Susan Hill

Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial

Background and aims: Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn’s disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn’s disease. Patients and methods: Fifty children with a paediatric Crohn’s disease activity index (PCDAI) >20 were randomly assigned to receive 50% (PEN) or 100% (TEN) of their energy requirement as elemental formula for six weeks. The PEN group was encouraged to eat an unrestricted diet while those receiving TEN were not allowed to eat. The primary outcome was achievement of remission (PCDAI <10). Secondary analyses of changes in erythrocyte sedimentation rate (ESR), C reactive protein, albumin, and platelets were performed to look for evidence of anti-inflammatory effects. Results: Remission rate with PEN was lower than with TEN (15% v 42%; p = 0.035). Although PCDAI fell in both groups (p = 0.001 for both), the reduction was greater with TEN (p = 0.005). Moreover, the fall in PCDAI with PEN was due to symptomatic and nutritional benefits. With both treatments there were significant improvements in relation to abdominal pain, “sense of wellbeing”, and nutritional status. However, only TEN led to a reduction in diarrhoea (p = 0.02), an increase in haemoglobin and albumin, and a fall in platelets and ESR. Conclusions: TEN suppresses inflammation in active Crohn’s disease but PEN does not. This suggests that long term nutritional supplementation, although beneficial to some patients, is unlikely to suppress inflammation and so prevent disease relapse.

Autoimmune enteropathy and colitis: is there a generalised autoimmune gut disorder?

Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of them) undergoing colonoscopy were used as control subjects. In all eight patients, but not in the control subjects, there was macroscopic and microscopic evidence of an accompanying colitis of variable severity, thus indicating that a more generalised intestinal disorder was present, which might affect the whole intestine. Aberrant expression of DR molecules on the colonic surface and crypt epithelium was also detected. Autoimmunity may play a role in the colitis.

Growth and bone health in pediatric intestinal failure patients receiving long-term parenteral nutrition

BACKGROUND Children with chronic intestinal failure (IF) treated with long-term parenteral nutrition (PN) may present with low bone mineral density (BMD). The cause may reflect small body size or suboptimal bone mineralization. OBJECTIVE We assessed growth and bone health in children with severe IF. DESIGN Height, weight, and fracture history were recorded. The lumbar spine bone mass was measured in 45 consecutive patients (24 male subjects) aged 5-17 y receiving PN for a median of 5 y. BMD and bone mineral apparent density (BMAD) [ie, adjusted-for-height SD scores (SDSs)] were calculated. RESULTS Diagnoses were short bowel syndrome in 12 patients (27%), intestinal enteropathy in 20 patients (44%), and motility disorder in 13 patients (29%). Mean (±SD) weight, height, and body mass index SDSs were -0.8 ± 1.3, -1.80 ± 1.5, and 0.4 ± 1.3, respectively. The height SDS was less than -2 in 23 children (50%). Patients with enteropathy or intestinal mucosal inflammation (associated with dysmotility or short bowel) were significantly shorter than patients without enteropathy (P = 0.007). The BMD SDS was -1.7 ± 1.6, and the BMAD SDS was -1.4 ± 1.5, independent of primary diagnosis or mucosal inflammation. Nineteen patients (42%) had low BMD (SDS less than -2.0), and 14 patients (31%) had low BMAD. In 25 patients studied at 1-2-y intervals, the BMD SDS fell significantly with time, whereas BMAD declined less, which suggested that a poor bone mineral accretion reflected poor growth. A total of 11 of 37 patients (24%) had nonpathologic fractures (P = 0.3 compared with the general population). CONCLUSIONS Approximately 50% of children were short, and one-third of children had low BMD and BMAD. Children with enteropathy or intestinal mucosal inflammation are at greatest risk of growth failure. Close nutritional monitoring and bespoke PN should maximize the potential for growth and bone mass.

Intestinal failure-associated liver disease in hospitalised children

Objective and aim Liver disease is a potentially life-threatening complication of intravenous/parenteral nutrition (PN). Our aim was to determine the incidence, aetiology and outcome of intestinal failure-associated liver disease (IFALD) in hospitalised children treated with long-term PN (>27 days). Methods Over 4 years all long-term intestinal failure (IF) patients were reviewed for the possible predisposing factors of age, diagnosis, PN lipid, sepsis, length of PN treatment and length of hospitalisation. Outcome measures were IFALD incidence, severity and prognosis. Results Of 60/279 (22%) children aged 0–18 years who developed IFALD, 13 (5%) progressed to type 3/end stage disease. IFALD was associated with younger age (p=0.03), longer treatment (p<0.001), longer hospitalisation (p=0.01), surgical diagnosis (p=0.005) and prematurity (p=0.03). IFALD was not associated with sepsis. Intestinal surgery was associated with IFALD independently of age (p=0.03). Survival was 86%, with three deaths attributed to IFALD (1% of all cases), all of which were surgical. Conclusion IFALD incidence was lower than previously reported in paediatric patients, with surgical neonates at greatest risk.

