Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Management of functional constipation in children and adults

Abstract

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.

Key points

  • Diagnosis of functional constipation is based on a thorough medical history and physical examination; additional testing is only indicated if alarm symptoms are present or conventional strategies fail.

  • Functional constipation can be caused by lifestyle factors, psychological factors and behavioural factors; withholding behaviour is a key factor in the pathophysiology of childhood functional constipation, whereas adults often have dyssynergic defaecation patterns.

  • In adults, additional testing is used to differentiate between different subtypes of functional constipation (normal transit, slow transit and evacuation disorders) as such information has important therapeutic consequences.

  • Patients with intractable constipation should be referred to a gastroenterologist for further management; tests such as colonic transit time, anorectal manometry and a balloon expulsion test (in adults) might provide useful information.

  • Surgery is a therapy of last resort; to date, no clear guidelines exist on the surgical management of functional constipation and procedures vary widely between children and adults.

  • Future comparative randomized clinical trials are needed to further clarify the role of newer (prokinetic and prosecretory) pharmacological agents for the management of paediatric and adult functional constipation.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Pathophysiological factors of functional constipation in adults and children.
Fig. 2: Algorithm for initial presentation of symptoms of constipation.
Fig. 3: Algorithm for children referred to a paediatric gastroenterologist with chronic functional constipation.
Fig. 4: Algorithm for adults referred to a gastroenterologist with chronic functional constipation.
Fig. 5: Different methods of neuromodulation for functional constipation.

References

  1. Benninga, M. A. et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 150, 1443–1455 (2016).

    Article  Google Scholar 

  2. Hyams, J. S. et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 150, 1456–1468 (2016).

    Article  Google Scholar 

  3. Lacy, B. E. et al. Bowel disorders. Gastroenterology 150, 1393–1407 (2016).

    Article  Google Scholar 

  4. Wald, E. R. et al. Bowel habits and toilet training in a diverse population of children. J. Pediatr. Gastroenterol. Nutr. 48, 294–298 (2009).

    Article  PubMed  Google Scholar 

  5. Burgers, R. E. et al. Management of functional constipation in children with lower urinary tract symptoms: report from the Standardization Committee of the International Children’s Continence Society. J. Urol. 190, 29–36 (2013).

    Article  PubMed  Google Scholar 

  6. Chan, A. O. et al. Familial aggregation in constipated subjects in a tertiary referral center. Am. J. Gastroenterol. 102, 149–152 (2007).

    Article  PubMed  Google Scholar 

  7. Nurko, S. & Scott, S. M. Coexistence of constipation and incontinence in children and adults. Best Pract. Res. Clin. Gastroenterol 25, 29–41 (2011).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  8. Nurko, S. & Saps, M. Treating constipation with prucalopride: one size does not fit all. Gastroenterology 147, 1214–1216 (2014).

    Article  PubMed  Google Scholar 

  9. Stivland, T. et al. Scintigraphic measurement of regional gut transit in idiopathic constipation. Gastroenterology 101, 107–115 (1991).

    CAS  Article  PubMed  Google Scholar 

  10. Nullens, S. et al. Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation. Gut 61, 1132–1139 (2012).

    Article  PubMed  Google Scholar 

  11. Koppen, I. J. N. et al. Prevalence of functional defecation disorders in children: a systematic review and meta-analysis. J. Pediatr. 198, 121–130 (2018).

    Article  PubMed  Google Scholar 

  12. Mugie, S. M., Benninga, M. A. & Di Lorenzo, C. Epidemiology of constipation in children and adults: a systematic review. Best Pract. Res. Clin. Gastroenterol. 25, 3–18 (2011).

    Article  PubMed  Google Scholar 

  13. Bongers, M. E. J., van Wijk, M. P., Reitsma, J. B. & Benninga, M. A. Long-term prognosis for childhood constipation: clinical outcomes in adulthood. Pediatrics 126, 156–162 (2010).

    Article  Google Scholar 

  14. van Ginkel, R. et al. Childhood constipation: longitudinal follow-up beyond puberty. Gastroenterology 125, 357–363 (2003).

    Article  PubMed  Google Scholar 

  15. Suares, N. C. & Ford, A. C. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am. J. Gastroenterol. 106, 1582–1591 (2011).

    Article  PubMed  Google Scholar 

  16. Camilleri, M., Cowen, T. & Koch, T. R. Enteric neurodegeneration in ageing. Neurogastroenterol. Motil. 20, 185–196 (2008).

    CAS  Article  PubMed  Google Scholar 

  17. Broad, J. et al. Changes in neuromuscular structure and functions of human colon during ageing are region-dependent. Gut 68, 1210–1223 (2019).

    CAS  Article  PubMed  Google Scholar 

  18. Loening-Baucke, V. Chronic constipation in children. Gastroenterology 105, 1557–1564 (1993).

    CAS  Article  PubMed  Google Scholar 

  19. Mounsey, A., Raleigh, M. & Wilson, A. Management of constipation in older adults. Am. Fam. Physician 92, 500–504 (2015).

    PubMed  Google Scholar 

  20. Keuzenkamp-Jansen, C. W., Fijnvandraat, C. J., Kneepkens C. M. F. & Douwes, A. C. Chronic constipation. Arch. Dis. Child. 36–41 (1996).

  21. Dehghani, S. M., Moravej, H., Rajaei, E. & Javaherizadeh, H. Evaluation of familial aggregation, vegetable consumption, legumes consumption, and physical activity on functional constipation in families of children with functional constipation versus children without constipation. Prz. Gastroenterol. 10, 89–93 (2015).

    PubMed Central  PubMed  Google Scholar 

  22. Chan, A. O. O. et al. Influence of positive family history on clinical characteristics of functional constipation. Clin. Gastroenterol. Hepatol. 5, 197–200 (2007).

    Article  PubMed  Google Scholar 

  23. Chang, J. Y., Locke, G. R., Schleck, C. D., Zinsmeister, A. R. & Talley, N. J. Lack of familial aggregation in chronic constipation excluding irritable bowel syndrome: a population-based study. Dig. Dis. Sci. 60, 1358–1365 (2015).

    Article  PubMed  Google Scholar 

  24. Benninga, M. A., Voskuijl, W. P. & Taminiau, J. A. Childhood constipation: is there new light in the tunnel? J. Pediatr. Gastroenterol. Nutr. 39, 448–464 (2004).

    CAS  Article  PubMed  Google Scholar 

  25. Miceli Sopo, S., Arena, R., Greco, M., Bergamini, M. & Monaco, S. Constipation and cow’s milk allergy: a review of the literature. Int. Arch. Allergy Immunol. 164, 40–45 (2014).

    CAS  Article  PubMed  Google Scholar 

  26. Iacono, G., Scalici, C. & Iacono, S. Chronic constipation as a symptom of food allergy. Austin J. Allergy 3, 1024 (2016).

    Google Scholar 

  27. Tabbers, M. M. et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J. Pediatr. Gastroenterol. Nutr. 58, 258–274 (2014).

    CAS  Article  PubMed  Google Scholar 

  28. Roma, E., Adamidis, D., Nikolara, R., Constantopoulos, A. & Messaritakis, J. Diet and chronic constipation in children: the role of fiber. J. Pediatr. Gastroenterol. Nutr. 28, 169–174 (1999).

    CAS  Article  PubMed  Google Scholar 

  29. Bouras, E. P. & Tangalos, E. G. Chronic constipation in the elderly. Gastroenterol. Clin. North Am. 38, 463–480 (2009).

