Fecal microbiota and volatile metabolome pattern alterations precede late-onset meningitis in preterm neonates.

OBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM. METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM. RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66). CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.

Sacral Neuromodulation Versus Conservative Treatment for Refractory Idiopathic Slow-transit Constipation: The Randomized Clinical No.2-Trial.

OBJECTIVE: Assess the effectiveness of sacral neuromodulation (SNM) versus personalized conservative treatment (PCT) in patients with refractory idiopathic slow-transit constipation (STC). BACKGROUND: Evidence on SNM for idiopathic STC is conflicting and of suboptimal methodological quality. METHODS: The No.2-Trial was a multicenter, open-label, pragmatic, randomized trial performed in 2 Dutch hospitals. Sixty-seven patients with idiopathic STC, a defecation frequency <3 per week and refractory (ie, unresponsive) to maximal conservative (nonoperative) treatment were included. Exclusion criteria included outlet obstruction, rectal prolapse, and previous colon surgery. Patients were randomized (3:2) to SNM (n=41) or PCT (n=26) with randomization minimization between February 21, 2017 and March 12, 2020. In SNM patients, an implantable pulse generator was implanted after a successful 4-week test stimulation. PCT patients received conservative treatment such as laxatives or retrograde colonic irrigation. The primary outcome was treatment success (defined as average defecation frequency ≥3 per week) after 6 months. Secondary outcomes included constipation severity, fatigue, quality of life, and adverse events. Analysis was according to intention-to-treat. RESULTS: After 6 months, 22 (53.7%) patients were successfully treated with SNM versus 1 (3.8%) patient with PCT (odds ratio 36.4, 95% CI 3.4-387.5, P =0.003). At 6 months, SNM patients reported lower constipation severity and fatigue scores ( P <0.001) and improved quality of life compared with PCT ( P <0.001). Eight serious adverse events (6 SNM, 2 PCT) and 78 adverse events (68 SNM, 10 PCT) were reported. CONCLUSIONS: SNM is a promising surgical treatment option in a homogeneous group of adults and adolescents with refractory idiopathic STC. No.2-Trial registered at ClinicalTrials.gov NCT02961582.

Effectiveness of strategies to suppress antibodies to infliximab in pediatric inflammatory bowel disease.

OBJECTIVES: Antibodies to infliximab (ATIs) are associated with loss of response in children with inflammatory bowel disease (IBD). We aimed to describe the effectiveness of strategies for treatment modification following ATI development in pediatric IBD: (1) treatment escalation; and (2) switching to another anti-TNF agent. METHODS: This multicenter retrospective study included children with IBD (4-18 years) on infliximab. Therapeutic drug monitoring (TDM) < 6 months and corticosteroid-free remission following each strategy were evaluated for low ATI titers (≤30 AU/mL) and high ATI titers (>30 AU/mL). RESULTS: Anti-infliximab antibodies were detected in 52/288 patients (18%) after a median of 15.3 months. Three of 52 ATI-positive patients were excluded due to alternative treatments. Of the remaining 49 patients, 19 had low titers and 30 had high titers. Of 19 low-ATIs, 16 (84%) underwent treatment escalation with infliximab (IFX). Of 13 patients with TDM available, seven (54%) achieved ATI suppression at subsequent TDM and 12 (92%) at any time point. Among 30 patients with high-ATIs, 17 (57%) continued with IFX; immunomodulators were started in seven patients. Of 14 patients with TDM, seven (50%) achieved ATI suppression at subsequent TDM and 10 (71%) at any time point. At 24 months of follow-up, 73% of low-ATI patients and 50% of high-ATI patients could continue with IFX without steroids. Thirteen of 30 high-ATI patients (43%) switched to another anti-TNF agent, of whom 54% and 46% had clinical response at 6 and 24 months, respectively. CONCLUSIONS: Dose optimization and/or adding an immunomodulator seem effective in suppressing low ATI titers. This strategy could also be considered in high ATI titers before switching.

