Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease.

BACKGROUND: There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn's disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn's disease. METHODS: The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn's disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. RESULTS: 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn's disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn's disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). CONCLUSIONS: Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn's disease is promising but warrants further investigation. TRIAL REGISTRATION: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet.

BACKGROUND AND AIMS: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). METHODS: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. RESULTS: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. CONCLUSIONS: Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

Corticosteroids for Preventing Caustic Esophageal Strictures: Systematic Review and Meta-analysis.

OBJECTIVES: Caustic ingestion can have a complicated clinical course. Corticosteroids are widely used but there is uncertainty about its role in preventing esophageal stricture formation following caustic ingestion. This systematic review and meta-analysis assessed the available clinical evidence regarding the efficacy and safety of corticosteroids for preventing esophageal strictures following caustic injury. METHODS: We assessed randomized controlled trials (RCTs) that compared corticosteroids versus no corticosteroids in the prevention of esophageal stricture formation following caustic ingestion. We searched the following databases from inception to March 2017: PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers retrieved eligible articles, assessed risk of bias, and performed data extraction. The main outcome measure was the prevention of esophageal stricture formation. RESULTS: The search identified 763 citations. Three RCTs involving 244 participants met the inclusion criteria. There was no benefit of corticosteroids in the prevention of esophageal strictures following the ingestion of caustic materials (risk ratio [RR] = 0.63, 95% CI = 0.29-1.37). CONCLUSIONS: The available evidence does not support the use of corticosteroids for the prevention of esophageal strictures following caustic ingestion. The overall quality of the evidence is limited because of methodological weaknesses and small sample sizes in the primary studies.

Persistence of Muscle-bone Deficits Following Anti-tumour Necrosis Factor Therapy in Adolescents With Crohn Disease.

OBJECTIVES: The aim of the study is to assess change in the muscle-bone unit in adolescents with Crohn disease (CD) on anti-tumour necrosis factor (anti-TNFα). METHODS: Prospective study following anti-TNFα in 19 adolescents with CD with a median age (range) of 15.1 years (11.2, 17.2). At baseline, 6 and 12 months, subjects had a biochemical assessment of insulin growth factor axis, bone turnover and muscle-bone health by dual energy absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and dynamic isometry. RESULTS: Significant clinical improvement in disease activity was observed by 2 weeks (P = 0.004 vs baseline) and maintained at 12 months (P = 0.038 vs baseline). Median bone specific alkaline phosphatase standard deviation score (SDS) increased from -1.7 (-3.6 to -1.0) to -1.2 (-3.6 to -0.5) by 6 weeks (P = 0.01). At baseline, DXA total body and lumbar spine bone mineral density (BMD) SDS was -0.9 (-2.3 to 0.5) and -1.1 (-2.9 to 0.4), respectively. At baseline, pQCT trabecular BMD SDS at 4% tibia and muscle cross-sectional area SDS at 66% radius was -1.6 (-3.2 to 1.1) and -2.4 (-4.3 to -0.3), respectively. At baseline, maximal isometric grip force (MIGF) of the non-dominant hand adjusted for height was -1.5 (-4.5 to 0.49). All these deficits in muscle-bone persisted at 6 and 12 months. CONCLUSIONS: Despite improvement in disease and osteoblast activity, bone and muscle deficits, as assessed by DXA, pQCT, and grip strength in adolescents with CD did not improve following twelve months of anti-TNFα.

Comparison of Clinical Methods With the Faecal Gluten Immunogenic Peptide to Assess Gluten Intake in Coeliac Disease.

OBJECTIVES: Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten-free diet (GFD). In the present study, recent gluten intake was measured by GIP in children with coeliac disease (CD) and compared to routine clinical measures to evaluate GFD compliance. METHODS: GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow-up samples at 6 and 12 months on GFD). Compliance to GFD was evaluated based on clinical assessment, tissue transglutaminase (tTG) levels, and Biagi score. RESULTS: GIP was detectable in 16% of patients with previous CD diagnosis on GFD. Body mass index z score (P = 0.774), height z score (P = 0.723), haemoglobin concentration (P = 0.233), age (P = 0.448), sex (P = 0.734), or disease duration (P = 0.488) did not differ between those with detectable and nondetectable GIP. In newly diagnosed patients, on gluten-containing diet, GIP was detectable in 95% of them. Following GFD initiation, GIP decreased (P < 0.001); 17% and 27% had detectable levels at 6 and 12 months, respectively. Compared to GIP, the Biagi score, tTG, and clinical assessment presented sensitivity of 17%, 42%, and 17%, respectively. Likewise, GIP was detectable in 16%, 16%, and 14% of patients evaluated as GFD compliant according to the Biagi score, tTG, and clinical assessment, respectively. A combination of methods did not improve identification of patients who were noncompliant. CONCLUSIONS: Inclusion of faecal GIP measurements is likely to improve identification of GFD recent noncompliance in CD management and could be incorporated into current follow-up strategies.

Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease.

BACKGROUND: Growth failure is well-recognized in pediatric inflammatory bowel disease (PIBD; <18 years). We aimed to examine whether antitumor necrosis factor (TNF) therapy improves growth in a PIBD population-based cohort. METHODS: A retrospective review of all Scottish children receiving anti-TNF (infliximab [IFX] and adalimumab [ADA]) from 2000 to 2012 was performed; height was collected at 12 months before anti-TNF (T-12), start (T0), and 12 (T+12) months after anti-TNF. RESULTS: Ninety-three of 201 treated with IFX and 28 of 49 with ADA had satisfactory growth data; 66 had full pubertal data. Univariate analysis demonstrated early pubertal stages (Tanner 1-3 n = 44 vs T4-5 n = 22), disease remission, disease duration ≥2 years, and duration of IFX ≥12 months were associated with improved linear growth for IFX; for ADA only improvement was seen in Tanner 1-3. For IFX, Tanner 1-3 median Δ standard deviation scores for height (Ht SDS) -0.3 (-0.7, 0.2) at T0 changed to 0.04 (-0.5, 0.7) at T+12 (P < 0.001) versus -0.01 (-0.5, 0.9) at T0 in T4-5 changed to -0.01 (-0.4, 0.2) at T+12 (P > 0.05). For IFX disease duration ≥2 year, median Δ Ht SDS was -0.13 (-0.6, 0.3) at T0 then 0.07 (-0.3, 0.6) at T+12 (P < 0.001). Remission improved Δ Ht SDS (median Δ Ht SDS -0.14 [-0.6, 0.3] at T0 to 0.17 [-0.2, 0.7] at T+12 [P < 0.001]). Multiple regression analysis demonstrated corticosteroid usage at T0 predicted improved Δ Ht SDS at T+12 for IFX and ADA. CONCLUSIONS: Anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty with remission a key growth-promoting strategy in pediatric Crohn disease.

Faecal Calprotectin in Treated and Untreated Children With Coeliac Disease and Juvenile Idiopathic Arthritis.

The present study aimed to provide evidence on whether children at risk of gastrointestinal inflammation have increased measurements of faecal calprotectin (FC). FC was measured in 232 children; 55 children (n = 11 treatment naïve) with juvenile idiopathic arthritis (JIA), 63 with coeliac disease (CD); 17 with new diagnosis before and after treatment on gluten-free diet and 114 controls. None of the treatment-naive children with JIA had raised FC. Four JIA patients on treatment had a raised FC but in all cases a repeat test was normal. In newly diagnosed patients with CD, the median (interquartile range) FC was higher 36.4 (26-61) than that in controls 25.0 (23-41) mg/kg (P = 0.045) but this significantly decreased 25 (25-25) mg/kg (P = 0.012) after 6 months on gluten-free diet. Random measurements of FC are not raised in children with JIA or CD. A significant elevation of FC in these groups is not explained by their diagnosis and therefore needs further investigation.

Extensive Modulation of the Fecal Metagenome in Children With Crohn's Disease During Exclusive Enteral Nutrition.

OBJECTIVES: Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn's disease (CD). METHODS: Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics. RESULTS: Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN. CONCLUSIONS: Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

A retrospective study showing maintenance treatment options for paediatric CD in the first year following diagnosis after induction of remission with EEN: supplemental enteral nutrition is better than nothing!

BACKGROUND: A limited body of research suggests that ongoing maintenance enteral nutrition (MEN) can be beneficial in maintaining disease remission in Crohn's Disease (CD). We aimed to assess how achievable MEN is and whether it helps to prolong remission. METHODS: Patients newly diagnosed with CD in 2010 and 2011 who commenced exclusive enteral nutrition (EEN) for 8 weeks were followed up for a year post diagnosis. All patients who took EEN were encouraged to continue MEN post EEN. Data on azathioprine use was also collected. Categorical variables were compared using chi-square/Fischer's exact test. Medians were expressed along with complete data ranges. RESULTS: 59 patients (34 male, median age 11.07 years, range 2.5-16.33 years) were identified. 11/59 (18%) had a poor response to EEN and were switched to steroids. 48/59 patients completed 8 weeks EEN and achieved clinical remission/response. 46/48 patients received Modulen IBD®, 29/48 (60%) consumed EEN orally and 19/48 (40%) via NGT. 15/48 (31%) patients were able to continue MEN post EEN completion. MEN was consumed for a mean of 10.8 months (range 4-14 months). 14/15 patients drank MEN and 1/15 had MEN via NGT. Remission rates at 1 year in patients continuing MEN were 60% (9/15) compared to 15% (2/13) in patients taking no treatment (p = 0.001) and 65% (13/20) in patients taking azathioprine (p = 0.14). CONCLUSION: A sub group of patients can continue MEN as a maintenance treatment and this seems a useful strategy, especially in those who are not commencing azathioprine.

