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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., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aim: To assess whether infants with colic (IC) demonstrate persisting developmental dysregulation into childhood, manifested as behavioural problems, and to determine if these behavioural problems are associated with parenting factors., Methods: Preschool children with a history of IC at the age of 0-3 months, as defined by the Wessel criteria, were invited to participate in an observational follow-up study, in which their caregivers completed the Child Behaviour Checklist (CBCL). Raw scores and clinical-range scores on the internalising, externalising and total behavioural problems scales were compared with a Dutch normative sample using independent t-tests and Chi-square tests. For the clinical-range scores, multivariable logistic regressions (odds ratios [99% confidence interval, CI]) were used to adjust for confounders and to identify variables associated with behavioural problems., Results: Two hundred and fifty-eight children with a history of IC (median age 5.1 (interquartile range, IQR 4.6-5.5) years, 51.9% boys) were included. The cases had a significantly higher adjusted risk (adjusted odds ratios (aORs) [99% CI]) of scoring in the clinical range of the emotionally reactive, internalising and total problems scale (2.96 [1.24-7.06]; 2.50 [1.35-4.62]; 2.98 [1.46-6.07], respectively). Internalising (P < 0.001), externalising (P < 0.001) and total (P < 0.001) behavioural problems in children with a history of IC were associated with higher parenting stress scores., Conclusions: Children with a history of IC demonstrated significantly more internalising behavioural problems at preschool age compared to the norm sample. Specific advice and support need to be available for parents to understand and regulate the behaviour of their child, from infancy to childhood., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background & Aims: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents., Methods: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately., Results: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%)., Conclusions: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Irritable bowel syndrome (IBS) is a common chronic medical condition, in both children and adults. Despite the availability of effective (non)pharmacological treatments, symptoms persist in a significant amount of patients with IBS. Faecal microbiota transplantation (FMT) may be an effective alternative treatment in adolescents with refractory IBS through manipulation of the intestinal microbiota., Methods and Analysis: This randomised, placebo-controlled single-centre pilot study will assess feasibility and efficacy of FMT in 30 adolescents (16-21 years) with refractory IBS. Patients will be randomly allocated (1:1) to receive two allogeneic (healthy donor) or two autologous (own) faecal infusions at baseline and after 6 weeks. Primary outcomes will assess feasibility, including patient and donor recruitment, adherence and incidence rates of adverse events. To evaluate clinical efficacy, secondary outcomes will include the proportion of patients with at least >50% reduction of their abdominal pain intensity and frequency 12 weeks after the first FMT, and after 6-month and 12-month follow-up. Other outcomes comprise changes in faecal gut microbiota composition, quality of life, depression and anxiety, school or work absenteeism and adequate relief, measured directly after FMTs and after 6 and 12 months of follow-up., Discussion: This randomised controlled trial will investigate the feasibility and effectiveness of repetitive FMTs in adolescents with refractory IBS., Ethics and Dissemination: The study is approved by the Medical Research Ethics Committees AMC (MEC-AMC) in the Netherlands., Trial Registration Number: NCT03074227., Competing Interests: Competing interests: MN is in the scientific advisory board of Caelus Health and Kaleido BioSciences; however, none of these are directly related to the current manuscript., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To ensure consistency and reduce outcome measure reporting heterogeneity in clinical trials on pediatric functional abdominal pain disorders (FAPDs), a core outcome set (COS) was developed for pediatric FAPD trials., Study Design: A mixed-method 2-round Delphi technique was used and key stakeholders, including healthcare professionals (HCPs), patients with FAPD, and their parents were invited to participate. In the first round, key stakeholders identified outcomes of importance through an open-ended questionnaire. Outcomes mentioned by ≥10% of the participants were included in a shortlist. In the second round, this shortlist was rated and prioritized. During a consensus meeting with an expert panel, the final COS was defined., Results: The first round was completed by 152 of 