OBJECTIVES: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. METHODS: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. RESULTS: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = ß = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). CONCLUSIONS: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.
Biomarkers , Celiac Disease , Haptoglobins , Protein Precursors , Celiac Disease/blood , Celiac Disease/diagnosis , Humans , Infant , Child, Preschool , Child , Haptoglobins/analysis , Male , Female , Anti-Bacterial Agents/administration & dosage , Protein Precursors/blood
Studies involving human intestinal tissue are essential for advancing the field of celiac disease (CeD), as diagnosis requires duodenal biopsies. Performing studies in children helps to better understand CeD in this important subpopulation. This study aims to determine the risk in obtaining duodenal research biopsies during pediatric endoscopy. In this retrospective chart review from 2016 to 2022 of 1180 research subjects and controls, there were 18 procedure-related adverse events within 48 hours. Most adverse events were for symptoms of pain and fever. There was no increased risk of adverse events if additional duodenal research biopsies were taken during pediatric endoscopy.
Celiac Disease , Duodenum , Humans , Child , Retrospective Studies , Biopsy/adverse effects , Duodenum/pathology , Endoscopy, Gastrointestinal/adverse effects , Intestinal Mucosa/pathology , Celiac Disease/diagnosis , Celiac Disease/pathology
Background: Despite a worldwide shift toward anesthesiologist-administered sedation for gastrointestinal endoscopy in children, ideal sedation regimens remain unclear and best practices undefined. Aim: The aim of our study was to document variation in anesthesiologist-administered sedation for pediatric endoscopy. Outcomes of interest included coefficients of variation, procedural efficiency, as well as adverse events. Methods: IRB approval was obtained to review electronic health records of children undergoing routine endoscopy at our medical center during a recent calendar year. Descriptive and multivariate analyses were used to examine predictors of sedation practices. Results: 258 healthy children [2-21 years (median 15, (Q1-Q3 = 10-17)] underwent either upper and/or lower endoscopies with sedation administered by anesthesiologists (n = 21), using different sedation regimens (29) that ranged from a single drug administered to 6 sedatives in combination. Most patients did not undergo endotracheal tube intubation for the procedure (208, 81%), and received propofol (255, 89%) either alone or in combination with other sedatives. A total of 10 (3.8%) adverse events (9 sedation related) were documented to occur. The coefficient of variation (CV) for sedation times was high at 64.2%, with regression analysis suggesting 8% was unexplained by procedure time. Multivariable model suggested that longer procedure time (p < 0.0001), younger age (p < 0.0001), and use of endotracheal tube intubation (p = 0.02) were associated with longer sedation time. Discussion: We found great variation in anesthesiologist administered regimens for pediatric endoscopy at our institution that may be unwarranted, presenting may opportunities for minimizing patient risk, as well as for optimizing procedural efficiency.
