Justine M. Turner

Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot study

Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom‐free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Methods: Eighteen eligible patients between the ages of 3–17 with mild to moderate acute UC received open‐label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre‐ and post‐VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI ≤3) was achieved in 56% of children (n = 10); response (decrease in SCCAI ≥2, but final score ≤5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post‐VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%.

Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis.

Objectives: Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. Materials and Methods: A retrospective chart review of the Stollery Childrens Hospital Celiac Clinic charts (April 1989–September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. Results: Seventy-four children (9.6 ± 3.7 years; range 3.3–16.0 years) were included. Lumbar BMD z scores more than or equal to −1 were observed in 58 cases (65%), z scores below −1 but above −2 were observed in 14 cases (19%) and z scores less than or equal to −2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P < 0.05). Conclusions: An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Parenteral ω-3 fatty acid lipid emulsions for children with intestinal failure and other conditions: a systematic review.

BACKGROUND There is growing interest in the use of ω-3 fatty acid (n-3FA) lipid emulsions to prevent complications associated with parenteral nutrition. The authors systematically reviewed the evidence on the benefits and safety of n-3FA compared with standard lipid emulsions in children with intestinal disease, critical illness, trauma, or postoperative complications. MATERIALS AND METHODS The authors searched 4 bibliographic databases from their inception to March 2011, conference proceedings, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodological quality, and rated the strength of the evidence. One reviewer extracted and a second reviewer verified data. The authors summarized findings qualitatively and conducted meta-analysis when appropriate. RESULTS Five randomized controlled trials with unclear risk of bias and 3 high-quality prospective cohort studies were included. The studies examined premature, low birth weight infants (n = 6) and children with heart disease (n = 1) or intestinal failure (n = 1). The strength of evidence was consistently low or very low across all lipid emulsion comparisons and outcomes. In young children, n-3FA emulsions resulted in improvement in some biochemical outcomes of intestinal failure-associated liver disease but no difference in mortality. Few studies examined patient-important outcomes, such as length of hospital and intensive care stay; need for transplantation, growth, and cognitive development; or the long-term effects and potential harms associated with these therapies. CONCLUSIONS Currently, there is a lack of sufficient high-quality data to support the use of parenteral n-3FA lipid emulsions in children. Future trials examining long-term clinical outcomes and harms are needed.

Novel Neonatal Piglet Models of Surgical Short Bowel Syndrome With Intestinal Failure

Objectives: Short bowel syndrome occurring after surgery for acquired or congenital intestinal abnormalities causes considerable neonatal morbidity and mortality. Animal models are a valuable research tool for this problem; however, few successful neonatal models have been developed and most do not include distal intestinal resection as seen commonly in human babies. We report novel piglet models addressing these gaps. Subjects and Methods: Neonatal piglets (1–6 days) underwent venous and gastric catheter insertion and 75% intestinal resection. Group 1 (n = 6) had midintestinal resection with jejunoileal anastomosis; group 2 (n = 5) had distal intestinal resection with jejunocolic anastomosis; group 3 (n = 5) were sham controls; and group 4 (n = 5) were sow reared. Postoperatively, groups 1 to 3 piglets commenced parenteral nutrition (PN), and enteral nutrition was introduced and advanced using a standard regimen. Data collection included days on PN, weight gain, fat absorption, small intestine lengthening, and bowel/liver histology. Results: Group 2 piglets had more days on PN (P = 0.008), less weight gain (P = 0.027), and greater malabsorption (P = 0.012). They did not show small intestine lengthening and had more cholestatic liver disease. Group 1 piglets had histological evident intestinal adaptation and 1.5-fold intestinal lengthening (P = 0.001). Conclusions: These novel piglet models of short bowel syndrome are the first to represent the full clinical spectrum of intestinal failure as observed in human neonates. By considering the impact of different short bowel anatomy on potential for adaptation and growth, these animal models are a significant advance. They permit evaluation of new therapies to promote intestinal adaptation and reduce complications, such as cholestasis.

10-year review of pediatric intestinal failure: clinical factors associated with outcome.