    Article  PubMed  Google Scholar 

  30. Youssef, N. N., Sanders, L. & Di Lorenzo, C. Adolescent constipation: evaluation and management. Adolesc. Med. Clin. 15, 37–52 (2004).

    Article  PubMed  Google Scholar 

  31. Koppen, I. J. N. et al. Functional defecation disorders and excessive body weight: a systematic review. Pediatrics 138, e20161417 (2016).

    Article  PubMed  Google Scholar 

  32. Eslick, G. D. Gastrointestinal symptoms and obesity: a meta-analysis. Obes. Rev. 13, 469–479 (2012).

    CAS  Article  PubMed  Google Scholar 

  33. Sileri, P. et al. Prevalence of defaecatory disorders in morbidly obese patients before and after bariatric surgery. J. Gastrointest. Surg. 16, 62–67 (2012).

    Article  PubMed  Google Scholar 

  34. Poylin, V. et al. Obesity and bariatric surgery: a systematic review of associations with defecatory dysfunction. Colorectal Dis. 13, e92–e103 (2011).

    CAS  Article  PubMed  Google Scholar 

  35. Ramalingam, K. & Monga, A. Obesity and pelvic floor dysfunction. Best Pract. Res. Clin. Obstet. Gynaecol. 29, 541–547 (2015).

    Article  PubMed  Google Scholar 

  36. Seidenfaden, S., Ormarsson, O. T., Lund, S. H. & Bjornsson, E. S. Physical activity may decrease the likelihood of children developing constipation. Acta Paediatr. 107, 151–155 (2018).

    Article  PubMed  Google Scholar 

  37. Rajindrajith, S., Devanarayana, N. M., Perera, B. J. C. & Benninga, M. A. Childhood constipation as an emerging public health problem. World J. Gastroenterol. 22, 6864–6875 (2016).

    PubMed Central  PubMed  Article  Google Scholar 

  38. Iovino, P. et al. New onset of constipation during long-term physical inactivity: a proof-of-concept study on the immobility-induced bowel changes. PLOS ONE 8, e72608 (2013).

    CAS  Article  Google Scholar 

  39. de Meij, T. G. J. et al. Characterization of microbiota in children with chronic functional constipation. PLOS ONE 11, e0164731 (2016).

    Article  CAS  Google Scholar 

  40. Mancabelli, L. et al. Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses. Sci. Rep. 7, 9879 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  41. Husebye, E., Hellström, P. M., Sundler, F., Chen, J. & Midtvedt, T. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G368–G380 (2001).

    CAS  Article  PubMed  Google Scholar 

  42. Hooper, L. V. et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291, 881–884 (2001).

    CAS  Article  PubMed  Google Scholar 

  43. Rao, S. S. C., Sadeghi, P., Beaty, J. & Kavlock, R. Ambulatory 24-hour colonic manometry in slow-transit constipation. Am. J. Gastroenterol. 99, 2405–2416 (2004).

    Article  PubMed  Google Scholar 

  44. van den Berg, M. M. et al. Colonic manometry as predictor of cecostomy success in children with defecation disorders. J. Pediatr. Surg. 41, 730–736 (2006).

    Article  PubMed  Google Scholar 

  45. Dinning, P. G. et al. Colonic motor abnormalities in slow transit constipation defined by high resolution, fibre-optic manometry. Neurogastroenterol. Motil. 27, 379–388 (2015).

    CAS  Article  PubMed  Google Scholar 

  46. Wessel, S. et al. Characterizing colonic motility in children with chronic intractable constipation: a look beyond high-amplitude propagating sequences. Neurogastroenterol. Motil. 28, 743–757 (2016).

    CAS  Article  PubMed  Google Scholar 

  47. Dinning, P. G., Benninga, M. A., Southwell, B. R. & Mark Scott, S. Paediatric and adult colonic manometry: a tool to help unravel the pathophysiology of constipation. World J. Gastroenterol. 16, 5162–5172 (2010).

    PubMed Central  PubMed  Article  Google Scholar 

  48. Dinning, P. G. A new understanding of the physiology and pathophysiology of colonic motility? Neurogastroenterol. Motil. 30, e13395 (2018).

    CAS  Article  PubMed  Google Scholar 

  49. Corsetti, M. et al. Pan-colonic pressurizations associated with relaxation of the anal sphincter in health and disease: a new colonic motor pattern identified using high-resolution manometry. Am. J. Gastroenterol. 112, 479–489 (2017).

    Article  PubMed  Google Scholar 

  50. Lin, A. Y., Dinning, P. G., Milne, T., Bissett, I. P. & O’Grady, G. The “rectosigmoid brake”: review of an emerging neuromodulation target for colorectal functional disorders. Clin. Exp. Pharmacol. Physiol. 44, 719–728 (2017).

    CAS  Article  PubMed  Google Scholar 

  51. Rao, S. S. C. & Patcharatrakul, T. Diagnosis and treatment of dyssynergic defecation. J. Neurogastroenterol. Motil. 22, 423–435 (2016).

    PubMed Central  PubMed  Article  Google Scholar 

  52. Bharucha, A. E., Pemberton, J. H. & Locke, G. R. American Gastroenterological Association technical review on constipation. Gastroenterology 144, 218–238 (2013).

    PubMed  Article  Google Scholar 

  53. Rao, S. S. C. et al. Anorectal disorders. Gastroenterology 150, 1430–1442 (2016).

    Article  Google Scholar 

  54. Ranasinghe, N., Devanarayana, N. M., Benninga, M. A., Van Dijk, M. & Rajindrajith, S. Psychological maladjustment and quality of life in adolescents with constipation. Arch. Dis. Child. 102, 268–273 (2017).

    Article  PubMed  Google Scholar 

  55. Philips, E. M. et al. Stressful life events in children with functional defecation disorders. J. Pediatr. Gastroenterol. Nutr. 61, 384–392 (2015).

    Article  PubMed  Google Scholar 

  56. Joinson, C., Grzeda, M. T., von Gontard, A. & Heron, J. Psychosocial risks for constipation and soiling in primary school children. Eur. Child. Adolesc. Psychiatry 28, 203–210 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Mason, H. J., Serrano-Ikkos, E. & Kamm, M. A. Psychological morbidity in women with idiopathic constipation. Am. J. Gastroenterol. 95, 2852–2857 (2000).

    CAS  Article  PubMed  Google Scholar 

  58. McKeown, C., Hisle-Gorman, E., Eide, M., Gorman, G. H. & Nylund, C. M. Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder. Pediatrics 132, e1210–e1215 (2013).

    PubMed Central  PubMed  Article  Google Scholar 

  59. Peeters, B., Noens, I., Philips, E. M., Kuppens, S. & Benninga, M. A. Autism spectrum disorders in children with functional defecation disorders. J. Pediatr. 163, 873–878 (2013).

    Article  PubMed  Google Scholar 

  60. van Dijk, M., Benninga, M. A., Grootenhuis, M. A. & Last, B. F. Prevalence and associated clinical characteristics of behavior problems in constipated children. Pediatrics 125, 309–317 (2010).

    Article  Google Scholar 

  61. Haug, T. T., Mykletun, A. & Dahl, A. A. Are anxiety and depression related to gastrointestinal symptoms in the general population? Scand. J. Gastroenterol. 37, 294–298 (2002).

    Article  PubMed  Google Scholar 

  62. Dykes, S., Smilgin-Humphreys, S. & Bass, C. Chronic idiopathic constipation: a psychological enquiry. Eur. J. Gastroenterol. Hepatol. 13, 39–44 (2001).

