TY - JOUR
AU - Buschang, Peter, H
AB - Summary Background Although post-treatment mandibular alignment has been extensively investigated, the findings remain controversial. Objectives The objective was to assess mandibular alignment changes, as measured by the irregularity index, of patients who underwent full-fixed orthodontic treatment and were followed up at least 1 year after retention. Search methods MEDLINE, EMBASE, and Cochrane library, in addition, the reference lists of included studies, were screened. The search was conducted up to April 2018. Selection criteria The study designs included both interventional and observational studies of orthodontic patients who received either extraction or non-extraction treatment. Data collection and analysis The interventional studies were assessed using the Cochrane Collaboration’s risk of bias assessment tool. The quality of the observational studies was evaluated using National Institution of Health quality assessment tools. The first two authors independently applied the eligibility criteria, extracted the data, and assessed the risk of bias. Any conflicts were resolved with consensus discussion with the third author. Results The search retrieved 11 326 articles, 170 of which were assessed for eligibility. There were 44 studies included in the qualitative assessments and 30 in the meta-analyses. The studies included 1 randomized control trial (RCT) and 43 observational studies. The RCT was judged to have a high risk of bias and all of the observational studies had either fair or poor quality. The meta-analysis was based on studies judged to be of fair quality, including a total of 1859 patients. All meta-analyses were performed using random-effect models. The standardized mean difference between post-treatment and post-retention irregularity was 1.22 (95% CI, 1.04–1.40) and 0.85 (95% CI, 0.63–1.07) after extraction and non-extraction treatments, respectively. There was a substantial heterogeneity for the extraction (I2 = 75.2%) and non-extraction (I2 = 70.1%) studies. The follow-up duration (1–10 versus 10–20 years) explained 33% of the heterogeneity, with longer follow-up studies showing more irregularity. Limitations The quality of evidence provided by the studies was low. There was a risk of publication bias, and the search was limited to English language. Conclusions and implications Post-treatment mandibular irregularity increases are limited. Irregularity increases are slightly greater in patients treated with mandibular premolars extractions, and in patients followed up over longer periods of time. Registration The study protocol was not registered. Introduction Rationale The maintenance of mandibular anterior alignment after orthodontic treatment is a major concern of orthodontists and patients. Clinicians want to maintain the quality of results they achieved during treatment and patients want their teeth to remain aligned after removal of the orthodontic appliances. Because mandibular teeth are less stable than their upper counterparts (1, 2), the focus has been on the maintenance of anterior mandibular alignment. Several factors are thought to play a role in the development of post-treatment mandibular alignment changes (3). These factors include retention methods (4), type of malocclusion (5), teeth extraction (6), craniofacial growth pattern (7), patient’s age during treatment (8), and various cephalometric and dental cast measurements. To