Enteral Nutrition in Pediatric Short-Bowel Syndrome.

Pediatric intestinal failure (IF) is the critical reduction of intestinal mass or function below the amount necessary for normal growth in children. Short-bowel syndrome (SBS) is the most common cause of IF in infants and children and is caused by intestinal resection. Enteral autonomy and freedom from parenteral nutrition is the mainstay of nutrition management in SBS. The goal is to achieve intestinal adaptation while maintaining proper growth and development. Treatment is variable, and there remains a paucity of evidence to draw well-informed conclusions for the care of individuals in this complex population. Physiological principles of enteral nutrition and practical recommendations for advancing the diet of patients with pediatric SBS are presented. Emerging trends in nutrition management, such as the growing interest in blending diets and the impact on SBS, are reviewed. Finally, the influence of the microbiome on enteral tolerance and small bowel bacterial overgrowth are considered.

The Impact of Lactobacillus Probiotics on the Gut Microbiota in Children With Short Bowel Syndrome.

BACKGROUND: Children with short bowel syndrome (SBS) frequently struggle with malabsorption and poor growth. The intestinal microbiota plays an important role in gut function, and children with SBS have known deficiencies in some commensal gut microbes. One strategy to enhance the gut microbiota is by taking probiotics. However, the efficacy of this approach is not well established. We hypothesized that probiotic supplementation would result in increased levels of the supplemented bacteria and improved growth. MATERIALS AND METHODS: Children with SBS who had weaned from parenteral nutrition but with suboptimal growth were randomized to receive probiotics (Lactobacillus rhamnosus and Lactobacillus johnsonii) or placebo daily for 2 mo. The gut microbiota from monthly stool samples were compared between groups using 16S ribosomal ribonucleic acid sequencing and quantitative polymerase chain reaction. Growth between groups was also compared. Statistical analysis was completed using Mann-Whitney, Kruskal-Wallis, and chi-square tests as appropriate. RESULTS: Eighteen children with SBS completed the study (n = 9 per group). There were no significant changes to the major bacterial families in either group. Median relative abundance of Lactobacillus did not differ between groups at baseline or at the end of the study (7.67 versus 13.23, P = 0.523 and 1.93 versus 15.8, P = 0.161). Median z scores for weight and length did not differ between groups at the beginning or end of the study. CONCLUSIONS: The efficacy of daily probiotic use in children with intestinal failure is unknown. In this study, Lactobacillus probiotics did not result in a predictable change to the fecal microbiota or overall growth compared with placebo in these patients.

A comparison of small bowel and fecal microbiota in children with short bowel syndrome.

BACKGROUND: Babies with short bowel syndrome (SBS) have small intestinal microbial disturbances that impact gut function. Characterizing the small bowel microbiota is challenging, and the utility of sampling stool is unclear. This study compares the microbiota from fecal samples and the small bowel. METHODS: Stool samples were collected (2016-2017) from infants with SBS and colon in continuity (COLON) or SBS with small bowel ostomy (sbSTOMA). The abundance and quantity of major bacterial genera was compared between groups and to healthy controls using 16S rRNA sequencing and qPCR. Kruskall-Wallis test was used for analysis with P values <0.05 considered significant. RESULTS: Samples (n = 41) were collected from 15 SBS infants (<2 years) (9 sbSTOMA, 6 COLON) and 3 healthy infants. Demographics and small intestinal length did not differ between sbSTOMA and COLON infants. The microbiota of SBS groups differed significantly from healthy controls. Fecal samples contained higher quantities of bacteria, but there were no significant differences between sbSTOMA and COLON groups in the abundance of facultative or obligate anaerobes, anti-inflammatory Clostridia, Enterobacteriaceae, or Bifidobacterium. CONCLUSION: Infants with SBS have disturbances to their intestinal microbiota. Sampling small intestinal effluent is challenging. Stool samples may provide a window into the more proximal microbial community. TYPE OF STUDY: Diagnostic. LEVEL OF EVIDENCE: Level II.

A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure.

