Jan A. J. M. Taminiau

Childhood constipation: longitudinal follow-up beyond puberty

BACKGROUND & AIMS Sparse data exist about the prognosis of childhood constipation and its possible persistence into adulthood. METHODS A total of 418 constipated patients older than 5 years at intake (279 boys; median age, 8.0 yr) participated in studies evaluating therapeutic modalities for constipation. All children subsequently were enrolled in this follow-up study with prospective data collection after an initial 6-week intensive treatment protocol, at 6 months, and thereafter annually, using a standardized questionnaire. RESULTS Follow-up was obtained in more than 95% of the children. The median duration of the follow-up period was 5 years (range, 1-8 yr). The cumulative percentage of children who were treated successfully during follow-up was 60% at 1 year, increasing to 80% at 8 years. Successful treatment was more frequent in children without encopresis and in children with an age of onset of defecation difficulty older than 4 years. In the group of children treated successfully, 50% experienced at least one period of relapse. Relapses occurred more frequently in boys than in girls (relative risk 1.73; 95% confidence interval, 1.15-2.62). In the subset of children aged 16 years and older, constipation still was present in 30%. CONCLUSIONS After intensive initial medical and behavioral treatment, 60% of all children referred to a tertiary medical center for chronic constipation were treated successfully at 1 year of follow-up. One third of the children followed-up beyond puberty continued to have severe complaints of constipation. This finding contradicts the general belief that childhood constipation gradually disappears before or during puberty.

Biofeedback training in treatment of childhood constipation: a randomised controlled study

BACKGROUND Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training. METHODS Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly. FINDINGS 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome. INTERPRETATION Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial

Background: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. Aims: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. Patients: One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. Methods: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children ⩾6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. Results: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. Conclusions: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Childhood constipation: Is there new light in the tunnel?

IntroductionConstipation is a common phenomenon in childhood worldwide. The symptoms vary from mild and short-lived to severe and chronic with faecal impaction and encopresis. Although our understanding of pathophysiology has grown rapidly in recent decades, the causes and management of constipation

Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: A hypothesis

BACKGROUND/AIMS Clinical interpretation of urinary recovery ratios of lactulose and mannitol is hampered by incomplete understanding of the mechanisms of transmucosal passage. The aim of this study was to compare in vivo and in vitro probe permeability. METHODS Stripped sheets of small intestine from rodents and human biopsy specimens were mounted in Ussing chambers, and mucosa-to-serosa fluxes of lactulose and mannitol were determined. Urinary recovery of orally applied probes was measured in rodents, cats, and humans. RESULTS In vitro lactulose/mannitol flux ratios were close to 0.8 in all species. Urinary recovery ratios differed between rodents and cats or humans; low ratios in cats and humans were due to high mannitol recovery. CONCLUSIONS Interspecies variation in urinary recovery of mannitol is caused by differences specific for the intact small intestines in vivo. Because hyperosmolality of villus tips in vivo varies, being highest in humans and cats as a result of vascular countercurrent multiplication, it is hypothesized that the high urinary recovery of mannitol in these species is caused by solvent drag through pores that allow the passage of mannitol but not of lactulose. Therefore, the lactulose/mannitol ratio is primarily a standard for the normal functioning of villus epithelial cells in metabolite absorption and for normal villus blood flow.

Treatment of inflammatory bowel disease in childhood: Best available evidence

The physician treating children with inflammatory bowel disease is confronted with a number of specific problems, one of them being the lack of randomized, controlled drug trials in children. In this review, the role of nutritional therapy is discussed with a focus on primary treatment, especially for children with Crohns disease. Then, the available medical therapies are highlighted, reviewing the evidence of effectiveness and side effects in children, as compared with what is known in adults. Nutritional therapy has proven to be effective in inducing and maintaining remission in Crohns disease while promoting linear growth. Conventional treatment consists of aminosalicylates and corticosteroids, whereas the early introduction of immunosuppressives (such as azathioprine or 6-mercaptopurine) is advocated as maintenance treatment. If these drugs are not tolerated or are ineffective, methotrexate may serve as an alternative in Crohns disease. Cyclosporine is an effective rescue therapy in severe ulcerative colitis, but only will postpone surgery. A novel strategy to treat Crohns disease is offered by infliximab, a monoclonal antibody to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Based on the best-available evidence, suggested usage is provided for separate drugs with respect to dosage and monitoring of side effects in children.