date, none have systematically evaluated these factors in patient out of retention. Currently, there are only two review articles pertaining to post-treatment mandibular malalignment (3, 9). One of them (3), focuses on the factors that might affect alignment changes (e.g. arch form, periodontal ligament and gingival fibers, mandibular incisors dimensions, third molars). The other provides a narrative review of long-term mandibular alignment changes (9).The primary studies that have been published are mostly observational, with conflicting findings. There are no systematic reviews evaluating the long-term post-treatment malalignment of mandibular anterior teeth. Meta-analyses are needed to provide a reliable estimate of post-treatment alignment changes. The type of study designs included in systematic reviews is usually based on the focus of the investigation (10). The purpose of the present systematic review was to synthesize the literature describing post-retention changes in mandibular alignment, which is a prognostic rather than treatment effectiveness question. For these types of questions randomized trials or prospective cohort studies would be too costly and time consuming. As such, the majority of studies are observational, usually retrospective longitudinal, in nature. Observational studies often have better external validity, and are considered more representative of the target population (11). Objectives The purpose of this systematic review was to evaluate the changes in the anterior alignment of mandibular teeth after orthodontic treatment. The primary objective was to compare post-treatment irregularity changes of orthodontic patients who underwent either extraction or non-extraction treatment. The secondary objectives were to assess the effects of follow-up duration, adjunctive procedures use, retention protocol, clinical setting, and pre-treatment irregularity on mandibular alignment changes after orthodontic treatment. Material and methods Protocol and registration This systematic review was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement (12). The protocol of the review was not registered. Eligibility criteria The following selection criteria were used to identify potential studies: Either interventional or observational study designs. Case reports, review articles, and techniques description studies were excluded. Orthognathic surgical treatments and craniofacial deformities were excluded. The study must have evaluated mandibular incisor irregularity changes in orthodontic patients who received full-fixed appliance therapy and were at least 1 year out of retention. The assessment of mandibular anterior teeth alignment had to be based on Little’s irregularity index (II), measured in millimetres, and reported separately for extraction and non-extraction groups (13). Post-treatment (T1) and post-retention (T2) irregularity, or the irregularity changes that occurred over time, had to have been reported. Information sources, search strategy, and study selection A comprehensive search of the literature was conducted to identify studies published on or before 1 April 2018. The search was restricted to studies published in English. The following databases were searched: MEDLINE (through PubMed), Cochrane library including CENTRAL, CDSR, DARE, and EMBASE database via OVID. Supplementary Table 1 provides the search strategy used for the MEDLINE (PubMed) database. Cochrane and EMBASE