Current practice in the care of children with functional constipation: What is the hold up?

OBJECTIVES: For children with intractable functional constipation (FC), there are no evidence-based guidelines for subsequent evaluation and treatment. Our objective was to assess the practice patterns of a large, international cohort of pediatric gastroenterologists. METHODS: We administered a survey to physicians who attended the 2nd World Congress of Pediatric Neurogastroenterology and Motility held in Columbus, Ohio (USA) in September 2023. The survey included 29 questions on diagnostic testing, nonpharmacological and pharmacological treatment, and surgical options for children with intractable FC. RESULTS: Ninety physicians from 18 countries completed the survey. For children with intractable FC, anorectal manometry was the most commonly used diagnostic test. North American responders were more likely than Europeans to use stimulant laxatives (97% vs. 77%, p = 0.032), prosecretory medications (69% vs. 8%, p < 0.001), and antegrade continence enemas (ACE; 83% vs. 46%, p = 0.009) for management. Europeans were more likely than North Americans to require colonic transit testing before surgery (85% vs. 30%, p < 0.001). We found major differences in management practices between Americans and the rest of the world, including use of prosecretory drugs (73% vs. 7%, p < 0.001), anal botulinum toxin injections (81% vs. 58%, p = 0.018), ACE (81% vs. 58% p = 0.018), diverting ileostomies (56% vs. 26%, p = 0.006), and colonic resections (42% vs. 16%, p = 0.012). No differences were found when respondents were compared by years of experience. CONCLUSIONS: Practice patterns in the evaluation and treatment of children with intractable FC differ widely among pediatric gastroenterologists from around the world. A clinical guideline regarding diagnostic testing and surgical decision-making is needed.

Age-dependent normal values for the 'Infant Gastroesophageal Reflux Questionnaire Revised'.

The Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) is used to score and evaluate gastroesophageal reflux (GER) related symptoms such as regurgitation, irritability and crying. A cut-off of ≥ 16 has been suggested to discriminate between GER and GER-disease. However, age-specific normal values were not assessed. Aim of this study was to determine age-specific normal values in healthy infants. Cross-sectional survey in healthy infants aged 0-24 months during their regular check-ups at well-baby clinics and through an online questionnaire using the I-GERQ-R. Infants with a history of (suspected) GER-disease were excluded. Spearman's correlation coefficient was calculated to explore age-related trends. A total of 979 healthy infants (47% male, median age 6 [0-24] months) were included. Median I-GERQ-R score, regardless of age, was 6 (range: 0-27). I-GERQ-R scores significantly decreased with age (rs = -0.569, p < 0.001). Of all infants, 49 (5%) had a score of ≥ 16 which previously has been considered 'suggestive of GER-disease'. Scores of ≥ 16 were most frequently seen in newborns aged 0-4 months (16% in 0-1 months to 4% in 3-4 months) and disappeared after the age of 16 months. High scores in the first months of life were caused by a high prevalence of regurgitation, colic-associated symptoms and hiccup frequency.  Conclusion: Age-dependent normal values for the I-GERQ-R show that reflux symptoms decrease in the first 24 months of life in healthy infants. Scores of ≥ 16 should not necessarily be considered abnormal in young infants. Validation as a diagnostic tool for GER-disease using age-appropriate normal values is needed. What is Known: • The Infant Gastro Esophageal Reflux Questionnaire Revised (I-GERQ-R) was developed to objectively score and evaluate GER-related symptoms in infants. • Previously a cut off of ≥ 16 has been suggested to differentiate between gastro esophageal reflux (GER) and GER-disease. What is New: • We present age-specific normal values of the I-GERQ-R in healthy infants. • I-GERQ-R scores clearly decrease with age and up to 16% of young healthy infants have a score that is above the previously suggested cut-off score of 16 for GER-disease.

Navigating through 65 years of insights: lessons learned on functional abdominal pain in children.