PURPOSE: Cholestasis is problematic for infants with intestinal failure (IF). The soy-based lipid Intralipid® (IL) has been implicated. An alternative, Smoflipid® (SMOF), is increasingly used. However, its role in cholestasis prevention is unclear. This study compares the incidence and degree of cholestasis between infants with IF receiving SMOF or IL. METHODS: Infants with IF receiving SMOF or IL during the first 8 weeks of parenteral nutrition (PN) support between 2014 and 2017 were reviewed. Clinical characteristics, cholestasis incidence (conjugated bilirubin (Cbili) >2 mg/dL for >2 weeks), and nutritional parameters were compared using Welch's t-test. RESULTS: 91% (21/23) of IL and 76% (16/21) of SMOF babies became cholestatic (p = 0.18). There was no significant difference in median peak Cbili, but SMOF babies normalized more quickly (p = 0.04). Median z-scores for weight were similar throughout the study. SMOF patients getting full PN had a lower incidence of cholestasis compared to IL patients (78% vs. 92%, p = 0.057), but those with cholestasis had similar peak Cbili, time to resolution, and growth. CONCLUSION: Early use of Smoflipid® did not reduce the incidence of cholestasis compared to Intralipid® in infants with IF, but hyperbilirubinemia did resolve more quickly. SMOF may be most beneficial for infants tolerating no enteral nutrition. LEVEL OF EVIDENCE: Level III Retrospective Comparative Treatment Study. TYPE OF STUDY: Retrospective Review.

Over the Scope Clips for Treatment of Acute Nonvariceal Gastrointestinal Bleeding in Children Are Safe and Effective.

OBJECTIVE: There is little published experience with the use of over-the-scope clips (OTSCs) in pediatric patients. The aim of this study is to present our single-center experience utilizing OTSCs for nonvariceal gastrointestinal (GI) bleeding. METHODS: This is a retrospective case series of pediatric patients who underwent endoscopic management of GI bleeding during which OTSCs were used. RESULTS: Eleven cases of OTSC utilization for hemostasis were identified in 10 unique patients between November 2014 and May 2016. The median age at intervention was 14.7 years (range 3.9-16.8 years) and median weight was 39 kg (range 17.4-85.8 kg). Technical success and hemostasis were achieved in all cases and there were no complications. Median follow-up was 32.9 months (range 21.2-39.4 months). All nonanastomotic ulcers (4), polypectomy bleeding (2), and sphincterotomy bleeding (1) had no evidence of recurrent GI bleeding at last follow-up. Two patients with anastomotic ulcerations required additional medical interventions. CONCLUSIONS: Our series demonstrates the safety and effectiveness of the OTSCs in the pediatric population for acute GI bleeding throughout the GI tract. In our experience, it is effective for nonanastomotic ulcers, postpolypectomy bleeding, and postsphincterotomy bleeding even when other hemostatic techniques have failed. OTSCs may be less effective in the setting of anastomotic ulcerations, reaffirming the refractory nature of these lesions.

Anticoagulation results in increased line salvage for children with intestinal failure and central venous thrombosis.

PURPOSE: The purpose of this study was to investigate whether anticoagulation (AC) results in thrombus resolution and increased line longevity in children with intestinal failure (IF) and catheter-associated central venous thrombosis (CVT). METHODS: A retrospective, single institution review was performed of children with IF who were dependent on parenteral nutrition with known CVT between 2006 and 2017. Frequency of catheter-related complications including infection, occlusion, and breakage were compared 18months prior to and after starting AC. Thrombus resolution during anticoagulation was also determined. Data were analyzed using Poisson regression. p-Values <0.05 were considered significant. RESULTS: Eighteen children had ≥1 CVT, with the subclavian vein most commonly thrombosed (44%). All children were treated with low molecular weight heparin, and 6 patients (33%) had clot resolution on re-imaging while receiving AC. Bloodstream infections decreased from 7.9 to 4.4 per 1000 catheter days during AC (p=0.01), and the number of infections requiring catheter replacement decreased from 3.0 to 1.0 per 1000 catheter days (p=0.01). There were no significant differences in line occlusions or breakages. CONCLUSION: Anticoagulation for children with intestinal failure and central venous thrombosis may prevent thrombus propagation, and decrease blood stream infections and line replacements. Further research is needed to determine optimal dosing and duration of therapy. LEVEL OF EVIDENCE: III; Retrospective Comparative Study.