    CAS  Article  PubMed  Google Scholar 

  63. Rajindrajith, S., Devanarayana, N. M. & Benninga, M. A. Fecal incontinence in adolescents is associated with child abuse, somatization, and poor health-related quality of life. J. Pediatr. Gastroenterol. Nutr. 62, 698–703 (2016).

    Article  PubMed  Google Scholar 

  64. Rajindrajith, S., Devanarayana, N. M. & Benninga, M. A. Constipation-associated and nonretentive fecal incontinence in children and adolescents: an epidemiological survey in Sri Lanka. J. Pediatr. Gastroenterol. Nutr. 51, 472–476 (2010).

    Article  PubMed  Google Scholar 

  65. Koch, T. & Hudson, S. Older people and laxative use: literature review and pilot study report. J. Clin. Nurs. 9, 516–525 (2000).

    CAS  Article  PubMed  Google Scholar 

  66. Carabotti, M., Scirocco, A., Maselli, M. A. & Severi, C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 28, 203–209 (2015).

    PubMed Central  PubMed  Google Scholar 

  67. Mugie, S. M. et al. Brain processing of rectal sensation in adolescents with functional defecation disorders and healthy controls. Neurogastroenterol. Motil. 30, e13228 (2018).

    Article  Google Scholar 

  68. Zhu, Q. et al. Distinct resting-state brain activity in patients with functional constipation. Neurosci. Lett. 632, 141–146 (2016).

    CAS  Article  PubMed  Google Scholar 

  69. Malowitz, S., Green, M., Karpinski, A., Rosenberg, A. & Hyman, P. E. Age of onset of functional constipation. J. Pediatr. Gastroenterol. Nutr. 62, 600–602 (2016).

    Article  PubMed  Google Scholar 

  70. Loening-Baucke, V. Constipation in early childhood: patient characteristics, treatment, and long-term follow up. Gut 34, 1400–1404 (1993).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  71. Benninga, M. A., Voskuijl, W. P. & Taminiau, J. A. J. M. Childhood constipation: is there new light in the tunnel? J. Pediatr. Gastroenterol. Nutr. 39, 448–464 (2004).

    CAS  Article  PubMed  Google Scholar 

  72. van der Plas, R. et al. Biofeedback training in treatment of childhood constipation: a randomised controlled study. Lancet 348, 776–780 (1996).

    Article  PubMed  Google Scholar 

  73. Rao, S. S. C., Mudipalli, R. S., Stessman, M. & Zimmerman, B. Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus). Neurogastroenterol. Motil. 16, 589–596 (2004).

    CAS  Article  PubMed  Google Scholar 

  74. Loening-Baucke, V. Biofeedback treatment for chronic constipation and encopresis in childhood: long-term outcome. Pediatrics 96, 105–110 (1995).

    CAS  PubMed  Google Scholar 

  75. Borowitz, S. M. et al. Precipitants of constipation during early childhood. J. Am. Board Fam. Pract. 16, 213–218 (2002).

    Article  Google Scholar 

  76. Scott, S. M., Van Den Berg, M. M. & Benninga, M. A. Rectal sensorimotor dysfunction in constipation. Best Pract. Res. Clin. Gastroenterol 25, 103–118 (2011).

    CAS  Article  PubMed  Google Scholar 

  77. van Dijk, M., de Vries, G.-J., Last, B. F., Benninga, M. A. & Grootenhuis, M. A. Parental child-rearing attitudes are associated with functional constipation in childhood. Arch. Dis. Child. 100, 329–333 (2015).

    Article  PubMed  Google Scholar 

  78. Peeters, B. et al. Parental characteristics and functional constipation in children: a cross-sectional cohort study. BMJ Paediatr. Open 1, e000100 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  79. Rao, S. S. C. Yamada’s Textbook of Gastroenterology 6th edn Vol. 2 (Wiley-Blackwell, 2016).

  80. Tantiphlachiva, K., Rao, P., Attaluri, A. & Rao, S. S. C. Digital rectal examination is a useful tool for identifying patients with dyssynergia. Clin. Gastroenterol. Hepatol. 8, 955–960 (2010).

    Article  PubMed  Google Scholar 

  81. Chedid, V., Vijayvargiya, P., Halawi, H., Park, S. & Camilleri, M. Audit of the diagnosis of rectal evacuation disorders in chronic constipation. Neurogastroenterol. Motil. 31, e13510 (2019).

    Article  PubMed  Google Scholar 

  82. Chogle, A. & Saps, M. Yield and cost of performing screening tests for constipation in children. Can. J. Gastroenterol. 27, e35–e38 (2013).

    PubMed Central  PubMed  Article  Google Scholar 

  83. National Institute for Health and Care Excellence. Constipation in children and young people: diagnosis and management (NICE, 2010).

  84. National Institute for Health and Care Excellence. Coeliac disease: recognition, assessment and management (NICE, 2015).

  85. Kearney, R., Edwards, T., Bradford, M. & Klein, E. Emergency provider use of plain radiographs in the evaluation of pediatric constipation. Pediatr. Emerg. Care 35, 624–629 (2018).

    Google Scholar 

  86. Berger, M. Y., Tabbers, M. M., Kurver, M. J., Boluyt, N. & Benninga, M. A. Value of abdominal radiography, colonic transit time, and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children: a systematic review. J. Pediatr. 161, 44–50 (2012).

    Article  PubMed  Google Scholar 

  87. Linet, M. S., Kim, K. P. & Rajaraman, P. Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations. Pediatr. Radiol. 39, S4–S26 (2009).

    Article  PubMed  Google Scholar 

  88. Park, S.-Y., Khemani, D., Nelson, A. D., Eckert, D. & Camilleri, M. Rectal gas volume measured by computerized tomography identifies evacuation disorders in patients with constipation. Clin. Gastroenterol. Hepatol. 15, 543–552 (2017).

    Article  PubMed  Google Scholar 

  89. Park, S.-Y., Khemani, D., Acosta, A., Eckert, D. & Camilleri, M. Rectal gas volume: defining cut-offs for screening for evacuation disorders in patients with constipation. Neurogastroenterol. Motil. 29, e13044 (2017).

    Article  Google Scholar 

  90. Krevsky, B., Malmud, L. S., D’Ercole, F., Maurer, A. H. & Fisher, R. S. Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans. Gastroenterology 91, 1102–12 (1986).

    CAS  Article  PubMed  Google Scholar 

  91. Manabe, N. et al. Lower functional gastrointestinal disorders: evidence of abnormal colonic transit in a 287 patient cohort. Neurogastroenterol. Motil. 22, 293-e82 (2010).

    Article  PubMed  Google Scholar 

  92. Mugie, S. M. et al. Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation. J. Pediatr. Gastroenterol. Nutr. 57, 598–602 (2013).

    Article  PubMed  Google Scholar 

  93. Camilleri, M. et al. Wireless pH-motility capsule for colonic transit: prospective comparison with radiopaque markers in chronic constipation. Neurogastroenterol. Motil. 22, 874–882, e233 (2010).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  94. Green, A. D. et al. Wireless motility capsule test in children with upper gastrointestinal symptoms. J. Pediatr. 162, 1181–1187 (2013).

    Article  PubMed  Google Scholar 

  95. Rao, S. S. C. et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin. Gastroenterol. Hepatol. 7, 537–544 (2009).

    Article  PubMed  Google Scholar 

  96. Koppen, I. J. N. et al. Management of functional nonretentive fecal incontinence in children: recommendations from the International Children’s Continence Society. J. Pediatr. Urol. 12, 56–64 (2016).

