{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:34:30Z","timestamp":1787776470914,"version":"build-2784847793"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malocclusion is a global public dental health problem with higher prevalence and treatment needs. However, there is a perplexing literature regarding early orthodontic intervention in the mixed dentition stage. \u20182 \u00d7 4 orthodontic appliances\u2019 have been highlighted in the literature as versatile appliances for the effective correction of various malocclusions in children. However, dental clinicians and researchers should also have updated knowledge about the negative aspects of \u20182 \u00d7 4 orthodontic appliances\u2019, which are reported in the exiting literature. Hence, this systematic review aimed to find out the evidence about the adverse effects\/complications of 2 \u00d7 4 orthodontic appliance therapy in mixed dentition phase of paediatric patients by extensively exploring and critically appraising the pertinent literature. This systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Its protocol was registered in International Prospective Register of Systematic Reviews. Literature was searched comprehensively in six databases and also manually. After the screening of the records (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1234) as per the eligibility criteria, finally, nine (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 5) articles were included and critically analysed using different Joanna Briggs Institute critical appraisal tools. Eligible studies including Randomized Controlled Trial (RCT) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1), non-RCT (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 2), retrospective study (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1), case-report (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1) published from 1999 to 2023 in which 82 patients with mean-age of 10-year, mostly with pseudo class-III malocclusion, anterior cross-bite and crowding treated using 2 x 4 appliance were found. The literature-based evidence related to the adverse effects of 2 \u00d7 4 orthodontic appliances was found to be inadequate in quantity, but majority was of high quality (low risk of bias). However, various negative aspects\/complications of this particular fixed orthodontic therapy were reported by the included primary studies.\n                  <\/jats:p>","DOI":"10.4103\/ijdr.ijdr_217_24","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T08:03:32Z","timestamp":1748505812000},"page":"94-102","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Adverse Effects of \u2018Two-by-Four Fixed Orthodontic Appliance\u2019 in Mixed Dentition Period - A Systematic Review"],"prefix":"10.4103","volume":"36","author":[{"given":"Mohammad Kamran","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Pediatric and Preventive Dentistry, I.T.S Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh, India"},{"name":"Department of Pediatric and Preventive Dentistry, Dr. Ziauddin Ahmad Dental College and Hospital, Faculty of Medicine, Aligarh Muslim University (A.M.U.), Aligarh, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramanandvignesh","family":"Pandiyan","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Preventive Dentistry, Adhiparasakthi Dental College and Hospital, Melmaruvathur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakir Hussain","family":"Rather","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Dr. Shakir\u2019s Dentzmania Dental Care Clinic, Shopian, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"R1-20250531","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41368-018-0012-3","article-title":"Common dental diseases in children and malocclusion","volume":"10","author":"Zou","year":"2018","journal-title":"Int J Oral 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