searches were conducted excluding the MEDLINE results. Hand searches of the studies’ reference lists were assessed to identify other primary studies. The first two authors (AJS and AEG) applied the eligibility criteria, extracted the data, and assessed the risk of bias independently, and in duplicate. Disagreements between reviewers were resolved by consensus discussions and consultations with the third author (PHB) Data collection process and data items A data extraction form was used to record the study design (observational or interventional), sample size and source, age of the patients at T1 and T2, male/female ratio, treatment approach (extraction or non-extraction), adjunctive procedures used (inter-proximal enamel reduction, supra-crestal fibreotomy, or both), retention protocol used (fixed or removable retainers), post-retention follow-up duration, and the pre-treatment (T0), post-treatment (T1), and post-retention (T2) irregularity indices. In case of missing or incomplete data, an effort was made to contact the corresponding authors via emails. Duplicate publications were eliminated after full text article reviews. To improve the homogeneity and comparability of the studies, only studies with mandibular premolar extractions were included in the extraction group. Risk of bias in individual studies The Cochrane Collaboration’s risk of bias assessment tool (14) was used to assess the randomized clinical trials. The following source of biases were evaluated: selection bias, detection bias, attrition bias, reporting bias, and other biases. They were judged as low, unclear, or high. National Institution of Health quality assessment tools were used to evaluate the observational studies (15). The number of questions in each tool depended on the study design, with a specific tool for each study design. The questions were answered either ‘yes’, ‘no’, or ‘cannot determine/not reported/not applicable’. Each study was judged to be either good, fair, or poor quality. Poor quality studies were not included in the meta-analysis. Summary measures and synthesis of results The primary outcome measure (i.e. summary effect measure) used in this study was the standardized mean difference (SMD) between T1 and T2 incisor irregularity [(IIT2 − IIT1)/pooled SD], along with the 95% confidence intervals. The estimates were combined using the Hedge’s random-effect model. Forest plots were used to graphically present the summary effect measures of the studies. Heterogeneity and risk of bias across studies assessments The heterogeneity of the studies was determined by analysing the treatment protocols, patients’ characteristics, studies’ methodologies, and any other relevant sources of heterogeneity. It was assessed statistically by visual appraisal of the summary effect forest plot, Q-statistics, tau-squared, and the I2 index. I2 indices of less than 25%, 50%, and 75% indicated low, moderate, and high heterogeneity, respectively (16). Publication bias was assessed by visual inspection of funnel plot symmetry, along with statistical tests (i.e. Begg and Mazumdar rank correlation method (17) and Egger weighted regression method) (18). Meta-regression and subgroup analyses Random-effect model meta-regression was performed to evaluate the effects of follow-up duration, study design, adjunctive procedures used, pre-treatment irregularity, clinical setting, type of retainer used, and treatment protocol (extraction versus