    CAS  Article  PubMed  Google Scholar 

  97. Benninga, M. A., Buller, H. A., Heymans, H. S. A., Tytgat, G. N. J. & Taminiau, J. A. J. M. Is encopresis always the result of constipation? Arch. Dis. Child. 71, 186–193 (1994).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  98. De Lorijn, F. et al. Prognosis of constipation: clinical factors and colonic transit time. Arch. Dis. Child. 89, 723–727 (2004).

    PubMed Central  PubMed  Article  Google Scholar 

  99. Degen, L. P. & Phillips, S. F. How well does stool form reflect colonic transit? Gut 39, 109–113 (1996).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  100. Keshtgar, A. S., Ward, H. C. & Clayden, G. S. Pathophysiology of chronic childhood constipation: functional and morphological evaluation by anorectal manometry and endosonography and colonic transit study. J. Pediatr. Surg. 48, 806–812 (2013).

    Article  PubMed  Google Scholar 

  101. Shin, A. et al. Interpretation of overall colonic transit in defecation disorders in males and females. Neurogastroenterol. Motil. 25, 502–508 (2013).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  102. Nullens, S. et al. Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation. Gut 61, 1132–1139 (2012).

    Article  PubMed  Google Scholar 

  103. Park, S.-Y., Burton, D., Busciglio, I., Eckert, D. & Camilleri, M. Regional colonic transit pattern does not conclusively identify evacuation disorders in constipated patients with delayed colonic transit. J. Neurogastroenterol. Motil. 23, 92–100 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  104. Sloots, C. E. J. & Felt-Bersma, R. J. F. Effect of bowel cleansing on colonic transit in constipation due to slow transit or evacuation disorder. Neurogastroenterol. Motil. 14, 55–61 (2002).

    CAS  Article  PubMed  Google Scholar 

  105. Quitadamo, P. et al. Effect of bowel cleansing on colonic transit time measurement in children with chronic constipation. J. Pediatr. 167, 1440–1442 (2015).

    Article  PubMed  Google Scholar 

  106. Tran, K. et al. Effect of propofol on anal sphincter pressure during anorectal manometry. J. Pediatr. Gastroenterol. Nutr. 58, 495–497 (2014).

    CAS  Article  PubMed  Google Scholar 

  107. Rodriguez, L., Sood, M., Di Lorenzo, C. & Saps, M. An ANMS-NASPGHAN consensus document on anorectal and colonic manometry in children. Neurogastroenterol. Motil. 29, e12944 (2017).

    Article  Google Scholar 

  108. Rao, S. S. C., Sadeghi, P., Beaty, J. & Kavlock, R. Ambulatory 24-hour colonic manometry in slow-transit constipation. Am. J. Gastroenterol. 99, 2405–2416 (2004).

    Article  PubMed  Google Scholar 

  109. Hagger, R., Kumar, D., Benson, M. & Grundy, A. Colonic motor activity in slow-transit idiopathic constipation as identified by 24-h pancolonic ambulatory manometry. Neurogastroenterol. Motil. 15, 515–522 (2003).

    CAS  Article  PubMed  Google Scholar 

  110. Camilleri, M. et al. American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice. Neurogastroenterol. Motil. 20, 1269–1282 (2008).

    CAS  Article  PubMed  Google Scholar 

  111. Koppen, I. J. N. et al. Surgical decision-making in the management of children with intractable functional constipation: what are we doing and are we doing it right? J. Pediatr. Surg. 51, 1607–1612 (2016).

    Article  PubMed  Google Scholar 

  112. Levitt, M. A., Martin, C. A., Falcone, R. A. & Peña, A. Transanal rectosigmoid resection for severe intractable idiopathic constipation. J. Pediatr. Surg. 44, 1285–1291 (2009).

    Article  PubMed  Google Scholar 

  113. Loening-Baucke, V. Factors determining outcome in children with chronic constipation and faecal soiling. Gut 30, 999–1006 (1989).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  114. Belkind-Gerson, J., Goldstein, A. M. & Kuo, B. Balloon expulsion test as a screen for outlet obstruction in children with chronic constipation. J. Pediatr. Gastroenterol. Nutr. 56, 23–26 (2013).

    Article  PubMed  Google Scholar 

  115. Minguez, M. et al. Predictive value of the balloon expulsion test for excluding the diagnosis of pelvic floor dyssynergia in constipation. Gastroenterology 126, 57–62 (2004).

    Article  PubMed  Google Scholar 

  116. Wald, A., Bharucha, A. E., Cosman, B. C. & Whitehead, W. E. ACG clinical guideline: management of benign anorectal disorders. Am. J. Gastroenterol. 109, 1141–1157 (2014).

    Article  PubMed  Google Scholar 

  117. Williams, C. L., Bollella, M. & Wynder, E. L. A new recommendation for dietary fiber in childhood. Pediatrics 96, 985–988 (1995).

    CAS  Article  PubMed  Google Scholar 

  118. ODPHP. 2015-2020 Dietary Guidelines for Americans. (2015). Available at: http://health.gov/dietaryguidelines/2015/guidelines/. (Accessed: August 2019)

  119. Fayet-Moore, F., Cassettari, T., Tuck, K., McConnell, A. & Petocz, P. Dietary fibre intake in Australia. Paper I: Associations with demographic, socio-economic, and anthropometric factors. Nutrients 10, 599 (2018).

    PubMed Central  Article  Google Scholar 

  120. Kranz, S., Brauchla, M., Slavin, J. L. & Miller, K. B. What do we know about dietary fiber intake in children and health? The effects of fiber intake on constipation, obesity, and diabetes in children. Adv. Nutr. 3, 47–53 (2012).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  121. Suares, N. C. & Ford, A. C. Systematic review: the effects of fibre in the management of chronic idiopathic constipation. Aliment. Pharmacol. Ther. 33, 895–901 (2011).

    CAS  Article  PubMed  Google Scholar 

  122. Rao, S. S. C., Yu, S. & Fedewa, A. Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome. Aliment. Pharmacol. Ther. 41, 1256–1270 (2015).

    CAS  Article  PubMed  Google Scholar 

  123. Choi, C. H. & Chang, S. K. Alteration of gut microbiota and efficacy of probiotics in functional constipation. J. Neurogastroenterol. Motil. 21, 004–007 (2015).

    Article  Google Scholar 

  124. Castillejo, G., Bullo, M., Anguera, A., Escribano, J. & Salas-Salvado, J. A controlled, randomized, double-blind trial to evaluate the effect of a supplement of cocoa husk that is rich in dietary fiber on colonic transit in constipated pediatric patients. Pediatrics 118, e641–e648 (2006).

    Article  PubMed  Google Scholar 

  125. Miller, L. E., Ouwehand, A. C. & Ibarra, A. Effects of probiotic-containing products on stool frequency and intestinal transit in constipated adults: systematic review and meta-analysis of randomized controlled trials. Ann. Gastroenterol. 30, 629–639 (2017).

    PubMed Central  PubMed  Google Scholar 

  126. Korterink, J. J. et al. Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. Acta Paediatr. 103, 365–372 (2014).

    Article  PubMed  Google Scholar 

  127. Chmielewska, A. & Szajewska, H. Systematic review of randomised controlled trials: probiotics for functional constipation. World J. Gastroenterol. 16, 69–75 (2010).