Granulomatous pneumonitis, sclerosing cholangitis, and pancreatitis in a child with Crohn disease: response to infliximab.

Fulminating acute ulcerative colitis (UC) is a potentially life threatening medical emergency. Up to 30% of individuals respond poorly to corticosteroids alone and second line medical or surgical therapies are indicated. We describe the successful use of chimeric anti-CD25 therapy in 4 such children poorly responsive to combined therapy with intravenous steroids and calcineurin inhibitors with a pretreatment predictive risk of colectomy of 85-100%. Clinical disease activity scores normalized within 72 hours of anti-CD25 administration and colonic histology provided evidence of mucosal healing within 10-14 days. None required emergency colectomy. Anti-CD25 is efficacious in fulminating UC and randomized placebo controlled trials appear indicated.

Intestinal failure-associated liver disease in surgical infants requiring long-term parenteral nutrition

PURPOSE Our aim was to determine incidence, severity, and outcome, as well as predisposing factors and underlying diagnoses, of intestinal failure-associated liver disease (IFALD) in surgical infants requiring long-term parenteral nutrition (PN). METHODS We retrospectively studied surgical infants receiving PN for at least 28 days for congenital or acquired intestinal anomalies over a 5-year period (January 2006 to December 2010). Intestinal failure-associated liver disease was defined as type 1 (early)--persistent elevation of alkaline phosphatase for 6 weeks or longer; type 2 (established)--additional elevated total bilirubin (≥ 50 μmol/L); and type 3 (late)--additional clinical signs of end-stage liver disease. RESULTS Eighty-seven infants required PN for at least 28 days. Intestinal failure-associated liver disease occurred in 29 infants (33%). Intestinal failure-associated liver disease was managed medically in all but 2 patients who underwent intestinal elongation. None were referred for intestinal or liver transplant. Intestinal failure-associated liver disease has been reversed in 17 (59%) of cases to date. Sixty-one children receiving long-term PN (70%) have achieved enteral autonomy, whereas 12 (14%) require home PN. Severity of IFALD was significantly associated with duration of PN and female sex. CONCLUSION Intestinal failure-associated liver disease remains a fairly common but rarely life-threatening complication of intestinal failure in surgical infants. Intestinal failure-associated liver disease can be reversed in more than half of these children, and enteral autonomy was achieved in more than two thirds, even with minimal use of intestinal elongation. This is the first study to demonstrate an association between the severity of IFALD in surgical infants and female sex.

A Qualitative Study of the Quality of Life of Children Receiving Intravenous Nutrition at Home

Objectives: To discover the views of children with severe intestinal failure treated with intravenous nutrition from early life and who remained heavily dependent on treatment throughout childhood. Methods: Seven children ages 7 to 17 years (mean 13 years) were interviewed. The diagnoses were enteropathy in 3, extreme short gut in 1, complex (associated mucosal inflammation and dysmotitlity) in 2, and intestinal pseudo-obstruction in 1. They were treated with intravenous nutrition overnight at home that was administered by trained parents using the simplest possible system. The children were individually questioned about their lifestyle and health. Transcripts were analysed using interpretive phenomenological analysis. Results: Children coped well with life with intravenous nutrition (apart from septicaemia in 2 cases), but were troubled when complications of the underlying disease persisted (eg, nocturnal disturbance, stool frequency, abdominal pain). Children were aware that life was restricted (eg, fewer sleepovers with friends, fewer late nights out). There was a high level of family functioning. Older children wished to take care of themselves. The burdens of life with intravenous nutrition appear to be less significant for these children than living with the effects of chronic illness. There was resilience and acceptance in the face of illness-related demands. Conclusions: This study has found that despite the problems they may face, it is possible for children fed intravenously at home to develop a level of resilience, maintain a positive outlook, and cope well with illness-related demands even when they have had virtually lifelong severe intestinal failure. Families can continue to function well.

Sepsis and its etiology among hospitalized children less than 1 year of age with intestinal failure on parenteral nutrition.

