Sage Journals: Discover world-class research

Abstract

Spina bifida is a birth defect that commonly causes bowel and bladder dysfunction in children with a significant negative impact on quality of life and emotional wellbeing. Fecal continence improves satisfaction and the quality of life of both children and their caretakers. Bowel management in children with spina bifida is hampered by limited controlled studies and variable practice within different institutions and subspecialists. The goals of a successful bowel management program in children with spina bifida consist of predictable bowel movements, social continence, and eventual independence. Treatment options range from conservative interventions such as diets and oral laxatives that modify stool consistency and transit, to trans-anal irrigations and antegrade continence enemas that facilitate predictable recto-sigmoid emptying and provide a greater degree of independence. In children, the treatment approach should be implemented in the context of the child’s developmental age in order to allow for optimum social integration with their age-appropriate peers. We present a review of a stepwise approach to bowel management in children with spina bifida and the challenges related to the proposed treatment options.

Keywords

Children spina bifida neurogenic bowel bowel management motility constipation fecal incontinence

1. Introduction

The live born prevalence of spina bifida worldwide ranges from 33.8 to 48.4 per 100,000 births [1]. Bowel and bladder dysfunction affects approximately 76% of both children and adults with spina bifida and has a negative impact on their quality of life [2, 3, 4]. Only 23% and 29% of patients with spina bifida aged 5–21 are reported to have bowel and bladder continence, respectively [5]. The impact of abnormal bowel function on quality of life and social activities increases with age [6, 7]. Approximately 60–86% of children with spina bifida are dependent on caretakers for evacuation of their bowels [8, 9]. Parents perceive bowel and bladder dysfunction to be more stressful than motor disability [8].

Abnormalities in the interaction between the extrinsic and intrinsic innervation, colorectal anatomy, sphincter and recto-sigmoid function, colonic transit, stool consistency, and sensation result in bowel dysfunction [10, 11]. Patients with spina bifida have slow colonic transit, abnormal rectal tone, compromised internal anal sphincter function, decreased sensation, and poor external anal squeeze effort [12, 13, 14, 15, 16, 17]. Such alterations of involuntary and voluntary properties of the colon and anorectum are further amplified if the child has underlying cognitive delays. Adolescents and young adults with present hydrocephalus are 9.5 times more likely to have fecal incontinence [18].

The goals of bowel management in children with spina bifida include predictable bowel movements, social continence, and independence. Independence in bowel care is critical, as those who are independent at toileting have been shown to have significantly higher quality of life scores [9]. A successful bowel program can both improve the child’s quality of life and family functioning while decreasing caregiver depression and anxiety [19, 20]. Bowel management should be implemented and modified in the context of the child’s development as well as any underlying renal, neurological, and orthopedic comorbidities.

Randomized controlled studies evaluating the efficacy of different bowel regimens in children with spina bifida are methodologically poor. The studies are limited by small sample size, variable practice amongst subspecialists and institutions, and inconsistent definitions of bowel continence. There are few tools available to assess neurogenic bowel symptoms in children with spina bifida. Two recently proposed items include the pediatric Neurogenic Bowel Dysfunction Score [21] and Adolescent Fecal Incontinence and Constipation Symptom Index [22]; however, these measures are limited by small sample size and need to be validated by larger studies.

2. Conservative management

The cornerstone to a successful bowel program is a strong relationship between the patient, the caretakers, and the medical team. The treatment should be tailored to achieve predictable bowel movements and social continence with the long-term goal of independence. A stepwise approach is recommended in most cases. See Fig. 1. In conjunction with behavioral modification, we can facilitate recto-sigmoid emptying as well as alter stool transit, consistency, and volume [10, 11]. With regards to behavioral modification, toilet training is an integral part of a child’s developmental and social milestones. The medical team is encouraged to provide the parents and caregivers with the appropriate resources and guidance to implement a scheduled toilet training program [23]. Based on the child’s mobility and development, then a bowel management plan can be devised. We propose a stepwise approach to the bowel management in children with spina bifida (Fig. 1) adapted from the proposed treatment of neurogenic bowel in adults [13, 24].

Bowel management protocols and techniques implemented by different centers commonly start with conservative treatments that modify the stool consistency and volume. Therapy should aim at avoiding loose and hard stool. Dietary changes in conjunction with fiber and appropriate fluid intake have been shown to improve stool consistency and increase stool frequency in otherwise healthy children [25]. Unfortunately, similar studies are lacking in children with spina bifida.

Figure 1.

Stepwise approach for bowel management in children with spina bifida. Adapted from the proposed treatment of neurogenic bowel in adults [13, 24]. Success at each step is defined as a bowel program where the child has predictable bowel movements and social continence with a long-term plan for independence.

