Treatments for intractable constipation in childhood.

BACKGROUND: Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe. OBJECTIVES: To evaluate the efficacy and safety of treatments used for intractable constipation in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome. MAIN RESULTS: This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 µg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes. AUTHORS' CONCLUSIONS: We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.

An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology.

Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered . Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low-FODMAP diet is considered in children.

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.

Controversies in the Management of Functional Constipation in Children.

PURPOSE OF REVIEW: Functional constipation (FC) in children is a common health problem with reported worldwide prevalence rates up to 32.2%. The majority of children with constipation respond to oral laxative treatment. After 5 years of intensive treatment, however, approximately 50% of children remain symptomatic. To discuss the evidence for new treatments in these children, including pre- and probiotics, pelvic physiotherapy, prucalopride, sacral nerve stimulation, and surgery, and to highlight the controversies surrounding them. RECENT FINDINGS: Pre- and probiotics and prucalopride are not effective in the treatment of childhood constipation. Pelvic physiotherapy and sacral nerve stimulation are promising treatment options but larger trials are needed. Surgery for pediatric constipation is the treatment of last resort. Large, well-designed placebo-controlled trials with proper outcome measures, as suggested by the Rome foundation pediatric subcommittee on clinical trials, are necessary to provide more insight regarding the efficacy of new treatments in childhood constipation.

Sacral neuromodulation versus personalized conservative treatment in patients with idiopathic slow-transit constipation: study protocol of the No.2-trial, a multicenter open-label randomized controlled trial and cost-effectiveness analysis.

PURPOSE: The evidence regarding the (cost-)effectiveness of sacral neuromodulation (SNM) in patients with therapy-resistant idiopathic slow-transit constipation is of suboptimal quality. The Dutch Ministry of Health, Welfare and Sports has granted conditional reimbursement for SNM treatment. The objective is to assess the effectiveness, cost-effectiveness, and budget impact of SNM compared to personalized conservative treatment (PCT) in patients with idiopathic slow-transit constipation refractory to conservative treatment. METHODS: This study is an open-label, multicenter randomized controlled trial. Patients aged 14 to 80 with slow-transit constipation, a defecation frequency (DF) < 3 per week and meeting at least one other Rome-IV criterion, are eligible. Patients with obstructed outlet, irritable bowel syndrome, bowel pathology, or rectal prolapse are excluded. Patients are randomized to SNM or PCT. The primary outcome is success at 6 months (DF ≥ 3 a week), requiring a sample size of 64 (α = 0.05, ß = 0.80, 30% difference in success). Secondary outcomes are straining, sense of incomplete evacuation, constipation severity, fatigue, constipation specific and generic quality of life, and costs at 6 months. Long-term costs and effectiveness will be estimated by a decision analytic model. The time frame is 57 months, starting October 2016. SNM treatment costs are funded by the Dutch conditional reimbursement program, research costs by Medtronic. CONCLUSIONS: The results of this trial will be used to make a final decision regarding reimbursement of SNM from the Dutch Health Care Package in this patient group. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov , identifier NCT02961582, on 12 October 2016.

Long-term outcome of intractable constipation treated by sacral neuromodulation: a comparison between children and adults.

AIM: Sacral neuromodulation (SNM) is a minimally invasive therapy for functional constipation (FC) and is most often used to treat adults. Recent studies suggest that SNM may also beneficial in children. However, comparative data regarding preferred age of SNM for FC are lacking. Therefore, long-term results of SNM for FC were compared between children and adults. METHOD: All patients treated with SNM for FC between 2004 and 2015 were evaluated. Outcomes of children (age 10-18 years) were compared with those for adults (≥ 18 years). The primary end-point was a defaecation frequency of three or more times per week, which is consistent with the ROME-III criteria. Secondary outcomes were quality of life (QoL; SF-36) and the Cleveland Clinic Constipation Score. RESULTS: One hundred and eighty patients (45 children, 135 adults) were eligible for SNM. The mean age was 15.8 (children) and 41.4 years (adults). One hundred and twenty-six patients received permanent SNM (38 children, 88 adults). Mean follow-up was 47 months in both groups. Defaecation frequency increased in both groups after SNM compared with baseline. Defaecation frequency in adults was higher than in children. The increased defaecation frequency was maintained during the entire follow-up period in both groups. QoL of children was impaired compared with the Dutch population with regard to bodily pain, general health and vitality. Adults had worse QoL with regard to physical functioning, bodily pain, general health, vitality and social functioning compared with the Dutch population. QoL of children did not differ from adults. CONCLUSION: Sacral neuromodulation (SNM) should be considered in children (< 18 years) with FC. However, the indication of SNM for FC remains debatable considering the limited improvements and high costs.