non-extraction) on the primary outcome measure. The subgroup analyses included comparisons of the SMD estimates based on study designs (i.e. interventional versus observational studies), and follow-up duration (1–10 versus 10–20 years) after orthodontic treatment. These durations were chosen to ensure that there were roughly equal numbers of primary studies in each category. All the statistical analyses in this meta-analysis were performed using the Stata® 14.2 software package (StataCorp, College Station, Texas, USA). Results Study selection A total of 10 759 articles were identified in the MEDLINE database, and another 567 were identified using the other resources (EMBASE, Cochrane, and hand search of reference lists; Figure 1). After duplicates were removed, there were 11 326 articles, of which 11 164 were excluded after title and/or abstract screening. Of the 170 articles that were fully assessed for eligibility, 126 were excluded (Supplementary Table 2). A total of 44 studies were included in the qualitative assessment, 14 of which were excluded from the meta-analysis (Supplementary Table 3). Figure 1. Open in new tabDownload slide Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) study flow diagram. Figure 1. Open in new tabDownload slide Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) study flow diagram. Study characteristics One randomized controlled trial (4) and 43 longitudinal (pre-post) observational studies were included in this systematic review (1, 2, 5–8, 19–54). The randomized trial (4), which was conducted in a private practice, included 49 patients treated with four premolars extractions, and followed up 5–9 years out of retention. The study had three subgroups based on different retention protocols; lower 3-3 fixed retainer, lower inter-proximal reduction (IPR), or pre-fabricated positioners. The 43 observational studies were conducted in academic clinics (2, 5, 6, 19, 24, 25, 27, 35, 38, 44, 46, 48, 54, 55), private practices (1, 7, 20, 21, 23, 28–30, 32, 33, 36, 37, 47, 51–53), or both (8, 26, 39–43, 45, 49). Settings were not reported for some studies (22, 31, 34, 50). There were 16 studies that reported mandibular premolars extraction treatment (1, 4, 7, 8, 20, 24–26, 28, 36, 39, 42, 43, 45, 46, 52), 15 that reported non-extraction treatment (5, 22, 23, 27, 29, 30, 32, 33, 35, 40, 41, 47, 48, 51, 53), and 11 that reported subgroups of extraction and non-extraction treatments (2, 6, 19, 31, 34, 37, 38, 44, 50, 54, 55). There were two studies that reported mandibular incisors extraction treatment protocol (21, 49). The follow-up duration after orthodontic treatment and retention ranged from 1 to 31.8 years. Adjunctive procedures were used in 7 studies (4, 20, 29, 30, 32, 51, 55), 35 studies reported no adjunctive procedures (1, 2, 5–8, 19, 21–28, 31, 33, 35–43, 45–50, 52–54). Two studies did not state whether adjunctive procedures were used (34, 44). There were 15 studies that used fixed lower 3-3 retainers, 9 used removable retainers (23, 27, 31, 36, 37, 46, 49, 54, 55), and 6 used either fixed or removable retainers (1, 4, 32, 35, 48, 52). Fourteen studies did not report the type of retention protocol used (2, 6, 19, 21, 22, 33, 34, 39–44, 50). Characteristics of studies included in the meta-analysis are provided in Table 1. Supplementary Table 4 provides the characteristics of studies excluded from the meta-analysis. Table 1. Characteristics of studies included in