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Gastroenterology, hepatology, and nutrition

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I. H. Davies, M. Ahmed, H. R. Jenkins. Department of Paediatric Gastroenterology, University Hospital of Wales, Cardiff, UK

Introduction: A previous retrospective study on paediatric inflammatory bowel disease (IBD) from a defined UK area reported a threefold increase in Crohn’s disease (CD) but no increase in ulcerative colitis (UC) over an 11 year period (1983–93). It is not clear whether the increase in incidence of CD has levelled out.

Aims: To report the incidence of CD/UC between 1996 and 2003 in the area previously studied.

Methods: A prospective study was undertaken over 8 years (1996–2003). All children diagnosed with IBD were recorded and data retrospectively cross-checked with the endoscopy and histopathology units. The incidence of CD/UC was calculated.

Results: The childhood population studied remained constant at 90 000 between 1996 and 2003. There were 39 cases (22 male) with IBD, 26 with CD, 11 with UC, and 2 with indeterminate colitis. The median age at diagnosis was 13 years (range 4–15 years) with the incidence of CD 3.6 cases per 100 000 children per year (3.1 between 1983–93) and UC 1.5 (0.75 between 1983–93).

Conclusions: In our area the incidence of CD has stopped its previous dramatic rise with a remarkably consistent annual incidence over the past 8 years.


M. G. Gnanalingham, J. Dandrea, M. E. Symonds, T. Stephenson. Centre for Reproduction and Early Life, University of Nottingham, Nottingham NG7 2UH, UK

Introduction: Uncoupling protein 2 (UCP2) is a member of the inner mitochondrial protein superfamily, whose exact function is not known. Postulated roles include a role in solute exchange, as well as regulating immune function within the neonatal lung. The effect of maternal nutrition during late gestation, coincident with the period of maximal lung growth, on UCP2 abundance in the ovine neonatal lung has not been determined.

Methods: Fourteen twin bearing ewes of similar age and body weight were individually housed from 110 days gestation. Six controls (C) were fed and consumed 100% of their energy requirements for maintenance and growth of the conceptus, while the nutrient restricted (NR) group received 60% of this amount, until term 147 days, when they all gave birth spontaneously. At 6 hours of age, one twin was randomly selected and humanely euthanased. The remaining twin was sampled at 30 days of life. Total lung RNA was extracted, reverse transcribed, and UCP2 mRNA abundance measured by RT-PCR using oligonucleotide primers designed specifically to ovine UCP2. Results are given as mean (SD) in arbitrary units, as a ratio of 18S rRNA and are expressed as a percentage of a reference sample. Differences between groups were analysed by Mann-Whitney U test.

Results: Lung fresh and dry weights and total protein concentration were similar between the groups and increased with postnatal age. UCP2 mRNA levels were higher at 6 hours of age compared with 30 days. UCP2 mRNA was increased in the NR groups at both 6 hours (C 115.8 (3.4); NR 135.7 (2.6), p<0.01) and 30 days (C 13.4 (0.8); NR 32.5 (1.4), p<0.01) in the lung.

Conclusion: Maternal nutrient restriction over the period of maximal lung growth promotes UCP2 mRNA abundance. The extent to which this may result in enhanced metabolic adaptation after birth in the lung remains to be established.


M. Thomson, R. Del Buono, T. Wenzl, G. Ball, S. Murch, R. Heuschkel. Centre for Paediatric Gastroenterology, Royal Free Hospital, London, UK

Introducion: Percutaneous endoscopic gastrostomy (PEG) has become increasingly popular for the provision of nutrition in neurologically impaired children. Post-operative follow up for gastro-oesophageal reflux (GOR) is essential because nutritional rehabilitation in disabled children is associated with increased morbidity and mortality secondary to GOR.

Aim: To investigate the effects of PEG feeding on GOR in a group of these children using combined intraluminal pH and multiple intraluminal impedance (pH/MII).

Methods: Ten neurologically impaired children underwent 12 hour combined pH/MII procedures at least 1 day before and at least 12 days after PEG placement.

