Growth and body composition in children with Inflammatory Bowel Disease

Abstract

Crohn`s Disease (CD) and Ulcerative Colitis (UC), two types of Inflammatory Bowel Disease (IBD), are chronic, relapsing inflammatory conditions of the gastro-intestinal tract. Approximately 25% of cases are diagnosed in childhood and adolescence; affected children suffer from symptoms such as abdominal pain, bloody diarrhoea, fatigue, and poor nutritional state. Poor growth, in terms of both height and weight, precedes diagnosis and further weight may be lost with successive inflammatory exacerbations. Changes in height and weight are used as a marker of both disease severity and response to treatment, but the associated changes in body composition with changes in weight are poorly characterised and understood, and rarely assessed in routine clinical care. Being able to determine the nature and size of any deficits in lean and fat mass may provide a better understanding of the disease process, whilst gains in height and lean tissue, relative to increases in fat mass, could also be used to mark the effectiveness of clinical management and improvement in nutritional state. Exclusive enteral nutrition is now being used in preference to anti-inflammatory therapy in children with IBD, but there are increasing concerns that the focus on weight gain as children move into remission with only modest gains in height reflects an inappropriate mix of tissue deposition with greater gains in fat than lean. The central hypothesis of this thesis is that children with IBD present at diagnosis with a lean deficit, greater that that which can be simply attributed to their lack of height, and that conventional therapy, including exclusive enteral nutrition, may not adequately correct the nutritional state and deficit of lean tissue. In order to test this hypothesis, the work described in this thesis is presented in three parts. Firstly, a cross-sectional study of a convenient sample of children with CD and UC drawn from the regional IBD outpatient clinic to explore the extent and nature of the differences in height, weight and BMI expressed as SD scores, together with simple measures of body composition using anthropometry. This initial study confirmed that whilst as a group, both CD and UC children exhibit only modest deficits in height, weight and BMI there was marked variance across the group with more pronounced deficits in some children. Lower Upper Arm Muscle Area SD scores and higher Triceps skinfold thickness SD scores would support the proposition of a general lean deficit and fat excess, even in children with BMI range within ± 2SD. The second part explored different approaches to assessing body composition by i) determining the concurrent and face validity of different bioelectrical impedance devices using deuterium dilution space as a reference method and ii) the potential of using SIFT-MS to conduct real-time near-patient measures of deuterium abundance on breath vapour was examined in comparison to measures of deuterium abundance in saliva and urine assessed by both SIFT-MS and IRMS. These studies demonstrated important differences in lean mass were evident between devices. Deuterium abundance in saliva and urine by SIFT-MS was directly comparable to that by IRMS although higher levels of D O administration were required for optimal analytical performance; greater imprecision was evident in determining deuterium abundance in breath. The third part described detailed measures of body composition (anthropometry, DXA, deuterium abundance in saliva by IRMS, and BIA) in a prospective inception cohort of eleven children with CD studied at diagnosis, and followed for the first year of treatment from active disease into remission using exclusive enteral nutrition. Lean deficits identified using both DXA and Upper Arm Muscle Area was evident at diagnosis greater than that which could be attributed to shortness. Treatment was associated with gains in height and weight, but in contrast to previous reports where corticosteroids were only used to induce remission, gains in lean mass over the first year of treatment using exclusive enteral nutrition were observed which were greater than that which could be attributed to an increase in height that reflect at least a partial correction of the lean deficit.

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