meta-analysis. E, extraction; IPR, inter-proximal reduction; NE, non-extraction. NR, not reported Study ID (author and date) Study design and clinical setting Sample size, n (M/F) Age at T1 (y) Age at T2 (y) Intervention Post-treatment follow-up (y) Adjunctive procedure use Retention type T2-T1 LII mean and SD (mm) Artun et al. 1996 (19) • Longitudinal (pre-post) study • University clinics 78 (33/45) NR 31.1 ± 5 E NE 14 ± 4.6 NO NR • 3.15 ± 1.5 • 2.55 ± 1.42 Boley et al. 2003 (20) • Longitudinal (pre-post) study • Private practice 32 (9/23) 15.5 (12.8–41.7) 31.6 (24.3–51.1) E ≥5 IPR L3-3 • 0.7 ± 1.1 Canut and Arias 1999 (22) • Longitudinal (pre-post) study • NR 30 (10/20) 15.14 ± 2.99 22.1 ± 3.59 NE 7 ± 2.8 NO NR • 2.24 ± 2.6 de Freitas et al. 2006 (24) • Longitudinal (pre-post) study • University clinics 94 (50/44) NR NR E 5.3 ± 1.6 NO L3-3 • 1 ± 1.15 de la Cruz et al. 1995 (26) • Longitudinal (pre-post) study • University clinics and private practice 87 (31/56) 15 y 8 m 33 y 7 m E ≥10 NO L3-3 • CL I: 2.3 ± 1.6 • CL II Div1: 2.9 ± 1.9 Driscoll-Gilliland et al. 2001 (28) • Longitudinal (pre-post) study • Private practice 43 (21/22) 15.2 ± 1.1 28.9 ± 3.6 E ≥5 NO L3-3 • 1.3 ± 1.9 Dugoni et al. 1995 (29) • Longitudinal (pre-post) study • Private practice 25 (8/17) 13 y 7 m ± 1 y 6 m 27 y 11 m ± 4 y 9 m NE 9.5 CSF, IPR L3-3 • 1.61 ±1.77 Dyer et al. 2012 (1) • Longitudinal (pre-post) study • Private practice 52 (0/52) NR 39.4 E 24.7 NO Either L3-3 or removable retainer • 1.1 ± 1.05 Tynelius et al. 2015 (4) • Randomized control trial (RCT) • Private practice 49 (16/33) 14.3 ± 1.5 21 E (5–9) IPR in one group Lower 3-3, IPR, positioner • 1.7 ± 0.67 • 1.7 ± 1.38 • 3.1 ± 1.51 Elms et al. 1996 (30) • Longitudinal (pre-post) study • Private practice 42 (8/34) 14.5 (12.1–17.6) 23.1 (18.2–28) NE 6.5 IPR L3-3 • 0.4 ± 1 Erdinc et al. 2006 (31) • Longitudinal (pre-post) study • NR 96 (38/60) 16 y 3 m 20 y 11 m E NE 4.6 NO Removable retainer • 0.97 ±1.4 • 0.99 ± 1.16 Freitas et al. 2004 (5) • Longitudinal (pre-post) study • University clinics 40 (16/24) 15 y 7 m 20 y 5 m NE 5 NO L3-3 • 1.08 ± 0.96 de Freitas et al. 2006 (25) • Longitudinal (pre-post) study • University clinics 56 (29/27) NR NR E 5.1 NO L3-3 • 1 ± 1.15 Glenn et al. 1987 (33) • Longitudinal (pre-post) study • Private practice 28 (NR) 14 y 9 m 26 y 7 m NE 8 NO NR • 1.2 ± 1.25 Goldberg et al. 2013 (7) • Longitudinal (pre-post) study • Private practice 75 (31/44) 15.4 (14.8–16.3) 32 (26.9–36.7) E 16.5 NO L3-3 • 0.9 ± 0.89 Hagler et al. 1998 (34) • Longitudinal (pre-post) study • NR 60 (13/47) 18.2 25.9 E NE 7.8 NR NR • 1.5 ± 3.28 • 0.8 ± 3.28 Harris and Vaden 1994 (36) • Longitudinal (pre-post) study • Private practice 74 (NR) GP1: 15.1± 1.53 GP2: 32.2 ± 5.85 GP1: 21.7 ± 2.08 GP2: 36.2 ± 5.72 E GP1: 6.6 ± 1.3 GP2: 4.1 ± 2.7 NO Hawley retainer • Early treatment 0.41 ± 0.87 • Late treatment 0.54 ± 0.54 Haruki and Little 1998 (8) • Longitudinal (pre-post) study • University clinics and private practice 83 (19/64) 15 y 5 m ± 19.98 m 31 y 5 m ± 5.6 E 15.9 ± 5 NO L3-3 • Early treatment 1.53 ± 1.14 • Late treatment 2.75 ± 1.95 Heiser et al 2008 (37) • Longitudinal (pre-post) study • Private practice 60 (12/48) GP1: 14.13 ± 3.78 GP2: 15.1 ± 4.38 GP1: 21.7 ± 4.16 GP2: 22.4 ± 6.4 E NE GP1: 6.3 ± 2.8 GP2: 6.5 ± 3 NO Removable retainer • 2.09 ± 1.39 • 2.02 ± 1.67 Janson et al. 2006 (38) • Longitudinal (pre-post) study • University clinics 66 (29/37) NR 21 E NE • 3.9 • 