Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients.

OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients. METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition. RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered. CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.

Mitigating Risks of Swallowed Button Batteries: New Strategies Before and After Removal.

Despite ongoing efforts of the national Button Battery Task Force (BBTF), cases of major morbidity and mortality continue to be reported at a higher rate after ingestion of higher voltage and larger button batteries. Initiation of sucralfate or honey shortly after some button battery ingestions is crucial to prevent further injury while awaiting emergent removal. Endoscopic acetic acid irrigation post removal of button battery may halt deeper injury. Gastroenterologists need to be aware of the updates to the National Capital Poison Center algorithm for button battery ingestion.

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive.

OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

Approach and Safety of Esophageal Dilation for Treatment of Strictures in Children With Epidermolysis Bullosa.

OBJECTIVE: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs). METHODS: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure). RESULTS: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs. CONCLUSIONS: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.

Mode of Delivery Determines Neonatal Pharyngeal Bacterial Composition and Early Intestinal Colonization.

OBJECTIVES: Bacterial colonization and succession of the human intestine shape development of immune function and risk for allergic disease, yet these processes remain poorly understood. We investigated the relations between delivery mode, initial bacterial inoculation of the infant oropharynx (OP), and intestinal colonization. METHODS: We prospectively collected maternal rectal and vaginal swabs, infant OP aspirates, and infant stool from 23 healthy mother/infant pairs delivering by cesarean (CS) or vaginal delivery (VD) in an academic hospital. Bacterial abundance (16S rRNA sequencing) and community similarity between samples were compared by delivery mode. Shotgun DNA metagenomic sequencing of infant stool was performed. RESULTS: VD infants had higher abundance of Firmicutes (mainly lactobacilli) in OP aspirates whereas CS OP aspirates were enriched in skin bacteria. OP aspirates were more similar to maternal vaginal and rectal microbiomes in VD compared with CS. Bacteroidetes were more abundant through 6 weeks in stool of VD infants. Infant fecal microbiomes in both delivery groups did not resemble maternal rectal or vaginal microbiomes. Differences in fecal bacterial gene potential between CS and VD at 6 weeks clustered in metabolic pathways and were mediated by abundance of Proteobacteria and Bacteroidetes. CONCLUSIONS: CS infants exhibited different microbiota in the oral inoculum, a chaotic pattern of bacterial succession, and a persistent deficit of intestinal Bacteroidetes. Pioneer OP bacteria transferred from maternal vaginal and intestinal communities were not prominent constituents of the early infant fecal microbiome. Oral inoculation at birth may impact the intestinal microenvironment, thereby modulating early succession of intestinal bacteria.

Developmental origins of nonalcoholic fatty liver disease.

Obese pregnant women may transmit their metabolic phenotype to offspring, leading to a cycle of obesity and diabetes over generations. Early childhood obesity predicts nonalcoholic fatty liver disease (NAFLD), the most common chronic human liver disease. The fetus may be vulnerable to steatosis because immature fetal adipose depots are not available to buffer the excess transplacental lipid delivery in maternal obesity. In animal models, in utero high-fat diet exposure results in an increase in the accumulation of liver triglycerides in offspring and increased hepatic oxidative stress and apoptosis, perhaps priming the liver for later development of NAFLD. Innate immune dysfunction and necroinflammatory changes have been observed in postnatal offspring liver of animals born to high-fat-fed dams. Postweaning, livers of offspring exposed to maternal high-fat feeding in utero share pathophysiologic features with human NAFLD, including increased de novo lipogenesis and decreased free fatty acid oxidation. Human studies using magnetic resonance imaging have shown that maternal BMI predicts infant intrahepatocellular lipid storage, as seen in animal models. The generational transfer of NAFLD may occur via epigenetic changes in offspring liver. Transmission of microbiota from mother to infant may impact energy retention and immune function that contribute to a predisposition to NAFLD.

Intrahepatic fat is increased in the neonatal offspring of obese women with gestational diabetes.

OBJECTIVES: To assess precision magnetic resonance imaging in the neonate and determine whether there is an early maternal influence on the pattern of neonatal fat deposition in the offspring of mothers with gestational diabetes mellitus (GDM) and obesity compared with the offspring of normal-weight women. STUDY DESIGN: A total of 25 neonates born to normal weight mothers (n = 13) and to obese mothers with GDM (n = 12) underwent magnetic resonance imaging for the measurement of subcutaneous and intra-abdominal fat and magnetic resonance spectroscopy for the measurement of intrahepatocellular lipid (IHCL) fat at 1-3 weeks of age. RESULTS: Infants born to obese/GDM mothers had a mean 68% increase in IHCL compared with infants born to normal-weight mothers. For all infants, IHCL correlated with maternal prepregnancy body mass index but not with subcutaneous adiposity. CONCLUSION: Deposition of liver fat in the neonate correlates highly with maternal body mass index. This finding may have implications for understanding the developmental origins of childhood nonalcoholic fatty liver disease.