    PubMed Central  PubMed  Google Scholar 

  128. Tabbers, M. M. & Benninga, M. A. Constipation in children: fibre and probiotics. BMJ Clin. Evid. 2015, 0303 (2015).

    PubMed Central  PubMed  Google Scholar 

  129. Huang, R. & Hu, J. Positive effect of probiotics on constipation in children: a systematic review and meta-analysis of six randomized controlled trials. Front. Cell. Infect. Microbiol. 7, 153 (2017).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  130. Koppen, I. J. N., Benninga, M. A. & Tabbers, M. M. Is there a role for pre-, pro- and synbiotics in the treatment of functional constipation in children? A systematic review. J. Pediatr. Gastroenterol. Nutr. 63, S27–S35 (2016).

    Article  PubMed  Google Scholar 

  131. Pourmand, H. & Esmaillzadeh, A. Consumption of a low fermentable oligo-, di-, mono-saccharides, and polyols diet and irritable bowel syndrome: a systematic review. Int. J. Prev. Med. 8, 104 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  132. Hill, P., Muir, J. G. & Gibson, P. R. Controversies and recent developments of the low-FODMAP diet. Gastroenterol. Hepatol. 13, 36–45 (2017).

    Google Scholar 

  133. Van Der Plas, R. N., Benninga, M. A., Taminiau, J. A. J. M. & Büller, H. A. Treatment of defaecation problems in children: the role of education, demystification and toilet training. Eur. J. Pediatr. 156, 689–692 (1997).

    Article  PubMed  Google Scholar 

  134. van Dijk, M. et al. Behavioral therapy for childhood constipation: a randomized, controlled trial. Pediatrics 121, e1334–e1341 (2008).

    Article  PubMed  Google Scholar 

  135. Brazzelli, M. & Griffiths, P. V. Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database Syst. Rev. 2, CD002240 (2006).

    Google Scholar 

  136. van Engelenburg-van Lonkhuyzen, M. L., Bols, E. M. J., Benninga, M. A., Verwijs, W. A. & de Bie, R. A. Effectiveness of pelvic physiotherapy in children with functional constipation compared with standard medical care. Gastroenterology 152, 82–91 (2017).

    Article  PubMed  Google Scholar 

  137. Rao, S. S. C. et al. ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol. Motil. 27, 594–609 (2015).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  138. Chiarioni, G., Whitehead, W. E., Pezza, V., Morelli, A. & Bassotti, G. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology 130, 657–664 (2006).

    Article  PubMed  Google Scholar 

  139. Heymen, S. et al. Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation. Dis. Colon Rectum 50, 428–441 (2007).

    Article  PubMed  Google Scholar 

  140. Rao, S. S. C. et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin. Gastroenterol. Hepatol. 5, 331–338 (2007).

    Article  PubMed  Google Scholar 

  141. Koppen, I. J. N. et al. Role of polyethylene glycol in the treatment of functional constipation in children. J. Pediatr. Gastroenterol. Nutr. 65, 361–363 (2017).

    CAS  Article  PubMed  Google Scholar 

  142. DiPalma, J. A., Cleveland, M. vB., McGowan, J. & Herrera, J. L. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am. J. Gastroenterol. 102, 1436–1441 (2007).

    CAS  Article  PubMed  Google Scholar 

  143. Williams, K. C., Rogers, L. K., Hill, I., Barnard, J. & Di Lorenzo, C. PEG 3350 administration is not associated with sustained elevation of glycol levels. J. Pediatr. 195, 148–153 (2018).

    CAS  Article  PubMed  Google Scholar 

  144. Harris, L. A., Horn, J., Kissous-Hunt, M., Magnus, L. & Quigley, E. M. M. The better understanding and recognition of the disconnects, experiences, and needs of patients with chronic idiopathic constipation (BURDEN-CIC) study: results of an online questionnaire. Adv. Ther. 34, 2661–2673 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  145. Koppen, I. J. N., van Wassenaer, E. A., Barendsen, R. W., Brand, P. L. & Benninga, M. A. Adherence to polyethylene glycol treatment in children with functional constipation is associated with parental illness perceptions, satisfaction with treatment, and perceived treatment convenience. J. Pediatr. 199, 132–139 (2018).

    Article  PubMed  Google Scholar 

  146. Pijpers, M. A. M., Bongers, M. E. J., Benninga, M. A. & Berger, M. Y. Functional constipation in children: a systematic review on prognosis and predictive factors. J. Pediatr. Gastroenterol. Nutr. 50, 256–268 (2010).

    CAS  Article  PubMed  Google Scholar 

  147. Johanson, J. F. & Kralstein, J. Chronic constipation: a survey of the patient perspective. Aliment. Pharmacol. Ther. 25, 599–608 (2007).

    CAS  Article  PubMed  Google Scholar 

  148. Wald, A. et al. A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation. Aliment. Pharmacol. Ther. 28, 917–930 (2008).

    CAS  PubMed  Google Scholar 

  149. Wald, A. et al. Survey of laxative use by adults with self-defined constipation in South America and Asia: a comparison of six countries. Aliment. Pharmacol. Ther. 31, 274–284 (2010).

    CAS  PubMed  Google Scholar 

  150. Batchelor, H. K. & Marriott, J. F. Paediatric pharmacokinetics: key considerations. Br. J. Clin. Pharmacol. 79, 395–404 (2015).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  151. Koppen, I. J. N. et al. Recommendations for pharmacological clinical trials in children with functional constipation: the Rome Foundation Pediatric Subcommittee on clinical trials. Neurogastroenterol. Motil. 30, e13294 (2018).

    CAS  Article  PubMed  Google Scholar 

  152. Simrén, M. & Tack, J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat. Rev. Gastroenterol. Hepatol. 15, 589–605 (2018).

    Article  CAS  PubMed  Google Scholar 

  153. Bassil, A. K. et al. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br. J. Pharmacol. 154, 126–135 (2008).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  154. Bijvelds, M. J. C., Bot, A. G. M., Escher, J. C. & De Jonge, H. R. Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology 137, 976–985 (2009).

    CAS  Article  PubMed  Google Scholar 

  155. Barish, C. F., Drossman, D., Johanson, J. F. & Ueno, R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig. Dis. Sci. 55, 1090–1097 (2010).

    CAS  Article  PubMed  Google Scholar 

  156. Johanson, J. F., Morton, D., Geenen, J. & Ueno, R. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. Am. J. Gastroenterol. 103, 170–177 (2008).

    CAS  Article  PubMed  Google Scholar 

  157. Johanson, J. F. & Ueno, R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment. Pharmacol. Ther. 25, 1351–1361 (2007).

    CAS  Article  PubMed  Google Scholar 

  158. Fukudo, S., Hongo, M., Kaneko, H., Takano, M. & Ueno, R. Lubiprostone increases spontaneous bowel movement frequency and quality of life in patients with chronic idiopathic constipation. Clin. Gastroenterol. Hepatol. 13, 294–301 (2015).

    CAS  Article  PubMed  Google Scholar 

  159. Hyman, P. E., Di Lorenzo, C., Prestridge, L. L., Youssef, N. N. & Ueno, R. Lubiprostone for the treatment of functional constipation in children. J. Pediatr. Gastroenterol. Nutr. 58, 283–291 (2014).

    CAS  Article  PubMed  Google Scholar 

  160. Benninga, M. A. et al. Long-term open-label safety extension study assessing oral lubiprostone in children with pediatric functional constipation aged 6-17 years [abstract Su1664]. Gastroenterology 154, S560 (2018).

    Article  Google Scholar 

  161. Benninga, M. A. et al. Efficacy and safety of lubiprostone in children with functional constipation: a multicenter, randomized, placebo-controlled, double-blind pivotal study [abstract Su1643]. Gastroenterology 154, S559–S560 (2018).