3.1 NO L3-3 • 0.98 ± 1.28 • 0.55 ± 1.48 Kahl-Nieke et al 1995 (2) • Longitudinal (pre-post) study • University clinics 226 (NR) NR 31.2 ± 4.8 E NE 15.7 ± 4.4 NO NR • 1.8 ± 2 • 2.3 ± 2.1 Little et al. 1990 (42) • Longitudinal (pre-post) study • University clinics and private practice 30 (6/24) 14 y 4 m (12 y 7 m–17 y) 29 y 1 m (24 y 3 m–42 y 3 m) E 11.25 (9.3–22.6) NO NR • 2.59 ± 1.32 Little et al. 1981 (43) • Longitudinal (pre-post) study • University clinics and private practice 65 (24/41) 15 y 2 m (12 y 6 m–19 y 11 m) 30 y 1 m (25 y– 43 y 4 m) E 12.6 (9.6–23.9) NO NR • 2.9 ± 1.42 Luppanapornlarp and Johnston 1993 (44) • Longitudinal (pre-post) study • University clinics 62 (26/36) 14.8 30.2 E NE 15.3 (10.8– 22.5) NR NR • 2.6 ± 3.38 • 3.1 ± 3.38 McReynolds and Little 1991 (45) • Longitudinal (pre-post) study • University clinics and private practice 46 (11/35) 15.3 30 y 8 m E • 14.4 • 16.6 NO L3-3 • 2 ± 1.09 • 2.6 ± 1.27 Miyazaki et al. 1997 (46) • Longitudinal (pre-post) study • University clinics 48 (NR) GP1: 22 y 4 m (18 y 1 m–28 y 5 m) GP2: 14 y (12 y 2 m–16) GP1: 26 y 7 m (20 y 7 m–33 y 4 m) GP2: 18 y 6 m (15 y 6 m–22 y 10 m) E ≥ 1 NO Removable retainer • Adults: 1.28 ± 1.17 • Adolescents: 2.36 ±1 .1 Moussa et al. 1995 (47) • Longitudinal (pre-post) study • Private practice 55 (16/39) 15.7 ± 2.6 30.2 ± 5.3 (20.8–51.1) NE 8 ± 3.1 NO L3-3 • 0.8 ± 1.2 Rossouw et al. 1999 (50) • Longitudinal (pre-post) study • NR 88 (NR) 14.7 (11.1–24.2) 21.5 (16.2–33.5) E NE 5 NO NR • 1.2 ± 1.3 • 1.4 ± 1.11 Vaden et al. 1997 (52) • Longitudinal (pre-post) study • Private practice 36 (7/29) 15.3 ± 1.95 30.5 ± 2.84 E 15 NO Either L3-3 or removable retainer • 1.44 ± 1.38 Yavari et al. 2000 (53) • Longitudinal (pre-post) study • Private practice 31 (NR) NR NR NE ≥2 NO L4-4 • 0 ± 1.1 Study ID (author and date) Study design and clinical setting Sample size, n (M/F) Age at T1 (y) Age at T2 (y) Intervention Post-treatment follow-up (y) Adjunctive procedure use Retention type T2-T1 LII mean and SD (mm) Artun et al. 1996 (19) • Longitudinal (pre-post) study • University clinics 78 (33/45) NR 31.1 ± 5 E NE 14 ± 4.6 NO NR • 3.15 ± 1.5 • 2.55 ± 1.42 Boley et al. 2003 (20) • Longitudinal (pre-post) study • Private practice 32 (9/23) 15.5 (12.8–41.7) 31.6 (24.3–51.1) E ≥5 IPR L3-3 • 0.7 ± 1.1 Canut and Arias 1999 (22) • Longitudinal (pre-post) study • NR 30 (10/20) 15.14 ± 2.99 22.1 ± 3.59 NE 7 ± 2.8 NO NR • 2.24 ± 2.6 de Freitas et al. 2006 (24) • Longitudinal (pre-post) study • University clinics 94 (50/44) NR NR E 5.3 ± 1.6 NO L3-3 • 1 ± 1.15 de la Cruz et al. 1995 (26) • Longitudinal (pre-post) study • University clinics and private practice 87 (31/56) 15 y 8 m 33 y 7 m E ≥10 NO L3-3 • CL I: 2.3 ± 1.6 • CL II Div1: 2.9 ± 1.9 Driscoll-Gilliland et al. 2001 (28) • Longitudinal (pre-post) study • Private practice 43 (21/22) 15.2 ± 1.1 28.9 ± 3.6 E ≥5 NO L3-3 • 1.3 ± 1.9 Dugoni et al. 1995 (29) • Longitudinal (pre-post) study • Private practice 25 (8/17) 13 y 7 m ± 1 y 6 m 27 y 11 m ± 4 y 9 m NE 9.5 CSF, IPR L3-3 • 1.61 ±1.77 Dyer et al. 2012 (1) • Longitudinal (pre-post) study • Private practice 52 (0/52) NR 39.4 E 24.7 NO Either L3-3 or removable retainer • 1.1 ± 1.05 Tynelius et al. 2015 (4) • Randomized control trial (RCT) • Private practice 49 (16/33) 14.3 ± 1.5 21 E (5–9) IPR in one group Lower 3-3, IPR, positioner • 1.7 ± 0.67 • 1.7 ± 1.38 • 3.1 ± 1.51 Elms et al. 1996 (30) • Longitudinal (pre-post) study • Private practice 