Objectives: Prolonged antibiotic use after birth is associated with neonatal feeding intolerance and functional gastrointestinal disorders (FGIDs). A gastric dysrhythmia (tachygastria) with frequencies >4-9 cycles per minute, measured by electrogastrography (EGG), is associated with FGIDs. The relationship between prolonged antibiotic use and % time spent in tachygastria is unknown in preterm infants. We aimed to compare weekly changes in % tachygastria between preterm infants receiving long (>48 h) versus short (≤48 h) courses of antibiotics for early onset sepsis evaluation (initiated at <3 days of life).
Methods: This was a longitudinal, prospective cohort study of 88 preterm infants (<34 weeks' gestation) with weekly EGG recordings from the first week of life until 40 weeks' post-menstrual age, discharge, or death. We calculated % of EGG recording time in tachygastria and determined the mean across weekly sessions. A mixed effects model assessed variance in % tachygastria between the short- and long-antibiotic exposure groups across all weeks.
Results: Baseline characteristics were similar between the two groups. There was no difference in % tachygastria between short and long antibiotic exposure groups across nine postnatal weeks (p = 0.08).
Conclusions: Early, prolonged antibiotic exposure among preterm infants may not lead to significant gastric dysrhythmia. Future studies including larger sample sizes and a "no antibiotic" exposure arm are essential in elucidating this potential relationship.
Objectives: Multiple studies in patients with Crohn's disease (CD) treated with anti-tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated (IFX) administration during induction resulted in improved outcomes.
Methods: This retrospective study included CD patients aged 5-17.9 years that were treated with IFX. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of IFX. Primary outcome was steroid-free clinical remission by Week 52.
Results: Sixty-eight patients were included, of whom seven discontinued IFX before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at IFX initiation. Despite receiving significantly more IFX, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn's disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough IFX levels by Week 52.
Conclusion: Accelerated IFX dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.
Objectives: Identify clinical and serologic features that more accurately predict a diagnosis of celiac disease (CD) in children with type 1 diabetes mellitus (T1DM), particularly focusing on the degree of elevation of tissue transglutaminase immunoglobulin A (TTG IgA) and dilution of positive endomysial antibody (EMA).
Methods: We performed a single-center retrospective review of patients with T1DM who underwent endoscopy from 2016 to 2022 for evaluation of CD. We compared demographic, anthropometric, and laboratory data as well as symptoms and endoscopy findings for subjects with and without CD.
Results: Of 123 subjects who underwent esophagogastroduodenoscopy, 74 (60%) were diagnosed with CD. Univariate logistic regression analysis revealed the factors associated with CD were degree of TTG IgA elevation, EMA positivity, and degree of EMA dilution. For every 10-fold increase in TTG IgA, there was a 4.7× increased risk of CD. TTG IgA ≥10 times the upper limit of normal (ULN) provided a positive predictive value (PPV) of 85% (confidence interval [CI]: [0.76-92]) in all subjects and 91% in asymptomatic subjects (CI: [0.75-0.98]). Of 66 subjects with EMA data, 41 (62%) were positive and 32 had CD (PPV = 0.78). Of 12 asymptomatic subjects with positive EMA, eight had CD (PPV = 0.67). For subjects with EMA ≥ 1:80, all were diagnosed with CD, and all had TTG IgA ≥10 times the ULN.
Conclusions: Among patients with T1DM, symptoms, adjunct labs, and anthropometrics do not help predict CD, but the degree of elevation of TTG IgA and dilution of a positive EMA result do.
Background: Evolving epidemiological data and increasing antibiotic resistance mandate an update of the European and North American Societies of Pediatric Gastroenterology, Hepatology and Nutrition guidelines.
Methods: Certainty of evidence and strength of recommendations were rated by experts according to the Grading of Recommendation Assessment, Development, and Evaluation approach. PICO (patient population, intervention, comparator, and outcome) questions were developed and voted on by the group. Recommendations were formulated using the Evidence to Decision framework.