Growth Trajectory in Children With Short Bowel Syndrome During the First 2 Years of Life.

OBJECTIVES: Infants with short bowel syndrome (SBS) require diligent nutritional support for adequate growth. Enteral independence is a primary goal, but must be balanced with ensuring sufficient nutrition. We aimed to describe growth trajectory in infants with SBS as function of nutritional intake during first 2 years of life. METHODS: Infants with SBS were reviewed (2008-2016). z Scores for weight, height, and head circumference (HC) were recorded at birth, 3, 6, 12, 18, and 24 months. Nutritional intake, serum liver enzyme, and bilirubin levels were assessed at all time points. Pearson correlation coefficients were used to measure association with P < 0.05 considered significant. RESULTS: Forty-one infants were included, with median gestational age of 34 weeks (interquartile range [IQR] 29-36 weeks). Median small bowel length was 36 cm (IQR 26-52 cm) and median % expected small bowel length was 28% (IQR 20%-42%). Mean z scores for weight and length were >0 at birth, but <0 from 3 months to 2 years. HC remained <0 throughout the study. Mean z scores at 2 years for weight, length, HC, and weight-for-length were -0.90 (SD 1.1), -1.33 (SD 1.4), -0.67 (SD 1.2), and -0.12 (SD 1.2), respectively. Percentage calories from PN was positively correlated with weight in the first 3 months of life (P = 0.01). CONCLUSIONS: Babies with SBS are high risk for poor growth during the first 2 years of life. Although weaning PN is important for these patients, doing so too quickly in infancy may contribute to compromised growth. The long-term impact on overall development is not known.

Abdominal Angiostrongyliasis: A Presentation of Eosinophilic Granulomatous Colitis.

We present a case of a 4-year-old girl with abdominal angiostrongyliasis who presented with persistent fevers, hepatosplenomegaly, acute abdominal pain, and eosinophilia. Computed tomography scan identified thickening of the ascending colon with a narrowed lumen. Endoscopic evaluation revealed ulcerations and erythema in the ascending colon. The microscopic findings in biopsies included active chronic inflammation with prominent eosinophils and granulomas. A subset of granulomas contained the eggs of Angiostrongylus costaricensis. The definitive method of diagnosing A costaricensis is histology; peripheral blood serology has low specificity and the stool from infected patients does not contain eggs or larvae. Pathologists from endemic regions (Central and South America) are familiar with the typical histologic changes; however, because of increasing global travel, all pathologists should become familiar with A costaricensis, which may mimic common gastrointestinal diseases such as Crohn's disease, appendicitis, and Meckel's diverticulum.

Caregiver Education Reduces the Incidence of Community-Acquired CLABSIs in the Pediatric Patient With Intestinal Failure.

Pediatric patients with intestinal failure often require central venous catheters for extended periods of time for parenteral nutrition, blood sampling, and medication administration, increasing morbidity, mortality, and costs. In 2007, we reported a central line-associated bloodstream infection rate of 7.0 per 1,000 catheter line-days in our pediatric patients with intestinal failure. On the basis of this high rate of catheter-associated infections, we developed and implemented a central line care curriculum for patients/family caregivers and home health nurses. We aim to show with the implementation of patient/family caregiver and home health nurse standardized education, the central line-associated bloodstream infection rate can be significantly reduced and that this is sustainable. A retrospective review of 80 pediatric outpatients with intestinal failure and long-term central venous access was performed between January 1, 2009, and December 31, 2014. During this time period, the nursing department at Children's Medical Center of Dallas implemented a systematic central line care education program for patients and/or caregivers. The number of community-acquired central line-associated bloodstream infections during this time period was collected and compared with our previously reported data from 2005 to 2007 prior to the implementation of education program. With the implementation of standardized care guidelines and a central venous catheter care curriculum, the community-acquired rate decreased from 4.8 to 2.9 per 1,000 catheter-days in 80 patients with intestinal failure between January 1, 2009, and December 31, 2014 (p < .001). This was also a significant decrease compared with the initial central line-associated bloodstream infection rate of 7.0 per 1,000 central line days in 2007 (p < .001) prior to the development of the central venous catheter care curriculum. We have shown that the incidence of community-acquired central line-associated bloodstream infections in children with intestinal failure can be reduced through formal education of central venous catheter care to family members.