3. Laxatives

Patients with spina bifida have slow colonic transit [16, 17]. The goal is to increase colonic transit without significantly altering the stool consistency, as liquid stool consistency results in increased fecal incontinence since there is compromised sensation and voluntary ability to squeeze to withhold stool. Lubricant laxatives such as mineral oil should be avoided as they alter stool consistency and increase fecal incontinence. Osmotic laxatives such as lactulose and polyethylene glycol have been shown to increase stool frequency and decrease frequency of fecal incontinence, particularly in the polyethylene glycol group [26]. However, osmotic laxatives at high doses may worsen fecal incontinence. We recommend the use of stimulant laxatives such as senna and bisacodyl to increase colonic transit and facilitate recto-sigmoid emptying [10, 11, 27, 28]. Administering stimulant medications at the same time of day establishes a predictable pattern. Dosing of these medications is typically determined depending on stool output, frequency, and amount of fecal incontinence. Given that stimulant medications increase colonic transit, stool consistency may become too loose and hence dosage should be adjusted accordingly and bulking agents including fiber (e.g., pectin, psyllium) added.

Children may fail oral medication therapy despite rigorous medication administration, as oral medications do not always produce predictable bowel movements. The absorptive capacity and bioavailability of oral medications vary depending on diet and brand of medication. Lubiprostone (a selective chloride channel-2 agonist) and Linaclotide (a peptide agonist of guanylate cyclase 2C) are FDA approved for chronic idiopathic constipation and constipation-predominant irritable bowel syndrome in adults. Although Lubiprostone has shown promising results in healthy children, it has not been studied in children with spina bifida [29]. These medications are most useful in children where stool consistency is difficult to control despite optimization of stimulant oral medications and rectal therapies. As previously reported, in our experience in patients with spinal anomalies and anorectal malformations, we have used Lubiprostone as an adjunct to other stimulant or rectal therapies in order to better regulate stool consistency and potentially achieve a more predictable stooling frequency as its action depends on serum levels [30].

4. Rectal therapies

If the child is not socially continent with diet or medical therapy, then rectal therapies should be implemented. Rectal therapies include manual disimpaction and rectal medications such as suppositories and enemas. Manual disimpaction (digital stimulation) in the setting of controlled constipation is commonly used in the spina bifida population. It stimulates the ano-colonic reflex and facilitates recto-sigmoid evacuation [33]. In patients with greater hand dexterity, this method is preferred because it can allow for independence and is also less time consuming [34]. Rectal medications such as over-the-counter suppositories include glycerin (pediatric, adult) and bisacodyl. Water-based suppositories and polyethylene glycol-based bisacodyl suppositories are reported to be more effective than those with an oil base since they are quicker to be absorbed by the rectal mucosa [10, 13]. There are a number of over-the-counter and prescription enemas such as sodium phosphate, glycerin, bisacodyl, mineral oil, and docusate-based enemas. Caution should be taken when having parents purchase enemas over the counter. Brand names and ingredients vary and may lead to confusion, inappropriate administration, and risk of complications. This is especially critical in children with spina bifida who may have abnormal renal function. In those with spina bifida, over-the-counter or prescription “saline” or sodium phosphate containing enemas should be avoided due to reports of hyperphosphatemia, hypocalcemia, and hypokalemia [31, 32]. Avoidance of the use of magnesium-based products in patients with severe constipation is because of the theoretical risk of hypermagnesemia and hypocalcemia [11]. An anal plug is a containment product that resembles a tampon and upon insertion into the anal canal provides a temporary seal with the goal of decreasing fecal incontinence. There is limited evidence to recommend the routine use of anal plugs in the prevention of fecal incontinence in children with spina bifida [35]. A recent Cochrane review of anal plugs in children and adults highlights the small sample size, high drop out rates, and the potential for bias in the literature [36]. The most common side effects reported within the spina bifida population were discomfort and displacement of the plug, especially within more ambulatory children [37, 38]. The smaller pediatric studies support the use of anal plugs as an intermittent and adjuvant therapy to an already established bowel management plan [37, 38, 39].

5. Trans-anal irrigations (TAI)

Due to poor intra-anal tone, children with spina bifida may not be able to retain a suppository or an enema. For these patients, we recommend TAIs where high volume enemas are administered rectally using either a cone tip or a continence catheter with a balloon. The cone-enema has a cone shaped tip that is inserted at the anus and held in place by the patient or caretaker. This allows for administration and retention of high volume enemas without leakage. This system is best used in children with a very patulous anus and low intra-anal pressures, where retention of a catheter would otherwise be very difficult. The continence enema catheter is a #24/26 French non-latex urinary Foley. The tip of the catheter has a balloon that is inflated to volumes of 30–60 mL in order to secure the catheter within the anal canal and administer the high volume enema. The above-mentioned methods continue to require parental or caregiver support to administer the enema that is gravity dependent. Children with low intra-anal pressures who can retain a rectal balloon during the enema administration would benefit from this system. The Peristeen ${}^{\@setsize{\scriptsize}{8pt}{\viipt}{\@viipt}\textregistered}$ transanal irrigation system (Coloplast Group, Denmark) was first introduced in Europe in 2006 and was FDA approved in the United States in 2012. It uses a continence enema catheter with a balloon and a pump system to allow for self-administration of retrograde enemas. Children who can retain a rectal balloon during enema administration, are able to toilet sit independently, and have appropriate hand dexterity, may benefit from this system.

