Crohn's Disease in a Patient With Bardet-Biedl Syndrome: Random Anomaly or Rare Phenotypic Trait?

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystem nonmotile ciliopathy. There are anecdotal reports of the co-occurrence of BBS and autoimmune diseases, including inflammatory bowel disease (IBD). We present the first case report of a child with BBS7 who developed Crohn disease, adding to the evidence on the association between BBS and IBD. A 13-year-old girl with BBS7 presented with abdominal pain and significant weight loss (-13%), but without other classical symptoms of IBD, such as diarrhea and blood loss. Fecal calprotectin was elevated, but on gastroscopy and colonoscopy, no macroscopic abnormalities were found. Ultrasound and MRI revealed an intestinal stenosis which was treated surgically. Histopathological examination confirmed the diagnosis Crohn disease. In conclusion, the reported co-occurrence of BSS and autoimmune diseases and the atypical presentation of IBD in this patient warrant a low threshold to perform diagnostic tests for IBD in patients with BBS and gastrointestinal symptoms.

What are Normal Defecation Patterns in Healthy Children up to Four Years of Age? A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize available data on defecation frequency and stool consistency of healthy children up to age 4 in order to estimate normal references values. STUDY DESIGN: Systematic review including cross-sectional, observational, and interventional studies published in English, that reported on defecation frequency and/or stool consistency in healthy children 0-4 years old. RESULTS: Seventy-five studies were included with 16 393 children and 40 033 measurements of defecation frequency and/or stool consistency. Based on visual inspection of defecation frequency data, a differentiation was made between two age categories: young infants (0-14 weeks old) and young children (15 weeks-4 years old). Young infants had a mean defecation frequency of 21.8 per week (95 % CI, 3.9-35.2) compared with 10.9 (CI, 5.7-16.7) in young children (P < .001). Among young infants, human milk-fed (HMF) infants had the highest mean defecation frequency per week (23.2 [CI, 8.8-38.1]), followed by formula-fed (FF) infants (13.7 [CI 5.4-23.9]), and mixed-fed (MF) infants (20.7 [CI, 7.0-30.2]). Hard stools were infrequently reported in young infants (1.5%) compared with young children (10.5%), and a reduction in the frequency of soft/watery stools was observed with higher age (27.0% in young infants compared with 6.2% in young children). HMF young infants had softer stools compared with FF young infants. CONCLUSIONS: Young infants (0-14 weeks old) have softer and more frequent stools compared with young children (15 weeks-4 years old).

Time to first passage of meconium and defecation frequency preceding necrotizing enterocolitis in preterm infants: a case-control study.

Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.). CONCLUSION: In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC. WHAT IS KNOWN: • Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease. WHAT IS NEW: • Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.

Long-Term Outcomes of Antegrade Continence Enemas to Treat Constipation and Fecal Incontinence in Children.

OBJECTIVES: The objective of this study is to investigate long-term outcomes of antegrade continence enema (ACE) treatment in children with constipation or fecal incontinence. METHODS: Prospective cohort study including pediatric patients with organic or functional defecation disorders who started ACE treatment. Data were collected at baseline and at follow-up (FU) from 6 weeks until 60 months. We assessed parent and patient-reported gastrointestinal health-related quality of life (HRQoL) using the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Module (PedsQL-GI), gastrointestinal symptoms, adverse events, and patient satisfaction. RESULTS: Thirty-eight children were included (61% male, median age 7.7 years, interquartile range 5.5-12.2). Twenty-two children (58%) were diagnosed with functional constipation (FC), 10 (26%) with an anorectal malformation, and 6 (16%) with Hirschsprung disease. FU questionnaires were completed by 22 children (58%) at 6 months, 16 children (42%) at 12 months, 20 children (53%) at 24 months, and 10 children (26%) at 36 months. PedsQL-GI scores improved overall with a significant increase at 12- and 24-month FU for children with FC and a significant increase in parent reported PedsQL-GI score at 36-month FU for children with organic causes. Minor adverse events, such as granulation tissue, were reported in one-third of children, and 10% of children needed a surgical revision of their ACE. The majority of all parents and children reported that they would "probably" or "definitely" choose ACE again. CONCLUSION: ACE treatment is perceived positively by patients and parents and can lead to long-term improvement in gastrointestinal HRQoL in children with organic or functional defecation disorders.

Accuracy of Anorectal Manometry to Detect the Rectoanal Inhibitory Reflex in Children: Awake Versus Under General Anesthesia.

