease (IBD) in children and is particularly common among those with Crohn disease [1]. The causes of growth failure are complex and include the inflammatory process itself, as well as malnutrition and perhaps treatment with glucocorticoids.

The pathogenesis, evaluation, and treatment of growth failure or poor weight gain in children and adolescents with IBD will be reviewed here. The assessment and management of micronutrient deficiencies in these patients is discussed separately. (See "Nutrient deficiencies in inflammatory bowel disease".)

PATHOGENESIS OF GROWTH FAILURE

A combination of factors contributes to the pathogenesis of growth failure in children with IBD, including inflammation, malnutrition, hypogonadism, and glucocorticoid treatment.

Inflammation — There is increasing evidence that inflammation is an important mediator of growth failure in children with IBD [2]. This notion is supported by observed improvements in linear growth that occur after a variety of treatments that reduce inflammation in IBD, including surgical resection [3], infliximab [4-7], or exclusive enteral nutrition [8,9]. The improvement in growth is independent of weight gain or reductions in corticosteroid dose [1,6].

Inflammation probably inhibits linear growth through proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Although anti-TNF-alpha antibodies reduce disease activity [10], a direct association between TNF-alpha and growth failure remains elusive. IL-6 inhibits insulin-like growth factor 1 (IGF-1), which modulates the physiologic effects of growth hormone in a pattern suggestive of growth hormone resistance [2,11-14] and stimulating lipolysis [15]. Similarly, in pediatric Crohn disease patients who are CARD15 deficient, defects in innate immunity due to auto-antibodies to GM-CSF (granulocyte-macrophage colony stimulating factor) are associated with linear growth failure [16]. The authors speculate that the GM-CSF antibody in these genetically susceptible hosts contributes to increased intestinal permeability. The subsequent endotoxin exposure in turn causes growth hormone resistance as a mechanism for the resulting growth failure. Indeed in their murine model of ileitis they were able to demonstrate liver growth hormone resistance.

                               

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Literature review current through: Nov 2016. | This topic last updated: Tue Oct 06 00:00:00 GMT 2015.
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