{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:02:56Z","timestamp":1785132176159,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Functional constipation (FC) is common in children with comorbid neurodevelopmental disorders (NDD) and its optimal treatment may be challenged by adherence and medication tolerability issues in this population. We assessed the efficacy and safety of linaclotide in pediatric patients with FC and NDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This post hoc analysis of a Phase 3, randomized, placebo\u2010controlled study assessed oral linaclotide 72\u2009\u00b5g once daily for 12 weeks in patients aged 6\u201317 years with FC and NDD. The primary endpoint was change from baseline (CFB) in weekly spontaneous bowel movement (SBM) frequency. In efficacy comparisons, an absolute standardized mean difference (SMD)\u2009&gt;\u20090.2 was considered indicative of a treatment difference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this analysis of 57 pediatric patients (linaclotide\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925; placebo\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200932), 91% had attention\u2010deficit\/hyperactivity disorder; other NDDs included autism spectrum disorder, tic disorders, and sensory processing disorders. CFB in weekly SBM frequency over 12 weeks was greater with linaclotide versus placebo (2.09 vs. 0.59, respectively; SMD 0.688). Linaclotide was also associated with greater improvements relative to placebo in stool consistency (CFB 1.37 vs. 0.55, respectively) and straining score (CFB \u20130.98 vs. \u20130.59). Most patients (\u226596%) achieved \u226580% dosing compliance with once\u2010daily administration of linaclotide or placebo. Linaclotide was well tolerated, with a safety profile consistent with that reported previously.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In children with FC and comorbid NDD, linaclotide 72\u2009\u00b5g once daily was associated with improved constipation outcomes, high adherence, and a well\u2010tolerated safety profile, similar to that seen in the overall study population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov identifier: NCT04026113 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/study\/NCT04026113\">https:\/\/clinicaltrials.gov\/study\/NCT04026113<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jpn3.70424","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:08:05Z","timestamp":1774937285000},"page":"21-28","source":"Crossref","is-referenced-by-count":0,"title":["A post hoc analysis of linaclotide in pediatric patients with functional constipation and neurodevelopmental disorders"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-8296","authenticated-orcid":false,"given":"Hannibal","family":"Person","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Washington School of Medicine Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Hyams","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Connecticut Children's Medical Center Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinarani M.","family":"Sanghavi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of Texas Southwestern Medical Center Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc. Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Kosch","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moming","family":"Li","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"D'Achino","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc. Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Khlevner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Columbia University Vagelos College of Physicians and Surgeons New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P.","family":"Chumpitazi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University School of Medicine Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Saps","sequence":"additional","affiliation":[{"name":"Miller School of Medicine University of Miami Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.12.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/5569563"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.5409\/wjcp.v11.i5.385"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0222-y"},{"issue":"1","key":"e_1_2_9_6_1","first-page":"S20","article-title":"Functional constipation: pathophysiology, evaluation, and management","volume":"60","author":"Kilgore A","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2019.03.020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14071471"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-1580"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPN-2010-0350"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.832877"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(13)61462-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000001036"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.015"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-018-1162-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2017.02.481"},{"key":"e_1_2_9_17_1","volume-title":"StatPearls","author":"Khan I","year":"2025"},{"key":"e_1_2_9_18_1","volume-title":"Data and Statistics on ADHD. 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