Sex-Dependent Efficacy of Dietary Fiber in Pediatric Functional Abdominal Pain.

BACKGROUND & AIMS: Functional abdominal pain disorders (FAPDs) are more prevalent in female patients. Dietary fiber may alleviate FAPD symptoms; however, whether this effect is sex dependent remains unclear. We investigated the sex dependency of dietary fiber benefit on abdominal pain in children with FAPDs and explored the potential involvement of the gut microbiome. METHODS: In 2 cross-sectional cohorts of children with FAPDs (n = 209) and healthy control individuals (n = 105), we correlated dietary fiber intake with abdominal pain symptoms after stratifying by sex. We also performed sex-stratified and sex-interaction analyses on data from a double-blind trial in children with irritable bowel syndrome randomized to psyllium fiber (n = 39) or placebo (n = 49) for 6 weeks. Shotgun metagenomics was used to investigate gut microbiome community changes potentially linking dietary fiber intake with abdominal pain. RESULTS: In the cross-sectional cohorts, fiber intake inversely correlated with pain symptoms in boys (pain episodes: r = -0.24, P = .005; pain days: r = -0.24, P = 0.004) but not in girls. Similarly, in the randomized trial, psyllium fiber reduced the number of pain episodes in boys (P = .012) but not in girls. Generalized linear regression models confirmed that boys treated with psyllium fiber had greater reduction in pain episodes than girls (P = .007 for fiber × sex × time interaction). Age, sexual development, irritable bowel syndrome subtype, stool form, and microbiome composition were not significant determinants in the dietary fiber effects on pain reduction. CONCLUSIONS: Dietary fiber preferentially reduces abdominal pain frequency in boys, highlighting the importance of considering sex in future dietary intervention studies for FAPDs. (ClincialTrials.gov, Number NCT00526903).

Achieving Enteral Autonomy in Children with Intestinal Failure Following Inpatient Admission: A Case Series.

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition after admission. Admissions included feeding and medication titration, interdisciplinary care, and a home parenteral nutrition team consultation.

Effect of cognitive-behavior therapy for children with functional abdominal pain: a meta-analysis.

BACKGROUND: Cognitive-Behavior Therapy (CBT) is the validated non-pharmacological treatment for chronic pain in pediatric patients. While some suggested CBT were comparable to the usual care in reducing children's functional abdominal pain. This meta-analysis was designed to systematically review the literature for RCTs that investigated the efficacy of CBT in children with functional abdominal pain (FAP). METHODS: PubMed, Embase, and the Cochrane library were searched for papers published up to October 2022. Studies applying different CBT delivery methods (in-person, web-based, phone-based) were included in this meta-analysis to evaluate the comprehensive effectiveness of CBT compared with usual care. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcome was the decrease of functional disability inventory (FDI) and the secondary outcomes were the decrease of severity in pain intensity, depression, anxiety, gastrointestinal symptoms, and improvement in physical quality of life (QoL). RESULTS: A total of 10 RCTs with 1187 children were included in the final analysis. The results showed that CBT resulted in better effect in reducing functional disability inventory (SMD=-2.282, 95%CI: -4.537 to -0.027, P = 0.047), pain intensity (SMD=-0.594, 95%CI: -1.147 to -0.040, P = 0.036), and improving QoL (SMD = 14.097, 95%CI: 0.901 to 27.292, P = 0.036) compared with the control groups. Comparable effects were observed in the severity of depression (SMD=-0.493, 95%CI: -1.594 to 0.608, P = 0.380), anxiety (SMD=-0.062, 95%CI: -0.640 to 0.517, P = 0.835), and gastrointestinal symptoms (SMD=-1.096 95%CI: -2.243 to 0.050, P = 0.061) between CBT and usual treatment. CONCLUSIONS: We observed the differences in post-treatment FAP and pain intensity for children receiving CBT compared with children receiving treatment as usual. CBT in the setting of FAP demonstrates promising developments and highlights the need for future research.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). METHODS: Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. RESULTS: A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). CONCLUSION: Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

Transitions of care for adolescents with disorders of gut-brain interaction.

