Abdominal Pain-related Functional Gastrointestinal Disorder Research Articles

Recurrent Abdominal Pain in Children

Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. We carried out a systematic review of randomised controlled trials (RCTs) in eleven databases and 2 trials registries from inception to June 2016. An update search was run in November 2017. All screening was performed by 2 independent reviewers. Included studies were appraised using the Cochrane risk of bias tool and the evidence assessed using GRADE. We included any dietary, pharmacological or psychosocial intervention for RAP, defined by Apley or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria, in children and adolescents. We included 55 RCTs, involving 3572 children with RAP (21 dietary, 15 pharmacological, 19 psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and there is some evidence of medium term effectiveness. There was insufficient evidence of effectiveness for all other dietary interventions and psychosocial therapies. There was no robust evidence of effectiveness for pharmacological interventions. Overall the evidence base for treatment decisions is poor. These data suggest that probiotics, CBT, and hypnotherapy could be considered as part of holistic management of children with RAP. The evidence regarding relative effectiveness of different strains of probiotics is currently insufficient to guide clinical practice. The lack of evidence of effectiveness for any drug suggests that there is little justification for their use outside of well-conducted clinical trials. There is an urgent need for high-quality RCTs to provide evidence to guide management of this common condition.

Pharmacological interventions for recurrent abdominal pain in childhood.

Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children. To determine the effectiveness of pharmacological interventions for RAP in children of school age. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies. Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life. Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results. This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies. There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.

Psychosocial interventions for recurrent abdominal pain in childhood.

This review supersedes the original Cochrane review first published in 2008 (Huertas-Ceballos 2008).Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. No organic cause for this pain can be found on physical examination or investigation for the majority of such children. Although many children are managed by reassurance and simple measures, a large range of psychosocial interventions involving cognitive and behavioural components have been recommended. To determine the effectiveness of psychosocial interventions for reducing pain in school-aged children with RAP. In June 2016 we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the references of identified studies and relevant reviews. Randomised controlled trials comparing psychosocial therapies with usual care, active control, or wait-list control for children and adolescents (aged 5 to 18 years) with RAP or an abdominal pain-related functional gastrointestinal disorder defined by the Rome III criteria were eligible for inclusion. We used standard methodological procedures expected by Cochrane. Five review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence using the GRADE approach. This review includes 18 randomised controlled trials (14 new to this version), reported in 26 papers, involving 928 children and adolescents with RAP between the ages of 6 and 18 years. The interventions were classified into four types of psychosocial therapy: cognitive behavioural therapy (CBT), hypnotherapy (including guided imagery), yoga, and written self-disclosure. The studies were carried out in the USA, Australia, Canada, the Netherlands, Germany, and Brazil. The majority of the studies were small and short term; only two studies included more than 100 participants, and only five studies had follow-up assessments beyond six months. Small sample sizes and the degree of assessed risk of performance and detection bias in many studies led to the overall quality of the evidence being rated as low to very low for all outcomes.For CBT compared to control, we found evidence of treatment success postintervention (odds ratio (OR) 5.67, 95% confidence interval (CI) 1.18 to 27.32; Z = 2.16; P = 0.03; 4 studies; 175 children; very low-quality evidence), but no evidence of treatment success at medium-term follow-up (OR 3.08, 95% CI 0.93 to 10.16; Z = 1.85; P = 0.06; 3 studies; 139 children; low-quality evidence) or long-term follow-up (OR 1.29, 95% CI 0.50 to 3.33; Z = 0.53; P = 0.60; 2 studies; 120 children; low-quality evidence). We found no evidence of effects of intervention on pain intensity scores measured postintervention (standardised mean difference (SMD) -0.33, 95% CI -0.74 to 0.08; 7 studies; 405 children; low-quality evidence), or at medium-term follow-up (SMD -0.32, 95% CI -0.85 to 0.20; 4 studies; 301 children; low-quality evidence).For hypnotherapy (including studies of guided imagery) compared to control, we found evidence of greater treatment success postintervention (OR 6.78, 95% CI 2.41 to 19.07; Z = 3.63; P = 0.0003; 4 studies; 146 children; low-quality evidence) as well as reductions in pain intensity (SMD -1.01, 95% CI -1.41 to -0.61; Z = 4.97; P < 0.00001; 4 studies; 146 children; low-quality evidence) and pain frequency (SMD -1.28, 95% CI -1.84 to -0.72; Z = 4.48; P < 0.00001; 4 studies; 146 children; low-quality evidence). The only study of long-term effect reported continued benefit of hypnotherapy compared to usual care after five years, with 68% reporting treatment success compared to 20% of controls (P = 0.005).For yoga therapy compared to control, we found no evidence of effectiveness on pain intensity reduction postintervention (SMD -0.31, 95% CI -0.67 to 0.05; Z = 1.69; P = 0.09; 3 studies; 122 children; low-quality evidence).The single study of written self-disclosure therapy reported no benefit for pain.There was no evidence of effect from the pooled analyses for any type of intervention on the secondary outcomes of school performance, social or psychological functioning, and quality of daily life.There were no adverse effects for any of the interventions reported. The data from trials to date provide some evidence for beneficial effects of CBT and hypnotherapy in reducing pain in the short term in children and adolescents presenting with RAP. There was no evidence for the effectiveness of yoga therapy or written self-disclosure therapy. There were insufficient data to explore effects of treatment by RAP subtype.Higher-quality, longer-duration trials are needed to fully investigate the effectiveness of psychosocial interventions. Identifying the active components of the interventions and establishing whether benefits are sustained in the long term are areas of priority. Future research studies would benefit from employing active control groups to help minimise potential bias from wait-list control designs and to help account for therapist and intervention time.