A comparison of lipid minimization strategies in children with intestinal failure.

PURPOSE: The purpose of this study was to compare outcomes of lipid minimization with either Intralipid (IL) or Omegaven® in children with intestinal failure (IF) who developed intestinal failure-associated liver disease (IFALD) while receiving parenteral nutrition (PN). METHODS: A retrospective review of children with IF requiring PN who developed IFALD (direct bilirubin >2 mg/dL) while receiving IL (2009-2016) was performed. Clinical characteristics, nutritional, and laboratory values were compared between children treated with reduced IL or Omegaven®. RESULTS: 16 children were reviewed (8 treated with IL and 8 treated with Omegaven® at a median dose of 1g/kg/d). Both groups had similar demographics, small bowel length, and parenteral nutritional intake during the study (82.9±27.1 kcal/kg/d vs. 75.9±16.5 kcal/kg/d, p=0.54). The mean direct bilirubin (DBili) prior to initiating treatment was 7.8±4.3 mg/dL and 7.5±3.5 mg/dL (p=0.87) in the IL and Omegaven® groups, respectively. The IL group took a median of 113 days to achieve a DBili <0.5 mg/dL compared to 124 days in the Omegaven® group (p=0.49). There were no differences in markers of liver function or growth trajectories among groups. CONCLUSIONS: Lipid minimization with either IL or Omegaven® has similar success in achieving a normal DBili in children with IF and IFALD without major differences in nutritional status or growth. TYPE OF STUDY: Treatment Study LEVEL OF EVIDENCE: III.

Predicting time to full enteral nutrition in children after significant bowel resection.

PURPOSE: Parenteral nutrition (PN) contributes to considerable morbidity in children after significant bowel resection. This study evaluates the utility of clinical variables in predicting time to independence from PN. METHODS: After IRB approval, a retrospective review (1999-2012) of 71 children who were on PN for >6weeks after intestinal resection and successfully weaned was performed. Clinical characteristics were evaluated to determine the relationship to time to full enteral nutrition. P-values<0.05 were significant. RESULTS: Most children had necrotizing enterocolitis (56%), intestinal atresia (20%), or gastroschisis (11%) with a median small bowel length of 55cm (IQR, 35-92cm). The duration of PN was independent of the etiology of intestinal loss, presence of the ileocecal valve or colon, or location of anastomosis, but was strongly associated with small bowel length (<0.01) and percent of expected small bowel based on gestational age (GA) (median 50%, <0.01). In general, children who had 25-50% of their small bowel were dependent on PN for at least 2years compared to approximately 1year for those with 51-75%. CONCLUSION: The duration of PN dependence in children after major bowel resection is best predicted by remaining small bowel length and can be estimated using a linear regression model. LEVEL OF EVIDENCE: 2b.

A comparison of Broviac® and peripherally inserted central catheters in children with intestinal failure.

PURPOSE: Central venous catheters (CVCs) are a source of morbidity for children with intestinal failure (IF). Complications include infection, breakage, occlusion, and venous thrombosis. Broviacs® have traditionally been preferred, but peripherally inserted central catheters (PICCs) are gaining popularity. This study compares complications between Broviacs® and PICCs in children with IF. METHODS: After IRB approval, children with IF receiving parenteral nutrition (2012-2016) were reviewed. Complications were compared between Broviacs® and PICCs using the generalized estimation equation population-averaged Poisson regression model. P values <0.05 were considered significant. RESULTS: 36 children (0.1-16years) with IF were reviewed, accounting for 27,331 catheter days, 108 Broviacs® (3F-9F), and 54 PICCs (2-11F). Broviacs® had a significantly higher infection rate (4.2 vs. 2.6/1000 catheter days, p=0.011), but PICCs were more likely to break (1.56 vs. 0.26/1000 catheter days, p=0.002). When comparing same size catheters (3F), there were no significant differences in infection, breakage, or occlusion. Twelve children (33%) had central venous thrombosis, all after Broviac® placement. Three children (8%) had basilic vein thrombosis after PICC placement. CONCLUSION: Although Broviacs® and PICCs had similar complication rates, there were fewer central venous thromboses associated with PICCs. This should be considered when choosing catheters for children with IF. LEVEL OF EVIDENCE: 11b (Prognosis Study).