OBJECTIVES: Little is known about the experience of adolescents and young adults (AYA) with disorders of gut-brain interaction (DGBI) who transition from pediatric to adult gastroenterology care. In this two-part study, we used quantitative and qualitative methods to: (1) assess incidence of optimal versus suboptimal transitions of care for AYA with DGBI, (2) characterize health and quality of life effects of the transition, and (3) identify barriers and facilitators for optimal transition of care. METHODS: In Part 1, we conducted a retrospective review of AYA referrals to our adult neurogastroenterology clinic who had transitioned from pediatric gastroenterology care (N = 109, 17-23 years, 72% female). We collected demographic, psychosocial, and healthcare utilization data to determine rate and risk factors for suboptimal transitions. In Part 2, we recruited 24 AYA and parents (n = 19 AYA, n = 5 parents) for completion of a survey and semistructured interview, which was analyzed using validated rapid qualitative analysis method. RESULTS: In Part 1, 20% (22/109) of AYA met the criteria for suboptimal transition of care, which was associated with treatment adherence concern and functional impairment. In Part 2, we identified two principal themes: (1) AYA's health and quality of life are impacted during the transition, and (2) parental involvement and collaboration with pediatric gastrointestinal (GI) are facilitators to successful transitions, whereas access to care and practice style change are barriers. CONCLUSION: AYA with DGBI have high rates of suboptimal care transitions, affecting their health and quality of life. Our study highlights the need for a comprehensive approach that incorporates parents and pediatric providers.

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.

Probiotics in Functional Gastrointestinal Disorders.

The most frequent functional gastrointestinal disorders (FGID) in children include infantile colic, constipation, functional abdominal pain (FAP), and irritable bowel syndrome (IBS). Unfortunately, treatment options for FGID in children are limited, therefore many dietary interventions have been evaluated, including probiotics. This chapter summarizes currently available evidence and recommendations for probiotic use in the treatment of frequent FGIDs in children. The strongest evidence exists for the use of Limosilactobacillus (L.) reuteri DSM 17938 and Bifidobacterium animalis subsp. lactis BB-12 for the treatment of infantile colic in breastfed infants. Limited but yet encouraging evidence exists for Lacticaseibacillus rhamnosus GG (LGG) for the treatment of IBS and L. reuteri DSM 17938 for FAP.

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.

Functional abdominal pain disorders in children in southern Anhui Province, China are related to academic stress rather than academic performance.

BACKGROUND: Functional abdominal pain disorders (FAPDs) are one of the most common gastrointestinal disorders in children. The aim of this study was to investigate the prevalence of FAPDs in children in southern Anhui Province, China and their association with academic stress. METHODS: In this cross-sectional survey, we randomly selected children aged 6-17 years from 11 public schools in southern Anhui Province. FAPDs were diagnosed according to the Rome IV criteria, and a custom-designed questionnaire was used to investigate the association between academic stress and FAPDs in children. RESULTS: A total of 2,344 children aged 6-17 years were enrolled. The mean age was 12.4 ± 3.0 years. Of these children, 335 (14.3%) were diagnosed with FAPDs according to the Rome IV criteria. Among the children with FAPDs, 156 (46.6%) were boys, and 179 (53.4%) were girls. The prevalence was higher in girls than in boys. The most common disorder was irritable bowel syndrome (IBS) (n = 182 (7.8%)). Other types of FAPDs included functional abdominal pain-not otherwise specified (FAPNOS) (n = 70 (3.0%)), functional dyspepsia (FD) (n = 55 (2.3%)), and abdominal migraine (AM) (n = 28 (1.2%)). Academic stress, not meeting parental expectations, poor relationships with parents, and sleep disturbances were independent risk factors for FAPDs in children; academic performance was not associated with the development of FAPDs. CONCLUSION: There was a high prevalence of FAPDs among children in southern Anhui Province, China, and IBS was the most common subtype of functional abdominal pain. Academic stress, rather than academic performance, was associated with FAPDs in children.