OBJECTIVES: Our objective was to investigate if there is a difference in the detection of the rectoanal inhibitory reflex (RAIR) when an anorectal manometry (ARM) is performed awake or under general anesthesia. METHODS: A retrospective review of ARM studies was performed to identify children who had undergone ARMs both while awake and under general anesthesia. We compared ARM outcomes including the detection of the RAIR and anal canal resting pressure. RESULTS: Thirty-four children had received ARMs both while awake and under general anesthesia (53% female, median age at first ARM 7.5 years [range 3-18 years]). In 9 of 34 (26%) children the RAIR was solely identified during ARM under general anesthesia and not during ARM while awake. In 6 of 9 (66%) this was unrelated to the balloon volumes used during balloon inflations. In 4 of 34 (12%) children, assessment of the RAIR was inconclusive during ARM under general anesthesia due to too low, or loss of anal canal pressure. In 2 of those children, ARMs while awake showed presence of a RAIR. Anal canal resting pressures were higher during ARM while awake versus ARM under general anesthesia (median 70 [interquartile range, IQR 59-85] vs 46 mmHg [IQR 36-65] respectively, P < 0.001). CONCLUSIONS: General anesthesia may affect the detection of a RAIR in 2 ways. On the one hand, it may facilitate better visualization in children in whom a RAIR could not be visualized while awake. On the other hand, it may cause a loss of anal canal pressure resulting in an inconclusive test result.

An Update of Pharmacological Management in Children with Functional Constipation.

Functional constipation is a common problem in childhood worldwide and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. It is a clinical diagnosis based on the Rome IV criteria. Non-pharmacological treatment involves education, demystification, lifestyle advice, and toilet training. Pharmacological treatment consists of disimpaction, maintenance treatment, and eventually weaning if possible. Polyethylene glycol is considered as the first choice of laxative for both disimpaction and maintenance treatment. Different osmotic laxatives, stimulant laxatives, lubricants, and enemas are available as alternative pharmacological treatment options. Novel drugs are emerging but evidence to support the widespread application of these drugs in the pediatric population is often lacking and more high-quality research is needed in this field. If children remain symptomatic despite optimal pharmacological treatment, botulinum toxin injections in the anal sphincter can be considered as an alternative, more invasive treatment option. This review provides an update on currently available literature concerning the pharmacologic treatment of functional constipation in children.

Fatal gastrointestinal complications in Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Transanal Irrigation in Children: Treatment Success, Quality of Life, Adherence, Patient Experience, and Independence.

OBJECTIVES: To investigate the clinical effectiveness and patient experience of transanal irrigation (TAI) in children with constipation or fecal incontinence. METHODS: Combined retrospective and cross-sectional study including pediatric patients who used a Navina TAI system. We retrospectively collected baseline characteristics and data on treatment success at 1- and 6-month follow-up (FU). Treatment success was defined as defecating at least 3 times per week and having less than 1 episode of fecal incontinence per week. We cross-sectionally assessed health-related quality of life (HRQoL), treatment adherence, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), illness perceptions, medication beliefs, and patient empowerment with validated questionnaires. RESULTS: Thirty-four patients were included (median age at start TAI: 11 years old [range, 6-18]), 32 in the retrospective review, and 26 in the cross-sectional survey (median of 3 years after initiation). Most patients were diagnosed with functional constipation (n = 26; 76%) or a neurogenic bowel disorder (n = 6; 18%). Treatment success rates significantly improved at each FU compared with baseline (baseline: 4/25 [16%]; 1-month FU: 12/16 [75%], P = 0.008; 6-month FU: 11/18 [61%], P = 0.016; cross-sectional FU: 13/26 [50%], P = 0.008). HRQoL scores were high (PedsQL median, 73 [IQR, 54-85]). Adherence (defined as Medication Adherence Report Scale [MARS] ≥ 23) was low (36%), whereas TSQM effectiveness scores were high (median, 69 [IQR, 47-86]). The majority of children (61%) reported an increase in independence since TAI treatment. Patient empowerment (GYPES) levels were similar to those reported in children with other chronic conditions. CONCLUSIONS: TAI with a Navina system is an effective bowel management system for children with intractable constipation or fecal incontinence.

Hypnosis to Reduce Distress in Children Undergoing Anorectal Manometry: A Randomized Controlled Pilot Trial.