In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.

Infant gastroesophageal reflux disease management consensus.

AIM: Infant gastroesophageal reflux is mostly benign; however, when associated with complications like failure to thrive, it may be indicative of gastroesophageal reflux disease. There are currently several unmet needs pertaining to the management of infant gastroesophageal reflux (disease). Reflux in infants is mostly composed of breast milk or formula, so this population is significantly different to older children and adults. The objective of this Delphi consensus was to establish recommendations based on published literature and the experience of clinical experts in paediatric gastroenterology in the context of infant gastroesophageal reflux (disease). METHODS: The Delphi methodology was used to obtain a consensus on 18 statements relating to clinical aspects of infant gastroesophageal reflux (disease). RESULTS: The expert panel comprising paediatric gastroenterology clinical specialists reached a consensus for all statements by means of an online, anonymised voting system. CONCLUSION: It was highlighted that there is generally low awareness of or adherence to guidelines in clinical practice and that acid suppression therapy should not be indicated for non-acid reflux, which constitutes a significant proportion of total gastroesophageal reflux episodes among infants. Furthermore, it was emphasised that there is an unmet medical need for therapy for some symptomatic infants with non-acid reflux disease.

Functional gastrointestinal disorders, quality of life, and behaviour in adolescents with history of infant colic.

AIM: To assess the prevalence of functional gastrointestinal disorders (FGIDs), health-related quality of life (HRQOL), and behavioural problems in a cohort of adolescents with a history of infant colic (IC), as defined by Wessel's criteria. METHODS: 388 adolescents, aged 15-18 years, who participated in a randomised controlled trial for infants with colic, were invited for our observational follow-up study. Prevalence of FGIDs was assessed with the Rome IV Questionnaire on Paediatric Gastrointestinal Disorders (RIV-QPGD), HRQOL through self-report of the Paediatric Quality of Life Inventory (PedsQL), and behavioural problems through parent-report of the child behaviour checklist (CBCL). Multivariable models were used to compare prevalence rates of FGIDs and HRQOL scores. RESULTS: 190 (49%) adolescents with a history of IC (cases) and 381 controls were included (median age 17.0 [IQR 16.0-17.0] and 16.0 [15.0-17.0] years, respectively). Cases had a significantly higher risk for postprandial distress syndrome compared to controls (aOR 2.49 (95%CI 1.18-5.25), p = 0.002). After multivariable regression, total, physical and school HRQOL scores were significantly lower in cases compared to controls (p = 0.003, 0.001, and 0.009). CONCLUSION: Adolescents with a history of IC demonstrate higher prevalence rates of postprandial distress syndrome compared to controls. However, conclusions should be made with caution due to attrition and information bias.

Metabolome Changes With Diet-Induced Remission in Pediatric Crohn's Disease.

BACKGROUND & AIMS: The Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric CD. CDED+PEN is better tolerated and able to sustain remission. We characterized the changes in fecal metabolites induced by CDED+PEN and EEN and their relationship with remission. METHODS: A total of 216 fecal metabolites were measured in 80 fecal samples at week (W) 0, W6, and W12, of children with mild to moderate CD in a prospective randomized trial comparing CDED+PEN vs EEN. The metabolites were measured using liquid chromatography coupled to mass spectrometry. Metagenome Kyoto Encyclopedia of Genes and Genomes Orthology analysis was performed to investigate the differential functional gene abundance involved in specific metabolic pathways. Data were analyzed according to clinical outcome of remission (W6_rem), no remission (W6_nr), sustained remission (W12_sr), and nonsustained (W12_nsr) remission. RESULTS: A decrease in kynurenine and succinate synthesis and an increase in N-α-acetyl-arginine characterized CDED+PEN W6_rem, whereas changes in lipid metabolism characterized EEN W6_rem, especially reflected by lower levels in ceramides. In contrast, fecal metabolites in EEN W6_nr were comparable to baseline/W0 samples. CDED+PEN W6_rem children maintained metabolome changes through W12. In contrast, W12_nsr children in the EEN group, who resumed a free diet after week 6, did not. The metabolome of CDED+PEN differed from EEN in the purine, pyrimidine, and sphingolipid pathways. A significant differential abundance in several genes involved in these pathways was detected. CONCLUSION: CDED+PEN- and EEN-induced remission are associated with significant changes in inflammatory bowel disease-associated metabolites such as kynurenine, ceramides, amino acids, and others. Sustained remission with CDED+PEN, but not EEN, was associated with persistent changes in metabolites. CLINICALTRIALS: gov, Number NCT01728870.