Infections accompany intestinal failure (IF) more commonly in children than in adults, with reported incidences of 2% to 29%. Appropriate care of the central venous catheter is the most important factor preventing infections; but in addition, bacteria translocate from the dysmotile gut as a possible source of septicemia. The aim of this retrospective analysis was to investigate the rate and the epidemiologic profile of septicemia in the patient group at greatest risk, namely, children less than 1 year of age with IF on parenteral nutrition (PN). Among 63 children less than 1 year of age who were included over a 2-year period, 55% were boys. The overall median age at the start of PN was 0.3 years, with a mean duration of 80 days. Some 68% of patients had at least one episode of septicemia, experiencing a mean of 1.5 episodes (range, 1-12). Also, 19% of children displayed polymicrobial bloodstream infections. The most common Gram-positive pathogens were Staphylococcus spp and Enterococcus spp; the Gram-negative pathogens were Klebsiella spp followed by Enterobacter spp and E. coli. Infants less than 1 year of age with IF >28 days experienced a high (68%) rate of sepsis. There was no difference in the incidence of catheter-related blood stream infection according to the primary underlying diagnosis. The most common pathogens were Staphylococcus spp and Enterococcus spp, similar to etiologies of sepsis among children in intensive care units.

Body composition in paediatric intestinal failure patients receiving long-term parenteral nutrition

Objective Outcome of children with intestinal failure (IF) has improved on treatment with parenteral nutrition (PN). The effects of PN and IF on body composition (BC) are unknown. The aim was to review BC in PN-treated children and those weaned off and to compare with reference data. Design Children on long-term/home PN underwent measurement of regional fat mass (FM) and lean mass (LM) using dual energy X-ray absorptiometry. Underlying diseases were intestinal enteropathy, n=15, short bowel syndrome (SBS), n=8 and intestinal dysmotility, n=11. PN duration was median 10 years. Fat Mass Index (FMI) and Lean Mass Index (LMI) were compared in children with and without intestinal inflammation, steroid treatment and according to PN dependency. Results 34 children aged 5–20 years were studied. They were short, mean height SD score (SDS) −1.8 (p<0.001) and light (mean weight SDS −0.86, p<0.001) with high body mass index (BMI) SDS: mean 0.4 (p=0.04) and low Limb LMI SDS −0.9 (p<0.001). Children with SBS had low FMI SDS −0.8 (p=0.01). BC did not significantly differ between diagnostic groups or with steroid treatment. Patients with intestinal inflammation (n=20) had higher BMI SDS than those without, p=0.007. Totally, PN-dependent children, n=11 had higher BMI SDS, p=0.004, total body FMI SDS, p=0.008 and trunk FMI SDS, p=0.001 compared with patients partially dependent and off PN. Conclusions Significantly low limb LM was seen in all patient groups with high FM in children on total PN. Children with IF requiring PN treatment >27 days may benefit from BC monitoring and PN adjustment according to results in order to maximise linear growth and health in later life.

Comparison of liver function with two new/mixed intravenous lipid emulsions in children with intestinal failure.

Background/objective:The high incidence of liver disease associated with intravenous soybean lipid has led to development and use of alternative intravenous lipid emulsions (ILEs). The aim of this study was to compare two new/mixed ILEs: a medium-chain triglyceride (MCT) combined with soybean (i.e., Lipofundin) and a combination of both these lipids with additional olive and fish oils (SMOF).Subjects/methods:Neonates/premature infants newly starting parenteral nutrition (PN) treatment and children with abnormal liver function tests, alanine transferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT) 1.5x upper limit of normal and/or total bilirubin >50 μmol/l for >2 weeks on treatment with PN containing pure soybean ILE (Intralipid 20%; Fresenius Kabi), were started on/changed to either SMOF or Lipofundin. Results of biochemistry and clinical outcome were compared on commencing and discontinuing treatment according to the new ILE used.Results:One hundred and twenty-seven children aged 0–16 (median 0.6) years were included. Fifity-six were given Lipofundin and 71 SMOF. Fifty-three of 127 started PN for the first time and 74 had had previous treatment with Intralipid. During treatment, ALT and ALP levels fell significantly (P<0.008 on SMOF; P<0.05 on Lipofundin), with additional significant reduction in γ-GT with SMOF. Hyperbilirubinaemia incidence decreased from 34% on starting to 24% on discontinuing treatment (P⩽0.05). Infection rate/1000 catheter days, full blood count, serum triglyceride and cholesterol levels were similar with both ILEs.Conclusion:Addition of MCT to soybean ILE was associated with improved liver function. There was an even greater improvement when olive and fish oils were also added with higher incidence of resolution of abnormal liver function tests and reduced inflammation.