In children and adults, TAIs have been shown to improve constipation, decrease fecal incontinence, and increase overall satisfaction and quality of life in both patients and their caregivers [19, 40, 41, 42]. Success rates using TAIs in children with spina bifida are reported between 66–87.5% [19, 41, 43, 44]. Variability in success rates may be due to lack of standardization of definitions and reporting of fecal continence between the studies. In addition, some studies include patients who have functional and organic fecal incontinence where the success rates of each group are not discussed separately. Bischoff et al. reported a 95% success rate with their TAI-based bowel management program; however, only 12 of 212 children had spina bifida and their specific success rate was not disclosed [45]. Despite their high success rate, TAIs require parental and caregiver support for administration. Matsuno et al. reported that only 23.1% of the children with spina bifida were able to independently perform TAIs, versus 66.7% observed in patients with a Malone antegrade continence enema (MACE) [43]. Their findings are in agreement with other studies, where the overall independence rate of TAI varies between 12%–20% [9, 34, 46]. Two long-term follow up studies assessed the efficacy of trans-anal irrigations in a mixed population of children and adults with neurogenic bowel. They reported lower success rates of 50% and 67% at follow up [42]. These lower success rates may be secondary to decreased independence when receiving TAIs, poor available resources for the transition of care to adulthood, and increased patient reliability on their caretaker for support. Vande Velde et al. reported that adults who were followed for bowel management since they were children were more likely to be continent than those who were lost to follow up during transition of care [46].

Pediatric studies in the use of Peristeen ${}^{\@setsize{\scriptsize}{8pt}{\viipt}{\@viipt}\textregistered}$ transanal irrigation system (Coloplast Group, Denmark) for organic fecal incontinence are limited but promising. Pacilli et al. reported that 70% of their patients achieved full continence and 13% had an improvement in soiling in their mixed cohort of spina bifida and anorectal malformation patients [47]. In their mixed cohort of pediatric patients, Corbett et al. reported that 72% attained full continence with significant improvement in quality of life scores and a decrease in time spent toileting [48]. In a European prospective multicenter study of 37 children with spina bifida, Midrio et al. reported an increase in quality of life scores with a decrease in constipation from 92.7% to 41.5%, fecal incontinence from 39% to 9.8%, and flatus incontinence from 31.7% to 10% [49]. Significant improvement in the Neurogenic Bowel Dysfunction Score (NBDS) using the Peristeen system was demonstrated at 2 weeks, 2 months, and 6 months post initiation of irrigations in a recent prospective study of 24 children with spina bifida [50]. In their cohort of children with spina bifida, Lopez Pereira et al. reported an increase in independence from 28% to 46% [51]. However, high cost, pain, discomfort, leaking, balloon bursting, balloon expulsion, and difficulties with administration have been reported to cause early cessation in as high as 55% of patients [41, 47, 49, 52].

The enema solution and the additives vary between centers and subspecialists. There are no standardized guidelines regarding enema solutions, additives, and weight-based dosing [53]. Commonly used enema solutions include tap water, normal saline, and GoLytely [54]. In our experience, we prefer the use of normal saline (10–15 mL per kg) [10]. However, parents should be educated about the proper ratio of non-iodized salt to tap water given the inadvertent risk of hypo-or-hypernatremia [55]. In our centers, we recommend mixing 1000 mL of tap water with 1.5 teaspoons of non-iodized salt using a measuring spoon. Tap water enemas have been safely used in a multitude of studies in the literature [41, 49, 56, 57]. In our centers, we recommend the use of tap water enemas with caution given the risk of electrolyte shifts and hyponatremia [58, 59]. Risk of water intoxication and hyponatremia may be increased in children who receive multiple consecutive enemas and in those with megacolon/colonic dysmotility that predisposes them to increased risk of incomplete rectal emptying and fluid retention. Different additives can also be added to the main solution as an adjunct and have been shown to improve fecal incontinence in children and adults with neurogenic bowel [54, 60, 61, 62]. Common additives are glycerin, castile soap, and bisacodyl. Additives should be added with caution due to lack of manufacturing standards and weight-based dosing recommendations. Of note, phosphate-based additives should be avoided, particularly in children with spina bifida with abnormal renal function given the increased risk of hyperphosphatemia, hypocalcemia, and hypokalemia [31, 32]. Chemical colitis has been reported with the use of castile or glycerin soaps and therefore caution should be taken when increasing the concentration of these additives in the base solution [63]. Signs of chemical colitis include bloody and mucoid stools with or without associated abdominal pain. The enemas should be discontinued and the patient should be evaluated urgently by a pediatric gastroenterologist. Complications that may be associated with trans-anal irrigations include pain on insertion, emotional distress, catheter expulsion, burst of balloon, leakage, abdominal pain, and lastly bowel perforation which is very rare with a risk of 2 per million [64, 65].

6. Antegrade continence enemas (ACE)

The developmental stage, degree of dexterity, and comorbid conditions of a child with spina bifida may impede him or her from being able to independently self-administer trans-anal irrigations. In order to achieve greater independence both for the child and the caretaker, antegrade continence enemas are the next recommended step. An antegrade continence enema (ACE) is administered via a surgically constructed catheterizable conduit or a button conduit between the skin and the colon. The procedure may be done surgically (open or laparoscopic), percutaneously by interventional radiology, or endoscopically in conjunction with laparoscopy. In children with spina bifida, this procedure may be done in conjunction with a Mitrofanoff appendicovesicostomy as the appendix may be deemed adequate to split in order to provide a separate conduit for urine and stool access [66, 67, 68].

