Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years of age with functional constipation (FC). This study evaluated the dose-response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2-5 years of age with FC. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72 µg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72 µg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded. RESULTS: Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72 µg group versus placebo. A dose-response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment-emergent AEs, one of which was treatment-related (mild diarrhea). All AEs were mild or moderate and none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 µg versus placebo.

Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS: In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS: Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS: Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

Quality of life measures in children with Down syndrome with disorders of gut-brain interaction.

Down syndrome (DS) is associated with multiple medical comorbidities. Perhaps related to such, caregivers of individuals with DS report lower quality of life (QoL) compared to individuals without DS. It has been shown that disorders of gut-brain interaction (DGBI) such as functional constipation (FC) and irritable bowel syndrome (IBS) are common in individuals with DS. We measured caregiver-reported QoL in individuals with DS with a DGBI and compared them to individuals with DS without a DGBI via a cross-sectional national survey. All measures of QoL were lower in those with DS who meet criteria for a DGBI compared to those with DS without a DGBI. Males and females with DS and at least one DGBI had similar QoL scores. While FC was the most common DGBI seen in individuals with DS, there was no difference in any aspect of QoL in subjects with FC when compared to individuals with other DGBIs. However, all measures of QoL were lower in those with IBS compared to individuals with other DGBIs. These findings suggest that management of gastrointestinal symptoms from DGBIs, particularly IBS, may serve as a target for increasing QoL in a notable subset of individuals with DS.

Risk Factors for Abdominal Pain-Related Disorders of Gut-Brain Interaction in Adults and Children: A Systematic Review.

BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.

Efficacy of transcutaneous posterior tibial nerve stimulation in functional constipation.

Most children with functional constipation (FC) improve with conventional treatments. However, a proportion of children have poor treatment outcomes. Management of intractable FC may include botulinum toxin injections, transanal irrigation, antegrade enemas, colonic resections, and in some cases sacral nerve stimulation (SNS). SNS is surgically placed, not readily available and expensive. Posterior tibial nerve stimulation (PTNS) allows transmission of electronic impulses and retrograde stimulation to the sacral nerve plexus in a portable, simple and non-invasive fashion. To assess the efficacy and safety of transcutaneous PTNS for the treatment of FC in children. Single-center, prospective interventional study. Children 4-14 years with Rome IV diagnosis of FC received ten daily PTNS (30 min/day) sessions. Electrodes placed over skin of ankle. Strength of stimulus was below pain threshold. Outcomes were assessed during treatment and 7 days after. Twenty-three subjects enrolled. Two children excluded (acute gastroenteritis, COVID-19 contact). Twenty completed the study (4-14 years), (8.4 ± 3.2 years, 71.4% female). We found significant improvement in the consistency of bowel movements (BM) (p = 0.005), fecal incontinence (FI) (p = 0.005), abdominal pain presence (p = < 0.001) and intensity (p = 0.005), and a significant for improvement in blood in stools (p = 0.037). There was 86.3% improvement in abdominal pain. 96.7% reported treatment satisfaction. Only one child required rescue therapy. CONCLUSION: We found significant improvement in stool consistency, FI, abdominal pain, and hematochezia. This suggests that transcutaneous PTNS could be a promising noninvasive treatment for FC in children. Large studies are needed. WHAT IS KNOWN: • Functional constipation is one of the most common disorders in children. • Current management of functional constipation consists of an integrative approach that includes medications, diet and behavioral strategies. WHAT IS NEW: • Posterior tibial nerve stimulation is a novel noninvasive and easy to use therapy that can improve stool consistency, fecal incontinence and blood in stools.

A therapeutic guide on pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified.

Disorders of the gut-brain interaction negatively impact quality of life and carry a substantial socioeconomic burden. Irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) are common functional abdominal pain disorders in childhood. The pathophysiology is not fully understood, and high-quality intervention trials and international guidelines are missing. Therefore, the management of these disorders remains challenging. This review aims to provide an up-to-date overview of therapeutic possibilities for pediatric IBS or FAP-NOS and recommends management strategies. To prevent unnecessary referrals and extensive costs, it is fundamental to make a positive diagnosis of IBS or FAP-NOS in children with chronic abdominal pain with only minimal investigations. A tailor-made approach for each patient, based on the accompanying physical and psychological symptoms, is proposed to date. CONCLUSION: Shared decision-making including non-pharmacological and pharmacological interventions should be considered and discussed with the family. WHAT IS KNOWN: • Irritable bowel syndrome and functional abdominal pain-not otherwise specified are common in childhood. • Although the number of treatment options has grown recently, managing these disorders can be challenging and unsatisfactory, and no evidence-based international management guidelines are available. WHAT IS NEW: • We suggest using a stepwise individualized approach to management, where after first-line management, both non-pharmacological and pharmacological interventions should be discussed.

Probiotics for treatment of chronic constipation in children.

BACKGROUND: Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date. OBJECTIVES: To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children. SEARCH METHODS: On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations. Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low-certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low-certainty evidence). The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD -0.01, 95% CI -0.57 to 0.56; 268 participants; low-certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low-certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low-certainty evidence). Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI -0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes. One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI -0.96, 2.44; 66 participants; very low-certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD -1.53, 95% CI -3.00, -0.06; 60 participants; very low-certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. All secondary outcomes were either not reported or reported in a way that did not allow for analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events. There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome. Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.

Is Celiac Disease Testing Necessary in Functional Abdominal Disorders? A Study in Predominantly Latino Children.

BACKGROUND: Functional abdominal pain disorders (FAPDs) are among the most common causes of consultation in general pediatrics and pediatric gastroenterology. The Rome IV criteria recommend testing for celiac disease (CD) in children with irritable bowel syndrome-diarrhea (IBS-D) and leaves testing in cases of other FAPDs to the practitioner's discretion. These recommendations were based on a single study that showed a 4-fold increase of CD among patients with IBS in Italy. It is unclear if these findings can be extrapolated to other populations. Understanding whether those results are reproducible in areas with different racial/ethnic backgrounds can optimize patient care. AIM: The aim of the study was to assess the prevalence of CD in a sample of children consulting for FAPDs to a tertiary care center in Miami. METHODS: The charts of all pediatric patients consulting for FAPDs from January 2016 to November 2019 at the University of Miami were reviewed. Demographics, diagnosis, and CD testing for each child were analyzed. RESULTS: One hundred eighty-one children with FAPDs and celiac testing were seen. Mean age of 12.89 years, girls 61.34%. 84 (46.40%) had a diagnosis of IBS and 97 (53.59%) had a diagnosis of other FAPD. One of 181 children with FAPDs (0/84 with IBS and 1/97 with other FAPDs) had positive CD serological testing and EGD confirmation. CONCLUSIONS: Our study suggests that the prevalence of CD among children with FAPDs is similar to the community prevalence. This data questions the benefit of testing all children FAPDS (including IBS) for CD. Studies with larger sample size and various racial/ethnic makeup should be done to confirm our findings.

Diagnostic Accuracy of the Rome IV Criteria for the Diagnosis of Functional Gastrointestinal Disorders in Children.

ABSTRACT: The diagnosis of functional gastrointestinal disorders (FGIDs) centers on symptoms-based criteria (Rome criteria). The last edition of the criteria was published in 2016. Still, few data on its validity support its use in children. We conducted a study aimed at determining the diagnostic accuracy of the Rome IV criteria through the application of questionnaires (Questionnaire of Pediatric Gastrointestinal Symptoms-Rome IV QPGS-IV) to diagnose FGIDs in children. We hypothesized that the Rome IV criteria has adequate diagnostic accuracy supporting its use for diagnosing FGIDs in children. METHODS: School children ages 10 to 18 years from Cali (Colombia) completed the Spanish version of the QPGS-IV. Children with FGIDs were matched with a group of children without FGIDs. Both groups had a medical consultation with a blinded experienced pediatric gastroenterologist (criterion standard) who provided his diagnosis. The questionnaire-based diagnoses were compared with the consultation's diagnoses. RESULTS: Of 487 schoolchildren surveyed with the QPGS-IV, 97 (20.8%) had FGIDs. Eighty-nine with FGIDs were matched with 92 children without FGIDs (mean age 13.1 years [±1.3]). We found a higher prevalence of FGIDs during the medical visit than using the self-report QPGS-IV (66.3% vs 49.2%, P = 0.001), mainly in abdominal pain disorders (19.3% vs 10.5%, P = 0.013). The Rome IV diagnostic criteria using the QPGS-IV had a sensitivity of 75% (95% confidence interval, 59-79) and 90% specificity (95% confidence interval, 83-98). Positive predictive value is 85.8%, and negative predictive value is 79.9%. CONCLUSION: Our study suggests that the QPGS-IV has adequate diagnostic accuracy.

A Collaborative Effort to Advance Drug Development in Pediatric Constipation and Irritable Bowel Syndrome.

ABSTRACT: Pediatric functional gastrointestinal disorders including irritable bowel syndrome with constipation and functional constipation are common conditions in childhood, but no drugs are U.S. Food and Drug Administration (FDA) approved for chronic use in pediatric patients with these disorders. Despite efforts to better standardize the diagnosis of these conditions in children (including recent modifications to the Rome criteria), conducting pediatric clinical trials to support drug approval remains a challenge. In March 2018, FDA, in collaboration with the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, American Gastroenterological Association, and American College of Gastroenterology, convened a public workshop to discuss the challenges and opportunities in conducting pediatric clinical trials in functional gastrointestinal conditions. The workshop assembled gastroenterologists, psychologists, patients, patient advocates, regulators, and industry representatives to discuss trial design and conduct including alternative designs, eligibility criteria, instruments for patient- and observer-reported outcomes, and optimal primary endpoints to support regulatory approval. This report summarizes the workshop, key challenges and knowledge gaps identified, and outlines areas where further research efforts are needed to overcome barriers to developing drugs to treat these conditions.

Development of Entrustable Professional Activities and Standards in Training in Pediatric Neurogastroenterology and Motility: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and American Neurogastroenterology and Motility Society Position Paper.

ABSTRACT: Neurogastroenterology and motility (NGM) disorders are common in childhood and are often very debilitating. Although pediatric gastroenterology fellows are expected to obtain training in the diagnosis and management of patients with these disorders, there is an ongoing concern for unmet needs and lack of exposure and standardized curriculum. In the context of tailoring training components, outcome and expressed needs of pediatric gastroenterology fellows and programs, members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and American Neurogastroenterology and Motility Society (ANMS) developed guidelines for NGM training in North America in line with specific expectations and goals of training as delineated through already established entrustable professional activities (EPAs). Members of the joint task force applied their expertise to identify the components of knowledge, skills, and management, which are expected of NGM consultants. The clinical knowledge, skills and management elements of the NGM curriculum are divided into domains based on anatomic regions including esophagus, stomach, small bowel, colon and anorectum. In addition, dedicated sections on pediatric functional gastrointestinal (GI) disorders, research and collaborative approach, role of behavioral health and surgical approaches to NGM disorders and transition from pediatric to adult neurogastroenterology are included in this document. Members of the NASPGHAN-ANMS task force anticipate that this document will serve as a resource to break existing barriers to pursuing a career in NGM and provide a framework towards uniform training expectations at 3 hierarchical tiers corresponding to EPA levels.

Functional gastrointestinal disorders in children: agreement between Rome III and Rome IV diagnoses.

To evaluate the agreement between the Rome III and Rome IV criteria in diagnosing pediatric functional gastrointestinal disorders (FGIDs), we conducted a prospective cohort study in a public school in Cali, Colombia. Children and adolescents between 11 and 18 years of age were given the Spanish version of the Questionnaire on Pediatric Functional Gastrointestinal Disorders Rome III version on day 0 and Rome IV version on day 2 (48 h later). The study protocol was completed by 135 children. Thirty-nine (28.9%) children were excluded because of not following the instructions of the questionnaire. The final analysis included data of 96 children (mean 15.2 years old, SD ± 1.7, 54% girls). Less children fulfilled the criteria for an FGID according to Rome IV compared to Rome III (40.6% vs 29.2%, p=0.063) resulting in a minimal agreement between the two criteria in diagnosing an FGID (kappa 0.34, agreement of 70%). The prevalence of functional constipation according to Rome IV was significantly lower compared to Rome III (13.5% vs 31.3%, p<0.001), whereas functional dyspepsia had a higher prevalence according to Rome IV than Rome III (11.5% vs 0%).Conclusion: We found an overall minimal agreement in diagnosing FGIDs according to Rome III and Rome IV criteria. This may be partly explained by the differences in diagnostic criteria. However, limitations with the use of questionnaires to measure prevalence have to be taken into account. What is Known: • The Rome IV criteria replaced the previous Rome III criteria providing updated criteria to diagnose functional gastrointestinal disorders (FGIDs). • Differences found between Rome IV and historic Rome III FGID prevalence may have been affected by changes in prevalence over time or differences in sample characteristics. What is New: • We found a minimal agreement between Rome III and Rome IV FGID diagnosis, especially in the diagnoses of functional constipation, irritable bowel syndrome, and functional dyspepsia. • The minimal agreement may be partly explained by changes in diagnostic criteria, but limitations with the use of questionnaires to measure prevalence have to be taken into account.

Celiac Disease in Children with Functional Constipation: A School-Based Multicity Study.

OBJECTIVE: To determine whether children in the community with functional constipation have increased prevalence of celiac disease. STUDY DESIGN: Between April 4, 2015, and April 25, 2017, we enrolled 1809 children from 5 schools in Colombia and screened them for functional gastrointestinal disorders (FGIDs), including functional constipation, using questionnaires recommended in the Rome III/IV criteria. We matched children with functional constipation with healthy controls without a FGID and tested them for celiac disease with tissue transglutaminase (tTG)-Immunoglobulin A (IgA) and total IgA screening. In those who tested positive for tTG-IgA, we performed HLA genotyping and endoscopy to obtain 4 duodenal biopsy specimens for classification of celiac disease using the Marsh criteria. Analysis of statistical significance between groups of children with and without functional constipation was done using a 2-tailed Fisher exact test. RESULTS: Patients diagnosed with functional constipation (n = 203) were matched with 419 healthy controls without FGIDs. The overall prevalence of celiac disease in the entire cohort was 0.6%. Of those with functional constipation, 1 (0.5%) was diagnosed with celiac disease, and 3 (0.7%) of the control patients without FGIDs had celiac disease (P = .743). CONCLUSIONS: The prevalence of celiac disease in our cohort was similar to worldwide estimates. The prevalence of celiac disease in schoolchildren with functional constipation in Colombia is similar to those without FGIDs. Thus, routine testing of schoolchildren with functional constipation for celiac disease is not indicated.

Functional Gastrointestinal Disorders, Autonomic Nervous System Dysfunction, and Joint Hypermobility in Children: Are They Related?

OBJECTIVES: To evaluate the prevalence of orthostatic intolerance and joint hypermobility in schoolchildren with and without functional gastrointestinal disorders (FGIDs) and to assess autonomic nervous system dysfunction in children with FGIDs and joint hypermobility. STUDY DESIGN: Schoolchildren (10-18 years) attending public schools from 3 Colombian cities (Cali, Palmira, and Bucaramanga) completed validated questionnaires for FGIDs and underwent testing for hypermobility and autonomic nervous system dysfunction. Heart rate and blood pressure were assessed in recumbency and upright position at regular intervals. The differences in characteristics between schoolchildren with and without FGIDs were compared with a t-test for continuous variables and with a Fisher exact test (2 × 2 contingency tables) for categorical variables. RESULTS: In total, 155 children with FGIDs were matched with 151 healthy controls. Children with FGIDs had historically significant greater frequency of 10 of 12 symptoms of orthostatic intolerance, no significant difference in any symptoms of orthostatic intolerance during recumbency, significantly greater frequency in 6 of 12 symptoms of orthostatic intolerance during orthostasis, trend toward statistical significance for orthostatic intolerance (P = .0509), and no significant difference in prevalence of orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS). There was no significant difference in prevalence of orthostatic intolerance, OH, and POTS between those with joint hypermobility and those without. CONCLUSIONS: Children with FGIDs have a greater prevalence of symptoms of orthostatic intolerance but were not more likely to have OH and POTS as compared with children without FGIDs. Children with joint hypermobility did not have a greater prevalence of orthostatic intolerance, OH, and POTS.

Complementary and Alternative Medicine Use in Pediatric Functional Abdominal Pain Disorders at a Large Academic Center.

OBJECTIVE: To describe the use of complementary and alternative medicine (CAM) in pediatric functional abdominal pain disorders at a large Midwestern pediatric gastroenterology center. STUDY DESIGN: A survey of patients attending a follow-up visit for functional abdominal pain disorders was completed. Data were collected on demographics, quality of life, use of conventional therapies, patient's opinions, and perception of provider's knowledge of CAM. RESULTS: Of 100 respondents (mean age, 13.3 ± 3.5 years), 47 (60% female) had irritable bowel syndrome, 29 (83% female) had functional dyspepsia, 18 (67% female) had functional abdominal pain, and 6 (83% female) had abdominal migraine (Rome III criteria). Ninety-six percent reported using at least 1 CAM modality. Dietary changes were undertaken by 69%. Multivitamins and probiotics were the most common supplements used by 48% and 33% of respondents, respectively. One-quarter had seen a psychologist. Children with self-reported severe disease were more likely to use exercise (P < .05); those with active symptoms (P < .01) or in a high-income group (P < .05) were more likely to make dietary changes; and those without private insurance (P < .05), or who felt poorly informed regarding CAM (P < .05), were more likely to use vitamins and supplements. Seventy-seven percent of patients described their quality of life as very good or excellent. CONCLUSIONS: The use of CAM in children with functional abdominal pain disorders is common, with a majority reporting a high quality of life. Our study underscores the importance of asking about CAM use and patient/family knowledge of these treatments.

The Relationship Between Prematurity, Method of Delivery, and Functional Gastrointestinal Disorders in Children.

OBJECTIVE: The pathogenesis of functional gastrointestinal disorders (FGIDs) remains unknown. Early life events including method of delivery and length of gestation may be risk factors for FGIDs. Data from studies on early life events and the development of FGIDs are scarce and contradictory. OBJECTIVE: The aim of the study was to assess the association between mode of delivery, length of gestation, and FGIDs in children. We hypothesized that delivery via Cesarean section and prematurity would be associated with an increased prevalence of FGIDs. METHODS: Questionnaires were mailed to families from 3 cities in Colombia. Parents provided information on mode of delivery, demographics, and medical history. School children completed the Spanish version of the Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV. Categorical data were analyzed using Fisher exact tests. Calculation of odds ratio with 95% confidence interval was performed. RESULTS: A total of 1497 children (535 preadolescents 10-12 years, 962 adolescents 13-18 years) participated. For participants born via Cesarean delivery, there was no significant increase in prevalence of any of the Rome IV FGIDs compared with vaginal delivery. There was a significant association between prematurity and FGIDs for those born between 28 and 32 weeks (confidence interval 0.99-3.37; P = 0.03). In this group, functional nausea was the only category of FGID to reach significance (0.16-112.23) (P = 0.02). However, statistical significance was lost when gestational ages were grouped together with multivariate analysis. CONCLUSIONS: Our findings provide evidence that Cesarean delivery and prematurity are not risk factors for the development of FGIDs. Future studies are indicated to further evaluate the relationship between early life events and FGIDs.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

The Effects of the Rome IV Criteria on Pediatric Gastrointestinal Practice.

PURPOSE OF REVIEW: To evaluate the impact of the implementation of the Rome IV criteria on pediatric gastrointestinal practice. RECENT FINDINGS: In 2016, the Rome IV criteria were published, providing an update of symptom-based criteria to diagnose children with functional gastrointestinal disorders (FGIDs). For neonates and toddlers, Wessel's criteria for diagnosing infant colic were abandoned, and a differentiation was made between toilet-trained and non-toilet-trained children in the diagnosis of functional constipation. For children and adolescents, two new disorders (functional nausea and functional vomiting) are described, and in the diagnosis of functional dyspepsia, pain does not have to be the chief complaint anymore. This change has made functional dyspepsia the most common functional abdominal pain disorder, exceeding the prevalence of irritable bowel syndrome (IBS). Lastly, the diagnosis of abdominal migraine was narrowed, causing an appropriate drop in its prevalence.

Abdominal migraines: Variations in diagnosis and care between pediatric gastroenterologists and neurologists. / Migraña Abdominal: Variaciones en el diagnóstico y tratamiento entre gastroenterólogos y neurólogos pediatras.

INTRODUCTION: Abdominal migraine (AM) is uncommon and understudied. Our objective was to investigate the diagnosis and treatment of children and adolescents with AM and compare with that of pediatric gastroenterologists and neurologists. PATIENTS AND METHOD: All AM cases (1-18 years) from a USA hospital with diagnosis of abdominal migraine or its variants (ICD-9 346.2 or IC-10 G43.D, G43.D0, G43.D1) between 2011 and 2017 were reviewed. Information on diagnosis, interval from onset of symptoms, diagnostic criteria, diagnostic tests, treatment, and outcome were analyzed. RESULTS: 69 medical records were identified. The mean age at diagnosis was 9.7 years, and 48% of patients were female. 50/69 (72.4%) patients were exclusively treated by a pediatric gastroenterologist and 10/69 (14.5%) exclusively by a pediatric neurologist. 6/69 (8.7%) were initially evaluated by gas troenterology and referred to neurology, and 2/69 (2.9%) were initially evaluated by neurology and then referred to gastroenterology. 3/10 (30%) of the AM diagnosed by neurologists did no report ab dominal pain (AP), however, all diagnoses made by gastroenterologists did (p = 0.0035). 5/50 (10%) of the gastroenterology medical records and no neurology medical records mentioned Rome criteria. CONCLUSIONS: Most of the children were diagnosed by pediatric gastroenterologists. Gastroenterolo gists rarely use the Rome criteria. Patients evaluated by neurologists are frequently diagnosed with AM even without AP (a criterion that is required for its diagnosis). Education is recommended for the correct and timely diagnosis of AM.