Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study.

BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).

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.

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.

Prehabilitation: The Impact of Preoperative Exclusive Enteral Nutrition on Paediatric Patients With Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri-operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; P = 0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction.

BACKGROUND: Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition. AIMS: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. METHODS: Children with Crohn's disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. RESULTS: Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: -0.573, P = .041), kcals (rho: -0.584, P = .036) and % energy intake (rho: -0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. CONCLUSIONS: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.

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.

Dietary treatment of Crohn's disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey.

BACKGROUND: Diet is strongly associated with the aetiology of Crohn's Disease (CD) and exclusive enteral nutrition (EEN) is the primary induction treatment in paediatric CD. This study explored opinions around the use of EEN and alternative novel, solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN and their parents. METHODS: This anonymous questionnaire surveyed families of CD patients treated with EEN over 1 year. Two questionnaire forms were completed; one asking the patients' opinions and another referring to their main carer. This questionnaire explored participants' demographic characteristics; acceptability of a repeat EEN course to treat a future flare (EEN repeat); their opinion on how difficult EEN would be compared to an example SFD; and their intention to participate in a future clinical trial assessing the therapeutic efficacy of an SFD in CD. RESULTS: Forty-one families of CD patients were approached with 29 sending replies (71%). Most of our participants were positive on completing another EEN course, however the majority would choose an SFD alternative (Patients:66, Parents:72%). Both patients and their parents rated EEN to be more difficult to adhere to compared to an example SFD (p < 0.05), and their ratings were strongly correlated (EEN:r = 0.83, SFD:r = 0.75, p < 0.001). The majority of our respondents would agree to participate in a clinical trial assessing an SFD's effectiveness (Patients:79, Parents:72%) for the management of active CD. CONCLUSIONS: While patients with CD and their families would accept an EEN repeat, the majority would prefer an SFD alternative. CD families surveyed are supportive of the development of solid food-based dietary treatments.

Dietitians' perceptions and experience of blenderised feeds for paediatric tube-feeding.

OBJECTIVE: There is an emerging interest in the use of blenderised food for tube-feeding (BFTF). This survey explored paediatric dietitians' perceptions and experiences of BFTF use. DESIGN: A web-based questionnaire was distributed to the Paediatric group of the British Dietetic Association. The survey captured dietitians' personal opinions and experience supporting children on BFTF, and the perceptions of carers. RESULTS: Of the 77 respondents, 19 were aware of professional guidelines and 63 had never received training on BFTF. Thirty-four would not recommend BFTF and 11 would advise against its use; yet 43 would recommend it to supplement commercial feeds. Fifty-seven would change their perception about BFTF if there were evidence-based guidelines. Forty-four would feel confident to support a patient using BFTF. Forty-three had previous experience supporting a patient with BFTF. The main concerns perceived by dietitians, pertinent to the use of BFTF, were nutritional inadequacy (n=71), tube blockages (n=64) and increased infection risk (n=59) but these were significantly higher than those experienced by themselves in clinical practice (p<0.001 for all three). A reduction in reflux and vomiting and increased carer involvement were the main perceived and observed benefits by both dietitians and carers. CONCLUSIONS: The use of these feeds for tube-fed children is increasingly being seen as a viable choice. Dietitians experienced significantly fewer issues with the use of BFTF in clinical practice compared with their self-reported apprehensions in the survey. Well-controlled studies are now needed to objectively assess the benefits, risks, costs and practicality of BFTF.

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.

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.

The epidemiology of anemia in pediatric inflammatory bowel disease: prevalence and associated factors at diagnosis and follow-up and the impact of exclusive enteral nutrition.

BACKGROUND: Anemia is poorly studied in pediatric inflammatory bowel disease. This study explored the epidemiology and associated factors of anemia at diagnosis, after 1 year, and during treatment with exclusive enteral nutrition (EEN). METHODS: Three cohorts were included: (1) a representative population of newly diagnosed inflammatory bowel disease children (n = 184); (2) patients currently receiving care with data available at diagnosis (n = 179) and after 1 year (n = 139); and (3) 84 children treated with EEN. RESULTS: At diagnosis, 72% were anemic. Abnormal inflammatory markers were more common in Crohn's disease with severe anemia (severe versus no anemia [%]: raised C-reactive protein; 89% versus 48%; suboptimal albumin; 97% versus 29%; P < 0.002). Anemic children with Crohn's disease had shorter diagnosis delay and lower BMI than nonanemic patients (severe versus mild versus no anemia, median [interquartile range]; diagnosis delay [months]: 3 [3.9] versus 6 [10] versus 8 [18], P < 0.001; BMI z score [SD]: -1.4 [1.4] versus -1.3 [1.5] versus -0.2 [1.4], P = 0.003). Extensive colitis was associated with severe anemia in ulcerative colitis. The proportion of severely anemic patients decreased from 34% to 9% and mild anemia doubled at 1 year. After EEN, severe anemia decreased (32% to 9%; P < 0.001) and the hemoglobin concentration increased by 0.75 g/dL. This was observed only after 8 weeks of treatment. Disease improvement and low hemoglobin at EEN initiation but not weight gain were associated with hemoglobin improvement. CONCLUSIONS: Anemia is high at diagnosis and follow-up and should receive more attention from the clinical team; however, the focus should remain suppression of inflammatory process in active disease.

