{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:56:01Z","timestamp":1780491361489,"version":"3.54.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018778","name":"Al-Azhar University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion.\u00a0Two independent reviewers evaluated the identified studies\u2019 titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome,\u00a0we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200\u00a0mg dosage (overall mean difference: -3.53, <jats:italic>p<\/jats:italic>\u2009=\u20090.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200\u00a0mg dosage (overall mean difference: -0.34, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200\u00a0mg), vomiting (200\u00a0mg), and irritability (200\u00a0mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200\u00a0mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12887-024-04526-3","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T07:13:36Z","timestamp":1711178016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1186","volume":"24","author":[{"given":"Abdallah","family":"Abbas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya M","family":"Fayoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa Hossam","family":"El Din Moawad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Ashraf","family":"Hamad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Hamouda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Fouad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"issue":"4","key":"4526_CR1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.14238\/pi44.4.2004.160-4","volume":"44","author":"ES Herini","year":"2016","unstructured":"Herini ES, Mangunatmadja I, Solek P, Pusponegoro HD. Rett syndrome in childhood: the clinical characteristics. Paediatr Indones. 2016;44(4):160.","journal-title":"Paediatr Indones"},{"issue":"1","key":"4526_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13643-023-02169-6","volume":"12","author":"U Petriti","year":"2023","unstructured":"Petriti U, Dudman DC, Scosyrev E, Lopez-Leon S. Global prevalence of Rett syndrome: systematic review and meta-analysis. Syst Rev. 2023;12(1):5.","journal-title":"Syst Rev"},{"issue":"3","key":"4526_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.31887\/DCNS.2012.14.3\/jneul","volume":"14","author":"JL Neul","year":"2012","unstructured":"Neul JL. The relationship of Rett syndrome and MECP2 disorders to autism. Dialogues Clin Neurosci. 2012;14(3):253\u201362.","journal-title":"Dialogues Clin Neurosci"},{"issue":"10","key":"4526_CR4","first-page":"733","volume":"89","author":"Z Abbes","year":"2011","unstructured":"Abbes Z, Bouden A, Halayem S, Othman S. Bechir Halayem M. [Clinical characteristics of Rett Syndrome]. Tunis Med. 2011;89(10):733\u20137.","journal-title":"Tunis Med"},{"issue":"15","key":"4526_CR5","doi-asserted-by":"publisher","first-page":"5114","DOI":"10.3390\/jcm12155114","volume":"12","author":"SA Hudu","year":"2023","unstructured":"Hudu SA, Elmigdadi F, Qtaitat AA, Almehmadi M, Alsaiari AA, Allahyani M, et al. Trofinetide for Rett Syndrome: highlights on the Development and related inventions of the first USFDA-Approved treatment for Rare Pediatric Unmet Medical need. J Clin Med. 2023;12(15):5114.","journal-title":"J Clin Med"},{"issue":"6","key":"4526_CR6","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1038\/s41591-023-02398-1","volume":"29","author":"JL Neul","year":"2023","unstructured":"Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. 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Neurosci Lett. 2012;520(1):51\u20136.","journal-title":"Neurosci Lett"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04526-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12887-024-04526-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04526-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T07:14:20Z","timestamp":1711178060000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-024-04526-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,23]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4526"],"URL":"https:\/\/doi.org\/10.1186\/s12887-024-04526-3","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,23]]},"assertion":[{"value":"23 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study is a systematic review and meta-analysis that did not require ethical approval, as it did not involve direct participation of individuals who would provide informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Consent to publication is not applicable in this case since this study is not a primary research study but rather a review and analysis of existing literature.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"No conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"206"}}