Outcome after restorative proctocolectomy and ileal pouch-anal anastomosis in children and adults.

BACKGROUND: Studies comparing the outcome of ileal pouch-anal anastomosis (IPAA) in children and adults are scarce. This complicates decision-making in young patients. The aim of this study was to compare adverse events and pouch function between children and adults who underwent IPAA. METHODS: This cross-sectional cohort study included all consecutive children (aged less than 18 years) and adults with a diagnosis of inflammatory bowel disease or familial adenomatous polyposis who underwent IPAA in a tertiary referral centre between 2000 and 2015. Adverse events were assessed by chart review, and pouch function by interview using a pouch function score (PFS). RESULTS: In total, 445 patients underwent IPAA: 41 children (median age 15 years) and 404 adults (median age 39 years), with a median follow-up of 22 (i.q.r. 8-68) months. Being overweight (P = 0·001), previous abdominal surgery (P = 0·018), open procedures (P < 0·001) and defunctioning ileostomy (P = 0·014) were less common among children than adult patients. The occurrence of anastomotic leakage, surgical fistulas, chronic pouchitis and Crohn's of the pouch was not associated with paediatric age at surgery, nor was pouch failure. The development of anastomotic strictures was associated with having IPAA surgery during childhood (odds ratio 4·22, 95 per cent c.i. 1·13 to 15·77; P = 0·032). Pouch function at last follow-up was similar in the children and adult groups (median PFS 5·0 versus 6·0 respectively; P = 0·194). CONCLUSION: Long-term pouch failure rates and pouch function were similar in children and adults. There is no need for a more cautious attitude to use of IPAA in children based on concerns about poor outcome.

Cost-effectiveness of sacral neuromodulation for chronic refractory constipation in children and adolescents: a Markov model analysis.

AIM: This study aimed to assess the cost-effectiveness of sacral neuromodulation (SNM) compared with conservative treatment in children and adolescents with constipation refractory to conservative management. METHOD: A Markov probabilistic model was used, comparing costs and effectiveness of SNM and conservative treatment in children and adolescents aged 10-18 years with constipation refractory to conservative management. Input for the model regarding transition probabilities, utilities and healthcare costs was based on data from a cohort of patients treated in our centre. This cohort consisted of 30 female patients (mean age 16 years) with functional constipation refractory to conservative management. The mean duration of laxative use in this group was 5.9 years. All patients had a test SNM, followed by a permanent SNM in 27/30. Median follow-up was 22.1 months (range 12.2-36.8). The model was run to simulate a follow-up period of 3 years. RESULTS: The mean cumulative costs for the SNM group and the conservative treatment group were €17 789 (SD €2492) and €7574 (SD €4332) per patient, respectively. The mean quality adjusted life years (QALYs) in the SNM group was 1.74 (SD 0.19), compared with 0.86 (SD 0.14) in the conservatively managed group. The mean incremental cost-effectiveness ratio was €12 328 per QALY (SD €4788). Sensitivity analysis showed that the outcomes were robust to a wide range of model assumptions. CONCLUSION: Chronic constipation seriously affects the quality of life of children and adolescents. Preliminary evidence suggests that SNM can improve symptoms and quality of life at a reasonable cost.

Intensive lifestyle treatment for non-alcoholic fatty liver disease in children with severe obesity: inpatient versus ambulatory treatment.