Colonic transit time in constipated children: does pediatric slow-transit constipation exist?

In adults, slow-transit constipation is a well-established form of constipation with abdominal pain and an empty rectum on examination. Marker studies in these patients, mainly women, show a markedly slowed transit time in all colonic segments. No studies in constipated children are available that assess the existence of slow-transit constipation. In a prospective study, a total of 94 referred constipated pediatric patients, 63 boys and 31 girls (median age, 8.0 years), underwent colonic-transit-time measurements using radioopaque markers to evaluate the pattern of transit. In addition, orocecal-transit-time measurements using the hydrogen breath (lactulose) test, anorectal manometry, and behavior studies using the Child Behavior Checklist were performed in all children. Based on the upper limit (mean + 2 SD) of total colonic transit time (CTT) in constipated children, we arbitrarily separated patients into two groups. Children with CTTs > 100 h were said to have pediatric slow-transit constipation (PSTC), while patients with CTTs < 100 h were said to have normal- or delayed-transit constipation (NDTC). In 94 constipated children, PSTC was found in 24 children; in 70 children, total CTT was < 100 h (NDTC). Total and segmental CTTs were significantly prolonged in PSTC (median, 189 h; range, 104.4-384) versus NDTC (median, 46.8 h; range, 3.6-99.4) hours. No significant differences were found in orocecal transit time. Significant clinical differences in children with PSTC versus those with NDTC existed regarding nighttime soiling (71 vs. 11%); daytime soiling episodes (14 vs. 7 each week, median), and nighttime soiling episodes (5 vs. 0 each week, median); absent urge to defecate (33 vs. 14%); and palpable abdominal (71 vs. 39%) and/or rectal (71 vs. 13%) masses. All manometric parameters were comparable in the two groups, except for a significantly lower maximal squeeze pressure with PSTC. Using the Child Behavior Checklist, both groups differed significantly from controls (26 and 43%, respectively), with no significant differences in behavior problems found between the NDTC and the PSTC groups. In conclusion, based on objective marker studies, our findings suggest the existence of pediatric slow-transit constipation. This entity can be recognized by clinical features, most importantly nighttime soiling and a palpable rectal mass. The probability of PSTC with both of these symptoms was 0.82; in the absence of these two symptoms, it was 0.07. It is of interest that CTTs in PSTC are comparable with CTTs in adults with slow-transit constipation, although the clinical presentation is clearly different. Further studies are needed to investigate whether the prolonged CTT characterizes a distinct form of constipation in children or is an epiphenomenon of the underlying constipation itself. The mechanisms responsible for the slow transit in these children and the appropriate therapeutic approach need to be studied.

Randomised trial of biofeedback training for encopresis.

AIMS: To evaluate biofeedback training in children with encopresis and the effect on psychosocial function. DESIGN: Prospective controlled randomised study. PATIENT INTERVENTIONS: A multimodal treatment of six weeks. Children were randomised into two groups. Each group received dietary and toilet advice, enemas, oral laxatives, and anorectal manometry. One group also received five biofeedback training sessions. MAIN OUTCOME MEASURES: Successful treatment was defined as less than two episodes of encopresis, regular bowel movements, and no laxatives. Psychosocial function after treatment was assessed using the Child Behaviour Checklist. RESULTS: Children given laxatives and biofeedback training had higher success rates than those who received laxatives alone (39% v 19%) at the end of the intervention period. At 12 and 18 months, however, approximately 50% of children in each group were successfully treated. Abnormal behaviour scores were initially observed in 35% of children. Most children had improved behaviour scores six months after treatment. Children with an initial abnormal behaviour score who were successfully treated had a significant improvement in their behavioural profiles. CONCLUSIONS: Biofeedback training had no additional effect on the success rate or behaviour scores. Psychosocial problems are present in a subgroup of children with encopresis. The relation between successful treatment and improvement in behavioural function supports the idea that encopresis has an aetiological role in the occurrence and maintenance of behavioural problems in children with encopresis.