210 (72%) HCPs, 103 (100%) parents, and 50 of 54 (93%) patients. A total of 104 from 167 (62%) HCPs, 102 (100%) parents, and 53 (100%) patients completed round 2. Pain intensity, pain frequency, quality of life, school attendance, anxiety/depression, adequate relief, defecation pattern (disease specific, irritable bowel syndrome), and adverse events were included in the final COS for FAPDs., Conclusion: A set of 8 core outcomes has been identified that should minimally be measured in pediatric FAPD trials. Implementation of the use of this COS will increase comparison between studies and, therefore, improve management of children with FAPDs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the prevalence of functional gastrointestinal disorders (FGIDs) in young children in a cross-sectional, multicenter study in Belgium, Italy, and The Netherlands., Study Design: Children were enrolled if they were age 0-48 months, attending a general pediatrician (Belgium, Italy) or a well-baby clinic (The Netherlands) for routine follow-up. Separate questionnaires were developed for infants age 0-12 months and for toddlers age 13-48 months. Questionnaires evaluated the clinical history, symptoms, sociodemographic information on the family, and exposure to stressful life events. FGIDs were defined according to Rome IV criteria., Results: In total 2751 children were included: 1698 infants age 0-12 months and 1053 children age 13-48 months. The prevalence of any FGID in infants age 0-12 months and 13-48 months was 24.7% and 11.3%, respectively. The most common disorders were infant regurgitation (13.8%) in infants and functional constipation (9.6%) in toddlers. Multivariable regression analyses demonstrated that younger age (P = .030) and formula feeding (P = .045) were associated with the prevalence of any FGID among infants. Country (Italy) (P = .033) and parents subjected to domestic violence (P = .035) were associated with the prevalence of any FGID in toddlers age 13-48 months., Conclusions: FGIDs are common in a community sample of Western European infants and toddlers. Regurgitation is most prevalent in infants and functional constipation is most common in toddlers. Younger age, formula feeding, and domestic violence to parents are associated with the prevalence of FGIDs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the additional value of blood parameters (hemoglobin, C-reactive protein, erythrocyte sedimentation rate) to anti-tissue transglutaminase (anti-tTG), fecal calprotectin, and Giardia lamblia when discriminating a functional from an organic cause in the clinical evaluation of children with chronic abdominal pain., Study Design: This retrospective cohort study included patients (4-18 years of age) with abdominal pain for >2 months. Data on hemoglobin, C-reactive protein, erythrocyte sedimentation rate, anti-tTG, fecal calprotectin, alarm symptoms, and diagnosis were collected., Results: We identified 853 patients, of whom 102 (12%) had an organic disorder. Sensitivity and the area under the curve of strategy 1 (fecal calprotectin, anti-tTG, G lamblia, blood parameters) were 90% (95% CI, 83-95) and 0.87 (95% CI, 0.81-0.93), respectively, compared with 88% (95% CI, 81-93) and 0.85 (95% CI, 0.79-0.91), respectively, for strategy 2 (fecal calprotectin, anti-tTG, G lamblia) (P = NS). In the presence of ≥1 alarm symptoms, the sensitivity of strategies 1 and 2 was 92% (95% CI, 83-96) and 92% (95% CI, 83-96), and the areas under the curve were 0.93 (95% CI, 0.89-0.98) and 0.90 (95% CI, 0.84-0.97) (P = NS)., Conclusions: To distinguish between a functional and an organic cause for chronic abdominal pain, hemoglobin, C-reactive protein, and erythrocyte sedimentation rate can be left out from the clinical evaluation as they might have no additional diagnostic yield. However, caution should be taken not to miss extraintestinal infections (2%)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To systematically review definitions of functional abdominal pain orders (FAPDs) and outcome measures used in therapeutic randomized controlled trials in pediatric FAPDs adhering to the Outcome Measures in Rheumatology recommendations., Study Design: Cochrane, MEDLINE, Embase, and Cinahl databases were systematically searched from inception to April 2018. English-written therapeutic randomized controlled trials concerning FAPDs in children aged 4-18 years were included. Definitions of FAPDs, interventions, outcome measures, measurement instruments, and outcome assessors of each study were tabulated descriptively. Quality was assessed using the Delphi List., Results: A total of 4771 articles were found, of which 64 articles were included (n = 25, 39% of high methodologic quality). The Rome III (50%), Rome II (17%), Apley (16%), and author-defined (17%) criteria were used to define FAPDs. Fourteen studies (22%) assessed a pharmacologic, 25 (39%) a dietary, and 25 (39%) a psychosocial intervention. Forty-four