    Article  Google Scholar 

  162. Lembo, A. J. et al. Two randomized trials of linaclotide for chronic constipation. N. Engl. J. Med. 365, 527–536 (2011).

    CAS  PubMed  Article  Google Scholar 

  163. McWilliams, V., Whiteside, G. & McKeage, K. Linaclotide: first global approval. Drugs 72, 2167–2175 (2012).

    CAS  PubMed  Article  Google Scholar 

  164. Barish, C. F. & Griffin, P. Safety and tolerability of plecanatide in patients with chronic idiopathic constipation: long-term evidence from an open-label study. Curr. Med. Res. Opin. 34, 751–755 (2018).

    CAS  Article  PubMed  Google Scholar 

  165. Shailubhai, K. et al. Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig. Dis. Sci. 58, 2580–2586 (2013).

    CAS  Article  PubMed  Google Scholar 

  166. Miner, P. B. et al. A randomized phase III clinical trial of plecanatide, a uroguanylin analog, in patients with chronic idiopathic constipation. Am. J. Gastroenterol. 112, 613–621 (2017).

    CAS  Article  PubMed  Google Scholar 

  167. Thomas, R. H. & Luthin, D. R. Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents. Pharmacotherapy 35, 613–630 (2015).

    CAS  Article  PubMed  Google Scholar 

  168. Cross-Adame, E. & Rao, S. S. Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings. Curr. Gastroenterol. Rep. 16, 379 (2014).

    Article  Google Scholar 

  169. Mendzelevski, B. et al. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study. Br. J. Clin. Pharmacol. 73, 203–209 (2012).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  170. Camilleri, M. et al. Efficacy and safety of prucalopride in chronic constipation: an integrated analysis of six randomized, controlled clinical trials. Dig. Dis. Sci. 61, 2357–2372 (2016).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  171. Aboumarzouk, O. M., Agarwal, T., Antakia, R., Shariff, U. & Nelson, R. L. Cisapride for intestinal constipation. Cochrane Database Syst. Rev. 1, CD007780 (2011).

    Google Scholar 

  172. US Food and Drug Administration. Joint meeting of the gastrointestinal drugs advisory committee and drug safety and risk management advisory committees (FDA, 2018).

  173. Sajid, M. S., Hebbar, M., Baig, M. K., Li, A. & Philipose, Z. Use of prucalopride for chronic constipation: a systematic review and meta-analysis of published randomized, controlled trials. J. Neurogastroenterol. Motil. 22, 412–422 (2016).

    PubMed Central  PubMed  Article  Google Scholar 

  174. Winter, H. S. et al. Oral prucalopride in children with functional constipation. J. Pediatr. Gastroenterol. Nutr. 57, 197–203 (2013).

    CAS  Article  PubMed  Google Scholar 

  175. Mugie, S. M. et al. Prucalopride is no more effective than placebo for children with functional constipation. Gastroenterology 147, 1285–1295 (2014).

    CAS  Article  PubMed  Google Scholar 

  176. Cinca, R., Chera, D., Gruss, H.-J. & Halphen, M. Randomised clinical trial: macrogol/PEG 3350+electrolytes versus prucalopride in the treatment of chronic constipation — a comparison in a controlled environment. Aliment. Pharmacol. Ther. 37, 876–886 (2013).

    CAS  Article  PubMed  Google Scholar 

  177. Goldberg, M. et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation — a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment. Pharmacol. Ther. 32, 1102–1112 (2010).

    CAS  Article  PubMed  Google Scholar 

  178. Shin, A. et al. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment. Pharmacol. Ther. 39, 239–253 (2014).

    CAS  Article  PubMed  Google Scholar 

  179. Rao, A. S. et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology 139, 1549–1558 (2010).

    Article  CAS  Google Scholar 

  180. Hofmann, A. F. et al. Altered bile acid metabolism in childhood functional constipation: inactivation of secretory bile acids by sulfation in a subset of patients. J. Pediatr. Gastroenterol. Nutr. 47, 598–606 (2008).

    CAS  Article  PubMed  Google Scholar 

  181. Simrén, M., Bajor, A., Gillberg, P. G., Rudling, M. & Abrahamsson, H. Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation — a double-blind study. Aliment. Pharmacol. Ther. 34, 41–50 (2011).

    Article  CAS  PubMed  Google Scholar 

  182. Wong, B. S. et al. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am. J. Gastroenterol. 106, 2154–2164 (2011).

    CAS  Article  PubMed  Google Scholar 

  183. Nakajima, A. et al. Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial. Lancet Gastroenterol. Hepatol. 3, 537–547 (2018).

    Article  PubMed  Google Scholar 

  184. Acosta, A. & Camilleri, M. Elobixibat and its potential role in chronic idiopathic constipation. Therap. Adv. Gastroenterol 7, 167–175 (2014).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  185. Soufi-Afshar, I., Moghadamnia, A., Bijani, A., Kazemi, S. & Shokri-Shirvani, J. Comparison of pyridostigmine and bisacodyl in the treatment of refractory chronic constipation. Casp. J. Intern. Med. 7, 19–24 (2016).

    Google Scholar 

  186. O’Dea, C. J., Brookes, S. J. H. & Wattchow, D. A. The efficacy of treatment of patients with severe constipation or recurrent pseudo-obstruction with pyridostigmine. Colorectal Dis. 12, 540–548 (2009).

    Article  Google Scholar 

  187. Manini, M. L., Camilleri, M., Grothe, R. & Di Lorenzo, C. Application of pyridostigmine in pediatric gastrointestinal motility disorders: a case series. Pediatr. Drugs 20, 173–180 (2018).

    Article  Google Scholar 

  188. Mosiello, G. et al. Consensus review of best practice of transanal irrigation in children. J. Pediatr. Gastroenterol. Nutr. 64, 343–352 (2017).

    Article  PubMed  Google Scholar 

  189. Krogh, K. et al. Consensus review of best practice of transanal irrigation in adults. Spinal Cord 51, 732–738 (2013).

    Article  PubMed  Google Scholar 

  190. Mosiello, G. et al. Consensus review of best practice of transanal irrigation in children. J. Pediatr. Gastroenterol. Nutr. 64, 343–352 (2017).

    Article  PubMed  Google Scholar 

  191. Cazemier, M., Felt-Bersma, R. J. F. & Mulder, C. J. J. Anal plugs and retrograde colonic irrigation are helpful in fecal incontinence or constipation. World J. Gastroenterol. 13, 3101–3105 (2007).

    PubMed Central  PubMed  Article  Google Scholar 

  192. Chrzan, R., Klijn, A. J., Vijverberg, M. A. W., Sikkel, F. & de Jong, T. P. V. M. Colonic washout enemas for persistent constipation in children with recurrent urinary tract infections based on dysfunctional voiding. Urology 71, 607–610 (2008).

    Article  PubMed  Google Scholar 

  193. Nasher, O., Hill, R. E., Peeraully, R., Wright, A. & Singh, S. J. Peristeen transanal irrigation system for paediatric faecal incontinence: a single centre experience. Int. J. Pediatr. 2014, 954315 (2014).

    PubMed Central  PubMed  Article  Google Scholar 

  194. Ng, J. et al. Transanal irrigation for intractable faecal incontinence and constipation: outcomes, quality of life and predicting non-adopters. Pediatr. Surg. Int. 31, 729–734 (2015).

