{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:00:47Z","timestamp":1791489647846,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>In this review, we summarize current insights into the treatment of functional constipation (FC) in children. Constipation is a global issue in the pediatric population, with a prevalence of approximately 9.5%. Initial management involves a combination of non-pharmacological and pharmacological interventions. However, a significant number of children continue to experience therapy-resistant FC despite optimal non-pharmacological and pharmacological treatments. While studies on novel pharmacological options in children are limited, adult trials have shown promising results. New agents such as lubiprostone, prucalopride, linaclotide, and plecanatide have demonstrated improved outcomes compared to placebo or conventional therapies, particularly in increasing spontaneous bowel movements. Neurostimulation presents an additional treatment modality. Posterior tibial nerve stimulation appears to be a promising new option, offering high treatment satisfaction and a favorable safety profile with a low rate of severe adverse events. For children who do not respond to optimal conservative therapy, the impact on quality of life can be substantial. In such cases, surgical interventions may be considered, including intrasphincteric botulinum toxin injections, antegrade continence enema surgery, and, in severe cases, colonic resection or a diverting ostomy. The choice of surgical treatment remains a subject of ongoing debate. Therapy-resistant FC in children is a complex and impactful condition. An individualized, stepwise approach is essential, with surgical options such as colonic resection reserved as a last resort.<\/jats:p>","DOI":"10.3390\/children12070857","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Current Treatment Options for Children with Functional Constipation\u2014What Is in the Pipeline?"],"prefix":"10.3390","volume":"12","author":[{"given":"Charlotte A. L.","family":"Jonker","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Pediatric Surgery, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Division of Colorectal and Pelvic Reconstruction, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirza M.","family":"van Os","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon R.","family":"Gorter","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Levitt","sequence":"additional","affiliation":[{"name":"Division of Colorectal and Pelvic Reconstruction, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Benninga","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jpeds.2018.02.029","article-title":"Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis","volume":"198","author":"Koppen","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jpn3.12437","article-title":"Prevalence of functional defecation disorders in European children: A systematic review and meta-analysis","volume":"80","author":"Bloem","year":"2025","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13052-024-01623-y","article-title":"The ten \u201chard\u201d questions in pediatric functional constipation","volume":"50","author":"Fedele","year":"2024","journal-title":"Ital. J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s43054-024-00282-2","article-title":"Overlooked anterior anal misplacement: A \u2018forme fruste\u2019 anomaly and potentially correctable cause of constipation","volume":"72","author":"AbouZeid","year":"2024","journal-title":"Egypt. Pediatr. Assoc. Gaz."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00383-004-1233-4","article-title":"Thickening of the internal anal sphincter in idiopathic constipation in children","volume":"20","author":"Keshtgar","year":"2004","journal-title":"Pediatr. Surg. Int."},{"key":"ref_6","first-page":"469","article-title":"Constipation in Children and Adolescents: Evaluation and Treatment","volume":"105","author":"Mulhem","year":"2022","journal-title":"Am. Fam. Physician"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hyams, J.S., Di Lorenzo, C., Saps, M., Shulman, R.J., Staiano, A., and van Tilburg, M. (2016). Functional Disorders: Children and Adolescents. Gastroenterology.","DOI":"10.1053\/j.gastro.2016.02.015"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1053\/j.gastro.2016.02.016","article-title":"Childhood Functional Gastrointestinal Disorders: Neonate\/Toddler","volume":"150","author":"Benninga","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41575-019-0222-y","article-title":"Management of functional constipation in children and adults","volume":"17","author":"Vriesman","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","first-page":"Cd009118","article-title":"Osmotic and stimulant laxatives for the management of childhood constipation","volume":"8","author":"Gordon","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/MPG.0000000000000266","article-title":"Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN","volume":"58","author":"Tabbers","year":"2014","journal-title":"J. Pediatr Gastroenterol. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e002380","DOI":"10.1136\/bmjpo-2023-002380","article-title":"How do we define therapy-resistant constipation in children aged 4-18 years old? A systematic review with meta-narrative synthesis","volume":"8","author":"Sinopoulou","year":"2024","journal-title":"BMJ Paediatr. Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2147\/CIA.S2938","article-title":"Lubiprostone: A novel treatment for chronic constipation","volume":"3","author":"Lacy","year":"2008","journal-title":"Clin. Interv. Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/s10620-009-1068-x","article-title":"Efficacy and Safety of Lubiprostone in Patients with Chronic constipation","volume":"55","author":"Barish","year":"2010","journal-title":"Dig. Dis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1365-2036.2008.03881.x","article-title":"Clinical trial: Lubiprostone in patients with constipation-associated irritable bowel syndrome\u2014Results of two randomized, placebo-controlled studies","volume":"29","author":"Drossman","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/MPG.0000000000003280","article-title":"Safety of Lubiprostone in Pediatric Patients With Functional Constipation","volume":"73","author":"Hussain","year":"2021","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.cgh.2021.04.005","article-title":"Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension","volume":"20","author":"Benninga","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_18","first-page":"CD014580","article-title":"Treatments for intractable constipation in childhood","volume":"6","author":"Gordon","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1002\/jpn3.12135","article-title":"Efficacy of lubiprostone for functional constipation treatment in adolescents and children: Randomized controlled trial","volume":"78","author":"Elkaragy","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.lfs.2010.03.015","article-title":"Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract","volume":"86","author":"Bryant","year":"2010","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13762","DOI":"10.1111\/nmo.13762","article-title":"European society of neurogastroenterology and motility guidelines on functional constipation in adults","volume":"32","author":"Serra","year":"2020","journal-title":"Neurogastroenterol Motil"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40272-021-00444-4","article-title":"The Use of Linaclotide in Children with Functional Constipation or Irritable Bowel Syndrome: A Retrospective Chart Review","volume":"23","author":"Baaleman","year":"2021","journal-title":"Paediatr. Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S2468-1253(23)00398-9","article-title":"Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: A randomised, double blind, placebo-controlled, multicentre, phase 3 trial","volume":"9","author":"Khlevner","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref_24","unstructured":"(2020). Highlights of Prescribing Information, Prucalopride."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1517\/14656566.2015.996547","article-title":"Efficacy and safety of prucalopride in adults and children with chronic constipation","volume":"16","author":"Diederen","year":"2015","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-2999(01)01087-1","article-title":"The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound","volume":"423","author":"Briejer","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5056\/jnm16004","article-title":"Use of Prucalopride for Chronic Constipation: A Systematic Review and Meta-analysis of Published Randomized, Controlled Trials","volume":"22","author":"Sajid","year":"2016","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1365-2036.2008.03884.x","article-title":"Clinical trial: The efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation\u2014A 12-week, randomized, double-blind, placebo-controlled study","volume":"29","author":"Quigley","year":"2009","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1053\/j.gastro.2014.09.005","article-title":"Prucalopride Is No More Effective Than Placebo for Children with Functional Constipation","volume":"147","author":"Mugie","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s40272-023-00612-8","article-title":"Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms","volume":"26","author":"Velez","year":"2024","journal-title":"Paediatr. Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1053\/j.gastro.2014.10.024","article-title":"Treating constipation with prucalopride: One size does not fit all","volume":"147","author":"Nurko","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.amjmed.2018.11.027","article-title":"Plecanatide for Treatment of Chronic Constipation and Irritable Bowel Syndrome","volume":"132","author":"Love","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1053\/j.gastro.2023.03.214","article-title":"American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation","volume":"164","author":"Chang","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e14632","DOI":"10.1111\/nmo.14632","article-title":"Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation","volume":"35","author":"Cash","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ajg.2016.611","article-title":"A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation","volume":"112","author":"Miner","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e14658","DOI":"10.1111\/nmo.14658","article-title":"Long-term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO-3 study","volume":"35","author":"Lembo","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.14309\/ajg.0000000000001056","article-title":"Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2)","volume":"116","author":"Chey","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S2468-1253(18)30165-1","article-title":"Safety and efficacy of the sodium-glucose cotransporter 1 inhibitor