Randomised controlled trial of melatonin for paediatric functional abdominal pain disorders.

AIM: Melatonin seems to have a positive impact on the brain-gut axis and many direct and indirect effects on the gastrointestinal tract. This trial aimed at assessing the efficacy of melatonin combined with Lactobacillus Rhamnosus GG given in the treatment of paediatric patients with functional abdominal pain disorders. METHODS: Forty-two patients aged 4-18 years old who fulfilled the Rome IV Diagnostic Criteria for functional abdominal pain disorders were enrolled. Melatonin 3 or 5 mg in combination with Lactobacillus Rhamnosus GG (group 1, n = 22) or a placebo in combination with Lactobacillus Rhamnosus GG (control group, n = 20) were taken in the evening for a period of 4 weeks. The study duration was 12 weeks. The primary study endpoint was represented by clinical improvement at week 12 - defined as at least a 50% reduction in mean abdominal pain index (API) from baseline to week 12. RESULTS: The mean API was reduced by more than 50% between T0 and T2 in the group of children treated with melatonin. However, the difference in the distributions of the variations of the scores between the two groups was not significant between T0 and T2 (P = 0.082), while it was significant between T0 and T1 (P = 0.001). Similar results were obtained by analysing the API variables 'weekly frequency of pain' (item 1) and 'perceived intensity of pain' (item 4) individually. CONCLUSIONS: This is the first study to investigate the role of the combination of melatonin and Lactobacillus Rhamnosus GG in the treatment of children with functional abdominal pain disorders. Melatonin combined with Lactobacillus Rhamnosus GG can be considered a therapeutic option for these conditions in children.

A systematic review and meta-analysis of randomized control trials: efficacy of cognitive behavioral therapies for the management of functional and recurrent abdominal pain disorders in children and adolescents.

Cognitive behavioral therapy (CBT) is effective for pain relief in children and adolescents with functional abdominal pain disorders (FAPDs). However, few studies have focused on the FAPDs specifically and the medium-term or long-term results of CBT. In this meta-analysis, we investigated the efficacy of CBT in pediatric FAPDs and unclassified chronic or recurrent abdominal pain (CAP and RAP, respectively). We searched the PubMed, Embase, and Cochrane Library databases for related randomized controlled trials until August 2021. Eventually, 10 trials with 872 participants were included. The methodological quality of the studies was assessed, and data on two primary and four secondary outcomes of interest were extracted. We used the standardized mean difference (SMD) to measure the same outcome, and precisions of effect sizes were reported as 95% confidence intervals (CIs). We found that CBT had significantly positive effects on reducing pain intensity immediately (SMD: -0.54 [CI: -0.9, -0.19], p = 0.003), 3 months after the intervention (SMD: -0.55; [CI: -1.01, -0.1], p = 0.02) and 12 months after the intervention (SMD: -0.32; [CI: -0.56, -0.08], p = 0.008). CBT also reduced the severity of gastrointestinal symptoms, depression, and solicitousness, improved the quality of life and decreased the total social cost. Future studies should consider uniform interventions in the control group and comparing different CBT delivery methods.

Efficacy of amitriptyline in pediatric functional abdominal pain disorders: A randomized placebo-controlled trial.