BACKGROUND/AIMS: Lifestyle intervention is the only established therapy for non-alcoholic fatty liver disease (NAFLD). The optimal treatment schedule and predictors of response of this treatment have not been established in children. We aimed to evaluate the 2-year efficacy of an inpatient versus ambulatory intensive lifestyle intervention for treating NAFLD in children with severe obesity. METHODS: A cohort study of 51 severely obese non-diabetic children (mean age 14.7 (±2.4) years; BMI-z-score 3.5 (±0.5)) with liver steatosis were non-randomly allocated to inpatient treatment (2 or 6 months), ambulatory treatment or usual care. Proton Magnetic Resonance Spectroscopy determined liver steatosis and serum alanine aminotransferase (ALT) at 6 months were the primary outcome measures. Baseline variables were evaluated as predictors of treatment response. RESULTS: Liver steatosis had disappeared in 43, 29 and 22% and serum ALT normalized in 41, 33 and 6% at the end of 6 months in the inpatient, ambulatory or usual care treatment groups, respectively. Only the proportions of ALT normalization in inpatient and ambulatory treatment compared with usual care were significantly higher. Treatment effects of inpatient and ambulatory treatment were sustained at 1.5 years follow-up. No baseline characteristic, including PNPLA3 polymorphism or leptin, was consistently predictive for treatment response. CONCLUSIONS: A 6-month intensive inpatient and ambulatory lifestyle treatment in children with severe obesity reverses NAFLD in a minority of patients. This study suggests that inpatient compared with ambulatory intensive treatment does not importantly increase treatment success. Further efforts to optimize and individualize lifestyle interventions and additional treatments options are needed particular for children with severe obesity resistant to conventional lifestyle interventions.

How to use a plain abdominal radiograph in children with functional defecation disorders.

Defecation-related functional gastrointestinal disorders (FGIDs), such as infant dyschezia, functional constipation and functional non-retentive faecal incontinence, as defined by the Rome IV criteria, are common problems in childhood. The symptomatology varies from relatively mild, such as crying before passage of soft stools or infrequent defecation to severe problems with faecal impaction and the daily involuntary loss of faeces in the underwear. Conventional radiography is widely available, relatively cheap and is non-invasive. The drawback however, is radiation exposure. This review describes and evaluates the value of different existing scoring methods to assess faecal loading on an abdominal radiograph with or without the use of radio-opaque markers, to measure colonic transit time, in the diagnosis of these defecation-related FGIDs. Insufficient evidence exists for a diagnostic association between clinical symptoms of functional constipation or functional nonretentive faecal incontinence and faecal loading on an abdominal radiograph. Furthermore, evidence does not support the routine use of colonic transit studies to diagnose functional constipation. Colonic transit time measurement may be considered in discriminating between functional constipation and functional non-retentive faecal incontinence and in patients in which the diagnosis is not clear such as having an unreliable medical history. In children with the suspicion of defecation-related FGIDs, the diagnosis should be made based on the Rome IV criteria.

Gallstone disease in severely obese children participating in a lifestyle intervention program: incidence and risk factors.

INTRODUCTION: Cholelithiasis is increasingly encountered in childhood and adolescence due to the rise in obesity. As in adults, weight loss is presumed to be an important risk factor for cholelithiasis in children, but this has not been studied. METHODS: In a prospective observational cohort study we evaluated the presence of gallstones in 288 severely obese children and adolescents (mean age 14.1±2.4 years, body mass index (BMI) z-score 3.39±0.37) before and after participating in a 6-month lifestyle intervention program. RESULTS: During the lifestyle intervention, 17/288 children (5.9%) developed gallstones. Gallstones were only observed in those losing >10% of initial body weight and the prevalence was highest in those losing >25% of weight. In multivariate analysis change in BMI z-score (odds ratio (OR) 3.26 (per 0.5 s.d. decrease); 95% CI:1.60-6.65) and baseline BMI z-score (OR 2.32 (per 0.5 s.d.); 95% CI: 1.16-4.70) were independently correlated with the development of gallstones. Sex, family history, OAC use, puberty and biochemistry were not predictive in this cohort. During post-treatment follow-up (range 0.4-7.8 years) cholecystectomy was performed in 22% of those with cholelithiasis. No serious complications due to gallstones occurred. CONCLUSION: The risk of developing gallstones in obese children and adolescents during a lifestyle intervention is limited and mainly related to the degree of weight loss and initial body weight.

Prolonged colonic manometry in children with defecatory disorders.