Results: Prior to PEG placement (pre-PEG) a total of 183 GOR episodes were detected, 156 (85.2%) were non-acidic. After PEG placement (post-PEG) a total of 355 episodes were detected, 182 (51.3%) were non-acidic. The total number of distal acid reflux events significantly increased post-PEG placement (pre-PEG median 1 (range 0–11), post-PEG 13 (0–50)) and the mean distal pH decreased by 1.1 units. The distal reflux index therefore also significantly increased post-PEG (pre-PEG 0.25 (0–2), post-PEG 2.95 (0–40)). Average proximal pH was lower post-PEG but the within subject difference was not statistically significant. Median number of non-acid GOR, average reflux height, total acid clearance time, and total bolus clearance time were all lower pre-PEG, but not statistically significant.

Conclusions: PEG placement increases GOR episodes in neurologically impaired children. Over half the reflux events in these children are non-acidic and would go undetected by conventional pH-metry. However, only acid reflux events increased significantly in the distal oesophagus after the procedure.


N. A. Afzal1, M. U. Shenoy2, S. Haque2, D. T. Wilcox2, N. Shah1. Departments of Paediatric 1Gastroenterology and 2Urology, Great Ormond Street Hospital, London

Aim: Genitourological (GU) complications of Crohn’s disease (CD) are a leading cause for morbidity. Little is known of the incidence of these complications in a paediatric population. The aim of this study was to determine incidence and spectrum of urological complications in paediatric CD.

Methods: Case notes of all children diagnosed with CD between 1997 and 2003 were reviewed. Complete records of GU complications, treatment of CD, and follow up data (median 2.5 years) were available in 62 patients (35 male, 27 female, age range 6–17 years, median 12 years).

Results: The incidence of GU complications in our series was 10.3% (6 patients). Initial presentation of CD in two children was with GU problems, the remaining four developed GU complications later in the course of their disease.

Conclusions: GU complications are common in paediatric CD. Vigilance for GU complications is important, as they are associated with multiple surgical procedures, delayed diagnosis, and significant morbidity.

Abstract G20


S. Rosseneu, R. Heuschkel, A. Phillips, S. Murch. Centre for Paediatric Gastroenterology, Royal Free Hospital, London

Aims: We and others have reported abnormalities in composition of the gut flora in autistic children, with low grade mucosal inflammation. As persistence of bacterial species within the colon relates to binding to surface carbohydrates on the epithelial glycocalyx, we aimed to study mucosal O-glycan expression.

Methods: We studied ileal and serial colonic biopsies from 5 children with autism in comparison to 5 with colonic Crohn’s disease, 5 with ulcerative colitis (UC), and 5 histologically normal controls. A lectin panel specific for fucosyl and sialyl residues was used. Fucosyl specific lectins were aleuria aurantia lectin (AAL), lotus tetragonolobus lectin (LTL), and ulex europaeus agglutinin 1 (UEA 1). Sialic specific lectins were maackia amurensis lectin (MAL) and sambucus nigra lectin. Staining was assessed strictly blinded in glycocalyx, goblet cells, basement membrane, and in lamina propria, normalised to endothelial expression.

Results: Expression patterns in controls and IBD correlated with previous reports. In the glycocalyx, there was decreased expression of LTL in UC, and of SNA and AAL in autism compared to all other groups. The autistic group also showed decreased MAL compared to controls. While no significant changes were seen in epithelial lectin expression, basement membrane thickening was notable in the autistic group, as previously reported, and fucose expression particularly increased.

Conclusions: Our data show quite distinct patterns of O-glycosylation within the glycocalyx in children with autism, not simply due to inflammation. The expression of α2–6 and α2–3 linked sialic acids is particular reduced, as is that of α1–2 linked fucose residues. This may contribute to alterations in the colonic mucosal flora. As clinical improvement has been reported in autistic children when enteric dysbiosis is treated, these changes warrant further study if confirmed in a larger series.


C. Conlon1, P. Ekin1, J. Hawkins1, D. St Louis, M. Elawad1, K. Lindley1, M. Sury2, N. Shah1. Departments of 1Gastroenetrology and 2Anaesthesia, Great Ormond St Hospital, London

Background: Propofol is widely used in anaesthesia for short procedures but there is only limited evidence for its use in children undergoing endoscopy. The aim of this pilot study was to investigate both the efficacy and safety of propofol as a single agent during paediatric gastrointestinal endoscopy without endotracheal intubation. We compared this with our current practice of low dose midazolam and pethidine.