Prediction of outcomes in pediatric intestinal failure is challenging but essential to guide intestinal rehabilitation and transplantation decisions. This review of intestinal failure patients spanning 10 years examines clinical details in relation to outcome to identify factors that may refine predictive accuracy. A search was conducted to identify all children with intestinal failure managed at Stollery Childrens Hospital between January 1994 and December 2003. They were divided into 3 groups: early death occurring <or=30 days of age, parenteral nutrition dependence for 30-100 days, and parenteral nutrition dependence for >100 days. The long-term group was divided according to outcome: death or adaptation. Demographics, diagnosis, nutrition requirements, laboratory parameters, and clinical data were recorded. Groups were compared to identify factors associated with outcome. Necrotizing enterocolitis, gastroschisis, and intestinal atresias were the most common causes for intestinal failure; outcome was not related to diagnosis. Although withdrawal of therapy was common in the early death group, most babies had one or more additional significant comorbidity. Among the 29 babies requiring parenteral nutrition for >100 days with known outcomes, 12 died, 16 adapted fully, and 1 received a multivisceral transplant. Intestinal length >40 cm was associated with a significantly increased risk of mortality (P< .001). Abnormal laboratory values (bilirubin, aspartate aminotransferase, alanine aminotransferase, albumin, and platelet count) after 5 months of age were also significantly different between groups. This data, together with data from previous reviews, should be used to investigate potential predictive factors in prospective studies, particularly in the context of expert multidisciplinary care.

Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs☆

BACKGROUND The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates and infants, and thus a detailed understanding of the effects of GLP-2 during the phase of rapid growth during infancy is required to guide the development of therapeutic applications. We studied the effects of GLP-2 in the neonatal pig to determine the potential effects of exogenous administration. METHODS Two day old newborn domestic piglets were treated with GLP-2 (1-33) at 40 μg/kg/day or control drug vehicle (saline), by subcutaneous injection, given in two doses per day, (n=6/group) for 42 days. Animals were weaned normally, over days 21-25. In the fifth week of life, they underwent neuro-developmental testing, and a pharmacokinetic study. On day 42, they were euthanized, and a complete necropsy performed, with histological assessment of tissues from all major organs. RESULTS GLP-2 treatment was well tolerated, one control animal died from unrelated causes. There were no effects of GLP-2 on weight gain, feed intake, or behavior. In the treated animals, GLP-2 levels were significantly elevated at 2400±600 pM while at necropsy, organ weights and histology were not affected except in the intestine, where the villus height in the small intestine and the crypt depth, throughout the small intestine and colon, were increased. Similarly, the rate of crypt cell proliferation (Ki-67 staining) was increased in the GLP-2 treated animals and the rate of apoptosis (Caspase-3) was decreased, the depth of the microvilli was increased and the expression of the mRNA for the GLP-2 receptor was decreased throughout the small and large intestine. CONCLUSIONS In these growing animals, exogenous GLP-2 at pharmacologic doses was well tolerated, with effects confined to the gastrointestinal tract.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome

Background:Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS.Methods:In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC). Parenteral nutrition (PN) commenced on day 1 and was weaned as enteral nutrition (EN) advanced. IV GLP-2 (11 nmol/kg/d) or saline was initiated on day 2. Piglets were maintained for 14 d. Clinical, functional, morphological, and histological outcomes were obtained.Results:JC-GLP-2 piglets had fewer days on PN (10.0 ± 0.6 vs. 13.8 ± 0.2), more days on EN (4.0 ± 0.6 vs. 0.2 ± 0.2), a higher percentage of EN at termination (92 ± 5 vs. 52 ± 10%), fewer days of diarrhea (8.0 ± 0.7 vs. 12.3 ± 0.4), increased intestinal length (19 ± 4 vs. −5 ± 3%), and deeper jejunal crypts (248 ± 21 vs. 172 ± 12 μm), compared with saline piglets.Conclusion:GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

Patient and Parent Satisfaction with a Dietitian-and Nurse-Led Celiac Disease Clinic for Children at the Stollery Children’S Hospital, Edmonton, Alberta