BACKGROUND AND AIM: Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the efficacy of amitriptyline in pediatric FAPD. METHODS: In this open-label trial, children (≤ 18 years) diagnosed as FAPD based on ROME IV criteria were randomized to amitriptyline or placebo for 12 weeks. Post-treatment improvement of pain and quality of life (QOL) from the baseline were compared between the two groups. RESULTS: The mean age of 149 children (amitriptyline 75, placebo 74) was 11.3 ± 3.5 years (79 boys). There was a significant difference in pain improvement in terms of reduction in scores for intensity (3.4 vs 0.9), frequency (3.6 vs 0.6), duration (3.5 vs 0.9), and QOL (2.3 vs 0.9) between amitriptyline and placebo group (P < 0.001 in all). Responders (> 50% reduction) in pain was seen in 76% in amitriptyline compared with 14.9% in the placebo group (P < 0.001). On multivariate analysis, the use of amitriptyline was the only factor predictive of response (odds ratio 24.1, 95% confidence interval: 9.1-64.6, P < 0.001). Minor adverse events were comparable between the groups (25.3% vs 13.5%, respectively, P = 0.07). Eighty-nine percent of children (24/27) who had extended treatment duration (6.8 ± 1.8 months) had pain improvement. After discontinuation of amitriptyline, 70% had sustained response over a mean follow up of 15.84 ± 5.6 months. CONCLUSIONS: A 3-month trial of amitriptyline gives sustained relief of pain in two-thirds of children with FAPD. The safety profile of the drug and its efficacy necessitate more frequent use in the clinical settings.

Place and Pain: Association Between Neighborhood SES and Quantitative Sensory Testing Responses in Youth With Functional Abdominal Pain.

OBJECTIVE: Neighborhood socioeconomic status (SES) is linked to self-reported pain severity and disability but its association with evoked pain responsiveness in individuals with chronic pain remains unclear. The present study examined relations between neighborhood SES, assessed through the area deprivation index (ADI), and static and dynamic pain response indices. It was hypothesized that youth with functional abdominal pain (FAP) living in lower SES neighborhoods would exhibit lower pain threshold, lower pain tolerance, and reduced conditioned pain modulation (CPM) compared to youth living in higher SES neighborhoods. METHODS: Participants were 183 youth with FAP and their parents. Youth completed a quantitative sensory testing protocol. Family addresses were used to compute ADI scores. Thermal stimuli for pain threshold and tolerance were delivered to participants' forearms using thermodes. CPM, an index of descending pain inhibition, was determined using a thermode as test stimulus and a hot water bath as conditioning stimulus. RESULTS: As hypothesized, youth with FAP living in lower SES neighborhoods exhibited weaker CPM. Contrary to hypotheses, lower neighborhood SES was associated with neither pain thresholds nor with pain tolerance. CONCLUSIONS: These findings demonstrated the independent contribution of place of residence-an often neglected component of the biopsychosocial model-to efficiency of descending pain inhibition. Understanding the mechanisms that account for such associations between place and pain could guide the development of public health and policy initiatives designed to mitigate chronic pain risk in underserved and economically marginalized communities.

Sex Moderates the Relationship Between Nausea Severity and Heart Rate Variability in Adolescents and Young Adults.

BACKGROUND: Nausea is a common complaint among children and is particularly prevalent in children with functional abdominal pain (FAP), with nearly half of children with FAP also endorsing nausea. Dysfunction of the autonomic nervous system, which can be indexed by heart rate variability (HRV), leads to abnormalities in gastric electrical activity that are associated with GI symptoms. AIMS: To evaluate that relationship between nausea severity and HRV in adolescents and young adults with a history of FAP and to assess for sex differences. METHODS: Participants were pediatric patients with a diagnosis of FAP who were recruited from a pediatric GI clinic between 1993 and 2007 for a prospective study of the course of FAP. Study analyses focused on the cross-sectional relationship between HRV, indexed by standard deviation of the R-R interval (SDRRI) and high-frequency (HF) power, and nausea severity collected during a follow-up visit in late adolescence and young adulthood. RESULTS: Controlling for age and BMI, a significant nausea by sex interaction emerged for both SDRRI and HF power. Tests of conditional effects of nausea by sex showed that the inverse relation between nausea severity and both SDRRI and HF was significant for females but not for males. CONCLUSIONS: This is the first study to evaluate the relationship between nausea severity and HRV. Greater nausea severity was associated with lower HRV in females but not in males. Further validation of these results may provide insight into novel treatment approaches for females with nausea that target vagal tone.

Prevalence of functional abdominal pain disorders and functional constipation in adolescents.