Methods: A prospective study was performed on 49 children. Entry criteria were all children deemed to be safe for deep sedation endoscopy. 32 (age 1.1–15 years median 6.4 years) were given midazolam (0.1–0.2 mg/kg) and pethidine (1–2 mg/kg). 17 children (1.5 to 14 years) were recruited to have propofol anaesthesia. A single observer recorded outcomes.

Results: 16 out of 17 children tolerated the procedure under propofol of 3–6 mg/kg. 1 child needed a maximum of 9 mg/kg. Airway support was unnecessary. See table.

Abstract G22

Conclusion: Anaesthesia with propfol without tracheal intubation is safe, well tolerated by patients, and provides excellent sedation for efficient endoscopic evaluation with short recovery times.


BSPGHAN IBD Working Group.

Background: Clinical guidelines can play an important role in delivering appropriate, effective, and efficient health care.

Aim: To develop evidence-based guidelines for paediatric IBD.

Methods: A search strategy was developed to identify existing guidelines and/or evidence of efficacy of drug or nutritional treatment of paediatric IBD. Electronic databases (Cochrane, Medline, and Embase) and the abstracts of major paediatric gastroenterology meeting were searched and recognised experts in the field contacted. The titles and abstracts were examined by 2 reviewers to exclude irrelevant publications. Full manuscripts of the remaining publications were sent to subgroups (2+ reviewers) for critical appraisal by criteria of the Scottish Intercollegiate Guidelines Network.

Results: No existing evidence-based guidelines were identified. 5220 publications were identified and 4849 were excluded on initial examination of the title or abstract. Full text versions of the remaining 371 publications were obtained and 167 of these were excluded because they were not relevant (mainly because they did not include children). The remaining 204 publications were sent for critical appraisal by the subgroups. One systematic review and 9 randomised controlled trials were identified but all had major methodological flaws.

Discussion: A systematic search failed to reveal any published evidence-based guidelines and no high quality studies for the medical management of paediatric IBD. There is a great need for adequately powered, high quality studies. In the meantime guideline development will proceed using a Delphi style consensus conference.


M. Abeya, R. Heuschkel, S. Murch, O. Ogunbiyi, S. Keshav. Academic departments of Medicine, Paediatric Gastroenterology, and Surgery, Royal Free and University College Medical School, London, UK

Introduction and Aims: Crohn’s disease affecting children and young adults is increasing in incidence worldwide. Its pathogenesis probably includes an abnormal mucosal immune response to bacteria in genetically susceptible hosts. NOD2 is the first susceptibility gene identified in Crohn’s disease, and mutations are associated with terminal ileitis. We recently showed that NOD2 was expressed strongly and specifically in Paneth cells of the ileum, possibly explaining this association. Paneth cells are specialised intestinal epithelial cells that produce antibacterial proteins. It is likely that an inherited defect in Paneth cell function could predispose to an earlier onset of Crohn’s disease in children. We therefore examined the genotype and phenotype of a group of paediatric and adult patients with Crohn’s disease and determined if NOD2 mutations affected Paneth cell morphology and function.

Methods: 152 patients with Crohn’s disease including 46 children were genotyped for NOD2 mutations. Phenotypes were determined by questionnaire and examination of clinical records. Terminal ileal surgical resection specimens of patients were used for immunohistochemistry to detect expression of Paneth cell specific antimicrobial proteins.

Results: 32.6% of children (mean age of onset 10.8 years, range 2–16 years) had NOD2 mutations compared with 24.5% of adults, although overall allele frequency showed no significant difference. NOD2 mutations were more frequent in those patients who had undergone surgery (18.9%) compared with a non-surgical group (10%). Mutations were associated with stricturing terminal ileitis in children. Paneth cell antimicrobial products were expressed regardless of the NOD2 genotype; however, there were distinct morphological changes in Paneth cells of patients with NOD2 mutations.

Conclusions: There is a significant increase in NOD2 mutations in children with severe and complicated Crohn’s disease. We also show expression of all antimicrobial products with clear evidence of altered Paneth cell differentiation in patients with NOD2 mutations, which merits further investigation.


