Wieger P. Voskuijl

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

Health related quality of life in disorders of defecation: the Defecation Disorder List

Background: Constipation and encopresis frequently cause problems with respect to emotional wellbeing, and social and family life. Instruments to measure Health Related Quality of Life (HRQoL) in these disorders are not available. Methods: A disease specific HRQoL instrument, the “Defecation Disorder List” (DDL) for children with constipation or functional non-retentive faecal soiling (FNRFS) was developed using accepted guidelines. For each phase of the process, different samples of patients were used. The final phase of development included 27 children. Reliability was assessed in two ways: internal consistency of domains with Cronbach’s alpha, and test-retest reliability with intra-class correlation coefficients (ICC). To assess validity, comparable items and domains were correlated with Tacqol, a generic HRQoL instrument for children (TNO-AZL). Results: In the final phase of the development, 27 children completed the instrument. It consisted of 37 items in four domains. The response rate was 96%. Reliability was good for all domains, with Cronbach’s alpha values ranging from 0.61 to 0.76. Measures of test-retest stability were good for all four domains with ICCs ranging from 0.82 to 0.92. Validity based on comparison with the Tacqol instrument was moderate. Conclusion: The DDL is promising as a measure of HRQoL in childhood defecation disorders.

Rectal compliance and rectal sensation in constipated adolescents, recovered adolescents and healthy volunteers

Objectives: A subgroup of children with functional constipation (FC) are unresponsive to conventional treatment. Abnormal rectal function due to increased distensibility (compliance) might be an underlying mechanism of therapy-resistant FC. It is hypothesised that rectal compliance is normal in patients who are successfully recovered from FC (RC). Methods: Using a barostat, a pressure-controlled intermittent distension protocol was performed in FC patients, RC subjects free of symptoms for at least 4 years and healthy volunteers (HVs). Rectal compliance was calculated using a non-linear mixed-effect model for volume–pressure curves. Results: Forty-seven FC patients, median (range) age of 12 (11–17) years, and 20 RC subjects, 15 (11–18) years, were studied and compared with 22 HVs, 14 (8–16) years. The median (5th–95th percentile) rectal compliance in HVs was 16 (12–20) ml/mm Hg. FC patients had a median rectal compliance of 25 (13–47) ml/mm Hg and RC subjects 20 (12–35) ml/mm Hg, which was significantly higher compared with HVs (p<0.001 and p = 0.003). RC subjects had lower rectal compliance when compared with FC patients (p = 0.02). Forty-five percent of RC subjects had a rectal compliance above the upper limit of normal (>95th percentile of HVs), which was significantly less compared with 75% of FC patients (p = 0.02). Conclusion: While rectal compliance in RC subjects is lower when compared with adolescents with FC, almost half of the RC subjects showed an increased rectal compliance. The role of rectal compliance in therapy-resistant FC seems limited, because recovery is possible despite an increased rectal compliance.

A Randomized Controlled Trial of Enemas in Combination With Oral Laxative Therapy for Children With Chronic Constipation

BACKGROUND & AIMS After 5 years of intensive oral laxative use, up to 30% of constipated children still have an unsuccessful outcome. Children refractory to oral laxatives might benefit from regular rectal evacuation by enemas. This randomized controlled trial compared the effects of additional treatment with rectal enemas (intervention) with conventional treatment alone (oral laxatives, control) in severely constipated children. METHODS In a tertiary hospital in the Netherlands, 100 children, aged 8-18 years, with functional constipation for at least 2 years were randomly assigned to intervention or control groups. The control group received education, behavioral strategies, and oral laxatives. The intervention group was also given 3 rectal enemas/week, reduced by 1 enema/week every 3 months. Outcome measures were defecation and fecal incontinence frequency and overall success at 12, 26, 39, and 52 weeks. Overall success was defined as 3 or more defecations/week and less than 1 fecal incontinence episode/week, irrespective of laxative use. RESULTS Defecation frequency normalized in both groups but was significantly higher in the intervention group compared with controls at 26 and 52 weeks (5.6 vs 3.9/week, P = .02, and 5.3 vs 3.9/week, P = .02, respectively). There were no significant differences between groups in reduction of fecal incontinence episodes (P = .49) and overall success rates (P = .67). After 1 year of treatment, the overall success rate was 47.1% in the intervention group versus 36.1% in the control group. CONCLUSIONS There is no additional effect of enemas compared with oral laxatives alone as maintenance therapy for severely constipated children.

Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM. Design: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6–59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling. Results: Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443–535 mg/kg feces) compared with 698 mg/kg feces (1438–244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112–22 ng/mL) compared with 2036 ng/mL (5800–149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831–131 ng/mL) compared with 3174 ng/mL (5819–357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation. Conclusions: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of inflammatory changes in SAM, which may lead to improved therapies. This trial was registered at www.controlled-trials.com as ISRCTN13916953.