studies (69%) predefined their primary outcomes. In total, 211 reported predefined outcome measures were grouped into 23 different outcome domains; the majority being patient-reported (n = 27, 61%). Of the 14 studies that evaluated a pharmacologic intervention, 12 (86%) reported on adverse events., Conclusions: Studies on pediatric FAPDs are of limited methodologic quality and show large heterogeneity and inconsistency in defining FAPDs and outcome measures used. Development of a core outcome set is needed to make comparison between intervention studies possible., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: To systematically review the literature regarding the side effects of pharmacotherapy in children with irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS). Areas covered: Cochrane Library, PubMed, and Embase databases were searched from inception to May 2018. The following inclusion criteria were applied: (1) randomized controlled trials (RCTs), cohort studies or case-control studies; (2) in children aged 4-18 years or adult studies if children are reported separately; (3) reporting a diagnosis of IBS or FAP-NOS as defined by the authors; and (4) reporting the occurrence of side effects of pharmacotherapy. Quality assessment of included studies was conducted. Expert opinion: A total of 4619 articles were identified; 17 were included. In 10/17 (59%) studies, side effects of pharmacotherapy (antispasmodics, antidepressants, antihistaminic agents, serotonergic agents and antibiotics) occurred. The majority of side effects were: (1) limited to the gastrointestinal tract and central nervous system and, 2) mild and transient. No serious adverse events were reported. This systematic review shows that data on safety in children with functional abdominal pain disorders are scarce, and highlights the lack of high-quality research for potential side effects of pediatric IBS and FAP-NOS. Further research by means of large well-designed-follow-up studies is necessary.

Objectives: Parental factors are suggested to play a role in pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) and may influence treatment. Since studies on parental factors mainly focus on mothers, this study aims to compare physical health, psychological distress, personality dimensions, and parenting behavior of both parents of children with IBS or FAP-NOS to parents of controls., Methods: Parents of 91 children with IBS or FAP-NOS were included in this explorative cross-sectional cohort study. Parents of 74 age-matched healthy children were used as controls. Questionnaires were used to measure demographics, physical health, psychological distress and symptoms, personality dimensions, and child-rearing practices., Results: A total of 59 mothers and 52 fathers of 61 children with IBS/FAP-NOS (response rate 61.0%) and 56 mothers and 49 fathers of 59 controls completed the study (response rate 70.9%). Mothers of children with IBS/FAP-NOS reported more physical problems. Psychological distress and symptoms, personality dimensions, and child-rearing practices did not differ between mothers of both groups. Fathers of children with IBS/FAP-NOS had significantly lower scores on the child-rearing practice subscale of ignoring of unwanted behavior. In the IBS/FAP-NOS group, fathers were more depressed and less agreeable than mothers. No differences on all assessed outcomes were found between parents of children with IBS and children with FAP-NOS., Conclusions: Mothers of children with IBS/FAP-NOS and healthy peers differ with respect to physical health. Fathers in both groups differ with respect to child-rearing style. Clinicians should be aware of these differences when treating children with these disorders.

Infant colic is a commonly reported phenomenon of excessive crying in infancy with an enigmatic and distressing character. Despite its frequent occurrence, little agreement has been reached on the definition, pathogenesis or the optimal management strategy for infant colic. This Review aims to delineate the definitional entanglement with the Rome IV criteria, which were published in 2016, as the leading, most recent diagnostic criteria. Moreover, neurogenic, gastrointestinal, microbial and psychosocial factors that might contribute to the pathophysiology of infant colic are explored. This Review underlines that a comprehensive medical history and physical examination in the absence of alarm symptoms serve as guidance for the clinician to a positive diagnosis. It also highlights that an important aspect of the management of infant colic is parental education and reassurance. Management strategies, including behavioural, dietary, pharmacological and alternative interventions, are also discussed. Owing to a lack of large, high-quality randomized controlled trials, none of these therapies are strongly recommended. Finally, the behavioural and somatic sequelae of infant colic into childhood are summarized.