Conjugated hyperbilirubinemia in children.

A variety of anatomic, infectious, autoimmune, and metabolic diseases can lead to conjugated hyperbilirubinemia, both in the newborn period and later in childhood. The pediatric practitioner is most likely to encounter conjugated hyperbilirubinemia in the neonatal period.It is crucial to maintain a high degree of suspicion for cholestasis in the persistently jaundiced newborn. The goal is recognition of conjugated hyperbilirubinemia between 2 and 4 weeks after birth, allowing for the prompt identification and management of infants who have biliary atresia, which remains the most common cause of neonatal cholestasis.

Management of button battery-induced hemorrhage in children.

OBJECTIVES: Button battery ingestions are potentially life threatening for children. Catastrophic and fatal injuries can occur when the battery becomes lodged in the esophagus, where battery-induced injury can extend beyond the esophagus to the trachea or aorta. Increased production of larger, more powerful button batteries has coincided with more frequent reporting of fatal hemorrhage secondary to esophageal battery impaction, but no recommendations exist for the management of button battery-induced hemorrhage in children. MATERIALS AND METHODS: We reviewed all of the reported pediatric fatalities due to button battery-associated hemorrhage. Our institution engaged subspecialists from a wide range of disciplines to develop an institutional plan for the management of complicated button battery ingestions. RESULTS: Ten fatal cases of button battery-associated hemorrhage were identified. Seven of the 10 cases have occurred since 2004. Seventy percent of cases presented with a sentinel bleeding event. Fatal hemorrhage can occur up to 18 days after endoscopic removal of the battery. Guidelines for the management of button battery-associated hemorrhage were developed. CONCLUSIONS: Pediatric care facilities must be prepared to act quickly and concertedly in the case of button battery-associated esophageal hemorrhage, which is most likely to present as a "sentinel bleed" in a toddler.

Transforming surgical morbidity and mortality into a systematic case review.

BACKGROUND/PURPOSE: The surgical morbidity and mortality (M&M) conferences at a regional children's hospital achieved the goals of case by case peer review and education for trainees but provided limited data for trending and analysis. In 2019, an institution-wide effort was initiated to create an electronic case review system with the goals of improving event capture and real-time practice performance feedback. Surgical M&M was migrated to this structured case review format to provide a platform for surgical performance improvement. METHODS: An online secure database was created with a 3-step classification system based on Clavien-Dindo severity score, peer review, and causality fishbone analysis. The data entered were available in an interactive dashboard. Retrospective tabulation of the 2018 M&M data was performed using the archived paper system used prior to 2019. RESULTS: For the calendar year of 2019, the division of pediatric surgery captured and categorized 193 complications in the case review system. The capture rate was 50 per 1000 surgical procedures. For a similar time frame in 2018, the capture rate was 35 per 1000 surgical procedures. The dashboard provided run charts of the incidence and types of complications by procedure and by surgeon. Similar trend data were not available in 2018. The dashboard output has made possible the creation of (non- risk adjusted) individual surgeon performance reports. The output has been used to direct process improvement projects and educational content. CONCLUSION: Creation of an online database with interactive dashboard has allowed surgical M&M to evolve into a systematic case review that greatly facilitates quality improvement efforts. This system increased the event capture rate and provided novel practice performance feedback, resulting in process improvement projects and educational objectives predicated on the trending data. These electronic reporting tools are now available to all surgical divisions and represent a transformative approach to surgical case review. TYPE OF STUDY: Retrospective Historical control; Quality improvement. LEVEL OF EVIDENCE: Level III.

A Pediatric Hospital Policy for Medical Marijuana Use.