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease.

BACKGROUND: The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis. METHODS: Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls. RESULTS: No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference. CONCLUSIONS: No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet.

Microbiota of de-novo pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn's but not in ulcerative colitis.

OBJECTIVES: The gastrointestinal microbiota is considered important in inflammatory bowel disease (IBD) pathogenesis. Discoveries from established disease cohorts report reduced bacterial diversity, changes in bacterial composition, and a protective role for Faecalibacterium prausnitzii in Crohn's disease (CD). The majority of studies to date are however potentially confounded by the effect of treatment and a reliance on established rather than de-novo disease. METHODS: Microbial changes at diagnosis were examined by biopsying the colonic mucosa of 37 children: 25 with newly presenting, untreated IBD with active colitis (13 CD and 12 ulcerative colitis (UC)), and 12 pediatric controls with a macroscopically and microscopically normal colon. We utilized a dual-methodology approach with pyrosequencing (threshold >10,000 reads) and confirmatory real-time PCR (RT-PCR). RESULTS: Threshold pyrosequencing output was obtained on 34 subjects (11 CD, 11 UC, 12 controls). No significant changes were noted at phylum level among the Bacteroidetes, Firmicutes, or Proteobacteria. A significant reduction in bacterial α-diversity was noted in CD vs. controls by three methods (Shannon, Simpson, and phylogenetic diversity) but not in UC vs. controls. An increase in Faecalibacterium was observed in CD compared with controls by pyrosequencing (mean 16.7% vs. 9.1% of reads, P=0.02) and replicated by specific F. prausnitzii RT-PCR (36.0% vs. 19.0% of total bacteria, P=0.02). No disease-specific clustering was evident on principal components analysis. CONCLUSIONS: Our results offer a comprehensive examination of the IBD mucosal microbiota at diagnosis, unaffected by therapeutic confounders or changes over time. Our results challenge the current model of a protective role for F. prausnitzii in CD, suggesting a more dynamic role for this organism than previously described.

Serial fecal calprotectin changes in children with Crohn's disease on treatment with exclusive enteral nutrition: associations with disease activity, treatment response, and prediction of a clinical relapse.

BACKGROUND: Exclusive enteral nutrition (EEN) induces clinical remission in pediatric Crohn's disease (CD). GOALS: This study explored changes in fecal calprotectin concentration during treatment with EEN. STUDY: Fecal calprotectin was measured in 4 serial stool samples from CD children during EEN. The Pediatric Crohn's Disease Activity Index (PCDAI) and systemic markers of disease activity were measured at the beginning and end of treatment. RESULTS: Fifteen CD children (7 girls; 11.6±2.3 y) participated. PCDAI decreased in 14 children and 7 children achieved clinical remission (PCDAI ≤10). Fecal calprotectin concentration decreased (30 d, P=0.014; 60 d, P<0.0001) only in those children who entered clinical remission (PCDAI ≤10). In the whole group mean calprotectin concentration at baseline (2158±642 mg/kg) was reduced by 975 mg/kg (95% confidence interval -1783; -167) after 30 days and 1700 mg/kg (95% confidence interval -2508; -892) on EEN completion. Only one child reached normal levels by the end of EEN. Decrease of pretreatment calprotectin levels by more than 18% after 30 days on EEN predicted clinical response at the end of EEN. Calprotectin levels at the end of EEN treatment did not predict the length of time lapsed to a future relapse. CONCLUSIONS: In this pilot study calprotectin decreased in patients who achieved clinical remission and may be useful to predict response to treatment.

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet.