Results: The current literature supports many of the previous recommendations and several new recommendations. Invasive testing with strain antimicrobial susceptibility analysis is recommended for the diagnosis and selection of eradication therapy for H. pylori infection. Molecular methods are acceptable for detection of infection and of antibiotic resistance in gastric biopsy specimens. Reliable, noninvasive tests can be used as a screening method for children with history of gastric cancer in a first-degree relative. When investigating causes of chronic immune thrombocytopenic purpura, testing for H. pylori is no longer recommended. When investigating other diseases such as inflammatory bowel disease, celiac disease, or eosinophilic esophagitis, specific diagnostic biopsies for H. pylori infection are not indicated. However, if H. pylori is an incidental finding, treatment may be considered after discussing the risks and benefits. Treatment should be based on antibiotic antimicrobial susceptibility testing and, if unavailable, regimens containing clarithromycin should be avoided.
Conclusions: Due to decreasing prevalence of infection, increasing challenges with antibiotic resistance, and emerging evidence regarding complications of infection, clinicians must be aware of these recommended changes to appropriately manage H. pylori infection and its clinical sequelae in children.
Objectives: To compare the recently proposed Capsule Endoscopy-Crohn's Disease index (CE-CD) to pre-existing capsule endoscopy (CE) scores, to measure its precision and accuracy to predict adverse clinical outcomes in children with Crohn's disease (CD).
Methods: Children with CD who underwent CE at diagnosis and had, at least, 1-year follow-up postprocedure were selected. Capsule study was viewed and the different indices were independently scored by two trained paediatric gastroenterologists. The relationship between pre-existing scores and CE-CD was assessed by linear regression analysis. Clinical outcomes prediction assessment was based on receiver operating characteristics curves, survival analysis and Cox regression. Finally, interobserver agreement was measured.
Results: Fifty-nine patients were finally included. CE-CD showed a strong positive correlation with the Lewis score (ρ = 0.947) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) (ρ = 0.982). Both CE-CD and CECDAI were significant predictors of treatment escalation (hazard ratio 1.07 and 1.09, respectively, with both p-values < 0.01). However, no score predicted risk of hospital admission, surgery or clinical/endoscopic relapse. The presence of moderate-to-severe small bowel (SB) inflammation, defined as a score of ≥9 on CE-CD, provided a hazard ratio of treatment escalation of 2.6 (95% confidence interval: 1.3-5.3). This cut-off provided the optimal sensitivity/specificity pair: 48.4%/89.3%. No interobserver misclassification among inflammation categories given by CE-CD were observed (kappa 100%).
Conclusion: CE-CD is a useful tool to document SB inflammation in children with CD. It correlates strongly with classical scores, can better predict need for treatment escalation and shows good interobserver agreement.
Objectives: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years of age with functional constipation (FC). This study evaluated the dose-response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2-5 years of age with FC.
Methods: In this phase 2, randomized, double-blind, placebo-controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72 μg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72 μg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded.
Results: Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72 μg group versus placebo. A dose-response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment-emergent AEs, one of which was treatment-related (mild diarrhea). All AEs were mild or moderate and none were severe.
Conclusions: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 μg versus placebo.
Objective: The objective of this study was to describe feeding practices and weight status in a cohort of children with congenital Zika syndrome (CZS) in northeastern Brazil.
Methods: This longitudinal study of children with CZS (N = 156) included data collection on child feeding practices and weight status at five timepoints between 2018 and 2022. The average age of the children was 32.1 months at enrollment and 76.6 months at the fifth assessment. Multilevel models, with repeated observations nested within children, were used to estimate time-related differences in each outcome.
Results: Use of enteral feeding, such as gastrostomy, increased from 19.2% to 33.3% over 4 years (p < .001). Among children who did not exclusively use an enteral feeding method, the percentage experiencing at least one dysphagia-associated behavior, such as coughing or gagging, increased from 73.9% to 85.3% (p = .030) while consuming liquids and from 36.2% to 73.5% (p = .001) while consuming solids. Based on weight-for-age z-scores, the percentage of children who were moderately or severely underweight increased from 42.5% to 46.1% over the 4 years but was not statistically significant. Children exclusively using an enteral feeding method had significantly decreased odds of being underweight at assessments 3, 4, and 5.
Conclusions: These data highlight the ongoing and increasing challenges of feeding young children with CZS. Our findings elucidate the physiological reasons children with CZS may be underweight and point to intervention targets, such as enteral feeding, to improve their feeding practices.