Severe Gut Microbiota Dysbiosis Is Associated With Poor Growth in Patients With Short Bowel Syndrome.

BACKGROUND: Children with short bowel syndrome (SBS) can vary significantly in their growth trajectory. Recent data have shown that children with SBS possess a unique gut microbiota signature compared with healthy controls. We hypothesized that children with SBS and poor growth would exhibit more severe gut microbiota dysbiosis compared with those with SBS who are growing adequately, despite similar intestinal anatomy. MATERIALS AND METHODS: Stool samples were collected from children with SBS (n = 8) and healthy controls (n = 3) over 3 months. Gut microbiota populations (16S ribosomal RNA sequencing and metagenomic shotgun sequencing) were compared, including a more in-depth analysis of SBS children exhibiting poor and good growth. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, and χ2 tests as appropriate. RESULTS: Children with SBS had a significant deficiency of the commensal Firmicutes order Clostridiales ( P = .025, Kruskal-Wallis) compared with healthy children. Furthermore, children with SBS and poor growth were deficient in beneficial bacteria known to produce short-chain fatty acids and had expansion of proinflammatory Enterobacteriaceae ( P = .038, Kruskal-Wallis) compared with children with SBS who were growing adequately. Using metabolic function analyses, SBS/poor growth microbiomes were deficient in genes needed for gluconeogenesis but enriched in branched and aromatic amino acid synthesis and citrate cycle pathway genes. CONCLUSIONS: Patients with SBS, particularly those with suboptimal growth, have a marked gut dysbiosis characterized by a paucity of beneficial commensal anaerobes, resulting in a deficiency of key metabolic enzymes found in the gut microbiomes of healthy children.

Central venous thrombosis in children with intestinal failure on long-term parenteral nutrition.

PURPOSE: Central venous thrombosis (CVT) is a serious complication of long-term central venous access for parenteral nutrition (PN) in children with intestinal failure (IF). We reviewed thse incidence of CVT and possible risk factors. METHODS: Children with IF on home PN (2010-2014) with central venous imaging were reviewed. Patient demographics, catheter characteristics and related complications, and markers of liver function were compared between children with and without CVT. Serum thrombophilia markers were reviewed for patients with CVT. RESULTS: Thirty children with central venous imaging were included. Seventeen patients had thrombosis of ≥1 central vein, and twelve had ≥2 thrombosed central veins. Patients with and without CVT had similar demographics and catheter characteristics. Patients with CVT had a significantly lower albumin level (2.76±0.38g/dL vs. 3.12±0.41g/dL, p=0.0223). The most common markers of thrombophilia in children with CVT were antithrombin, protein C and S deficiencies, and elevated factor VIII. There was a statistically significant correlation between a combined protein C and S deficiency and having >1 CVT. CONCLUSIONS: Children with IF on long-term PN are at high risk for CVT potentially owing to low levels of natural anticoagulant proteins and elevated factor FVIII activity, likely a reflection of liver insufficiency and chronic inflammation.

Single-balloon enteroscopy in children: initial experience at a pediatric center.

Single-balloon enteroscopy (SBE) allows deep endoscopic access to the jejunum and ileum in adults; however, there are no published series describing the safety of, and indications for, SBE in a pediatric population.Seven pediatric patients (5-17 years) underwent SBE in a 9-month period. Five of 7 procedures achieved the goal. There were no serious complications, and SBE positively affected patient management in 5 of 7 cases.We conclude that SBE is feasible in a pediatric population and can positively affect patient care.

De novo cholangiocarcinoma after liver transplantation in a pediatric patient.

To date, no child has been reported to develop de novo CCA after liver transplantation although patients with transplants have a significantly higher risk of malignancy than the general population. CCA is extremely rare in the pediatric age group, seen mostly in patients with a history of choledochal cysts, Caroli's disease, or PSC. We report the first case of pediatric de novo CCA in the liver allograft 12 yr after liver transplantation.