Most US states have now legalized medical marijuana (MMJ) use, giving new hope to families dealing with chronic illness, despite only limited data showing efficacy. Access to MMJ has presented several challenges for patients and families, providers, and pediatric hospitals, including the discrepancy between state and federal law, potential patient safety issues, and drug interaction concerns. Colorado was one of the first states to legalize MMJ and has remained at the forefront in addressing these challenges. Children's Hospital Colorado has created and evolved its MMJ inpatient use policy and has developed a unique consultative service consisting of a clinical pharmacist and social worker. This service supports patients and families and primary clinical services in situations in which MMJ is actively being used or considered by a pediatric patient. The first 50 patients seen by this consultative service are reported. Eighty percent of patients seen had an oncologic diagnosis. Symptoms to be ameliorated by active or potential MMJ use included nausea and vomiting, appetite stimulation, seizures, and pain. In 64% of patients, MMJ use was determined to be potentially unsafe, most often because of potential drug-drug interactions. In 68% of patients, a recommendation was made to either avoid MMJ use or adjust its administration schedule. As pediatric hospitals address the topic of MMJ use in their patients, development of institutional policy and clinical support services with specific expertise in MMJ is a recommended step to support patient and families and hospital team members.

First successful antegrade single-balloon enteroscopy in a 3-year-old with occult GI bleeding.

BACKGROUND: Balloon enteroscopy is an emerging technique to allow access to the small intestine for both diagnostic and therapeutic purposes. To date, there have been few published data documenting the safety and efficacy of balloon enteroscopy in small children. OBJECTIVE: To describe our experience with single-balloon enteroscopy (SBE) in a 37-month-old toddler with occult GI bleeding. DESIGN: A single case report. SETTING: A free-standing, academic children's hospital in Denver, Colorado. PATIENT: The patient was a 37-month-old, 13.5-kg toddler with persistent heme-positive stools, severe microcytic anemia, and hypoalbuminemia. Previous workup was significant for eosinophilic inflammation in the antrum and a video capsule study showing erythematous lesions in the small bowel. INTERVENTION: An antegrade SBE was performed with the child under general endotracheal anesthesia, with biopsy specimens obtained from identified lesions in the jejunum and ileum. MAIN OUTCOME MEASUREMENTS: Complications and successful treatment of symptoms were the primary endpoints. RESULTS: The procedure was performed successfully in 85 minutes, passing an estimated 200 cm beyond the pylorus, without complications. Identification of the lesions as consistent with eosinophilic enteropathy led to successful treatment with an elimination diet and corticosteroids. LIMITATIONS: The primary limitation of this study is that it is a single case report. Therefore, it is difficult to make a generalized statement regarding the safety and efficacy of balloon enteroscopy in toddlers of this size. CONCLUSIONS: Antegrade SBE can be a well-tolerated and effective procedure to evaluate occult GI bleeding in children as young as 3 years of age. Further study is needed to better establish safety parameters for balloon enteroscopy in small pediatric patients.

Nutritional and Gastrointestinal Management of the Patient With Duchenne Muscular Dystrophy.

Advances in treatment and multidisciplinary management have resulted in improved survival of individuals with Duchenne muscular dystrophy (DMD). Updated DMD treatment recommendations as found in the 2018 DMD Care Considerations are aimed to assist multidisciplinary care teams in providing standardized care to their patients, including attention to nutritional and gastrointestinal health. Challenges remain for care teams in accurately estimating height and nutritional status for individuals with DMD. It can be difficult for patients to maintain a healthy weight. Risk factors for obesity include glucocorticoid therapy and loss of ambulation. In contrast, in the later stages of the disease, swallowing dysfunction can lead to poor nutrition and consideration for gastrostomy tube placement. Constipation is highly prevalent, underrecognized, and undertreated in DMD. With this article, we address the assessment and management of gastrointestinal and nutritional issues, as well as clinical controversies.

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management.

Since the publication of the Duchenne muscular dystrophy (DMD) care considerations in 2010, multidisciplinary care of this severe, progressive neuromuscular disease has evolved. In conjunction with improved patient survival, a shift to more anticipatory diagnostic and therapeutic strategies has occurred, with a renewed focus on patient quality of life. In 2014, a steering committee of experts from a wide range of disciplines was established to update the 2010 DMD care considerations, with the goal of improving patient care. The new care considerations aim to address the needs of patients with prolonged survival, to provide guidance on advances in assessments and interventions, and to consider the implications of emerging genetic and molecular therapies for DMD. The committee identified 11 topics to be included in the update, eight of which were addressed in the original care considerations. The three new topics are primary care and emergency management, endocrine management, and transitions of care across the lifespan. In part 1 of this three-part update, we present care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management.

Informed Consent for Pediatric Endoscopy.

Informed consent and refusal for pediatric procedures involves a process in which the provider, child, and parents/guardians participate. In pediatric gastroenterology, many procedures are considered elective and the process generally begins with an office visit and ends with the signing of the consent document. If the process is emergent then this occurs more expeditiously and a formal consent may not be required. Information about the procedure should be shared in a way that allows a decision-making process to occur for both the parent/guardian and the child, if of assenting age.