J. Hart, A. R. Bremner, S. A. Wootton, R. M. Beattie. Paediatric Medical Unit, Southampton General Hospital, UK

Introduction: Increased resting energy expenditure (REE) associated with active inflammation is implicated in the nutritional impairment seen in active Crohn’s disease (CD). Nutritional supplementation when well is debated.

Aims: To determine if energy intakes based upon dietary reference values for basal metabolic rate (BMR) and estimated average requirements (EAR) were likely to meet the energy requirements of children with inactive CD.1

Subjects: 17 children (median age 14 years range 7–16 years) with inactive CD (Paediatric Crohn’s Disease Activity Index <15, and off steroids or nutritional therapy for at least 3 months).

Methods: REE was measured by indirect calorimetry after an overnight fast and compared with BMR predicted by the Schofield equation (variables: age, weight, and sex).1 Physical activity level (PAL) was measured by a 3 day activity diary. Total energy expenditure (TEE) was calculated by multiplying REE by PAL. Actual TEE would have been greater as energy for growth and losses were not measured. TEE was compared with the EAR for age and sex.1

Results: Median REE was not significantly different from median BMR (p = 0.124), although the range was large. TEE was greater than EAR in 15 out of 17 patients. Individual TEE values ranged from 94% to 188% of the EAR for age and sex (median 124%).

Conclusion: Providing EAR alone would not have met the likely energy requirements for most of these children with CD, even when well. Increased requirements were more often due to exercise than raised REE. Caution is required if feeding targets are based on EAR alone and individualised management plans are essential.

Abstract G25



J. L. Hartley1, J. Mears3, K. Saunders2, S. Beath1, P. Davies, D. A. Kelly1, C. Lloyd1, A. Johnson2. 1The Liver Unit, Departments of 2Clinical Psychology and 3Physiotherapy, Birmingham Children’s Hospital, West Midlands B4 6NH, UK

Background: Developmental delay is known to occur in infants with liver failure but the associated effect of CIFx with liver failure is not known.

Aim: To report the cognitive and motor development of children with CIFx and ascertain whether delay is due to severity of liver failure by comparing with infants with liver failure secondary to extra hepatic biliary atresia (EHBA).

Methods: 15 patients with CIFx median age 10 months (range 3.6–14.5) and 27 with EHBA median age 6.13 months (3.7–15) were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), to calculate a mental developmental index (MDI) and a psychomotor developmental index (PDI). 8 of the CIFx patients and none of the EHBA were born prematurely.

Results: See table.

Abstract G26

There was significant delay of cognitive and motor development in both groups, which was greater in the CIFx group. These results cannot be explained by liver failure as bilirubin and albumin levels were similar. The CIFx patients had a significantly longer period of hospitalisation, which may be one factor influencing developmental outcome.

Conclusion: CIFx with severe liver disease is associated with significant developmental delay and provides a rational for targeting intensive physiotherapy and play therapy while in hospital.


F. Kiparissi1, D. Sohi1, N. Thapar1, A. Ramsay2, P. Veys3, H. Gaspar3, P. Milla1, K. Lindley1, M. Elawad1, S. Hill1, N. Shah1. Departments of 1Paediatric Gastroenterology, Histopathology2, and Haematology3, Great Ormond Street Hospital, London

Introduction: Crohn’s, like enterocolitis, is rare in infancy and is usually indicative of an underlying immunodysregulation. One group of such infants suffer from intractable ulcerating enterocolitis of infancy (IE) in which there is characteristically marked oro-anal involvement and deep flask like mucosal ulcers seen throughout the colon. These children are poorly responsive to immunosuppressive therapy, require early colectomy, and have a high incidence of EBV driven non-Hodgkin’s lymphoma (NHL) (40%).

Methods: We describe successful treatment of IE by allogenic bone marrow transplant (BMT) in two brothers. The patients aged 8 and 5 years were born of 4th cousin consanguineous marriage and diagnosed with IE within the first week of life. Both had had disease unresponsive to immunosuppression. The older sibling developed EBV-NHL at age 4 years. Both underwent successful unrelated donor allogenic BMT aged 5 and 4.8 years, respectively.