mizagliflozin for functional constipation: A randomised, placebo-controlled, double-blind phase 2 trial","volume":"3","author":"Fukudo","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2017.04.010","article-title":"Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation","volume":"806","author":"Inoue","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S2468-1253(19)30246-8","article-title":"Efficacy of drugs in chronic idiopathic constipation: A systematic review and network meta-analysis","volume":"4","author":"Luthra","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S2468-1253(18)30123-7","article-title":"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","volume":"3","author":"Nakajima","year":"2018","journal-title":"Lancet Gastroenterol Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/j.gastro.2023.02.013","article-title":"Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation","volume":"164","author":"Rao","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"G543","DOI":"10.1152\/ajpgi.00233.2023","article-title":"NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons","volume":"326","author":"King","year":"2024","journal-title":"Am. J. Physiol. Gastrointest. Liver. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1080\/14656566.2025.2471524","article-title":"Pharmacological treatment for children with constipation: Present and future","volume":"26","author":"Koppen","year":"2025","journal-title":"Expert Opin Pharmacother"},{"key":"ref_45","first-page":"Cd004464","article-title":"Sacral nerve stimulation for faecal incontinence and constipation in adults","volume":"8","author":"Thaha","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00384-016-2604-8","article-title":"Sacral neuromodulation in children and adolescents with chronic constipation refractory to conservative treatment","volume":"31","author":"Sturkenboom","year":"2016","journal-title":"Int. J. Colorectal. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.jpedsurg.2015.03.043","article-title":"Sacral nerve stimulation: A promising therapy for fecal and urinary incontinence and constipation in children","volume":"50","author":"Sulkowski","year":"2015","journal-title":"J. Pediatr. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jpedsurg.2016.11.003","article-title":"Sacral nerve stimulation allows for decreased antegrade continence enema use in children with severe constipation","volume":"52","author":"Lu","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1097\/SLA.0000000000006158","article-title":"Sacral Neuromodulation Versus Conservative Treatment for Refractory Idiopathic Slow-transit Constipation: The Randomized Clinical No.2-Trial","volume":"279","author":"Heemskerk","year":"2024","journal-title":"Ann. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e13184","DOI":"10.1111\/nmo.13184","article-title":"Sacral nerve stimulation for constipation and fecal incontinence in children: Long-term outcomes, patient benefit, and parent satisfaction","volume":"30","author":"Lu","year":"2018","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e14865","DOI":"10.1111\/nmo.14865","article-title":"Sacral nerve stimulation leads to long- term improvement in fecal incontinence and quality of life for children with functional and organic defecation disorders","volume":"36","author":"Park","year":"2024","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e14808","DOI":"10.1111\/nmo.14808","article-title":"Sacral neuromodulation in children and adolescents with defecation disorders","volume":"36","author":"Knorr","year":"2024","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13809","DOI":"10.1111\/nmo.13809","article-title":"Comparison of antegrade continence enema treatment and sacral nerve stimulation for children with severe functional constipation and fecal incontinence","volume":"32","author":"Vriesman","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/DCR.0b013e3182405ab2","article-title":"Sacral nerve stimulation for constipation in children: A caution for a treatment in development","volume":"55","author":"Dudding","year":"2012","journal-title":"Dis. Colon Rectum."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.jpedsurg.2023.04.007","article-title":"Sacral Nerve Stimulation in Children with Medically Refractory Fecal Incontinence or Severe Constipation","volume":"58","author":"Trinidad","year":"2023","journal-title":"J. Pediatr Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/codi.16876","article-title":"Effectiveness, safety and cost-effectiveness of sacral neuromodulation for idiopathic slow-transit constipation: A systematic review","volume":"26","author":"Heemskerk","year":"2024","journal-title":"Colorectal Dis."},{"key":"ref_57","first-page":"6","article-title":"Posterior tibial nerve electrical stimulation in chronic constipation: A systematic review and meta-analysis","volume":"17","author":"Hamedfar","year":"2024","journal-title":"Gastroenterol Hepatol. Bed. Bench."