42 (8/34) 14.5 (12.1–17.6) 23.1 (18.2–28) NE 6.5 IPR L3-3 • 0.4 ± 1 Erdinc et al. 2006 (31) • Longitudinal (pre-post) study • NR 96 (38/60) 16 y 3 m 20 y 11 m E NE 4.6 NO Removable retainer • 0.97 ±1.4 • 0.99 ± 1.16 Freitas et al. 2004 (5) • Longitudinal (pre-post) study • University clinics 40 (16/24) 15 y 7 m 20 y 5 m NE 5 NO L3-3 • 1.08 ± 0.96 de Freitas et al. 2006 (25) • Longitudinal (pre-post) study • University clinics 56 (29/27) NR NR E 5.1 NO L3-3 • 1 ± 1.15 Glenn et al. 1987 (33) • Longitudinal (pre-post) study • Private practice 28 (NR) 14 y 9 m 26 y 7 m NE 8 NO NR • 1.2 ± 1.25 Goldberg et al. 2013 (7) • Longitudinal (pre-post) study • Private practice 75 (31/44) 15.4 (14.8–16.3) 32 (26.9–36.7) E 16.5 NO L3-3 • 0.9 ± 0.89 Hagler et al. 1998 (34) • Longitudinal (pre-post) study • NR 60 (13/47) 18.2 25.9 E NE 7.8 NR NR • 1.5 ± 3.28 • 0.8 ± 3.28 Harris and Vaden 1994 (36) • Longitudinal (pre-post) study • Private practice 74 (NR) GP1: 15.1± 1.53 GP2: 32.2 ± 5.85 GP1: 21.7 ± 2.08 GP2: 36.2 ± 5.72 E GP1: 6.6 ± 1.3 GP2: 4.1 ± 2.7 NO Hawley retainer • Early treatment 0.41 ± 0.87 • Late treatment 0.54 ± 0.54 Haruki and Little 1998 (8) • Longitudinal (pre-post) study • University clinics and private practice 83 (19/64) 15 y 5 m ± 19.98 m 31 y 5 m ± 5.6 E 15.9 ± 5 NO L3-3 • Early treatment 1.53 ± 1.14 • Late treatment 2.75 ± 1.95 Heiser et al 2008 (37) • Longitudinal (pre-post) study • Private practice 60 (12/48) GP1: 14.13 ± 3.78 GP2: 15.1 ± 4.38 GP1: 21.7 ± 4.16 GP2: 22.4 ± 6.4 E NE GP1: 6.3 ± 2.8 GP2: 6.5 ± 3 NO Removable retainer • 2.09 ± 1.39 • 2.02 ± 1.67 Janson et al. 2006 (38) • Longitudinal (pre-post) study • University clinics 66 (29/37) NR 21 E NE • 3.9 • 3.1 NO L3-3 • 0.98 ± 1.28 • 0.55 ± 1.48 Kahl-Nieke et al 1995 (2) • Longitudinal (pre-post) study • University clinics 226 (NR) NR 31.2 ± 4.8 E NE 15.7 ± 4.4 NO NR • 1.8 ± 2 • 2.3 ± 2.1 Little et al. 1990 (42) • Longitudinal (pre-post) study • University clinics and private practice 30 (6/24) 14 y 4 m (12 y 7 m–17 y) 29 y 1 m (24 y 3 m–42 y 3 m) E 11.25 (9.3–22.6) NO NR • 2.59 ± 1.32 Little et al. 1981 (43) • Longitudinal (pre-post) study • University clinics and private practice 65 (24/41) 15 y 2 m (12 y 6 m–19 y 11 m) 30 y 1 m (25 y– 43 y 4 m) E 12.6 (9.6–23.9) NO NR • 2.9 ± 1.42 Luppanapornlarp and Johnston 1993 (44) • Longitudinal (pre-post) study • University clinics 62 (26/36) 14.8 30.2 E NE 15.3 (10.8– 22.5) NR NR • 2.6 ± 3.38 • 3.1 ± 3.38 McReynolds and Little 1991 (45) • Longitudinal (pre-post) study • University clinics and private practice 46 (11/35) 15.3 30 y 8 m E • 14.4 • 16.6 NO L3-3 • 2 ± 1.09 • 2.6 ± 1.27 Miyazaki et al. 1997 (46) • Longitudinal (pre-post) study • University clinics 48 (NR) GP1: 22 y 4 m (18 y 1 m–28 y 5 m) GP2: 14 y (12 y 2 m–16) GP1: 26 y 7 m (20 y 7 m–33 y 4 m) GP2: 18 y 6 m (15 y 6 m–22 y 10 m) E ≥ 1 NO Removable retainer • Adults: 1.28 ± 1.17 • Adolescents: 2.36 ±1 .1 Moussa et al. 1995 (47) • Longitudinal (pre-post) study • Private practice 55 (16/39) 15.7 ± 2.6 30.2 ± 5.3 (20.8–51.1) NE 8 ± 3.1 NO L3-3 • 0.8 ± 1.2 Rossouw et al. 1999 (50) • Longitudinal (pre-post) study • NR 88 (NR) 14.7 (11.1–24.2) 21.5 (16.2–33.5) E NE 5 NO NR • 1.2 ± 1.3 • 1.4 ± 1.11 Vaden et al. 1997 (52) • Longitudinal (pre-post) study • Private practice 36 (7/29) 15.3 ± 1.95 30.5 ± 2.84 E 15 NO Either L3-3 or removable retainer • 1.44 ± 1.38 Yavari et al. 2000 (53) • Longitudinal (pre-post) study • Private practice 31 (NR) NR