AIM: Functional abdominal pain disorders (FAPDs) and functional constipation (FC) are the common functional gastrointestinal disorders in adolescents. We aimed to determine the prevalence of FAPDs and FC in adolescents using the Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms and the factors associated with these two functional gastrointestinal disorders. METHODS: A survey for the prevalence of FAPDs and FC in adolescents was carried out at two high schools. A translated and validated Thai version of Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms was used. Potential associated factors were also collected. Psychosocial problems were evaluated by using the Strengths and Difficulties Questionnaire. RESULTS: A total of 1700 adolescents (55.5% females) with a mean age (SD) of 16.1 (0.9) years were enrolled. The prevalence of FAPDs and FC was 5.3% and 8.1%, respectively. The subtypes of FAPDs were functional dyspepsia (4.7%; postprandial distress syndrome 3.9% and epigastric pain syndrome 0.8%), irritable bowel syndrome (0.6%), abdominal migraine (0.4%) and functional abdominal pain not otherwise specified (0.3%). Multiple logistic regression analysis revealed that FAPDs were associated with female gender (odds ratio (OR) 3.3, 95% confidence interval (CI): 1.7-6.4), underlying allergic diseases (OR 3.2, 95% CI: 1.6-6.6) and concomitant emotional problem (OR 2.7, 95% CI: 1.2-5.9). No significant associated factors with FC were found. CONCLUSION: FAPDs and FC are common in adolescents. Postprandial distress syndrome is the most common subtype of FAPD. Associated factors for FAPDs may suggest hormonal, immune-related and psychological involvement in the disease pathogenesis.

Altered tryptophan metabolism in patients with recurrent functional abdominal pain.

The causes of functional abdominal pain are still unclear. The role of food factors in their pathogenesis has been assessed by many researches, but the obtained results are varied. AIM: The aim of present study was to evaluate metabolism of tryptophan, which is substrate for serotonin synthesis and other bioactive compounds, in patients with recurrent functional abdominal pain. MATERIALS AND METHODS: Thirty patients with recurrent abdominal pain and 30 healthy subjects were enrolled in this study. Urinary levels of tryptophan (TRP), 5-hydroxyindoleacetic acid(5-HIAA), L-kynurenine (KYN), xanthurenic acid(XA), and quinolinic acid(QA) were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS), and related to creatinine level (mg/gCr), during active phase(day with acute pain), and silence period, which recommended optimalisation of tryptophan intake. RESULTS: 5-HIAA/TRP ratio and KYN/TRP ratio as well as QA level s were significantly higher in patients compared to control group (p<0.001). After reducing TRP consumption, the above results improved, in particular, the level of QA decreased from 6.88±1.04 mg/Cr to 4,32±0.97 mg/gCr (p<0.001). CONCLUSIONS: Altered tryptophan metabolism may affect locally-andcentrally mediated recurrent functional abdominal pain.

Hyperuricosuria and hypercalciuria, probable etiologies of functional abdominal pain: A case-control study.

Background: Functional abdominal pain (FAP) is a common complaint causing several referrals to pediatricians. On the other hand, the most common presentation of hyperuricosuria and also hypercalciuria is chronic/recurrent abdominal pain. Therefore, a hypothesis has been raised; abdominal pain due to hyperuricosuria and/or hypercalciuria may be misdiagnosed as FAP. The current study has aimed to respond to this theory. Materials and Methods: This is a case-control study conducted on children diagnosed with FAP based on Rome IV criteria and age-matched normal controls. Blood and random urine samples were taken from healthy children and those with FAP. Random urine samples were examined for calcium, uric acid, oxalate, and creatinine concentrations. Random urine calcium to urine creatinine above 0.2 mg/mg was considered hypercalciuria and random urine uric acid above 0.56 mg/dl, GFR as hyperuricosuria. The data were analyzed using logistic models. Results: Hypercalciuric children had a significantly lower chance of FAP (odds ratio [OR] =0.425, 95% confidence interval [CI] =0.204-0.886). Although an inverse association was seen between hyperuricosuria and FAP (OR = 0.693, 95% CI = 0.395-1.214), it was not statistically significant. In stratified analyses by gender for both hyperuricosuria and hypercalciuria, a marginal inverse significant association was seen in male gender (P < 0.1). Conclusion: Our study showed that hypercalciuria is significantly in inverse association with FAP but not hyperuricosuria. Therefore, these disorders, particularly hyperuricosuria may not be considered as the possible causes of FAP. Further studies with larger sample size for providing more reliable evidence are recommended.

Activation of the Innate Immune System in Children With Irritable Bowel Syndrome Evidenced by Increased Fecal Human ß-Defensin-2.

BACKGROUND & AIMS: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of ß-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation. METHODS: Fecal ß-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care. RESULTS: ß-defensin-2 concentration was greater in children with IBS (P = .003) and FAP (P = .03) than in HCs. ß-defensin-2 was greater in girls with IBS than female HCs (P = .007) and in girls with IBS vs boys with IBS (P = .036). There was no difference by sex in the FAP and HC groups. For the entire cohort, ß-defensin-2 correlated with multiple pain symptoms. In the IBS group, ß-defensin-2 correlated with pain interference (P = .014). No correlation with pain was found in the FAP or HC group. Gut permeability was greater in the IBS vs the FAP and HC groups (P = .038). For the entire cohort, permeability correlated with the number of pain episodes (P = .041) and interfering pain episodes (P = .049). For the entire cohort there was a correlation between ß-defensin-2 and permeability (P = .003), with borderline correlation in the IBS group (P = .086). For the cohort and IBS and HC groups, the number of bowel movements was modestly inversely related to fecal ß-defensin-2 concentrations. CONCLUSIONS: Increased fecal ß-defensin-2 concentration in children with IBS suggests activation of the innate immune system in some, which, along with increased gut permeability, appears related to abdominal pain symptoms. Sex is an important variable in interpreting ß-defensin-2 concentration in children with IBS.

Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years-a birth cohort study.

BACKGROUND: Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular. METHOD: Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1-2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals. RESULTS: The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1-2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05). CONCLUSIONS: This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders.

The growing gap between demand and availability of clinical psychology in Paediatric Gastroenterology: a retrospective analysis of clinical routine care.

Clinical psychology intervention in paediatric gastroenterology is vital given the biopsychosocial aetiology of paediatric functional gastrointestinal disorders, and the psychological impact of chronic conditions. The aim was to assess the availability and benefit of clinical psychology in paediatric gastroenterology across the UK and Germany. A retrospective assessment of referrals (n = 936 referrals) to clinical psychology was performed at our tertiary paediatric gastroenterology centre between 2010 and 2018. The availability of clinical psychologists and outcome of psychology intervention for children with functional abdominal pain were also assessed. Access to clinical psychology across the UK and Germany was assessed using an online questionnaire. We observed a substantial rise in the number of clinical psychology referrals between 2010 and 2018. Increasing demand was not matched by sufficient increase in availability of clinical psychology, leading to longer waiting times. A major benefit of clinical psychology intervention was highlighted with 95% of patients (n = 20) reporting a significant reduction in symptoms. Of the 12 centres who responded, 11 centres have direct access to clinical psychology with a mean of 13% of patients requiring psychology referrals annually.Conclusion: Despite evidence of its benefit and increasing demand, there is insufficient access to clinical psychological services, highlighting the urgent need to address this important issue. What is known: • The biopsychosocial pathophysiology of functional gastrointestinal disorders involves a disordered brain-gut interaction, which emphasizes the close link between psychological factors and altered gut function. • Psychological intervention, as an adjunct to medical treatment, improves outcomes in paediatric patients with gastrointestinal (GI) disease such as functional gastrointestinal disorders and inflammatory bowel diseases What is new: • There is a rising number of referrals from paediatric gastroenterology to clinical psychology in our centre which is not met by a sufficient increase in the availability of clinical psychologists. Similarly, access to clinical psychological services is lacking in several paediatric gastroenterology centres in the UK and Germany. • Strategic action is required to address this important gap in the care of children suffering from GI diseases.