OBJECTIVES: Colonic manometry is a test used in the evaluation of children with defecation disorders unresponsive to conventional treatment. The most commonly reported protocol in pediatrics consists of a study that lasts approximately 4 hours. Given the wide physiological variations in colonic motility throughout the day, longer observation may detect clinically relevant information. The aim of the present study was to compare prolonged colonic manometry studies in children referred for colonic manometry with the more traditional short water-perfused technology. METHODS: Colonic manometry studies of 19 children (8 boys, mean age 9.4 ± 0.9, range 3.9-16.3) with severe defecation disorders were analyzed. First, a "standard test" was performed with at least 1-hour fasting, 1-hour postprandial, and 1-hour postbisacodyl provocation recording. Afterwards, recordings continued until the next day. RESULTS: In 2 of the 19 children, prolonged recording gave us extra information. In 1 patient with functional nonretentive fecal incontinence who demonstrated no abnormalities in the short recording, 2 long clusters of high-amplitude contractions were noted in the prolonged study, possibly contributing to the fecal incontinence. In another patient evaluated after failing use of antegrade enemas through a cecostomy, short recordings showed colonic activity only in the most proximal part of the colon, whereas the prolonged study showed normal motility over a larger portion of the colon. CONCLUSIONS: Prolonged colonic measurement provides more information regarding colonic motor function and allows detection of motor events missed by the standard shorter manometry study.

Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.

BACKGROUND: Constipation is a pediatric problem commonly encountered by many health care workers in primary, secondary, and tertiary care. To assist medical care providers in the evaluation and management of children with functional constipation, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition were charged with the task of developing a uniform document of evidence-based guidelines. METHODS: Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to October 2011 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence-Based Medicine. During 3 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no randomized controlled trials were available to support the recommendation. RESULTS: This evidence-based guideline provides recommendations for the evaluation and treatment of children with functional constipation to standardize and improve their quality of care. In addition, 2 algorithms were developed, one for the infants <6 months of age and the other for older infants and children. CONCLUSIONS: This document is intended to be used in daily practice and as a basis for further clinical research. Large well-designed clinical trials are necessary with regard to diagnostic evaluation and treatment.

New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children.

In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen.

Pediatric neurogenic bowel dysfunction: ICCS review document.

INTRODUCTION: The International Children's Continence Society (ICCS) aims to improve the quality of life in children with lower urinary tract dysfunction. A substantial portion of children also have problems with bowel dysfunction. There is a lack of evidence-based information on managing neurogenic bowel dysfunction (NBD) in children. OBJECTIVE/METHODS: The ICCS aimed to provide an up-to-date, selective, non-systematic review of NBD's definitions, assessment, and treatment. RESULTS: Specific definitions and terminology are defined within the document. Recommendations and considerations for physical assessment, history taking, and diagnostic studies are made. Management updates, both surgical and non-surgical, are provided as well as recommendations for follow-up and monitoring of individuals with NBD. CONCLUSION: This review of the current literature will help guide NBD management and research to improve NBD care.

Bowel Lengthening Procedures in Children with Short Bowel Syndrome: A Systematic Review.

INTRODUCTION: The aims of the study are to systematically assess and critically appraise the evidence concerning two surgical techniques to lengthen the bowel in children with short bowel syndrome (SBS), namely, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP), and to identify patient characteristics associated with a favorable outcome. MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till December 2019. No language restriction was used. RESULTS: In all, 2,390 articles were found, of which 40 were included, discussing 782 patients. The median age of the patients at the primary bowel lengthening procedure was 16 months (range: 1-84 months). Meta-analysis could not be performed due to the incomparability of the groups, due to heterogeneous definitions and outcome reporting. After STEP, 46% of patients weaned off parenteral nutrition (PN) versus 52% after LILT. Mortality was 7% for STEP and 26% for LILT. Patient characteristics predictive for success (weaning or survival) were discussed in nine studies showing differing results. Quality of reporting was considered poor to fair. CONCLUSION: LILT and STEP are both valuable treatment strategies used in the management of pediatric SBS. However, currently it is not possible to advise surgeons on accurate patient selection and to predict the result of either intervention. Homogenous, prospective, outcome reporting is necessary, for which an international network is needed.

Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case-control study.

Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case-control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1-3 days before diagnosis of severe NEC (Bell's stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids-isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1-3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.

Is Bifidobacterium breve effective in the treatment of childhood constipation? Results from a pilot study.