The Use of Pictograms in the Evaluation of Functional Abdominal Pain Disorders in Children.

OBJECTIVE: To evaluate whether the use of pictograms improves symptom evaluation for children with functional abdominal pain disorders (FAPDs). STUDY DESIGN: This survey study was conducted in 2 academic centers and included patients aged 8-18 years visiting the outpatient clinic for FAPD symptom evaluation. Patients were randomized to fill out the questionnaire without or with accompanying pictograms to assess gastrointestinal symptoms. Afterwards, patients underwent clinical health assessment by the healthcare professional (HCP). Subsequently, the HCP filled out the same questionnaire without pictograms, while blinded to the questionnaire completed by the patient. Primary outcome was the level of agreement between identified symptoms as assessed by patients and HCP. RESULTS: We included 144 children (questionnaire without accompanying pictograms [n = 82] and with accompanying pictograms [n = 62]). Overall agreements rates were not significantly different (without pictograms median, 70% vs with pictograms median, 70%). Accompanying pictograms did not significantly improve the assessment of abdominal pain symptoms. Accompanying pictograms were beneficial for concordance rates for nausea and vomiting symptoms (without pictograms median, 67% vs with pictograms median, 100%; P = .047). Subgroup analyses for children aged 8-12 years of age revealed similar results (concordance on the presence of nausea and vomiting without pictograms median, 67% vs with pictograms median, 100%; P = .015). Subgroup analyses for children ages 12-18 years showed no significant differences in concordance rates. CONCLUSIONS: Pictograms do not seem to improve the assessment of FAPDs. However, the use of pictograms improves the evaluation of nausea and vomiting, especially for children aged 8-12 years. Therefore, HCPs could consider using pictograms in that setting during consultations.

What are Normal Defecation Patterns in Healthy Children up to Four Years of Age? A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize available data on defecation frequency and stool consistency of healthy children up to age 4 in order to estimate normal references values. STUDY DESIGN: Systematic review including cross-sectional, observational, and interventional studies published in English, that reported on defecation frequency and/or stool consistency in healthy children 0-4 years old. RESULTS: Seventy-five studies were included with 16 393 children and 40 033 measurements of defecation frequency and/or stool consistency. Based on visual inspection of defecation frequency data, a differentiation was made between two age categories: young infants (0-14 weeks old) and young children (15 weeks-4 years old). Young infants had a mean defecation frequency of 21.8 per week (95 % CI, 3.9-35.2) compared with 10.9 (CI, 5.7-16.7) in young children (P < .001). Among young infants, human milk-fed (HMF) infants had the highest mean defecation frequency per week (23.2 [CI, 8.8-38.1]), followed by formula-fed (FF) infants (13.7 [CI 5.4-23.9]), and mixed-fed (MF) infants (20.7 [CI, 7.0-30.2]). Hard stools were infrequently reported in young infants (1.5%) compared with young children (10.5%), and a reduction in the frequency of soft/watery stools was observed with higher age (27.0% in young infants compared with 6.2% in young children). HMF young infants had softer stools compared with FF young infants. CONCLUSIONS: Young infants (0-14 weeks old) have softer and more frequent stools compared with young children (15 weeks-4 years old).