Background/Aims: To assess the effectiveness and feasibility of a brief session of hypnosis to reduce distress in children with functional constipation undergoing anorectal manometry (ARM). Methods: A partially-blinded randomized controlled pilot trial was conducted in children 4-18 years old scheduled for ARM. Children were randomized to receive a brief session of hypnosis prior to ARM or standard care. Non-blinded and blinded observers rated the child's level of distress using the Observation Scale of Behavioral Distress and a 4-point-Likert scale, respectively. Differences between groups were analyzed using Fisher's exact test or Mann-Whitney U test as appropriate. Results: Data from 32 children (15 hypnosis and 17 standard care) were analyzed. Prior to insertion of the catheter, the observed mean levels of distress were lower in the hypnosis group according to both the non-blinded observer (median 0.0 [interquartile range {IQR} 0.0-0.3] vs 1.4 [IQR 0.3-2.4]; P = 0.009) and the blinded observer (median 0.0 [IQR 0.0-0.0] vs 0.5 [IQR 0.0-1.0]; P = 0.044). During ARM, observed and reported levels of distress did not differ significantly. In the hypnosis group, 92.9% of parents and children reported that hypnosis helped the child to relax. There were no significant differences in resting pressure, squeeze pressure, or duration of the procedure between both groups. Conclusion: A brief session of hypnosis for children before ARM is an easily incorporable intervention that lowers distress levels prior to the procedure and is positively perceived by children and parents.

Do we need an extra dimension? A pilot study on the use of three-dimensional anorectal manometry in children with functional constipation.

BACKGROUND: Recently, a new high-definition (or three-dimensional "3D") high-resolution anorectal manometry (3D-ARM) catheter has been introduced. This catheter allows for a more detailed visualization of the anal canal. However, its clinical utility and tolerability in children with constipation are unknown. Our primary objective was to evaluate the agreement between findings from solid-state high-resolution anorectal manometry (HR-ARM) and 3D-ARM. Secondary objectives were to investigate if 3D-ARM has additional value over HR-ARM and to evaluate patient and provider experience. METHODS: Prospective pilot study including children (8-18 years of age) with functional constipation scheduled for anorectal manometry. Children underwent HR-ARM and 3D-ARM consecutively. We compared manometry results of both procedures and collected data on patient and provider experience via self-developed questionnaires. KEY RESULTS: Data of ten patients were analyzed (60% female, median age 14.9 years). In the majority of patients, ARMs were performed awake (n = 8, 80%). In two patients, the recto-anal inhibitory reflex (RAIR) was visualized during HR-ARM but not during 3D-ARM. Anal canal resting pressures were significantly higher during 3D-ARM compared to HR-ARM (median 77 mmHg [IQR 59-94] vs. 69 mmHg [IQR 51-91], respectively, p = 0.037). No significant anatomical or muscular abnormalities were visualized during the 3D-ARM. The majority of children identified the 3D-ARM as the more unpleasant (5/7 [71%]) and more painful procedure (6/7 [86%]) and therefore preferred the HR-ARM (4/7 [57%]). CONCLUSIONS & INFERENCES: In our patient sample, 3D-ARM was associated with more discomfort without providing more useful information and even resulted in an inconsistent visualization of the RAIR.

Functional Constipation and Dyssynergic Defecation in Children.

Defecation is a complex physiological process, which relies on intricate mechanisms involving the autonomic and somatic nervous system, the pelvic floor muscles, and the anal sphincter complex. Anorectal dysfunction may result in constipation, a bothersome defecation disorder that can severely affect daily lives of children and their families. In this review, we focus on different mechanisms underlying anorectal dysfunction and specific treatment options aimed at improving defecation dynamics in children with functional constipation.

Characterization of the colonic response to bisacodyl in children with treatment-refractory constipation.

BACKGROUND: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. METHODS: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. RESULTS: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. CONCLUSIONS AND INFERENCES: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined.

Management of functional constipation in children and adults.

Functional constipation is common in children and adults worldwide. Functional constipation shows similarities in children and adults, but important differences also exist regarding epidemiology, symptomatology, pathophysiology, diagnostic workup and therapeutic management. In children, the approach focuses on the behavioural nature of the disorder and the initial therapeutic steps involve toilet training and laxatives. In adults, management focuses on excluding an underlying cause and differentiating between different subtypes of functional constipation - normal transit, slow transit or an evacuation disorder - which has important therapeutic consequences. Treatment of adult functional constipation involves lifestyle interventions, pelvic floor interventions (in the presence of a rectal evacuation disorder) and pharmacological therapy. When conventional treatments fail, children and adults are considered to have intractable functional constipation, a troublesome and distressing condition. Intractable constipation is managed with a stepwise approach and in rare cases requires surgical interventions such as antegrade continence enemas in children or colectomy procedures for adults. New drugs, including prokinetic and prosecretory agents, and surgical strategies, such as sacral nerve stimulation, have the potential to improve the management of children and adults with intractable functional constipation.

Quality of Life in Children with Functional Constipation: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review the literature on health-related quality of life (HRQoL) in children with functional constipation and to identify disease-related factors associated with HRQoL. STUDY DESIGN: The Pubmed, Embase, and PsycINFO database were searched. Studies were included if they prospectively assessed HRQoL in children with functional constipation according to the Rome criteria. Articles were excluded if patients had organic causes of constipation and if HRQoL was only assessed after successful therapeutic interventions. A meta-analysis was performed calculating sample size-weighted pooled mean and SD of HRQoL scores. The quality of the studies was also assessed. RESULTS: A total of 20 of 2658 studies were included, providing HRQoL data for 2344 children. Quality of evidence was considered to be poor in 9 of the 20 studies (45%); 13 of the 20 studies reported sufficient data to be included in the meta-analysis. Pooled total HRQoL scores of children with functional constipation were found to be lower compared with healthy reference samples (65.6 vs 86.1; P < .01). Similar HRQoL scores were found according to self-report and parent proxy report. Hospital-based studies reported lower HRQoL scores as compared with community-based studies. Two studies reported on HRQoL scores of children with and without fecal incontinence, but no significant difference was found. CONCLUSIONS: HRQoL is compromised in children with functional constipation.

Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review the literature regarding the epidemiology of functional constipation and functional nonretentive fecal incontinence (FNRFI) in children. Secondary objectives were to assess the geographical, age, and sex distribution of functional constipation and FNRFI and to evaluate associated factors. STUDY DESIGN: The Cochrane Library, PubMed, and Embase databases were searched from 2006 until September 2017. The following inclusion criteria were applied: (1) prospective studies of population-based samples; (2) reporting on the prevalence of functional constipation or FNRFI according to the Rome III/IV criteria; (3) in children aged 0-18 years; and (4) published in full manuscript form. A quality assessment of included studies was conducted. Random effect meta-analyses with meta-regression analyses of study characteristics were performed. RESULTS: Thirty-seven studies were included, of which 35 reported on the prevalence of functional constipation and 15 of FNRFI. The reported prevalence of functional constipation ranged from 0.5% to 32.2%, with a pooled prevalence of 9.5% (95% CI 7.5-12.1). The prevalence of FRNFI ranged from 0.0% to 1.8%, with a pooled prevalence of 0.4% (95% CI 0.2-0.7). The prevalence of functional constipation was 8.6% in boys compared with 8.9% in girls (OR 0.99, 95% CI 0.9-1.4). Geographical location, dietary habits, and exposure to stressful life events were reported to be associated with the prevalence of functional constipation. Data on FNRFI were scarce and no associated factors were identified. CONCLUSION: Functional constipation is common in childhood and is associated with geographical location, lifestyle factors, and stressful life events. FNRFI is rare, and no associated factors were identified.

Awareness and Implementation of the 2014 ESPGHAN/NASPGHAN Guideline for Childhood Functional Constipation.

OBJECTIVE: The aim of the study was to assess whether physicians approach children with functional constipation according to the 2014 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guideline. METHODS: We invited pediatricians and pediatric gastroenterologists in the Netherlands and the United States to participate in this anonymous survey using a self-developed questionnaire containing 19 multiple choice questions concerning evaluation and treatment of children with constipation. RESULTS: We included 328 physicians (67% from the United States, 34% from the Netherlands). The majority of US responders (53%) worked in primary care, whereas all Dutch responders worked in a hospital. In total, 31% of responders were not familiar with the guideline (38% US responders vs 16% Dutch responders, P < 0.001). Perianal inspection was frequently ("often" or "always" on a 5-point Likert scale) conducted by 78% of responders. Digital rectal examination was frequently done by 42%. Inquiry about sexual abuse was made by 18%. Commonly reported reasons for omitting these items were perceived patient or parental discomfort. Most frequently implemented initial nonpharmacological interventions included a toilet training program (89%), optimizing fluid and fiber intake (86% and 81%), a defecation diary (62%), and a reward system (60%). Polyethylene glycol was the most prescribed medication for disimpaction (68%) and maintenance treatment (57% for infants, 97% for children ≥1 year). CONCLUSIONS: Many responders were not familiar with the ESPGHAN/NASPGHAN guideline for functional constipation. Nonetheless, therapeutic decisions correlated fairly well with recommendations from the guideline, especially for children 1 year of age or older. Guideline awareness and adherence remain to be improved. Future studies should focus on exploring strategies to improve guideline implementation through the development of digital learning tools.