BACKGROUND: Probiotics are increasingly used in the treatment of functional gastrointestinal disorders. Studies in constipated adults with a Bifidus yoghurt (containing Bifidobacterium breve, Bifidobacterium bifidum and Lactobacillus acidophilus) showed a significant increase in defecation frequency. The aim of this pilot study was to determine if Bifidobacterium breve is effective in the treatment of childhood constipation. METHODS: Children, 3 to 16 years of age, with functional constipation according to the Rome III criteria were eligible for this study. During 4 weeks, children received one sachet of powder daily, containing 108- 1010 CFU Bifidobacterium breve. Furthermore, children were instructed to try to defecate on the toilet for 5-10 minutes after each meal and to complete a standardized bowel diary daily. The primary outcome measure was change in defecation frequency. Secondary outcome measures were stool consistency using the Bristol stool scale frequency of episodes of faecal incontinence, pain during defecation, frequency of abdominal pain, frequency of adverse effects (nausea, diarrhoea and bad taste), and frequency of intake of bisacodyl. RESULTS: Twenty children (75% male, mean age 7.4) were included in this pilot study. The defecation frequency per week significantly increased from 0.9 (0-2) at baseline to 4.9 (0-21) in week 4 (p < 0.01). The mean stool consistency score increased from 2.6 (2-4) at baseline to 3.5 (1-6) in week 4 (p = 0.03). The number of faecal incontinence episodes per week significantly decreased from 9.0 (0-35) at baseline to 1.5 (0-7) in week 4 (p < 0.01). Abdominal pain episodes per week significantly decreased from 4.2 (0-7) at baseline to 1.9 (0-7) in week 4 (p = 0.01). No side effects occurred. CONCLUSION: Bifidobacterium breve is effective in increasing stool frequency in children with functional constipation. Furthermore it has a positive effect with respect to stool consistency, decreasing the number of faecal incontinence episodes and in diminishing abdominal pain. A randomized placebo controlled trial is required to confirm these data.

Recurrent abdominal pain in 200 children: somatic causes and diagnostic criteria.

AIM: To establish to what extent somatic causes can be found in children referred to secondary care with recurrent abdominal pain. METHODS: For 2 years, all consecutive patients (age 4-16 years) fulfilling Apley criteria, referred to secondary care, were included. After a diagnostic work-up, stepwise therapeutic interventions were performed. A diagnosis was considered to be the cause of the pain when the patient became pain free following therapeutic intervention and remained so for at least 6 months. RESULTS: Two hundred and twenty children (128 F, 92 M; mean age 8.8 years) were enrolled, of which 20 were lost to follow-up. Spontaneous recovery was seen in 54 patients, (occult) constipation in 92 patients (of whom 18 also had a somatic cause), gastrointestinal infections in 40, food allergy in five, miscellaneous disorders in seven and uncertain diagnosis in 13. In five patients, stress most likely caused the pain. A total of 198 patients became pain free and remained so during follow-up (mean 18, range 6-60 months). CONCLUSION: In 200 children with recurrent abdominal pain, somatic causes were found in 26%. Laxative therapy was successful in 46%, resulting in nearly all patients with functional abdominal pain to become pain free. Eventually, 99% became pain free using a therapeutic intervention protocol.

Simultaneous assessment of colon motility in children with functional constipation by cine-MRI and colonic manometry: a feasibility study.

BACKGROUND: Colonic manometry is the current reference standard for assessing colonic neuromuscular function in children with intractable functional constipation (FC). Recently, cine magnetic resonance imaging (cine-MRI) has been proposed as a non-invasive alternative. We compared colonic motility patterns on cine-MRI with those obtained by manometry in children, by stimulating high-amplitude propagating contractions (HAPCs) with bisacodyl under manometric control while simultaneously acquiring cine-MRI. METHODS: After Institutional Review Board approval, adolescents with FC scheduled to undergo colonic manometry were included. A water-perfused 8-lumen catheter was used for colonic manometry recordings. After an intraluminal bisacodyl infusion, cine-MRI sequences of the descending colon were acquired for about 30 min simultaneously with colonic manometry. Manometry recordings were analysed for HAPCs. MRI images were processed with spatiotemporal motility MRI techniques. The anonymised motility results of both techniques were visually compared for the identification of HAPCs in the descending colon. RESULTS: Data regarding six patients (three males) were analysed (median age 14 years, range 12-17). After bisacodyl infusion, three patients showed a total of eleven HAPCs with colonic manometry. Corresponding cine-MRI recorded high colonic activity during two of these HAPCs, minimal activity during seven HAPCs, while two HAPCs were not recorded. In two of three patients with absent HAPCs on manometry, colonic activity was recorded with cine-MRI. CONCLUSIONS: Simultaneous acquisition of colonic cine-MRI and manometry in children with FC is feasible. Their motility results did not completely overlap in the identification of HAPCs. Research is needed to unravel the role of cine-MRI in this setting.