Results: These siblings have now been followed post-BMT for 3 and 0.3 years. Both have discontinued immunosuppression without disease recurrence. Post BMZ histological assessment of the older sibling reveals chronic inflammation in the lamina propria only.

Conclusion: Infants with IE are unresponsive to conventional immunosuppressive therapy. IE is successfully treated by allogenic bone marrow transplant, which is both curative and probably the treatment of choice for this condition.


A. Baker. Variety Club Children’s Hospital, Denmark Hill, London SE5 9RS on behalf of the BSPGHAN council and Mfanwy Morgan, Public Health Sciences, King’s College London, London SE13UD

Between April and July 2003 a questionnaire was sent to all 89 members of BSPGHAN with clinical GI responsibilities to provide data for job plans and workforce planning in keeping with the new consultant contract (CC) and the European Working Time Directive (EWD). 41 (46%) replied. We report working hours, work related stress, quality of life score (QoL), and best and worst aspects of job.

Results: Two trainees replied. Of 39 consultants, 9 had at least half academic roles, 7 were maximum part time and 2 part time. Median on call frequency was 1 in 5 (range 1 in 1.8 to 1 in 14) and 1 in 7 or 8 for trainees, 2 did no on call. They spent median 50 hours/week in hospital (9–64) with 25 (61%) exceeding 48 hours/week (CC and EWD maximum) by median 8 hrs (2–16). They were available, including on call, median 65 hours/week (22–168) with 11 (27%) over 72 hours/week. 36 experienced stress. Median QoL was 7 (2–9) with 6 respondents ⩽5. Those with QoL <7, n = 14 are Gp1 compared with QoL >7, n = 15, Gp2. Hours at work (55 v 50/week), hours available (70 v 55/week), or number working >48 hrs/week (8 v 10) were similar. All Gp1 reported stress but 5 in Gp2 did not. Best aspects reported for Gp1 were: team/colleagues, n = 9; clinical work, n = 9; patient feedback, n = 7; and teaching, n = 4. For Gp2 they were: team/colleagues, n =  7; research, n = 7; patient feedback, n = 6; and teaching, n = 5. Worst aspects for Gp1 were: resources, n = 14; professional interactions and availability of SpR, n = 7; own time/too busy, n = 6; and admin/bureaucracy, n = 4. For Gp2 they were: own time/too busy, n = 13; admin/bureaucracy, n = 6; professional interactions and availability of SpR, n = 6; and resources; n = 4.

Conclusions: 61% exceed CC and EWD hours by 16% on average, giving an estimate of 10% more consultants for these targets. 87% of consultants experience stress at work and 15% have poor QoL. Those with worse QoL were more likely to report stress, valued clinical work more often than research, and saw the problem as one of external resources rather than use of their own time. CC requires a radical review of priorities, roles, professional interactions, and resources.


K. Foster1, A. Shenoy2, P. McClean1, M. Sood3, S. Tanner2, S. Davison1. 1Department of Paediatric Gastroenterology and Hepatology, St James’s University Hospital, Leeds; 2Sheffield Children’s Hospital; 3Booth Hall Children’s Hospital, Manchester

Introduction: AILD is an important cause of chronic liver disease. Clinical features of autoimmune hepatitis (AIH) reported from a supra-regional centre1 may reflect the most severely affected children. This study describes the presentation and outcome of children referred locally to their tertiary centre.

Method: A retrospective case note review of children undergoing recent follow up for AILD at one of three centres.

Results: 38 children (22 male) were identified who had either AIH (30), primary sclerosing cholangitis (4), or overlap syndrome (4). Median age at presentation was 11 years 7 months (11 months – 14 years 11 months) and interval to diagnosis 1 months (0–29 months). Clinical presentation was acute hepatitis (19), acute liver failure (2), complications of cirrhosis (1), non-specific symptoms (6), or raised transaminases (8). Other autoimmune disease was present in 15/38, with 12/36 having a first degree relative with an autoimmune disorder. After median duration of follow up of 3 years remission was achieved in 27/34 with AIH or overlap syndrome with immunosupression (prednisolone + azathioprine (19), prednisolone + cyclosporin (2), prednisolone alone (6)). Two who achieved remission with prednisolone alone are currently off all treatment. Liver transplant was undertaken in 3 children (2 for acute failure and 1 for failure of medical therapy.) Two children have not yet achieved remission despite dual therapy greater than 6 months. There were no deaths.