Genetic susceptibility has a more important role in pediatric‐onset Crohn's disease than in adult‐onset Crohn's disease

Background: Genetic susceptibility may play a more important role in the etiology of early‐onset inflammatory bowel disease (IBD) than in late‐onset IBD, and therefore pediatric‐onset IBD patients can be expected to have a higher frequency of gene mutations. We aimed to determine genotypes and phenotypes of patients with pediatric‐onset IBD, to compare them with those of patients with adult‐onset IBD and with controls, and to identify genotype–phenotype associations. Methods: Polymorphisms R702W, G908R, and 3020insC of CARD15 (caspase activating recruitment domain 15); Asp299Gly and Thr399Ile of TLR4; ‐207G→C, 1672C→T (L503F), rs3792876, rs274551, rs272893, and rs273900 of SLC22A4/5; and 113G→A as well as rs2289311, rs1270912, and rs2165047 of DLG5 (Drosophila discs large homologue 5) were assessed in 103 pediatric‐onset and 696 adult‐onset IBD patients. Phenotypic classification was based on disease localization and behavior. Results: Homozygosity for 3020insC in CARD15 was significantly higher in patients with pediatric‐onset Crohns disease (CD) than in patients with adult‐onset CD (4.2% versus 0.6%, 95% confidence interval [CI] 1.2–42.0). Homozygosity for single‐nucleotide polymorphism (SNP) rs3792876 in SLC22A4/5 was significantly higher in patients with pediatric‐onset CD than in patients with adult‐onset CD (6.1% versus 1.1%, P = 0.02). Polymorphism 3020insC in CARD15 was associated with ileal involvement (1.9% versus 13.3%, CI 1.0–53.8) and a positive family history (6.1% versus 20%, CI 1.2–9.0). DLG5 SNP rs2165047 was significantly associated with perianal disease (50% versus 21.2%, CI 1.4–4). Conclusions: Polymorphisms 3020insC in CARD15 and SNP rs3792876 in SLC22A4/5 occurred statistically significantly more often in patients with pediatric‐onset CD than in patients with adult‐onset CD. Polymorphisms 3020insC in CARD15 and SNP rs2165047 in DLG5 were associated with specific phenotypes in this pediatric‐onset CD cohort.

The clinical effect of a new infant formula in term infants with constipation: a double-blind, randomized cross-over trial

BackgroundNutrilon Omneo (new formula; NF) contains high concentration of sn-2 palmitic acid, a mixture of prebiotic oligosaccharides and partially hydrolyzed whey protein. It is hypothesized that NF positively affects stool characteristics in constipated infants.MethodsThirty-eight constipated infants, aged 3–20 weeks, were included and randomized to NF (n = 20) or a standard formula (SF; n = 18) in period 1 and crossed-over after 3 weeks to treatment period 2. Constipation was defined by at least one of the following symptoms: 1) defecation frequency < 3/week; 2) painful defecation; 3) abdominal or rectal palpable mass.ResultsPeriod 1 was completed by 35 infants. A significant increase in defecation frequency (NF: 3.5 pre versus 5.6/week post treatment; SF 3.6 pre versus 4.9/week post treatment) was found in both groups, but was not significantly different between the two formulas (p = 0.36). Improvement of hard stool consistency to soft stool consistency was found more often with NF than SF, but did not reach statistical significance (90% versus 50%; RR, 1.8; 95% CI, 0.9–3.5; p = 0.14). No difference was found in painful defecation or the presence of an abdominal or rectal mass between the two groups. Twenty-four infants completed period 2. Only stool consistency was significantly different between the two formulas (17% had soft stools on NF and hard stools on SF; no infants had soft stools on SF and hard stools on NF, McNemar test p = 0.046).ConclusionThe addition of a high concentration sn-2 palmitic acid, prebiotic oligosaccharides and partially hydrolyzed whey protein resulted in a strong tendency of softer stools in constipated infants, but not in a difference in defecation frequency. Formula transition to NF may be considered as treatment in constipated infants with hard stools.