Phase III Randomized Non-Inferiority Study of OSS Versus PEG + Electrolyte Colonoscopy Preparation in Adolescents.

OBJECTIVES: Many protocols and preparations are used for bowel cleansing before pediatric colonoscopy but few are based on scientific evidence. We evaluated efficacy, safety, tolerability, and patient preference of oral sulfate solution (OSS) at 75% of the adult dose versus polyethylene glycol (PEG)-electrolyte solution in adolescents presenting for diagnostic colonoscopy. METHODS: Phase III, randomized, evaluator-blinded, non-inferiority study of OSS and PEG in adolescents aged 12-17 years. OSS and PEG were administered in 2 doses on the day before colonoscopy. Primary endpoint included proportion of patients with successful overall preparation (4-point scale). Secondary endpoints included overall and segmental bowel cleansing (Boston Bowel Preparation Scale; BBPS), completed colonoscopies, duration of examination, time to cecal intubation, proportion of nasogastric tubes (NGTs), adverse events (AEs) and acceptability. RESULTS: Successful cleansing was achieved in 71.4% and 79.0% of patients receiving OSS and PEG, respectively [adjusted difference -7.61 (95% confidence interval, CI, -18.45 to 3.24); P = 0.0907]. Segmental BBPS score for the left and transverse colon were similar between treatment groups, but better for the right colon with PEG than OSS [2.2 (95% CI, 2.0-2.4) and 1.9 (95% CI, 1.7-2.1), respectively; P = 0.0015]. Significantly fewer OSS patients needed NGT placement to ingest the whole solution [9/125 (7.2%)] than PEG patients [36/116 (31.0%); P < 0.0001]. Treatment acceptability was significantly higher with OSS than PEG ( P < 0.0001). Duration of examination, completed colonoscopies, and time to cecal intubation were similar between preparations. Gastrointestinal AEs including nausea, vomiting, abdominal pain, and distension were similar in both groups but more patients receiving PEG had AEs assessed as incapacitating. CONCLUSIONS: Non-inferiority of OSS to PEG was not demonstrated, but OSS was associated with a lower requirement for NGT, better acceptability, and less frequent severe AEs than with PEG.

Safety of Accelerated Infliximab Infusions in Children With Inflammatory Bowel Disease: A Retrospective Cohort Study.

OBJECTIVES: Accelerated infliximab (IFX) infusions have shown to be safe in adults with inflammatory bowel disease (IBD), but data on its safety in pediatric IBD is limited. This study aimed to assess the incidence and timing of infusion reactions (IR) in children with IBD who received accelerated (1-h) versus standard (2-h) IFX infusions. METHODS: This retrospective cohort study included IBD patients 4-18 years of age and initiated IFX between January 2006 and November 2021 at Amsterdam University Medical Centre, location Academic Medical Centre (AMC) and VU Medical Centre (VUmc). The AMC protocol was adjusted in July 2019 from standard to accelerated infusions with 1-h intrahospital post-infusion observation period, whereas in VUmc only standard infusions were administered without an observation period. After merging the departments in 2022, all VUmc patients were allocated to the accelerated infusions (AMC) protocol. Primary outcome was the incidence of acute IR among maintenance accelerated versus standard infusions. RESULTS: Totally, 297 (150 VUmc, 147 AMC) patients (221 Crohn disease; 65 ulcerative colitis; 11 IBD-unclassified) with cumulative n = 8381 IFX infusions were included. No statistically significant difference in the per-infusion incidence of IR was observed between maintenance standard infusions (26/4383, 0.6% of infusions) and accelerated infusions (9/3117, 0.3%) ( P = 0.33). Twenty-six of 35 IR (74%) occurred during the infusion, while 9 occurred post-infusion (26%). Only 3 of 9 IR developed in the intrahospital observation period following the switch to accelerated infusions. All post-infusion IR were mild, requiring no intervention or only oral medication. CONCLUSIONS: Accelerated IFX infusion without a post-infusion observation period for children with IBD seems a safe approach.