Introduction: Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on epidemiology, pathophysiology, risk factors related to pathophysiology, clinical evaluation and management of children with FAPDs. Expert commentary: FAPDs are a worldwide problem with a pooled prevalence of 13.5%. There are a number of predisposing factors and pathophysiological mechanisms including stressful events, child maltreatment, visceral hypersensitivity, altered gastrointestinal motility and change in intestinal microbiota. It is possible that the environmental risk factors intricately interact with genes through epigenetic mechanisms to contribute to the pathophysiology. The diagnosis mainly depends on clinical evaluation. Commonly used pharmacological interventions do not play a major role in relieving symptoms. Centrally directed, nonpharmacological interventions such as hypnotherapy and cognitive behavioral therapy have shown both short and long term efficacy in relieving pain in children with FAPDs. However, these interventions are time consuming and need specially trained staff and therefore, not currently available at grass root level. Clinicians and researchers should join hands in searching for more pragmatic and effective therapeutic modalities to improve overall care of children with FAPDs.

Objective: Symptoms of irritable bowel syndrome (IBS) are common in inflammatory bowel disease (IBD) and are believed to reflect ongoing inflammation. Consequently, a low prevalence of IBS-type symptoms in IBD patients with normal inflammatory markers is expected. We aimed to investigate the prevalence of IBS-type symptoms in IBD patients in biochemical remission (evidenced by low fecal calprotectin levels) and the relationship of these symptoms with fecal calprotectin levels., Patients and Methods: In this observational, cross-sectional study, we included all adults with a history of IBD who had calprotectin levels less than 200 µg/g during routine follow-up between August 2014 and May 2015 at our hospital. Patients were excluded if calprotectin was measured because of gastrointestinal complaints. All patients were approached by telephone to evaluate the presence of IBS-type symptoms using Rome III questionnaires. Patients fulfilling IBS criteria were subclassified according to bowel habits., Results: In total, 74 patients were included; 33 (45%, 95% confidence interval: 34-56%) fulfilled the IBS criteria. A larger proportion of Crohn's disease patients with IBS-type symptoms had ileal disease compared with Crohn's disease patients without IBS symptoms (55 vs. 24%; P=0.03). Other characteristics were similar between groups. No difference was found in calprotectin levels between patients with and without IBS-type symptoms (P=0.91). The majority of patients with IBS-type symptoms had diarrhea-predominant or mixed-type IBS (64 and 27% of patients with IBS-type symptoms, respectively)., Conclusion: The prevalence of IBS-type symptoms in IBD patients in biochemical remission is high. A significant proportion of IBS-type symptoms is unrelated to ongoing inflammation and probably reflects 'true IBS'.

Functional gastrointestinal disorders (FGIDs) are common worldwide and cover a wide range of disorders attributable to the gastrointestinal tract that cannot be explained by structural or biochemical abnormalities. The diagnosis of these disorders relies on the symptom-based Rome criteria. In 2016 the Rome criteria were revised for infants/toddlers and for children and adolescents. In this review, we discuss the novel Rome IV criteria for infants and toddlers. The criteria for infant colic were drastically changed, whereas only minor changes were made for regurgitation, cyclic vomiting syndrome, functional diarrhea, infant dyschezia and functional constipation. In addition to this, the new Rome IV discusses underlying mechanisms of pain in infants and toddlers, including the neuro-development of nociceptive and pain pathways, the various factors that are involved in pain experience, and methods of pain assessment in infants and toddlers is essential for the clinician who encounters functional pain in this age group. Overall, the Rome IV criteria have become more distinctive for all disorders in order to improve the process of diagnosing pediatric FGIDs.

Objective: To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders., Study Design: 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., Results: 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)., Conclusions: 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)