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s00431-022-04798-w","article-title":"Efficacy of transcutaneous posterior tibial nerve stimulation in functional constipation","volume":"182","author":"Villamarin","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mayara Padilha Rego, R., Machado, N.C., Carvalho, M.A., Graffunder, J.S., Fraguas, C., Ortolan, E.V.P., and Louren\u00e7\u00e3o, P.L.T.A. (2024). Transcutaneous Posterior Tibial Nerve Stimulation: An Adjuvant Treatment for Intractable Constipation in Children. Biomedicines, 12.","DOI":"10.3390\/biomedicines12010164"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Caruso, A.M., Milazzo, M.P.M., Bommarito, D., Girgenti, V., Amato, G., Paviglianiti, G., Casuccio, A., Catalano, P., Cimador, M., and Di Pace, M.R. (2021). Advanced Management Protocol of Transanal Irrigation in Order to Improve the Outcome of Pediatric Patients with Fecal Incontinence. Children, 8.","DOI":"10.3390\/children8121174"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/jpn3.12200","article-title":"Transanal irrigation in children with functional constipation: A systematic review and meta-analysis","volume":"78","author":"Bolia","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/MPG.0000000000003515","article-title":"Transanal Irrigation in Children: Treatment Success, Quality of Life, Adherence, Patient Experience, and Independence","volume":"75","author":"Baaleman","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/MPG.0000000000001236","article-title":"Transanal Irrigation in the Treatment of Children With Intractable Functional Constipation","volume":"64","author":"Koppen","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/MPG.0000000000000527","article-title":"Psychometric properties of PedsQL generic core scales for children with functional constipation in the Netherlands","volume":"59","author":"Hartman","year":"2014","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jpeds.2014.08.022","article-title":"Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module Testing Study Consortium. Health-related quality of life in pediatric patients with functional and organic gastrointestinal diseases","volume":"166","author":"Varni","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1097\/SLA.0000000000001191","article-title":"Current Surgical Management of Pediatric Idiopathic Constipation: A Systematic Review of Published Studies","volume":"262","author":"Siminas","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/MOP.0000000000000345","article-title":"Surgical options for the management of severe functional constipation in children","volume":"28","author":"Wood","year":"2016","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/MPG.0000000000003833","article-title":"Long-Term Outcomes of Antegrade Continence Enemas to Treat Constipation and Fecal Incontinence in Children","volume":"77","author":"Baaleman","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jpedsurg.2009.10.034","article-title":"Antegrade colonic enemas and intestinal diversion are highly effective in the management of children with intractable constipation","volume":"45","author":"Rodriguez","year":"2010","journal-title":"J. Pediatr. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1016\/j.jpedsurg.2019.04.009","article-title":"Transanal proximal rectosigmoidectomy. A new operation for severe chronic idiopathic constipation associated with megarectosigmoid","volume":"54","author":"Cogley","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_71","first-page":"147","article-title":"Technic permitting the easy assurance of continuity of the colon & conservation of sphincter after excision of the left transverse hemicolon & entire left colon; possible inclusion of rectum","volume":"75","author":"Deloyers","year":"1958","journal-title":"J. Chir."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jpedsurg.2016.05.023","article-title":"Surgical decision-making in the management of children with intractable functional constipation: What are we doing and are we doing it right?","volume":"51","author":"Koppen","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100028","DOI":"10.1016\/j.yjpso.2023.100028","article-title":"Functional Constipation Refractory to Medical Management: The Anal Sphincters are the Problem","volume":"2","author":"Tiusaba","year":"2003","journal-title":"J. Pediatr. Surg. Open"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jpedsurg.2022.10.022","article-title":"Functional constipation refractory to medical management: The colon is the problem","volume":"58","author":"Jacobs","year":"2023","journal-title":"J. Pediatr. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1016\/j.jpedsurg.2019.03.020","article-title":"Anal sphincter botulinum toxin injection in children with functional anorectal and colonic disorders: A large institutional study and review of the literature focusing on complications","volume":"54","author":"Halleran","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jpedsurg.2017.12.007","article-title":"Botulinum toxin injection for childhood constipation is safe and can be effective regardless of anal sphincter dynamics","volume":"53","author":"Kuo","year":"2018","journal-title":"J. Pediatr. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1055\/s-0042-1751048","article-title":"Anal Botulinum Toxin in Children with Hirschsprung Disease and Functional Constipation: A Prospective Cohort study","volume":"33","author":"Baaleman","year":"2023","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/jpn3.70040","article-title":"Efficacy of anal botulinum toxin injection in children with functional constipation","volume":"80","author":"Patel","year":"2025","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.14309\/ajg.0000000000000940","article-title":"Intrarectal Electromotive Botulinum Toxin Type A Administration in Children With Intractable Constipation: A Randomized Clinical Trial","volume":"115","author":"Kajbafzadeh","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s40272-023-00563-0","article-title":"An Update of