Impact of exclusive enteral nutrition on body composition and circulating micronutrients in plasma and erythrocytes of children with active Crohn's disease.

BACKGROUND: Nutritional therapy is the primary treatment for active pediatric Crohn's disease (CD) in the UK/Europe, improving disease activity and anthropometry. This study assessed changes in micronutrient status during exclusive enteral nutrition (EEN). METHODS: Seventeen children (male/female: 8/9; median age: 12.7 years) with active CD were treated exclusively for 6-8 weeks on a polymeric feed (Modulen IBD; Nestle, UK). Body impedance was measured at baseline, during EEN, and posttreatment on normal diet and converted to z-scores of fat and lean mass. Blood samples for nutrient analysis were collected from 13 children at baseline, end of EEN, and posttreatment. RESULTS: Lean but not fat mass improved at the end of EEN (initiation vs. end of EEN; fat mass [z-score]: -0.5 vs. -0.3; P = 0.141; lean mass [z-score]: -2.1 vs. -0.8; P < 0.0001). At baseline several children presented with suboptimal concentrations of carotenoids, trace elements, vitamin C, B6, and folate in plasma but not in erythrocytes. EEN improved concentrations for several nutrients, but more than 90% of patients had depleted concentrations of all carotenoids. The latter improved on normal diet but other micronutrients, which improved during EEN, returned toward pretreatment concentrations. CONCLUSIONS: Lean but not fat mass improved at the end of EEN. Median concentrations for several plasma micronutrients improved on EEN but carotenoids were depleted. These findings may have implications for clinical practice and producers of enteral feeds. As plasma concentrations for many micronutrients can be affected by the acute phase response, measurements in erythrocytes may be a better marker of actual body stores.

Performance of the novel Paediatric Yorkhill Malnutrition Score (PYMS) in hospital practice.

BACKGROUND & AIMS: Nutritional screening in paediatric inpatients is important. However, there is a lack of validated screening tools for this population. In this study the development of a nurse administered paediatric malnutrition screening tool is described and its performance evaluated. METHODS: The Paediatric Yorkhill Malnutrition Score (PYMS) rate BMI, weight loss, dietary intake and predicted effect of the current condition on nutritional status, with a score of 0-2 for each element. Patients with total score of 2 or more are referred for dietetic review. A four month pilot phase was conducted in three medical and one surgical wards of a tertiary hospital and the general paediatric ward of a district general hospital. Performance of the tool was assessed by auditing completion rates, yield, impact on dietetic workload, and by evaluating dietitians' feedback. RESULTS: 1571 patients (72% of admissions) were screened of whom 158 (10%) scored at high risk. Non-screened children were younger and had a shorter length of hospital stay. Of the 125 patients who scored at high risk, between the 2nd and 4th month of the pilot, 66 (53%) were assessed by a dietitian of whom 86% were judged to be at true risk of malnutrition and 50% of these were new to the dietetic service. Dietetic workload did not increase significantly during the pilot phase although the proportion of referrals from the acute receiving wards increased. Dietitians' feedback was positive, with recognition that PYMS identified patients at risk of malnutrition who may not have otherwise been referred. CONCLUSIONS: Nutrition screening by nurses using the new PYMS score is feasible for paediatric inpatients, identifies children at risk of malnutrition and uses available resources efficiently.

The symptom of night pain in a back pain triage clinic.

STUDY DESIGN: Prospective longitudinal study of patients attending a back pain triage clinic with night pain. OBJECTIVE: To assess the importance of the symptom of night pain in patients attending a back pain triage clinic. SUMMARY OF BACKGROUND DATA: The 1994 US Agency for Health Care Policy and Research guidelines suggest nighttime pain should be used as a "red flag." Night pain is known to occur in many conditions, and although common in patients with known serious pathology, the prevalence of night pain in a back pain triage clinic is not known. METHODS: A total of 482 consecutive patients attending a back pain triage clinic were assessed, including history of frequency and duration of night pain. Clinical examination was performed, and demographic data obtained. Magnetic resonance imaging was performed if indicated according to local guidelines. Oswestry, visual analog scales (for pain), and hospital anxiety depression scale, patient-based outcome scores were obtained. RESULTS: There were 213 patients who had night pain, with 90 having pain every night. No serious pathology was identified. Patients with night pain had 4.95 hours continuous sleep (range 2-7) and were woken 2.5 times/night (range 0-6). Patients with pain every night had higher Oswestry, visual analog scale, and hospital anxiety depression scale scores than those who did not. CONCLUSIONS: Although it is a significant and disruptive symptom for patients, these results challenge the specificity of the presence of night pain per se as a useful diagnostic indicator for serious spinal pathology in a back pain triage clinic.