Prevalence and Risk Factors of Functional Gastrointestinal Disorders: A Cross-Sectional Study in Italian Infants and Young Children.

OBJECTIVES: Reports of prevalence of functional gastrointestinal disorders (FGIDs) in infants/toddlers are widely variable. Reasons for this variability are not yet fully understood. The objective of this study is to estimate the prevalence of FGIDs according to Rome IV criteria and to evaluate associated factors, in Italian infants and toddlers. METHODS: Subjects aged 0-48 months were enrolled by general pediatricians from 3 Italian regions. Parents or legal guardians were administered questionnaires including information about the child, the family, and GI symptoms according to Rome IV criteria. RESULTS: Five hundred eight infants aged 0-12 months [mean age 4.4 ± 3.4 months; females (F) 40.9%], and 268 children aged 13-48 months (mean age 30.8 ± 10.7 months; F 44.4%) were included. In infants, prevalence of FGIDs was 21.1%, and the most prevalent FGID was infant colic (9.3%). In toddlers, prevalence of FGIDs was 19.6%, with functional constipation being the most frequent disorder (16.1%). In infants, multivariable analysis found that being older, being the only child, and living in a rural environment were associated with a lower rate of FGIDs. Prevalence was, in contrast, higher in infants fed with formula. CONCLUSIONS: One out of 5 Italian infants and young children is affected by at least 1 FGID. The most frequent FGID in infants is infant colic, while in toddlers this is functional constipation. In infants, prevalence of FGIDs is lower if the subject has no siblings, and in children living in a rural environment, while formula feeding represents a risk factor for FGIDs occurrence.

Do Polymorphisms Predict Hypnotherapy Response in Children With Functional Abdominal Pain Disorders: An Explorative Study.

Genetic variations, in specific COMT , OPRM1 , and MAO-A polymorphisms, have been associated with hypnotizability in adults. The aim of this exploratory study was to investigate whether these polymorphisms are also associated with response to hypnotherapy (HT) in children. Patients (8-18 years, n = 260) diagnosed with a functional abdominal pain disorder (FAPD) from a previous trial assessing HT efficacy were approached for participation and 144 agreed to collect a buccal sample. Primary aim was to explore the association between COMT , OPRM1 , and MAO-A polymorphisms with treatment success (TS) after 3-month HT. Additionally, associations between these polymorphisms and adequate relief, anxiety, depression, quality of life, somatization, hypnotic susceptibility, expectations, pain beliefs, and coping strategies were evaluated. Participants with different variations of COMT , MAO-A , and OPRM1 achieved similar TS levels ( P > 0.05). No associations were found between these polymorphisms and secondary outcomes. This suggest that in pediatric patients with FAPDs, COMT , OPRM1 , and MAO-A polymorphisms do not predict HT response.

Hypnotherapy in Pediatric Gastroenterology.

In several countries, gut-directed hypnotherapy is becoming an established and evidence-based treatment in pediatric gastroenterology. This article describes what hypnotherapy is, offers an overview of its effect in gut-brain disorders and explains its potential mode of action. Moreover, the use of hypnotherapy in other areas of pediatric gastroenterology, as a supportive tool to reduce pain, stress, depression, and anxiety and improve quality of life, will be also discussed. Guidance toward implementing hypnotherapy in clinical practice is provided, including examples of how you can explain hypnosis to patients with gastroenterological symptoms.

Accuracy of Anorectal Manometry to Detect the Rectoanal Inhibitory Reflex in Children: Awake Versus Under General Anesthesia.