Assessment of the rectoanal inhibitory reflex in preterm infants with delayed meconium passage.

Background: There is an inverse relationship between gestational age, birth weight and the time of first neonatal bowel movement. The authors hypothesized that delayed passage of meconium might result from a delayed maturation of the recto-anal inhibitory reflex (RAIR) in premature infants. Objective: To evaluate whether the RAIR is absent in very preterm infants 28-32 weeks postmenstrual age with delayed meconium production. Study design: Anorectal manometry was performed in 10 preterm infants (seven male) with delayed meconium production (no meconium in the first 48 hours). Median postmenstrual age was 30 weeks (28-31 weeks). Birth weight ranged from 780 to 1930 g (median, 1395 g). A micromanometric assembly (outer diameter, 2.0 mm) was used which incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressure and relaxation. Four side-holes recorded anal and rectal pressures. Rectal distension was performed with direct air insufflation to elicit the RAIR. Results: The time from birth to passage of meconium ranged from 48 to 105 hours (median, 82 hours). The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 22.0 ± 5.0 mm Hg, 6.9 ± 2.0 mm Hg, and 9.8 ± 1.9/min, respectively. A normal RAIR was elicited in all infants. Conclusion: Anorectal manometry recordings in premature infants with delayed passage of meconium showed normal anorectal pressures and a normal RAIR, suggesting that delayed meconium passage is not related to the absence of a RAIR.

No Role for Increased Rectal Compliance in Pediatric Functional Constipation

BACKGROUND & AIMS Increased rectal compliance has been proposed to contribute to pediatric functional constipation (FC). We evaluated the clinical relevance of increased rectal compliance and assessed whether regular use of enemas improves rectal compliance in children with FC. METHODS A prospective longitudinal study was conducted on children (8-18 years old) with FC. Pressure-controlled rectal distensions were performed at baseline and at 1 year. Rectal compliance was categorized into 3 groups: normal, moderately increased, or severely increased. Patients were randomly assigned to groups given conventional therapy or rectal enemas and conventional therapy. Clinical success was defined as >or=3 spontaneous defecations per week and fecal incontinence <1 per week. RESULTS Baseline measurements were performed in 101 children (11.0 +/- 2.1 years); rectal compliance was normal in 36%, moderately increased in 40%, and severely increased in 24%. Patients with severely increased rectal compliance had lower defecation frequency (P = .03), more fecal incontinence (P = .04), and more rectal fecal impaction (P < .001). After 1 year, success values were similar between groups: 42% normal, 41% moderately increased, and 40% with severely increased compliance. Barostat studies performed after 1 year in 80 children (37 conventional therapy and 43 rectal enemas in addition to conventional therapy) revealed that rectal compliance had not changed in either group and had not improved in successfully treated patients. CONCLUSIONS Constipated children with severely increased rectal compliance have severe symptoms. However, increased rectal compliance is not related to treatment failure. Regular use of enemas to avoid rectal fecal impaction does not improve rectal compliance in pediatric FC.

Loperamide suppositories in an adolescent with childhood-onset functional non-retentive fecal soiling.

Encopresis is characterized by the voluntary or involuntary passage of stool into the underwear after the age of 4 years. In most patients, encopresis is the result of constipation. However, in our practice, 20% of children experience encopresis as an isolated complaint, without any signs of constipation. These children have normal defecation frequency, no palpable abdominal or rectal fecal mass on physical examination, and normal colonic transit time. Laxatives have no or an adverse effect in these children (1). Recently, encopresis in the absence of signs of fecal retention has been classified as functional non-retentive fecal soiling by the new pediatric Rome-II criteria (2). The treatment of these children is often disappointing, with only 29% of patients cured after 2 years of intensive treatment (3). In contrast to earlier reports (4), recent data show that 24% of children with functional non-retentive fecal soiling do not outgrow their encopresis during puberty and still experience encopresis when reaching adulthood (5). This large number of patients with encopresis after the age of 18 justifies the search for treatment options for this patient group. The symptoms of children with functional nonretentive fecal soiling resembles those of adults with idiopathic fecal incontinence, incontinence without a known underlying cause. In most adult patients, however, fecal incontinence is a result of trauma (after delivery) or by the aging processes. In adulthood fecal incontinence, loperamide is a well-known and frequently used medication. A study in adults with chronic diarrhea and fecal incontinence showed that the oral administration of loperamide, an opioid agonist, resulted in significant improvement of continence (6). Here, we describe a 20-year-old male with childhoodonset, longstanding functional non-retentive fecal soiling who dramatically improved after rectal application of loperamide.

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: “In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?” Methods A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings Only two studies, both non–randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow–up period of 14 years; the other was done in Bangladesh (2002) with a six–month follow–up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight–for–age z–scores in the intervention group compared to the control group. Conclusions The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High–quality trials are needed to determine the effects of psychosocial stimulation interventions on outcomes in children with SAM.