Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt are often seen during adolescence. The underlying inflammatory state mediated by proinflammatory cytokines, prolonged use of glucocorticoid, and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the GH-IGF axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biological therapy may lead to improvement of growth in some of these children, but approximately one-third continue to grow slowly. There is increasing evidence that the use of relatively high-dose recombinant human GH may lead to partial catch-up growth in chronic inflammatory conditions, although long-term follow-up data are currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis, systemic abnormalities of the GH-IGF axis, and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human GH in these conditions and discussed the role of recombinant human IGF-1.
BackgroundDespite optimal therapy, many children with Crohn’s disease (CD) experience growth retardation.The objectives of the study are to assess the feasibility of a randomised control trial (RCT) of injectable forms of growth-promoting therapy and to survey the attitudes of children with CD and their parents to it.MethodsA feasibility study was carried out to determine study arms, sample size and numbers of eligible patients. A face-to-face questionnaire surveyed willingness to consent to future participation in the RCT. Eligibility to the survey was any child under 18 (with their parent/guardian) with CD whose height standard deviation score (HtSDS) was ≤+1. Of 118 questionnaires, 94 (80%) were returned (48 by children and 46 by parents).ResultsThe median age of the patients in the survey was 14.3 years (range 7.0 to 17.7), and 35 (73%) were male. Their median HtSDS was −1.2 (−3.01, 0.23), and it was lower than the median mid-parental HtSDS of −0.6 (−3.1, 1.4). We analysed the willingness of the children whose HtSDS <−1 to take part in the proposed RCT, being those most likely to require treatment. Overall, 18 (47%) children and 17 (46%) parents were willing. This increased to 61% of children who were slightly concerned about their height and 100% (4/4) of those very concerned. A common reason for not taking part in the RCT was fear of injections (44%); 111 children are required for randomisation into three study arms from nine centres.ConclusionsAlmost half of children and parents surveyed would take part in an RCT of growth-promoting therapy. Allaying fears about injections may result in higher recruitment rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s40814-016-0112-9) contains supplementary material, which is available to authorized users.
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