    Article  PubMed  Google Scholar 

  195. Koppen, I. J. N., Kuizenga-Wessel, S., Voogt, H. W., Voskeuil, M. E. & Benninga, M. A. Transanal irrigation in the treatment of children with intractable functional constipation. J. Pediatr. Gastroenterol. Nutr. 64, 225–229 (2017).

    Article  PubMed  Google Scholar 

  196. Etherson, K. J., Minty, I., Bain, I. M., Cundall, J. & Yiannakou, Y. Transanal irrigation for refractory chronic idiopathic constipation: patients perceive a safe and effective therapy. Gastroenterol. Res. Pract. 2017, 3826087 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  197. Siminas, S. & Losty, P. D. Current surgical management of pediatric idiopathic constipation. Ann. Surg. 262, 925–933 (2015).

    Article  PubMed  Google Scholar 

  198. Camilleri, M. et al. Chronic constipation. Nat. Rev. Dis. Primers 3, 17095 (2017).

    Article  PubMed  Google Scholar 

  199. Tse, Y. et al. Treatment algorithm for chronic idiopathic constipation and constipation-predominant irritable bowel syndrome derived from a Canadian national survey and needs assessment on choices of therapeutic agents. Can. J. Gastroenterol. Hepatol. 2017, 8612189 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  200. Curry, J. I., Osborne, A. & Malone, P. S. How to achieve a successful Malone antegrade continence enema. J. Pediatr. Surg. 33, 138–141 (1998).

    CAS  Article  PubMed  Google Scholar 

  201. Curry, J., Osborne, A. & Malone, P. S. The MACE procedure: experience in the United Kingdom. J. Pediatr. Surg. 34, 338–340 (1999).

    CAS  Article  PubMed  Google Scholar 

  202. King, S. K., Sutcliffe, J. R., Southwell, B. R., Chait, P. G. & Hutson, J. M. The antegrade continence enema successfully treats idiopathic slow-transit constipation. J. Pediatr. Surg. 40, 1935–1940 (2005).

    Article  PubMed  Google Scholar 

  203. Worsøe, J., Christensen, P., Krogh, K., Buntzen, S. & Laurberg, S. Long-term results of antegrade colonic enema in adult patients: assessment of functional results. Dis. Colon Rectum 51, 1523–1528 (2008).

    Article  PubMed  Google Scholar 

  204. Meurette, G., Lehur, P.-A., Coron, E. & Regenet, N. Long-term results of Malone’s procedure with antegrade irrigation for severe chronic constipation. Gastroentérol. Clin. Biol. 34, 209–212 (2010).

    CAS  Article  PubMed  Google Scholar 

  205. Levitt, M. A., Mathis, K. L. & Pemberton, J. H. Surgical treatment for constipation in children and adults. Best Pract. Res. Clin. Gastroenterol 25, 167–179 (2011).

    Article  PubMed  Google Scholar 

  206. Villarreal, J. et al. Colonic diversion for intractable constipation in children: colonic manometry helps guide clinical decisions. J. Pediatr. Gastroenterol. Nutr. 33, 588–591 (2001).

    CAS  Article  PubMed  Google Scholar 

  207. Singh, S., Heady, S., Coss-Adame, E. & Rao, S. S. C. Clinical utility of colonic manometry in slow transit constipation. Neurogastroenterol. Motil. 25, 487–e367 (2013).

    Article  CAS  Google Scholar 

  208. Martin, M. J. et al. A pilot study using total colonic manometry in the surgical evaluation of pediatric functional colonic obstruction. J. Pediatr. Surg. 39, 352–359 (2004).

    Article  PubMed  Google Scholar 

  209. Martin, M. J., Steele, S. R., Noel, J. M., Weichmann, D. & Azarow, K. S. Total colonic manometry as a guide for surgical management of functional colonic obstruction: preliminary results. J. Pediatr. Surg. 36, 1757–1763 (2001).

    CAS  Article  PubMed  Google Scholar 

  210. Eradi, B. et al. The role of a colon resection in combination with a Malone appendicostomy as part of a bowel management program for the treatment of fecal incontinence. J. Pediatr. Surg. 48, 2296–2300 (2013).

    Article  PubMed  Google Scholar 

  211. Kuizenga-Wessel, S. et al. Surgical management of children with intractable functional constipation; experience of a single tertiary children’s hospital. Neurogastroenterol. Motil. 29, e13005 (2017).

    Article  Google Scholar 

  212. Knowles, C. H. et al. Surgery for constipation: systematic review and practice recommendations: Results I: Colonic resection. Colorectal Dis. 19 (Suppl. 3), 17–36 (2017).

    Article  PubMed  Google Scholar 

  213. Knowles, C. H. et al. Surgery for constipation: systematic review and practice recommendations. Graded practice and future research recommendations. Colorectal Dis. 19 (Suppl. 3), 101–113 (2017).

    Article  PubMed  Google Scholar 

  214. Grossi, U. et al. Surgery for constipation: systematic review and practice recommendations. Results II: Hitching procedures for the rectum (rectal suspension). Colorectal Dis. 19 (Suppl. 3), 37–48 (2017).

    Article  PubMed  Google Scholar 

  215. Grossi, U. et al. Surgery for constipation: systematic review and practice recommendations. Results IV: Recto-vaginal reinforcement procedures. Colorectal Dis. 19 (Suppl. 3), 73–91 (2017).

    Article  PubMed  Google Scholar 

  216. Paquette, I. M. et al. The American Society of Colon and Rectal Surgeons’ clinical practice guideline for the evaluation and management of constipation. Dis. Colon Rectum 59, 479–492 (2016).

    Article  PubMed  Google Scholar 

  217. Knowles, C. H., Scott, M. & Lunniss, P. J. Outcome of colectomy for slow transit constipation. Ann. Surg. 230, 627–638 (1999).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  218. Keller, J. et al. Expert consensus document: advances in the diagnosis and classification of gastric and intestinal motility disorders. Nat. Rev. Gastroenterol. Hepatol. 15, 291–308 (2018).

    PubMed Central  PubMed  Article  Google Scholar 

  219. Schober, M. S. et al. Sacral nerve stimulation for pediatric lower urinary tract dysfunction: development of a standardized pathway with objective urodynamic outcomes. J. Urol. 194, 1721–1726 (2015).

    Article  PubMed  Google Scholar 

  220. Weil, E. H. et al. Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial. Eur. Urol. 37, 161–171 (2000).

    CAS  Article  PubMed  Google Scholar 

  221. Wexner, S. D. et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann. Surg. 251, 441–449 (2010).

    Article  PubMed  Google Scholar 

  222. Sulkowski, J. P. et al. Sacral nerve stimulation: a promising therapy for fecal and urinary incontinence and constipation in children. J. Pediatr. Surg. 50, 1644–1647 (2015).

    Article  PubMed  Google Scholar 

  223. Goldman, H. B. et al. International Continence Society best practice statement for use of sacral neuromodulation. Neurourol. Urodyn. 37, 1823–1848 (2018).

    Article  PubMed  Google Scholar 

  224. Thaha, M. A., Abukar, A. A., Thin, N. N., Ramsanahie, A. & Knowles, C. H. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst. Rev. 8, CD004464 (2015).

    Google Scholar 

  225. Carrington, E. V. et al. A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation. Neurogastroenterol. Motil. 26, 1222–1237 (2014).

    CAS  Article  PubMed  Google Scholar 

  226. van der Wilt, A. A. et al. Sacral neuromodulation in children and adolescents with chronic constipation refractory to conservative treatment. Int. J. Colorectal Dis. 31, 1459–1466 (2016).