Children with spina bifida who use an ACE have reported increased satisfaction and improved quality of life scores [9, 69]. Success rates have been reported between 69–93% [9, 54, 70, 71, 72] with full continence in 33–71% [9, 62, 70, 72]. Unfortunately, definitions of success and continence are not standardized between studies. In a mixed cohort of 117 patients, when compared to baseline, children with myelodysplasia ( $n=$ 40) were significantly more likely to have a successful bowel management with an ACE [54]. In their cohort of children with spina bifida, Chong et al. reported that 83% continued to use the ACE at 5 year follow up and 10% had weaned off the ACE [73]. On the other hand, Siddiqui et al. reported an initial success of 93% that dwindled to 64% at long-term follow-up, with an average time to relapse at 88 months differing significantly between diagnoses [54]. Similarly, Yardley et al. reported that only 59% of their patient cohort were using ACE at mean follow up of 11 years without any association between diagnosis and non-use [74]. The failure rate was thought to be secondary to complications (8.2%), non-compliance, and lack of effectiveness from the flushes (23%) [74]. Complication rates associated with the placement and/or use of ACE have been reported in 60–63% of patients [54, 62, 75]. Common minor complications include stoma stenosis and narrowing (14–50%), site infections (4–29%), leakage (3–43%), and granulation tissue at the stoma site [54, 60, 62, 76, 77]. Major complications are rare and include abscess formation, fistula, peritonitis, perforation of the conduit, volvulus, and obstruction [54, 60, 62, 76]. Mugie et al. reported that surgically placed cecostomy button, previous abdominal surgery, and abnormal colonic manometry were associated with poor outcomes [62]. Studies exploring ACE outcomes in adults with defecation disorders, specifically with spina bifida, are limited by small retrospective observational studies and by heterogeneous definitions of success. In a systematic review, Patel et al. reported that 47–100% of adults, with variable indications for the ACE, continue to use their ACE at the end of follow-up, ranging from 6 to 55 months [78]. They also report improved symptoms and quality of life [78]. Stenosis at the stoma (8–50%) was reported as the most common complication [78].

The antegrade flushes are very similar in concept and composition as the retrograde flushes. The base solution usually consists of tap water, normal saline, or GoLytely. As previously discussed, additives can be added to facilitate recto-sigmoid emptying. Mugie et al. demonstrated in their large cohort of patients that children whose irrigation solution contained stimulants were significantly more likely to be continent [62]. The antegrade flushes are administered through a catheterizable conduit or a cecostomy button over a 15–20 minutes period followed by toilet sitting for approximately 30–40 minutes. Similar to the TAI, the ACE is ideally administered around the same time each day. Depending on the patient and their response to therapy, some may be able to skip a day or two in between flushes. The goal of ACE is to provide independence and bowel management. However, depending on the patient’s development, cognition, and dexterity, this may not be possible. In children with truncal or upper body hypotonicity or spasticity, specialized chairs and toileting systems may be used for support during toilet sitting. In their cohort of children with spina bifida, Wide et al. reported that only 31% always and 6% occasionally had bowel movements independently [9]. This is critical in this population because the group also reported that those who toilet-sit independently have significantly higher quality of life [9]. On the other hand, Vande Velde et al. 2007 reported that 62.5% of patients were able to administer ACEs independently vs. 12.5% who used TAI [34]. It is unclear if the patients required any help for toileting. Appropriate patient selection and setting appropriate patient and caretaker expectations following ACE surgery is critical. In addition, the degree of patient’s independence at toileting should be assessed at each clinic visit with goals of identifying and resolving possible barriers.

7. Other surgical interventions

Sacral nerve stimulation (SNS) has been widely used for the treatment of adult fecal incontinence [79]. Studies examining the utility and safety of SNS in children with spina bifida are limited [80, 81].

The role of segmental resection, Malone appendicostomy combined with segmental resection, and diversion colostomy in children with spina bifida is very limited and has not been investigated in this population. Diverting colostomies [13] are used in adult patients as a last resort treatment option. However, some patients may continue to have abnormal colostomy output due to underlying abnormalities in the spinal innervation of the hindgut and may require retrograde or antegrade irrigations of their colostomy.

In summary, children with spina bifida commonly have bowel dysfunction that has a significant impact on their quality of life and emotional wellbeing. Fecal continence has been associated with increased satisfaction and quality of life of both children and their caretakers. The goals of a successful bowel management program are predictable bowel movements, social continence, and eventual independence. A stepwise approach should be implemented in the context of the patient’s developmental age to allow for optimum social integration with their peers.

Footnotes

Conflict of interest

The authors have no conflict of interest to report.

References

Atta

, Fiest

, Frolkis

, Jette

, Pringsheim

, St Germaine-Smith

, et al. Global birth prevalence of spina bifida by folic acid fortification status: A systematic review and meta-analysis. Am J Public Health2016; 106(1): e24-34. doi: 10.2105/AJPH.2015.302902.