Conclusion: Acute hepatitis is the most frequent clinical presentation of AIH to tertiary referral centres. Most children achieve remission with immunosupression. Acute liver failure is an uncommon presentation but likelihood of poor response to treatment necessitates referral for liver transplant.



T. Stephenson1, G. Gopalakrishnan1, S. M. Rhind2, C. Kyle2, D. Keisler3, M. E. Symonds1. 1Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham, NG7 2UH; 2Macaulay Land Use Research Institute, Aberdeen; 3Department of Animal Sciences, University of Missouri—Columbia, Missouri, USA

Aims: Inadequate maternal nutrition at specific stages of pregnancy can result in offspring with increased risk of adult obesity and hypertension. Maternal nutrient restriction targeted over the period of placental growth results in term fetuses with increased fat deposition (

). This study determined the longer term effects on blood pressure control and plasma leptin.

Methods: Fourteen male singleton bearing Scottish Blackface ewes of similar live weight were individually housed from day of mating. Eight were nutrient restricted (NR), consuming 4.0 Mj of metabolisable energy (ME) per day (≅50% of ME requirements for maintenance and growth of the conceptus) until 95 days gestation, with 6 controls (C) consuming 8.0 Mj/day. After 95 days gestation, until term (147 days), all animals consumed 100% of requirements. At ~2 years of age, a carotid artery and jugular vein were surgically catheterised to allow blood sampling plus measurement of blood pressure (BP) and heart rate, both before feeding and during a continuous infusion of noradrenaline (NA). Animals were then humanely euthanased to allow tissue sampling. Results are means and SD.

Results: At two years of age basal BP prior to feeding was significantly higher in NR offspring compared with the controls (e.g. systolic BP: C 86.4 (SD 1.9); NR 96.5 (2.7) mm Hg (p = 0.04)). Despite similar BP responses to NA between groups the decline in heart rate was blunted in the NR group. Fed NR, but not C offspring, also exhibited a significant increase in plasma leptin following NA infusion (C: pre-NA 3.22 (1.9); post-NA 3.16 (1.7); NR: pre-NA 3.47 (0.9); post-NA 4.5 (1.3) ng/ml, (p<0.05)). NR offspring possessed more fat than C.

Conclusion: Nutrient restriction through early gestation results in offspring with higher BP, a blunted heart rate response to a vasoconstrictor challenge, more fat, and increased leptin synthetic capacity. These effects may be mediated by increased sensitivity to sympathetic stimulation, thereby causing hypertension in later life.


L. Stewart1, M. Deane1, D. C. Wilson2, 3. Departments of 1Dietetics and 2Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh; 3Child Life and Health, University of Edinburgh

Introduction: There is currently an epidemic of obesity in children in the UK. Despite increasing interest, few results of management have been published. In our centre, routine care of paediatric obesity has fallen upon the paediatric dietitians, and this is common practice in the UK.

Aims: To audit clinical effectiveness, as well as patient and family compliance, of dietetic intervention in paediatric obesity care.

Methods: The records of 257 children (184 <11 years age) referred to our dietetic department for overweight or obesity over a 5 year period were audited for changes in weight, height, and body mass index (BMI); the number of dietetic appointments attended; overall time span of dietetic intervention; and completion or not of treatment.

Results: Only 58 (22%) children maintained or lost weight. The majority of patients (77%) attended for between 1–4 appointments; overall time span of dietetic intervention varied from 1 (17 children) to 46 months (1 child). The majority of children (134, 52%) failed to complete treatment (defaulted from dietetic follow up); of these, 95 children defaulted within 6 months. Only 20 children (8%) were referred on by the dietitians to other healthcare services.

Conclusions: We have shown that, using a common current model, the management of obesity is time consuming, with a low success rate. Changes to management are required. As noted in the SIGN guideline on childhood obesity of 04.03 (, we recommend that intervention is only commenced when a family is ready and willing to make necessary lifestyle changes. Patient appointments should be increased to allow for more time to be spent discussing motivation and lifestyle changes with the child and family.

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