OBJECTIVE To assess patient and parent satisfaction with a primarily nurse- and dietitian-led celiac disease clinic in a tertiary pediatric centre. METHODS An online survey was sent to families and patients attending the Stollery Childrens Hospitals Multidisciplinary Pediatric Celiac Clinic (Edmonton, Alberta) since 2007. The survey focused on clinic attendance, satisfaction with clinic structure, processes, and education and preference for alternatives to the current process. Respondents were asked to rank satisfaction or preference on a five-point Likert scale, with 1 being lowest and 5 being highest. RESULTS Most satisfaction related to follow-up with serology (4.6) and with a dietitian (4.3). The most preferred changes included either meeting the entire multidisciplinary team after the biopsy (4.7), or meeting with only the dietitian and nurse after the biopsy (4.4). The preferred education resources were the Internet (4.3) and the dietitian (4.2). The mean overall satisfaction score of the Multidisciplinary Pediatric Celiac Clinic was 4.0. CONCLUSIONS Results of the present survey suggested that patients and families value a multidisciplinary follow-up clinic for children with celiac disease. In particular, feedback based on repeat blood work and regular contact with a dietitian were highly valued. The present survey, outlining the most valued aspects of the clinic, may be useful for service delivery in other regions. In addition, it provides information on how to better support pediatric patients with celiac disease.

Parenteral Soy Oil and Fish Oil Emulsions: Impact of Dose Restriction on Bile Flow and Brain Size of Parenteral Nutrition-Fed Neonatal Piglets.

BACKGROUND Parenteral nutrition (PN)-associated liver disease (PNALD) remains a significant cause of morbidity and mortality for neonates dependent on PN. Total fat emulsion dose and composition, particularly the large amount of ω-6 long-chain polyunsaturated fatty acids in plant oils, have been proposed as risk factors for PNALD. We hypothesized restriction of the dose of emulsion would prevent PNALD, regardless of the composition, but growth could be compromised. METHODS Using a neonatal piglet model, we compared conventional soy oil emulsion (Intralipid), dosed high (SO10, n = 8: 10 g/kg/d) and low (SO5, n = 6: 5 g/kg/d), with fish oil (Omegaven), dosed low (FO5, n = 8: 5 g/kg/d). Piglets were given isonitrogenous PN for 14 days. The normal range for all parameters was determined by measurement in equivalent aged sow-reared piglets. RESULTS Bile flow was lower with high-dose Intralipid, outside the normal range, while higher for the other groups (SO10, 5.4 µg/g; SO5, 8.6 µg/g; FO5, 13.4 µg/g; P = .010; normal range, 6.5-12.2 µg/g). Total body weight was low in all treatment groups (SO10, 4.4 kg; SO5, 4.5 kg; FO5, 5.0 kg; P = .038; normal range, 5.2-7.3 kg). Brain weight was not different between groups (SO10, 40.3 g; SO5, 36.0 g; FO5, 36.6 g; P = .122; normal range, 41.8-51.4 g). Corrected for body weight, brain weight was lowest in the fish oil group (SO10, 9.3 g/kg; SO5, 8.0 g/kg; FO5, 7.3 g/kg; P < .001; normal range, 5.9-9.0 g/kg). CONCLUSION Low-dose fat emulsions reduce the risk of developing PNALD. Further investigation of the risk to brain development in neonates exposed to dose restriction, particularly with fish oil, is required.

Effects of Polymeric Formula vs Elemental Formula in Neonatal Piglets With Short Bowel Syndrome

BACKGROUND Intestinal adaptation is important for recovery in short bowel syndrome (SBS). This process is dependent on the presence of enteral nutrition (EN) and trophic factors, such as glucagon-like peptide-2 (GLP-2). In clinical practice, elemental formula is often used to feed neonates with SBS, whereas animal studies suggest polymeric formula promotes better intestinal adaptation. In neonatal piglet models of SBS, with or without ileum, we compared the elemental with the polymeric formula, including the effect on endogenous GLP-2. MATERIALS AND METHODS Forty-eight piglets underwent 75% mid-intestinal resection with jejunoileal anastomosis, 75% distal-intestinal resection with jejunocolic anastomosis (JC), or sham without resection. Parenteral nutrition (PN) started postoperatively, tapering as EN was increased, according to clinical criteria, based on diarrhea and weight. Within groups, piglets were randomized to an isocaloric/isonitrogenous elemental (amino acid) or polymeric (intact protein) diet. Plasma GLP-2 and histology for adaptation were measured at 14 days. RESULTS Within both SBS and control groups, no difference in adaptation was observed according to diet. A difference was observed only within the JC piglet group with regard to clinical outcomes. In these piglets, compared with elemental formula, the polymeric formula was associated with more diarrhea ( P = .023) and longer duration of PN support (P = .047). CONCLUSION An overall benefit of the polymeric formula over the elemental formula on gut adaptation was not observed. Furthermore, SBS piglets without ileum had less ability to tolerate polymeric formula, contributing to more days of PN support.