OBJECTIVES: Our objective was to investigate if there is a difference in the detection of the rectoanal inhibitory reflex (RAIR) when an anorectal manometry (ARM) is performed awake or under general anesthesia. METHODS: A retrospective review of ARM studies was performed to identify children who had undergone ARMs both while awake and under general anesthesia. We compared ARM outcomes including the detection of the RAIR and anal canal resting pressure. RESULTS: Thirty-four children had received ARMs both while awake and under general anesthesia (53% female, median age at first ARM 7.5 years [range 3-18 years]). In 9 of 34 (26%) children the RAIR was solely identified during ARM under general anesthesia and not during ARM while awake. In 6 of 9 (66%) this was unrelated to the balloon volumes used during balloon inflations. In 4 of 34 (12%) children, assessment of the RAIR was inconclusive during ARM under general anesthesia due to too low, or loss of anal canal pressure. In 2 of those children, ARMs while awake showed presence of a RAIR. Anal canal resting pressures were higher during ARM while awake versus ARM under general anesthesia (median 70 [interquartile range, IQR 59-85] vs 46 mmHg [IQR 36-65] respectively, P < 0.001). CONCLUSIONS: General anesthesia may affect the detection of a RAIR in 2 ways. On the one hand, it may facilitate better visualization in children in whom a RAIR could not be visualized while awake. On the other hand, it may cause a loss of anal canal pressure resulting in an inconclusive test result.

Drugs in Focus: Domperidone.

Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication ("off label") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an "off label/on evidence" prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.

Pediatric Magnet Ingestion, Diagnosis, Management, and Prevention: A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Position Paper.

Magnet ingestion is a special category of foreign body ingestion associated with high levels of morbidity and mortality worldwide, particularly if it is associated with staggered ingestion of multiple magnets or with simultaneous ingestion of other metallic foreign bodies, especially button batteries. A special category of magnet ingestion is the ingestion of earth magnets, which have higher levels of magnetism and therefore, potentially, carries a worse outcome. Legislative bodies, scientific Societies and community-led initiatives have been implemented worldwide with the aim of mitigating the effects of this growing, yet avoidable potential medical emergency. A scoping literature review summarized epidemiology, diagnosis, management, and prevention, including an algorithm for the diagnosis and management of magnet ingestion is presented and compared to previously published reviews and position papers (North American Society of Pediatric Gastroenterology, Hepatology and Nutrition, National Poison Center, Royal College of Emergency Medicine). The main emphasis of the algorithm is on identification of staggered/multiple magnet ingestion, and early joint gastroenterology and surgical consultation and management.

Long-Term Outcomes of Antegrade Continence Enemas to Treat Constipation and Fecal Incontinence in Children.

OBJECTIVES: The objective of this study is to investigate long-term outcomes of antegrade continence enema (ACE) treatment in children with constipation or fecal incontinence. METHODS: Prospective cohort study including pediatric patients with organic or functional defecation disorders who started ACE treatment. Data were collected at baseline and at follow-up (FU) from 6 weeks until 60 months. We assessed parent and patient-reported gastrointestinal health-related quality of life (HRQoL) using the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Module (PedsQL-GI), gastrointestinal symptoms, adverse events, and patient satisfaction. RESULTS: Thirty-eight children were included (61% male, median age 7.7 years, interquartile range 5.5-12.2). Twenty-two children (58%) were diagnosed with functional constipation (FC), 10 (26%) with an anorectal malformation, and 6 (16%) with Hirschsprung disease. FU questionnaires were completed by 22 children (58%) at 6 months, 16 children (42%) at 12 months, 20 children (53%) at 24 months, and 10 children (26%) at 36 months. PedsQL-GI scores improved overall with a significant increase at 12- and 24-month FU for children with FC and a significant increase in parent reported PedsQL-GI score at 36-month FU for children with organic causes. Minor adverse events, such as granulation tissue, were reported in one-third of children, and 10% of children needed a surgical revision of their ACE. The majority of all parents and children reported that they would "probably" or "definitely" choose ACE again. CONCLUSION: ACE treatment is perceived positively by patients and parents and can lead to long-term improvement in gastrointestinal HRQoL in children with organic or functional defecation disorders.