Pharmacological Management in Children with Functional Constipation","volume":"25","author":"Koppen","year":"2023","journal-title":"Paediatr Drugs"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1055\/a-2206-6508","article-title":"Antegrade Continence Enema Alone for the Management of Functional Constipation and Segmental Colonic Dysmotility (ACE-FC): A Pediatric Colorectal and Pelvic Learning Consortium Study","volume":"34","author":"Ahmad","year":"2024","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/0140-6736(90)92834-5","article-title":"Preliminary report: The antegrade continence enema","volume":"336","author":"Malone","year":"1990","journal-title":"Lancet"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/lap.2010.0359","article-title":"Laparoscopic-assisted Malone appendicostomy in the management of fecal incontinence in children","volume":"21","author":"Lawal","year":"2011","journal-title":"J. Laparoendosc. Adv. Surg. Tech. A"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.gie.2010.09.011","article-title":"Laparoscopic-assisted percutaneous endoscopic cecostomy in children with defecation disorders (with video)","volume":"73","author":"Rodriguez","year":"2011","journal-title":"Gastrointest Endosc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"161952","DOI":"10.1016\/j.jpedsurg.2024.161952","article-title":"Antegrade Continence Enemas for Pediatric Functional Constipation: A Systematic Review","volume":"60","author":"Jonker","year":"2025","journal-title":"J. Pediatr. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/MPG.0000000000001483","article-title":"Consensus Review of Best Practice of Transanal Irrigation in Children","volume":"64","author":"Mosiello","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s00383-022-05214-y","article-title":"The success rate of antegrade enemas for the management of idiopathic constipation","volume":"38","author":"Reppucci","year":"2022","journal-title":"Pediatr. Surg. Int."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Jonker, C.A.L., Koppen, I.J.N., Benninga, M.A., de Jong, J.R., and Gorter, R.R. (2025). Outcomes and Complications of Chait Trapdoor Cecostomy in Pediatric Patients with Therapy-Resistant Constipation and Fecal Incontinence: A 14-Year Retrospective Study. Eur. J. Pediatr. Surg.","DOI":"10.1055\/a-2511-9184"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jpedsurg.2018.10.008","article-title":"A comparison of Malone appendicostomy and cecostomy for antegrade access as adjuncts to a bowel management program for patients with functional constipation or fecal incontinence","volume":"54","author":"Halleran","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/jpn3.12130","article-title":"Outcomes of children with constipation and autism spectrum disorder treated with antegrade continence enemas","volume":"78","author":"Srinivas","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bpg.2010.12.007","article-title":"Surgical treatment for constipation in children and adults","volume":"25","author":"Levitt","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.jpedsurg.2018.02.074","article-title":"Surgical management of functional constipation: An intermediate report of a new approach using a laparoscopic sigmoid resection combined with malone appendicostomy","volume":"53","author":"Gasior","year":"2018","journal-title":"J. Pediatr. Surg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.jpedsurg.2009.02.049","article-title":"Transanal rectosigmoid resection for severe intractable idiopathic constipation","volume":"44","author":"Levitt","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jpn3.12297","article-title":"Significance of retrograde flow with antegrade continence enemas in children with fecal incontinence and constipation","volume":"79","author":"Pearlstein","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1016\/j.jpedsurg.2013.03.058","article-title":"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","volume":"48","author":"Eradi","year":"2013","journal-title":"J. Pediatr. Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e13005","DOI":"10.1111\/nmo.13005","article-title":"Surgical management of children with intractable functional constipation; experience of a single tertiary children\u2019s hospital","volume":"29","author":"Koppen","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1097\/MPG.0000000000003579","article-title":"Diverting Ileostomy in Children With Functional Constipation: A Study Evaluating the Utility of Colon Manometry","volume":"75","author":"Rodriguez","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7182429","DOI":"10.1155\/2017\/7182429","article-title":"Ileostomy Prolapse in Children with Intestinal Dysmotility","volume":"2017","author":"Sparks","year":"2017","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.jpedsurg.2020.05.027","article-title":"Outcomes after enterostomies in children with and without motility disorders: A description and comparison of postoperative complications","volume":"55","author":"Vriesman","year":"2020","journal-title":"J. Pediatr. Surg."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/7\/857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:41Z","timestamp":1760032841000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/7\/857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":99,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["children12070857"],"URL":"https:\/\/doi.org\/10.3390\/children12070857","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}