The Placebo Response in Pediatric Abdominal Pain-Related Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis

To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL were searched for systematic reviews and randomized placebo-controlled trials concerning children 4-18 years of age with an abdominal pain-related functional gastrointestinal disorder. The primary outcome was the pooled proportion of subjects assigned to placebo with improvement as defined by the authors. The effect of trial characteristics on the magnitude of the placebo response was investigated using univariate meta-regression analysis. Twenty-one trials were identified. The pooled proportion of subjects with improvement was 41% (95% CI, 34%-49%; 17 studies) and with no pain was 17% (95% CI, 8%-32%; 7 studies). The pooled standardized mean difference on the Faces Pain Scales compared with baseline was -0.73 (95% CI, -1.04 to -0.42; 8 studies). There was significant heterogeneity across studies with respect to both outcomes. Lower dosing frequency (P = .04), positive study (P = .03), longer duration of treatment (P < .001), and higher placebo dropout (P < .001) were associated with higher report of no pain. Response on Faces Pain Scales was greater in studies conducted in the Middle East (P = .002), in studies that did not report the randomization schedule (P = .02), and in studies with a higher percentage of females (P = .04). Approximately 41% of children with abdominal pain-related functional gastrointestinal disorders improve on placebo. Several trial characteristics are correlated significantly with the proportion of patients with no pain on placebo and with the magnitude of the placebo response on Faces Pain Scales. These data could be valuable for the design of future studies.

Vitamin D Status and Bone Mineral Density in Children with Inflammatory Bowel Disease Compared to Those with Functional Abdominal Pain.

Low vitamin D has been implicated in reduced bone mineral density (BMD) in children with inflammatory bowel disease (IBD). Our study aimed to evaluate differences in serum 25-hydroxyvitamin D (25[OH]D) and total body less head (TBLH) BMD z-scores in children with Crohn's disease (CD), ulcerative colitis (UC), and those with abdominal pain-related functional gastrointestinal disorder (AP-FGID) as the control group. We also examined the correlation between serum 25(OH)D and TBLH BMD z-score, and factors that affect each of these parameters. A total of 105 children were included and divided into 3 groups: AP-FGID (n = 45), CD (n = 43), and UC (n = 17). Among the 3 study groups, TBLH BMD z-scores were found to be significantly different (0.5 ± 0.8 in CD vs. 0.1 ± 0.8 in UC vs. −0.1 ± 1.1 in FGID; P = 0.037), despite similar levels of serum 25(OH)D. Within each study group, correlation between serum 25(OH)D and TBLH BMD z-score was not observed. Factors found to affect the TBLH BMD z-score were sex (P = 0.018), age (P = 0.005) and serum hemoglobin (P = 0.041), while factors influencing serum 25(OH)D were sex (P = 0.018), CD with reference to AP-FGID (P = 0.020), and serum phosphorus (P = 0.018). Based on our results, vitamin D is a relatively small contributor to bone loss in pediatric IBD and clinicians should consider female sex, older age, and low hemoglobin as risk factors for low BMD in children with IBD.

Non-pharmacological management of abdominal pain-related functional gastrointestinal disorders in children.

Abdominal pain-related functional gastrointestinal disorder (AP-FGID) comprises of 4 main conditions: functional dyspepsia, irritable bowel syndrome, abdominal migraine and functional abdominal pain. AP-FGIDs are diagnosed clinically based on the Rome IV criteria for FGIDs of childhood. There is limited evidence for pharmacological therapies. This review article discusses nonpharmacological management of AP-FGID based on the current literature including systematic reviews, randomized controlled trials, cohort and case control studies. We aim to provide a comprehensive overview on the available evidence for the pediatricians and pediatric gastroenterologists involved in managing children with AP-FGID. Managing AP-FGIDs can be challenging. This should follow a stepwise approach with focused history, identification of "red flag" signs and symptoms, physical examination and investigations done following initial consultation. Family needs explaining that there is nothing seriously wrong with the child's abdomen. This explanation and reassurance can achieve symptom control in large number of cases. Non-pharmacological interventions are delivered through lifestyle and dietary changes and bio-psychosocial therapies. Dietary interventions vary depending on the type of AP-FGID. Bio-psychosocial therapies such as hypnotherapy, cognitive behavioral therapy and yoga aim at stress reduction. There is increasing evidence for use of non-pharmacological interventions in children with APFGID.

Analysis of Gastric and Duodenal Eosinophils in Children with Abdominal Pain Related Functional Gastrointestinal Disorders According to Rome III Criteria.

Background/AimsAbdominal pain-related functional gastrointestinal disorder (AP-FGID) is common in children and adults. However, the mechanism of AP-FGID is not clearly known. Recently, micro-inflammation, especially eosinophilia in the gastrointestinal tract, was suggested in the pathophysiology of AP-FGID in adults. The aim of this study was to evaluate the association of gastric and duodenal eosinophilia with pediatric AP-FGID.MethodsIn total, 105 pediatric patients with AP-FGID were recruited and classified into 4 subgroups based on the Rome III criteria. Eosinophil counts in the gastric and duodenal tissues of children with AP-FGID were compared to those from normal pathology references or those of children with Helicobacter pylori infection. Tissue eosinophil counts were also compared among the 4 subtypes of AP-FGID.ResultsEosinophil counts in the gastric antrum and body were significantly higher in children with AP-FGID than normal reference values. Duodenal eosinophil counts were higher in children with AP-FGID, but not significantly when compared with normal reference values. There were no significant differences in eosinophil counts of the stomach or duodenum among the 4 subtypes of AP-FGID. Eosinophils counts in the gastric antrum and body were significantly higher in children with H. pylori infection than in those with AP-FGID. Duodenal eosinophilia was prominent in cases of H. pylori infection, but not statistically significant when compared with AP-FGID.ConclusionsOur study revealed that gastric eosinophilia is associated with AP-FGID in children, regardless of the subtype of functional abdominal pain. This suggests some contribution of gastrointestinal eosinophils in the development of pediatric AP-FGID.

Provider Communication Regarding Psychosocial Factors Predicts Pain Beliefs in Parent and Child.

To examine the role of provider communication about psychosocial causes of abdominal pain and recommendations for psychosocial intervention during a gastroenterology clinic visit in predicting families' causal beliefs and perceptions of treatment acceptability. Participants were 57 children with a diagnosed or suspected abdominal pain-related functional gastrointestinal disorder (FGID) presenting for an outpatient gastroenterology follow-up visit and their accompanying parent. Children and parents completed questionnaires assessing child anxiety and abdominal pain severity, recall of provider communication about causes of abdominal pain and recommendations for intervention, their own causal beliefs about pain, and perceived acceptability of cognitive behavioral therapy (CBT) and standard medical treatment (SMT) after reading descriptions of each treatment. Providers completed a questionnaire assessing their perceptions and communication about the causes of the child's abdominal pain and perceived acceptability of CBT. Provider communication about psychosocial causes and interventions was reported infrequently by parents, children, and providers. Parents rated psychosocial causes for abdominal pain as less likely than physical causes, and children and parents rated CBT as less acceptable than SMT. Parents' recall of provider communication about psychosocial causes was associated with their own causal beliefs about pain and their perceived acceptability of CBT. Children's and parents' recall of provider recommendations for psychosocial intervention was associated with their perceived acceptability of CBT. Results highlight the importance of provider communication about psychosocial contributors to abdominal pain and psychosocial interventions for children with FGIDs. Medical and mental health providers can partner to deliver care to children with FGIDs using a biopsychosocial approach.

Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis.

ObjectiveWe aimed to review the literature regarding epidemiology of functional abdominal pain disorders in children and to assess its geographic, gender and age distribution including associated risk factors of developing functional abdominal pain.MethodsThe Cochrane Library, MEDLINE, EMBASE, CINAHL and PsychInfo databases were systematically searched up to February 2014. Study selection criteria included: (1) studies of birth cohort, school based or general population samples (2) containing data concerning epidemiology, prevalence or incidence (3) of children aged 4-18 years (4) suffering from functional abdominal pain. Quality of studies was rated by a self-made assessment tool. A random-effect meta-analysis model was used to estimate the prevalence of functional abdominal pain in childhood.ResultsA total of 58 articles, including 196,472 children were included. Worldwide pooled prevalence for functional abdominal pain disorders was 13.5% (95% CI 11.8-15.3), of which irritable bowel syndrome was reported most frequently (8.8%, 95% CI 6.2-11.9). The prevalence across studies ranged widely from 1.6% to 41.2%. Higher pooled prevalence rates were reported in South America (16.8%) and Asia (16.5%) compared to Europe (10.5%). And a higher pooled prevalence was reported when using the Rome III criteria (16.4%, 95% CI 13.5-19.4). Functional abdominal pain disorders are shown to occur significantly more in girls (15.9% vs. 11.5%, pooled OR 1.5) and is associated with the presence of anxiety and depressive disorders, stress and traumatic life events.ConclusionFunctional abdominal pain disorders are a common problem worldwide with irritable bowel syndrome as most encountered abdominal pain-related functional gastrointestinal disorder. Female gender, psychological disorders, stress and traumatic life events affect prevalence.

Increased prevalence of celiac disease among pediatric patients with irritable bowel syndrome: a 6-year prospective cohort study.

Recurrent abdominal pain is a prevalent health issue in childhood. Clinical criteria (ie, the Rome criteria) have been established to aid diagnosis. Studies of adults have shown an increased prevalence of celiac disease among patients with irritable bowel syndrome (IBS); few data are available with regard to children. To assess the prevalence of celiac disease among children with abdominal pain-related functional gastrointestinal disorders classified according to the Rome criteria. Six-year (2006-2012) prospective cohort study conducted in a tertiary referral center for the diagnosis and follow-up of gastrointestinal disorders in southern Italy (ie, Bari, Italy). A total of 992 children (42.8% male; median age, 6.8 years) consecutively referred for recurrent abdominal pain by their primary care physicians without previous investigation were evaluated. Patients were classified according to Rome III criteria as having IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine. Prevalence of celiac disease in each category of abdominal pain-related functional gastrointestinal disorder. Concentrations of IgA, IgA antitissue transglutaminase, and endomysial antibodies were measured, and a duodenal biopsy was performed in case of antibody positivity. A total of 992 children were evaluated: 270 were classified as having IBS, 201 as having functional dyspepsia, and 311 as having functional abdominal pain, and 210 children were excluded from the study because they had an organic disorder or some other functional gastrointestinal disorder (not related to abdominal pain). Serologic testing was performed for all 782 children included in the study, and 15 patients tested positive for celiac disease (12 of 270 patients with IBS [4.4%], 2 of 201 patients with functional dyspepsia [1%], and 1 of 311 patients with functional abdominal pain [0.3%]). Children presenting with IBS have a 4 times higher risk of having celiac disease than children without IBS (odds ratio, 4.19 [95% CI, 2.03-8.49]; P < .001). The prevalence of celiac disease among children with IBS is 4 times higher than among the general pediatric population. Rome III classification of abdominal pain-related functional gastrointestinal disorders might help to select children who deserve screening for celiac disease.

Rome III criteria in parents’ hands

To determine (a) the prevalence of Rome III abdominal pain-related functional gastrointestinal disorders in a western community sample of children, (b) their associations with sociodemographic factors, and (c) whether children fulfilling Rome III abdominal pain diagnoses show higher rates of psychological distress and somatization. Data were collected from parents of 6-10-year-old children who were recruited from 22 public grammar schools in Germany. A total of 1537 questionnaires were included in the analysis. Abdominal pain-related functional gastrointestinal disorders were diagnosed on the basis of questionnaire responses by Rome III criteria. Further, somatic complaints as well as emotional and behavioral problems were assessed. In total, 7.7% of children aged 6-10 years fulfilled the criteria for at least one Rome III abdominal pain-related functional gastrointestinal disorder according to their parents. The most prevalent diagnoses were irritable bowel syndrome (4.9%) and functional abdominal pain (2.0%). Assigned diagnoses were not associated with sociodemographic factors. We could confirm that abdominal pain-related functional disorders, especially irritable bowel syndrome, were strongly associated with somatization and emotional problems in community. Rome III abdominal pain-related functional gastrointestinal disorders are a common health problem in children and are, even in community, strongly associated with other somatic complaints and psychological distress.

Efficacy of Sumatriptan in Two Pediatric Cases With Abdominal Pain-Related Functional Gastrointestinal Disorders: Does the Mechanism Overlap That of Migraine?

We successfully treated 2 pediatric cases of abdominal pain-related functional gastrointestinal disorder with sumatriptan. When 9 years old, patient 1 developed periodic abdominal pain that was intractable to medication and remitted spontaneously. She was diagnosed with abdominal migraine, categorized as H2c in the Rome III criteria for functional gastrointestinal disorders. At age 12, intranasal sumatriptan relieved her pain, and her attacks halted 2 years later. Patient 2 was a 9-year-old girl diagnosed with attention-deficit hyperactivity disorder (ADHD), who began to have intermittent abdominal pain of variable severity, which sometimes restricted daily activity. She was diagnosed with childhood functional abdominal pain syndrome, categorized as H2d1 using the Rome III criteria. Intranasal sumatriptan also relieved her pain. These cases suggest that the mechanism of pain in abdominal pain-related functional gastrointestinal disorders is similar to that of migraine, with probable central hypersensitivity, at least in a subset of cases.