INTRODUCTION: In coeliac disease (CD) micronutrient deficiencies may occur due to malabsorption in active disease and diminished intake during treatment with a gluten-free diet (GFD). This study assessed the micronutrient status in children with CD at diagnosis and follow-up. METHODS: Fifteen micronutrients were analysed in 106 blood samples from newly diagnosed CD and from patients on a GFD for <6 months, 6-12 months and with longstanding disease (>12 months). Predictors of micronutrient status included: demographics, disease duration, anthropometry, gastrointestinal symptoms, raised tissue transglutaminase antibodies (TGA), multivitamin use and faecal gluten immunogenic peptide (GIP). Micronutrient levels were compared against laboratory reference values. RESULTS: At CD diagnosis (n = 25), low levels in ≥10% of patients were observed for: vitamins E (88%), B1 (71%), D (24%), K (21%), A (20%) and B6 (12%), ferritin (79%), and zinc (33%). One year post-diagnosis, repletion of vitamins E, K, B6 and B1 was observed (<10% patients). In contrast, deficiencies for vitamins D, A and zinc did not change significantly post-diagnosis. Copper, selenium and magnesium did not differ significantly between diagnosis and follow-up. All samples for B2, folate, vitamin C (except for one sample) and B12 were normal. A raised TGA at follow-up was associated with low vitamins A and B1 (raised vs normal TGA; vitamin A: 40% vs 17%, p = 0.044, vitamin B1: 37% vs 13%, p = 0.028). Low vitamin A (p = 0.009) and vitamin D (p = 0.001) were more common in samples collected during winter. There were no associations between micronutrient status with GIP, body mass index, height, socioeconomic status, or gastrointestinal symptom. Multivitamin use was less common in patients with low vitamin D. CONCLUSIONS: Several micronutrient deficiencies in CD respond to a GFD but others need to be monitored long-term and supplemented where indicated.

Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease.

OBJECTIVES: The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. METHODS: This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. RESULTS: Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). CONCLUSION: Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.

Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease.

BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. METHODS: Anatomic locations and behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease [CD], 99 ulcerative colitis [UC], 41 IBD type unclassified [IBDU] diagnosed before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC) IBD using the Montreal classification. RESULTS: At the time of diagnosis in children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in 36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral characteristics progressed; 24% of children developed stricturing or penetrating complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio [OR], 3.32; 95% confidence interval [CI], 1.86-5.92). Compared with adults, childhood-onset disease was characterized by a "panenteric" phenotype (ileocolonic plus upper GI [L3+L4]; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during follow-up. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true for UC. CONCLUSIONS: Childhood-onset IBD is characterized by extensive intestinal involvement and rapid early progression.

Effects of Recombinant Human Growth Hormone in Children with Crohn's Disease on the Muscle-Bone Unit: A Preliminary Study.

BACKGROUND/AIMS: There is limited information on the impact of recombinant human growth hormone (rhGH) on the muscle-bone unit in children with Crohn's disease (CD). In this pilot study, we report on the effects of rhGH on bone formation, dual-energy X-ray absorptiometry (DXA) total body (TB) bone mineral density adjusted for height and lumbar spine (LS) bone mineral apparent density (BMAD), and body composition. METHODS: Prospective study of 8 children with CD (6 male), aged 14.8 years (9.0-16.4), who received rhGH for 24 months. Serum procollagen type 1 N-terminal propeptide (P1NP) was measured at baseline and at 6 months. DXA was performed every 6 months. RESULTS: Six months of rhGH led to improvement in P1NP SDS adjusted for bone age from -3.6 (-7.9 to -0.9) to -2.4 (-3.7 to 0.4) (p = 0.01). At baseline, reduction in LS-BMAD and TB lean mass SDS was observed being -1.2 (-3.6 to 0.8) (p = 0.01 vs. zero) and -0.8 (-2.4 to 3.0) (p = 0.11 vs. zero), respectively. No significant changes were seen in DXA bone and muscle parameters over the 24 months. CONCLUSION: Twenty-four months of therapy with rhGH in CD did not lead to an improvement in DXA BMD and lean mass, despite improvement in P1NP and linear growth.

Improving growth in children with inflammatory bowel disease.

BACKGROUND: Growth in children with inflammatory bowel disease (IBD) is affected through a number of mechanisms; controlling disease activity and supporting poor nutritional status are paramount in these patients. Further understanding of the basic mechanisms by which cytokines influence growth will facilitate the development of therapeutic modalities to improve growth. CONCLUSIONS: Clinical management that addresses growth and puberty in children with IBD should be a partnership between paediatric gastroenterologists and endocrinologists. Well-designed studies of growth-promoting hormonal treatment may answer questions regarding the efficacy and safety of treating growth retardation in the subgroup of patients who continue to fail to grow despite optimal management of their IBD.