    PubMed Central  PubMed  Article  Google Scholar 

  227. Van Wunnik, B. P. et al. Sacral neuromodulation therapy: a promising treatment for adolescents with refractory functional constipation. Dis. Colon Rectum 55, 278–285 (2012).

    Article  PubMed  Google Scholar 

  228. Lu, P. L. et al. Sacral nerve stimulation for constipation and fecal incontinence in children: long-term outcomes, patient benefit, and parent satisfaction. Neurogastroenterol. Motil. 30, 1–7 (2018).

    Article  Google Scholar 

  229. Kamm, M. A. et al. Sacral nerve stimulation for intractable constipation. Gut 59, 333–340 (2010).

    Article  PubMed  Google Scholar 

  230. Kenefick, N. J., Nicholls, R. J., Cohen, R. G. & Kamm, M. A. Permanent sacral nerve stimulation for treatment of idiopathic constipation. Br. J. Surg. 89, 882–888 (2002).

    CAS  Article  PubMed  Google Scholar 

  231. Holzer, B. et al. Sacral nerve stimulation in patients with severe constipation. Dis. Colon Rectum 51, 524–530 (2008).

    CAS  Article  PubMed  Google Scholar 

  232. Malouf, A. J., Wiesel, P. H., Nicholls, T., Nicholls, R. J. & Kamm, M. A. Short-term effects of sacral nerve stimulation for idiopathic slow transit constipation. World J. Surg. 26, 166–170 (2002).

    Article  PubMed  Google Scholar 

  233. Knowles, C. H. et al. Prospective randomized double-blind study of temporary sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity. Ann. Surg. 255, 643–649 (2012).

    Article  PubMed  Google Scholar 

  234. Maeda, Y. et al. Long-term outcome of sacral neuromodulation for chronic refractory constipation. Tech. Coloproctol 21, 277–286 (2017).

    PubMed Central  PubMed  Article  Google Scholar 

  235. Dinning, P. G. et al. Treatment efficacy of sacral nerve stimulation in slow transit constipation: a two-phase, double-blind randomized controlled crossover study. Am. J. Gastroenterol. 110, 733–740 (2015).

    Article  PubMed  Google Scholar 

  236. Patton, V., Stewart, P., Lubowski, D. Z., Cook, I. J. & Dinning, P. G. Sacral nerve stimulation fails to offer long-term benefit in patients with slow-transit constipation. Dis. Colon Rectum 59, 878–885 (2016).

    Article  PubMed  Google Scholar 

  237. Lu, P. L. & Di Lorenzo, C. Neurostimulation of the gastrointestinal tract in children: is it time to shock the gut? Curr. Opin. Pediatr. 28, 631–637 (2016).

    CAS  Article  PubMed  Google Scholar 

  238. Yik, Y. I., Hutson, J. & Southwell, B. Home-based transabdominal interferential electrical stimulation for six months improves paediatric slow transit constipation (STC). Neuromodulation 21, 676–681 (2017).

    Article  PubMed  Google Scholar 

  239. Clarke, M. C. C., Chase, J. W., Gibb, S., Hutson, J. M. & Southwell, B. R. Improvement of quality of life in children with slow transit constipation after treatment with transcutaneous electrical stimulation. J. Pediatr. Surg. 44, 1268–1273 (2009).

    Article  PubMed  Google Scholar 

  240. Clarke, M. C. C. et al. Decreased colonic transit time after transcutaneous interferential electrical stimulation in children with slow transit constipation. J. Pediatr. Surg. 44, 408–412 (2009).

    Article  PubMed  Google Scholar 

  241. Clarke, M. C. C. et al. Transabdominal electrical stimulation increases colonic propagating pressure waves in paediatric slow transit constipation. J. Pediatr. Surg. 47, 2279–2284 (2012).

    Article  PubMed  Google Scholar 

  242. Leong, L. C. Y. et al. Long-term effects of transabdominal electrical stimulation in treating children with slow-transit constipation. J. Pediatr. Surg. 46, 2309–2312 (2011).

    Article  PubMed  Google Scholar 

  243. Yang, Y., Yim, J., Choi, W. & Lee, S. Improving slow-transit constipation with transcutaneous electrical stimulation in women: a randomized, comparative study. Women Health 57, 494–507 (2017).

    Article  PubMed  Google Scholar 

  244. Patidar, N. et al. Transcutaneous posterior tibial nerve stimulation in pediatric overactive bladder: a preliminary report. J. Pediatr. Urol. 11, 351 (2015).

    Article  PubMed  Google Scholar 

  245. Lecompte, J.-F., Hery, G., Guys, J.-M. & Louis-Borrione, C. Evaluation of transcutaneous electrical posterior tibial nerve stimulation for the treatment of fecal and urinary leaks in children: preliminary results. J. Pediatr. Surg. 50, 630–633 (2015).

    Article  PubMed  Google Scholar 

  246. Iqbal, F. et al. Bilateral transcutaneous tibial nerve stimulation for chronic constipation. Colorectal Dis. 18, 173–178 (2016).

    CAS  Article  PubMed  Google Scholar 

  247. Collins, B., Norton, C. & Maeda, Y. Percutaneous tibial nerve stimulation for slow transit constipation: a pilot study. Colorectal Dis. 14, e165–e170 (2012).

    CAS  Article  PubMed  Google Scholar 

  248. Kumar, L. et al. Effectiveness of percutaneous tibial nerve stimulation in managing refractory constipation. Colorectal Dis. 19, 45–49 (2017).

    CAS  Article  PubMed  Google Scholar 

  249. Madbouly, K. M., Abbas, K. S. & Emanuel, E. Bilateral posterior tibial nerve stimulation in the treatment of rectal evacuation disorder: a preliminary report. Dis. Colon Rectum 60, 311–317 (2017).

    Article  PubMed  Google Scholar 

  250. Zhang, T. et al. Efficacy of acupuncture for chronic constipation: a systematic review. Am. J. Chin. Med. 41, 717–742 (2013).

    Article  PubMed  Google Scholar 

  251. Liu, Z. et al. Acupuncture for chronic severe functional constipation. Ann. Intern. Med. 165, 761–769 (2016).

    PubMed  Google Scholar 

  252. Ding, C. et al. Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up. Gastroenterol. Rep. 6, 101–107 (2018).

    Article  Google Scholar 

  253. Mitchell, P. J. & Sagar, P. M. Emerging surgical therapies for faecal incontinence. Nat. Rev. Gastroenterol. Hepatol. 11, 279–286 (2014).

    Article  PubMed  Google Scholar 

  254. Yik, Y. I., Ismail, K. A., Hutson, J. M. & Southwell, B. R. Home transcutaneous electrical stimulation to treat children with slow-transit constipation. J. Pediatr. Surg. 47, 1285–1290 (2012).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

M.H.V. researched data for the article. All authors were involved in the writing and review/editing of the manuscript before submission.

Corresponding author

Correspondence to Mana H. Vriesman.

Ethics declarations

Competing interests

M.A.B is a consultant for Shire, Norgine, Coloplast, Danone, Takeda, Allergan, FrieslandCampina, and Novalac. The remaining authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks O. Borrelli, A. Malcolm, G. Chiarioni and the other, anonymous, reviewers for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vriesman, M.H., Koppen, I.J.N., Camilleri, M. et al. Management of functional constipation in children and adults. Nat Rev Gastroenterol Hepatol 17, 21–39 (2020). https://doi.org/10.1038/s41575-019-0222-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-019-0222-y

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing