Suzanne M. Mugie

Epidemiology of constipation in children and adults: A systematic review

We aimed to review the published literature regarding the epidemiology of constipation in the general paediatric and adult population and to assess its geographic, gender and age distribution, and associated factors. A search of the Medline database was performed. Study selection criteria included: (1) studies of population-based samples; (2) containing data on the prevalence of constipation without obvious organic aetiology; (3) in paediatric, adult or elderly population; (4) published in English and full manuscript form. Sixty-eight studies met our inclusion criteria. The prevalence of constipation in the worldwide general population ranged from 0.7% to 79% (median 16%). The epidemiology of constipation in children was investigated in 19 articles and prevalence rate was between 0.7% and 29.6% (median 12%). Female gender, increasing age, socioeconomic status and educational level seemed to affect constipation prevalence.

Constipation in childhood

Constipation in children is an often long-lasting pediatric functional gastrointestinal disorder with a worldwide prevalence varying between 0.7% and 29.6%, and estimated health-care costs of US

Management of functional constipation in children with lower urinary tract symptoms: report from the Standardization Committee of the International Children's Continence Society

3.9 billion per year in the USA alone. The pathophysiology of childhood constipation is multifactorial and remains incompletely understood; however, withholding of stools, starting after an experience of a hard, painful, or frightening bowel movement is the most common cause found in children. A thorough medical history and physical examination, including a rectal examination in combination with a bowel diary, is sufficient in the majority of cases to diagnose constipation. The current standard treatment consists of education, toilet training, disimpaction, maintenance therapy and long-term follow-up. In the past decade, well-designed treatment trials in the pediatric population have emerged and long-term outcome studies have been completed. This Review summarizes the current knowledge of the clinical aspects of childhood constipation, including pathogenesis, diagnosis and treatment, with particular emphasis on the latest available data.

Ten-Year Experience Using Antegrade Enemas in Children

PURPOSE We present a consensus view of members of the International Childrens Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms. MATERIALS AND METHODS Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary. RESULTS Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined. CONCLUSIONS The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings.

Prucalopride Is No More Effective Than Placebo for Children With Functional Constipation

OBJECTIVE To describe a single-center, 10-year experience with the use of antegrade enemas. STUDY DESIGN Retrospective analysis of 99 patients treated with antegrade enemas at Nationwide Childrens Hospital. RESULTS Study subjects (median age 8 years) were followed for a mean time of 46 months (range 2-125 months) after cecostomy placement. Seventy-one patients had the cecostomy placed percutaneously and 28 by surgery. Thirty-five patients had functional constipation and 64 patients an organic disease (spinal abnormalities, cerebral palsy, imperforate anus, Hirschsprungs disease). While using antegrade enemas, 71% became symptom-free, in 20 subjects symptoms improved, in 2 subjects symptoms did not change, and in 7 subjects symptoms worsened. Poor outcome was associated with surgical placement of the cecostomy (P < .001), younger age (P = .02), shorter duration of symptoms (P = .01), history of Hirschsprungs disease (P = .05), cerebral palsy (P = .03), previous abdominal surgery (P = .001), and abnormal colonic manometry (P = .004). In 88%, successful irrigation solution included use of a stimulant laxative, and subjects who used a stimulant did significantly better (P < .001) than subjects who started without a stimulant. In 13 patients, the cecostomy was removed 49.7 months after placement without recurrence of symptoms. Major complications occurred in 12 patients and minor complications in 47. CONCLUSIONS Antegrade enemas represent a successful and relatively safe therapeutic option in children with severe defecatory disorders. Prognostic factors are identified.

Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation.

BACKGROUND & AIMS Prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine (serotonin) receptor 4 that enhances motility in the gastrointestinal tract. We performed a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of prucalopride in children (6 months to 18 years old) with functional constipation. METHODS Children with functional constipation, based on the Rome III criteria, were given prucalopride (children ≤ 50 kg were given a 0.04 mg/kg oral solution; children >50 kg were given a 2-mg tablet) or placebo once daily for 8 weeks. The primary efficacy end point was the proportion of children with toileting skills who had a mean of ≥ 3 spontaneous bowel movements/week and ≤ 1 episode of fecal incontinence/2 weeks, from study weeks 5-8 (responders). Adverse events, clinical laboratory values, and electrocardiograms were monitored. RESULTS Efficacy and safety were assessed in 213 children (106 prucalopride, 107 placebo). Twenty-five percent were younger than 4 years old, 50% were 4-11 years old, and 25% were 12-18 years old; 55.4% were girls. At screening, 62.3% of patients in the prucalopride group and 55.1% in the placebo group had a history of fecal incontinence; 60.4% and 55.1% in the prucalopride and placebo groups, respectively, had a mean of ≤ 1 spontaneous bowel movements/week. The proportion of responders was similar between groups (prucalopride, 17.0% and placebo, 17.8%). There were no statistically significant differences in the primary efficacy end point when patients were stratified by sex, age group, or country. The incidence of treatment-emergent adverse events was similar in the prucalopride (69.8%) and placebo (60.7%) groups. CONCLUSIONS Prucalopride, although generally well tolerated, was not more effective than placebo in children with functional constipation. ClinicalTrials.gov Number: NCT01330381.

Efficacy and safety of prucalopride in adults and children with chronic constipation

Objective: In adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. The objective of this study was to compare the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. Methods: Twenty-six children (mean age 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen &kgr; was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. Results: Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%. The &kgr; score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy. Eighty-eight percent of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. Conclusions: Colonic manometry and colonic scintigraphy have a fair agreement regarding the categorization of constipation. Scintigraphy is well tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation.

Brain processing of rectal sensation in adolescents with functional defecation disorders and healthy controls

Introduction: Chronic constipation (CC) is a debilitating condition with high prevalence rates both in children and adults. Despite the broad range of medical and pharmaceutical treatments, the bowel function does not restore in a fair amount of patients. Prucalopride is a first-in-class selective, high affinity serotonin 5-hydroxytryptamine type 4 (5-HT4) receptor agonist promoting gastro-intestinal prokinetic activity and has been evaluated for the treatment of CC. Areas covered: A PubMed search (1965 – 2014) using the following terms alone or in combination: prucalopride, 5-HT4, R093877, safety, toxicity, pharmacokinetics, pharmacodynamics, transit, cardiac, human ether-a-go-go related gene (hERG), arrhythmia, potassium current, elderly, children. Expert opinion: Prucalopride, a highly selective 5-HT4 receptor agonist, stimulates gastrointestinal motility and has been proven to be effective in the treatment of CC in adults by increasing stool frequency, reducing constipation-related symptoms and improving quality of life (QoL). The safety and tolerability have been proven to be excellent. More research would be preferable on the effect of prucalopride on men, children and in other gastrointestinal motility disorders.

242 Brain Processing of Rectal Sensation in Children With Chronic Functional Constipation

Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross‐sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs).

Epidemiology of Constipation in Children and Adults

Background and Objective: The pathophysiology underlying pediatric chronic functional constipation (FC) is poorly understood. These children often report loss of sensation of urge to defecate. Functional magnetic resonance imaging (fMRI) studies have been used to unravel brain processing of visceral sensation in adults with functional gastrointestinal disorders. However, brain-imaging data are lacking in both adults and children with constipation. The aim is to investigate the cerebral activity in response to rectal distension in children with FC and in healthy controls (HCs). Methods: 15 patients with FC (8M/7F; mean age 14.3 yrs, range 12-18 yrs) and 15 HCs (6M/9F; mean age 20.1 yrs, range 18-21 yrs) participated. Rectal barostat was performed prior to the fMRI scan. A stepwise pressure-controlled distension protocol was used to determine the pressure threshold for urge sensation. Subjects received 2 sessions of 5 stimulations consisting of repetitions of 30 sec of rectal stimulation with previous defined pressure threshold, followed by 30 sec of rest during acquisition blood oxygenation level-dependent (BOLD) fMRI. Images were acquired on a 3Tesla MRI scanner with an 8-channel SENSE head receive coil. A T2*-weighted echo planar imaging sequence was acquired with: TR/TE=3000/30 ms, slice thickness=3.0 mm, voxel size=1.72 x 1.72 x 3 mm, with 40 axial slices, in ascending mode covering the whole brain. fMRI signal differences were analyzed using SPM8 in Matlab, thresholded at p<0.001. Cerebral activation was defined as BOLD increase during rectal distension and cerebral deactivation as BOLD decrease during rectal distension. Results: FC patients had higher thresholds for urgency than HCs (p<0.001). FC patients needed a mean pressure of 18.2 mmHg above MDP to provoke urge sensation, compared to a mean pressure of 8.6 mmHg above MDP in HCs. The groups were differentiated by both activated and deactivated regions in response to rectal distension. FC patients showed activation in the dorsolateral prefrontal cortex and deactivation in the median somatosensory cortex, insula and amygdala. HCs showed deactivation in the same areas, but in contrast, no regions showed significant activation in response to rectal distension. Conclusion: This is the first study evaluating cerebral processing of rectal sensation in constipated patients. FC patients and HCs had a different pattern of cerebral activation and deactivation during rectal distension, suggesting different neural processing of rectal urge sensation in brain regions previously implicated in adult studies using visceral pain stimuli.