Malone

, Wheeler

, Williams

. Continence in patients with spina bifida: Long term results. Arch Dis Child1994; 70(2): 107-10.

Sawin

, Bellin

. Quality of life in individuals with spina bifida: A research update. Dev Disabil Res Rev2010; 16(1): 47-59. doi: 10.1002/ddrr.96.

Szymanski

, Misseri

, Whittam

, Kaefer

, Rink

, Cain

. Quantity, not frequency, predicts bother with urinary incontinence and its impact on quality of life in adults with spina bifida. J Urol2016; 195(4 Pt 2): 1263-9. doi: 10.1016/j.juro.2015.07.108.

Rocque

, Bishop

, Scogin

, Hopson

, Arynchyna

, Boddiford

, et al. Assessing health-related quality of life in children with spina bifida. J Neurosurg Pediatr2015; 15(2): 144-9. doi: 10.3171/2014.10.PEDS1441.

Bakaniene

, Prasauskiene

, Vaiciene-Magistris

. Health-related quality of life in children with myelomeningocele: A systematic review of the literature. Child Care Health Dev2016; 42(5): 625-43. doi: 10.1111/cch.12367.

Krogh

, Lie

, Bilenberg

, Laurberg

. Bowel function in Danish children with myelomeningocele. APMIS Suppl2003; (109): 81-5.

Lie

, Lagergren

, Rasmussen

, Lagerkvist

, Hagelsteen

, Borjeson

, et al. Bowel and bladder control of children with myelomeningocele: A Nordic study. Dev Med Child Neurol1991; 33(12): 1053-61.

Wide

, Mattsson

, Drott

, Mattsson

. Independence does not come with the method-treatment of neurogenic bowel dysfunction in children with myelomeningocele. Acta Paediatr2014; 103(11): 1159-64. doi: 10.1111/apa.12756.

10.

Ambartsumyan

, Nurko

. Review of organic causes of fecal incontinence in children: Evaluation and treatment. Expert Rev Gastroenterol Hepatol2013; 7(7): 657-67. doi: 10.1586/17474124.2013.832500.

11.

Pensabene

, Nurko

. Management of fecal incontinence in children without functional fecal retention. Curr Treat Options Gastroenterol2004; 7(5): 381-90.

12.

Krogh

, Christensen

, Laurberg

. Colorectal symptoms in patients with neurological diseases. Acta Neurol Scand2001; 103(6): 335-43.

13.

Krogh

, Christensen

. Neurogenic colorectal and pelvic floor dysfunction. Best Pract Res Clin Gastroenterol2009; 23(4): 531-43. doi: 10.1016/j.bpg.2009.04.012.

14.

Agnarsson

, Warde

, McCarthy

, Clayden

, Evans

. Anorectal function of children with neurological problems. I: Spina bifida. Dev Med Child Neurol1993; 35(10): 893-902.

15.

Arhan

, Faverdin

, Devroede

, Pierre-Kahn

, Scott

, Pellerin

. Anorectal motility after surgery for spina bifida. Dis Colon Rectum1984; 27(3): 159-63.

16.

Velde

, Pratte

, Verhelst

, Meersschaut

, Herregods

, Van Winckel

, et al. Colon transit time and anorectal manometry in children and young adults with spina bifida. Int J Colorectal Dis2013; 28(11): 1547-53. doi: 10.1007/s00384-013-1733-6.

17.

Pigeon

, Leroi

, Devroede

, Watier

, Denis

, Weber

, et al. Colonic transit time in patients with myelomeningocele. Neurogastroenterol Motil1997; 9(2): 63-70.

18.

Verhoef

, Lurvink

, Barf

, Post

, van Asbeck

, Gooskens

, et al. High prevalence of incontinence among young adults with spina bifida: description, prediction and problem perception. Spinal Cord2005; 43(6): 331-40. doi: 10.1038/sj.sc.3101705.

19.

Choi

, Shin

, Im

, Kim

, Han

. The effects of transanal irrigation as a stepwise bowel management program on the quality of life of children with spina bifida and their caregivers. Spinal Cord2013; 51(5): 384-8. doi: 10.1038/sc.2013.8.

20.

Sanders

, Bray

, Driver

, Harris

. Parents of children with neurogenic bowel dysfunction: Their experiences of using transanal irrigation with their child. Child Care Health Dev2014; 40(6): 863-9. doi: 10.1111/cch.12117.

21.

Kelly

, Hannan

, Cassidy

, Hidas

, Selby

, Khoury

, et al. Development, reliability and validation of a neurogenic bowel dysfunction score in pediatric patients with spina bifida. Neurourol Urodyn2016; 35(2): 212-7. doi: 10.1002/nau.22694.

22.

Hubert

, Sideridis

, Sherlock

, Queally

, Rosoklija

, Kringle

, et al. Validation of a bowel dysfunction instrument for adolescents with spina bifida. J Pediatr Urol2015; 11(4): 199e1-7. doi: 10.1016/j.jpurol.2015.06.001.

23.

Leibold

. Achieving continence with a neurogenic bowel. Pediatr Clin North Am2010; 57(4): 1013-25. doi: 10.1016/j.pcl.2010.08.002.

24.

Emmanuel

, Krogh

, Bazzocchi

, Leroi

, Bremers

, Leder

, et al. Consensus review of best practice of transanal irrigation in adults. Spinal Cord2013; 51(10): 732-8. doi: 10.1038/sc.2013.86.

25.

Tabbers

, DiLorenzo

, Berger

, Faure

, Langendam

, Nurko

, et al. Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr2014; 58(2): 258-74. doi: 10.1097/MPG.0000000000000266.

26.

Rendeli

, Ausili

, Tabacco

, Focarelli

, Pantanella

, Di Rocco

, et al. Polyethylene glycol 4000 vs. lactulose for the treatment of neurogenic constipation in myelomeningocele children: A randomized-controlled clinical trial. Aliment Pharmacol Ther2006; 23(8): 1259-65. doi: 10.1111/j.1365-2036.2006.02872.x.

27.

Manabe

, Cremonini

, Camilleri

, Sandborn

, Burton

. Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers. Aliment Pharm Ther2009; 30(9): 930-6. doi: 10.1111/j.1365-2036.2009.04118.x.

28.

Kamm

, Mueller-Lissner

, Wald

, Richter

, Swallow

, Gessner

. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol H2011; 9(7): 577-83. doi: 10.1016/j.cgh.2011.03.026.

29.

Hyman

, Di Lorenzo

, Prestridge

, Youssef

, Ueno

. Lubiprostone for the treatment of functional constipation in children. J Pediatr Gastroenterol Nutr2014; 58(3): 283-91. doi: 10.1097/MPG.0000000000000176.

30.

Ambartsumyan

, Rodriguez

. Gastrointestinal motility disorders in children. Gastroenterol Hepatol (N Y)2014; 10(1): 16-26.

31.

Ladenhauf

, Stundner

, Spreitzhofer

, Deluggi

. Severe hyperphosphatemia after administration of sodium-phosphate containing laxatives in children: Case series and systematic review of literature. Pediatr Surg Int2012; 28(8): 805-14. doi: 10.1007/s00383-012-3124-4.

32.

Mendoza

, Legido

, Rubio

, Gisbert

. Systematic review: The adverse effects of sodium phosphate enema. Aliment Pharmacol Ther2007; 26(1): 9-20. doi: 10.1111/j.1365-2036.2007.03354.x.

33.

Wyndaele

, Kovindha

, Igawa

, Madersbacher

, Radziszewski

, Ruffion

, et al. Neurologic fecal incontinence. Neurourol Urodyn2010; 29(1): 207-12. doi: 10.1002/nau.20853.

34.

Vande Velde

, Van Biervliet

, Van Renterghem

, Van Laecke

, Hoebeke

, Van Winckel

. Achieving fecal continence in patients with spina bifida: A descriptive cohort study. J Urol2007; 178(6): 2640-4; discussion 4. doi: 10.1016/j.juro.2007.07.060.

35.

Bond

, Youngson

, MacPherson

, Garrett

, Bain

, Donald

, et al. Anal plugs for the management of fecal incontinence in children and adults: A randomized control trial. J Clin Gastroenterol2007; 41(1): 45-53. doi: 10.1097/MCG.0b013e31802dcba5.

36.

Deutekom

, Dobben

. Plugs for containing faecal incontinence. Cochrane Database Syst Rev2015; (7): CD005086. doi: 10.1002/14651858.CD005086.pub4.

37.

Van Winckel

, Van Biervliet

, Van Laecke

, Hoebeke

. Is an anal plug useful in the treatment of fecal incontinence in children with spina bifida or anal atresia? J Urol2006; 176(1): 342-4. doi: 10.1016/S0022-5347(06)00302-8.

38.

Cazemier

, Felt-Bersma

, Mulder

. Anal plugs and retrograde colonic irrigation are helpful in fecal incontinence or constipation. World J Gastroenterol2007; 13(22): 3101-5.

39.

Shoshan

, Ben-Zvi

, Katz-Leurer

. Use of the anal plug in the treatment of fecal incontinence in patients with meningomyelocele. J Pediatr Nurs2008; 23(5): 395-9. doi: 10.1016/j.pedn.2006.09.006.

40.

Velde

, Biervliet

, Bruyne

, Winckel

. A systematic review on bowel management and the success rate of the various treatment modalities in spina bifida patients. Spinal Cord2013; 51(12): 873-81. doi: 10.1038/sc.2013.123.

41.

Choi

, Han

, Shin

, Ji

, Chon

, Im

. Long-term outcome of transanal irrigation for children with spina bifida. Spinal Cord2014; 53: 216-220. doi: 10.1038/sc.2014.234.

42.

Emmanuel

. Review of the efficacy and safety of transanal irrigation for neurogenic bowel dysfunction. Spinal Cord2010; 48(9): 664-73. doi: 10.1038/sc.2010.5.

43.

Matsuno

, Yamazaki

, Shiroyanagi

, Ueda

, Suzuki

, Nishi

, et al. The role of the retrograde colonic enema in children with spina bifida: Is it inferior to the antegrade continence enema? Pediatr Surg Int2010; 26(5): 529-33. doi: 10.1007/s00383-010-2585-6.

44.

Ausili

, Focarelli

, Tabacco

, Murolo

, Sigismondi

, Gasbarrini

, et al. Transanal irrigation in myelomeningocele children: An alternative, safe and valid approach for neurogenic constipation. Spinal Cord2010; 48(7): 560-5. doi: 10.1038/sc.2009.186.

45.

Bischoff

, Levitt

, Bauer

, Jackson

, Holder

, Pena

. Treatment of fecal incontinence with a comprehensive bowel management program. J Pediatr Surg2009; 44(6): 1278-83; discussion 83-4. doi: 10.1016/j.jpedsurg.2009.02.047.

46.

Vande Velde

, Van Biervliet

, Van Laecke

, De Bruyne

, Verhelst

, Hoebeke

, et al. Colon enemas for fecal incontinence in patients with spina bifida. J Urol2013; 189(1): 300-4. doi: 10.1016/j.juro.2012.09.007.

47.

Pacilli

, Pallot

, Andrews

, Downer

, Dale

, Willetts

. Use of Peristeen(R) transanal colonic irrigation for bowel management in children: A single-center experience. J Pediatr Surg2014; 49(2): 269-72; discussion 72. doi: 10.1016/j.jpedsurg.2013.11.036.

48.

Corbett

, Denny

, Dick

, Malone

, Griffin

, Stanton

. Peristeen integrated transanal irrigation system successfully treats faecal incontinence in children. J Pediatr Urol2014; 10(2): 219-22. doi: 10.1016/j.jpurol.2013.08.006.

49.

Midrio

, Mosiello

, Ausili

, Gamba

, Marte

, Lombardi

, et al. Peristeen (R) transanal irrigation in paediatric patients with anorectal malformations and spinal cord lesions: A multicentre Italian study. Colorectal Dis2016; 18(1): 86-93. doi: 10.1111/codi.13101.

50.

Kelly

, Dorgalli

, McLorie

, Khoury

. Prospective evaluation of Peristeen (R) transanal irrigation system with the validated neurogenic bowel dysfunction score sheet in the pediatric population. Neurourol Urodyn2017; 36(3): 632-5. doi: 10.1002/nau.22979.

51.

Lopez Pereira

, Salvador

, Arcas

, Martinez Urrutia

, Romera

, Monereo

. Transanal irrigation for the treatment of neuropathic bowel dysfunction. J Pediatr Urol2010; 6(2): 134-8. doi: 10.1016/j.jpurol.2009.07.004.

52.

King

, Stathopoulos

, Pinnuck

, Wells

, Hutson

, Heloury

. Retrograde continence enema in children with spina bifida: Not as effective as first thought. J Paediatr Child Health2017; 53(4): 386-90. doi: 10.1111/jpc.13408.

53.

Kuizenga-Wessel

, Mousa

, Benninga

, Di Lorenzo

. Lack of agreement on how to use antegrade enemas in children. J Pediatr Gastroenterol Nutr2016; 62(1): 71-9. doi: 10.1097/MPG.0000000000000899.

54.

Siddiqui

, Fishman

, Bauer

, Nurko

. Long-term follow-up of patients after antegrade continence enema procedure. J Pediatr Gastroenterol Nutr2011; 52(5): 574-80. doi: 10.1097/MPG.0b013e3181ff6042.

55.

Schreiber

, Stone

. Fatal hypernatremia associated with the antegrade continence enema procedure. J Urol1999; 162(4): 1433, discussion 4.

56.

Mattsson

, Gladh

. Tap-water enema for children with myelomeningocele and neurogenic bowel dysfunction. Acta Paediatr2006; 95(3): 369-74. doi: 10.1080/08035250500437507.

57.

Yerkes

, Rink

, King

, Cain

, Kaefer

, Casale

. Tap water and the Malone antegrade continence enema: A safe combination? J Urol2001; 166(4): 1476-8.

58.

Chertow

, Brady

. Hyponatraemia from tap-water enema. Lancet1994; 344(8924): 748.

59.

Meier

, Foster

, Guzzetta

, Coln

. Antegrade continent enema management of chronic fecal incontinence in children. J Pediatr Surg1998; 33(7): 1149-51, discussion 51-2.

60.

Bani-Hani

, Cain

, King

, Rink

. Tap water irrigation and additives to optimize success with the Malone antegrade continence enema: The Indiana University algorithm. J Urol2008; 180(Suppl 4): 1757-60; discussion 60. doi: 10.1016/j.juro.2008.04.074.

61.

Chu

, Balsara

, Routh

, Ross

, Wiener

. Experience with glycerin for antegrade continence enema in patients with neurogenic bowel. J Urol2013; 189(2): 690-3. doi: 10.1016/j.juro.2012.08.209.

62.

Mugie

, Machado

, Mousa

, Punati

, Hogan

, Benninga

, et al. Ten-year experience using antegrade enemas in children. J Pediatr2012; 161(4): 700-4. doi: 10.1016/j.jpeds.2012.04.042.

63.

Sheibani

, Gerson

. Chemical colitis. J Clin Gastroenterol2008; 42(2): 115-21. doi: 10.1097/MCG.0b013e318151470e.

64.

Christensen

, Krogh

, Perrouin-Verbe

, Leder

, Bazzocchi

, Petersen Jakobsen

, et al. Global audit on bowel perforations related to transanal irrigation. Tech Coloproctol2016; 20(2): 109-15. doi: 10.1007/s10151-015-1400-8.

65.

Mosiello

, Marshall

, Rolle

, Cretolle

, Santacruz

, Frischer

, et al. Consensus review of best practice of transanal irrigation in children. J Pediatr Gastroenterol Nutr2017; 64(3): 343-52. doi: 10.1097/MPG.0000000000001483.

66.

Kajbafzadeh

, Chubak

. Simultaneous Malone antegrade continent enema and Mitrofanoff principle using the divided appendix: Report of a new technique for prevention of stoma complications. J Urol2001; 165(6 Pt 2): 2404-9.

67.

Lendvay

, Shnorhavorian

, Grady

. Robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy and antegrade continent enema colon tube creation in a pediatric spina bifida patient. J Laparoendosc Adv Surg Tech A2008; 18(2): 310-2. doi: 10.1089/lap.2007.0083.

68.

Lorenzo

, Chait

, Wallis

, Raikhlin

, Farhat

. Minimally invasive approach for treatment of urinary and fecal incontinence in selected patients with spina bifida. Urology2007; 70(3): 568-71. doi: 10.1016/j.urology.2007.04.026:

69.

Tiryaki

, Ergun

, Celik

, Ulman

, Avanoglu

. Success of Malone’s antegrade continence enema (MACE) from the patients’ perspective. Eur J Pediatr Surg2010; 20(6): 405-7. doi: 10.1055/s-0030-1265156.

70.

Imai

, Shiroyanagi

, Kim

, Ichiroku

, Yamazaki

. Satisfaction after the Malone antegrade continence enema procedure in patients with spina bifida. Spinal Cord2014; 52(1): 54-7. doi: 10.1038/sc.2013.111.

71.

Sinha

, Grewal

, Ward

. Antegrade continence enema (ACE): Current practice. Pediatr Surg Int2008; 24(6): 685-8. doi: 10.1007/s00383-008-2130-z.

72.

Masadeh

, Krein

, Peterson

, Bauer

, Phearman

, Pitcher

, et al. Outcome of antegrade continent enema (ACE) procedures in children and young adults. J Pediatr Surg2013; 48(10): 2128-33. doi: 10.1016/j.jpedsurg.2013.04.009.

73.

Chong

, Featherstone

, Sharif

, Cherian

, Cuckow

, Mushtaq

, et al. 5 years after an ACE: what happens then? Pediatr Surg Int2016; 32(4): 397-401. doi: 10.1007/s00383-016-3857-6.

74.

Yardley

, Pauniaho

, Baillie

, Turnock

, Coldicutt

, Lamont

, et al. After the honeymoon comes divorce: Long-term use of the antegrade continence enema procedure. J Pediatr Surg2009; 44(6): 1274-6; discussion 6-7. doi: 10.1016/j.jpedsurg.2009.02.030.

75.

Basson

, Zani

, McDowell

, Athanasakos

, Cleeve

, Phelps

, et al. Antegrade continence enema (ACE): Predictors of outcome in 111 patients. Pediatr Surg Int2014; 30(11): 1135-41. doi: 10.1007/s00383-014-3602-y.

76.

Mattix

, Novotny

, Shelley

, Rescorla

. Malone antegrade continence enema (MACE) for fecal incontinence in imperforate anus improves quality of life. Pediatr Surg Int2007; 23(12): 1175-7. doi: 10.1007/s00383-007-2026-3.

77.

Hoekstra

, Kuijper

, Bakx

, Heij

, Aronson

, Benninga

. The Malone antegrade continence enema procedure: The Amsterdam experience. J Pediatr Surg2011; 46(8): 1603-8. doi: 10.1016/j.jpedsurg.2011.04.050.

78.

Patel

, Saratzis

, Arasaradnam

, Harmston

. Use of antegrade continence enema for the treatment of fecal incontinence and functional constipation in adults: A systematic review. Dis Colon Rectum2015; 58(10): 999-1013. doi: 10.1097/DCR.0000000000000428.

79.

Tan

, Ngo

, Darzi

, Shenouda

, Tekkis

. Meta-analysis: Sacral nerve stimulation versus conservative therapy in the treatment of faecal incontinence. Int J Colorectal Dis2011; 26(3): 275-94. doi: 10.1007/s00384-010-1119-y.

80.

Lansen-Koch

SMP

, Govaert

, Oerlemans

, Melenhorst

, Vles

, Cornips

, et al. Sacral nerve modulation for defaecation and micturition disorders in patients with spina bifida. Colorectal Disease2012; 14(4): 508-14. doi: 10.1111/j.1463-1318.2011.02678.x.

81.

Haddad

, Besson

, Aubert

, Ravasse

, Lemelle

, El Ghoneimi

, et al. Sacral neuromodulation in children with urinary and fecal incontinence: A multicenter, open label, randomized, crossover study. J Urol2010; 184(2): 696-701. doi: 10.1016/j.juro.2010.03.054.