NR NE ≥2 NO L4-4 • 0 ± 1.1 CSF: circumferential supracrestal fibrotomy; CL: class; GP: group; NO: not used. Open in new tab Table 1. Characteristics of studies included in meta-analysis. E, extraction; IPR, inter-proximal reduction; NE, non-extraction. NR, not reported Study ID (author and date) Study design and clinical setting Sample size, n (M/F) Age at T1 (y) Age at T2 (y) Intervention Post-treatment follow-up (y) Adjunctive procedure use Retention type T2-T1 LII mean and SD (mm) Artun et al. 1996 (19) • Longitudinal (pre-post) study • University clinics 78 (33/45) NR 31.1 ± 5 E NE 14 ± 4.6 NO NR • 3.15 ± 1.5 • 2.55 ± 1.42 Boley et al. 2003 (20) • Longitudinal (pre-post) study • Private practice 32 (9/23) 15.5 (12.8–41.7) 31.6 (24.3–51.1) E ≥5 IPR L3-3 • 0.7 ± 1.1 Canut and Arias 1999 (22) • Longitudinal (pre-post) study • NR 30 (10/20) 15.14 ± 2.99 22.1 ± 3.59 NE 7 ± 2.8 NO NR • 2.24 ± 2.6 de Freitas et al. 2006 (24) • Longitudinal (pre-post) study • University clinics 94 (50/44) NR NR E 5.3 ± 1.6 NO L3-3 • 1 ± 1.15 de la Cruz et al. 1995 (26) • Longitudinal (pre-post) study • University clinics and private practice 87 (31/56) 15 y 8 m 33 y 7 m E ≥10 NO L3-3 • CL I: 2.3 ± 1.6 • CL II Div1: 2.9 ± 1.9 Driscoll-Gilliland et al. 2001 (28) • Longitudinal (pre-post) study • Private practice 43 (21/22) 15.2 ± 1.1 28.9 ± 3.6 E ≥5 NO L3-3 • 1.3 ± 1.9 Dugoni et al. 1995 (29) • Longitudinal (pre-post) study • Private practice 25 (8/17) 13 y 7 m ± 1 y 6 m 27 y 11 m ± 4 y 9 m NE 9.5 CSF, IPR L3-3 • 1.61 ±1.77 Dyer et al. 2012 (1) • Longitudinal (pre-post) study • Private practice 52 (0/52) NR 39.4 E 24.7 NO Either L3-3 or removable retainer • 1.1 ± 1.05 Tynelius et al. 2015 (4) • Randomized control trial (RCT) • Private practice 49 (16/33) 14.3 ± 1.5 21 E (5–9) IPR in one group Lower 3-3, IPR, positioner • 1.7 ± 0.67 • 1.7 ± 1.38 • 3.1 ± 1.51 Elms et al. 1996 (30) • Longitudinal (pre-post) study • Private practice 42 (8/34) 14.5 (12.1–17.6) 23.1 (18.2–28) NE 6.5 IPR L3-3 • 0.4 ± 1 Erdinc et al. 2006 (31) • Longitudinal (pre-post) study • NR 96 (38/60) 16 y 3 m 20 y 11 m E NE 4.6 NO Removable retainer • 0.97 ±1.4 • 0.99 ± 1.16 Freitas et al. 2004 (5) • Longitudinal (pre-post) study • University clinics 40 (16/24) 15 y 7 m 20 y 5 m NE 5 NO L3-3 • 1.08 ± 0.96 de Freitas et al. 2006 (25) • Longitudinal (pre-post) study • University clinics 56 (29/27) NR NR E 5.1 NO L3-3 • 1 ± 1.15 Glenn et al. 1987 (33) • Longitudinal (pre-post) study • Private practice 28 (NR) 14 y 9 m 26 y 7 m NE 8 NO NR • 1.2 ± 1.25 Goldberg et al. 2013 (7) • Longitudinal (pre-post) study • Private practice 75 (31/44) 15.4 (14.8–16.3) 32 (26.9–36.7) E 16.5 NO L3-3 • 0.9 ± 0.89 Hagler et al. 1998 (34) • Longitudinal (pre-post) study • NR 60 (13/47) 18.2 25.9 E NE 7.8 NR NR • 1.5 ± 3.28 • 0.8 ± 3.28 Harris and Vaden 1994 (36) • Longitudinal (pre-post) study • Private practice 74 (NR) GP1: 15.1± 1.53 GP2: 32.2 ± 5.85 GP1: 21.7 ± 2.08 GP2: 36.2 ± 5.72 E GP1: 6.6 ± 1.3 GP2: 4.1 ± 2.7 NO Hawley retainer • Early treatment 0.41 ± 0.87 • Late treatment 0.54 ± 0.54 Haruki and Little 1998 (8) • Longitudinal (pre-post) study • University clinics and private practice 83 (19/64) 15 y 5 m ± 19.98 m 31 y 5 m ± 5.6 E 15.9 ± 5 NO L3-3 • Early treatment 1.53 ± 1.14 • Late treatment 2.75 ± 1.95 Heiser et al 2008 (37) • Longitudinal (pre-post) study • Private practice 60 (12/48) GP1: 14.13 ± 3.78 GP2: 15.1 ± 4.38 GP1: 21.7 ± 4.16 GP2: 22.4 ± 6.4 E NE GP1: 6.3 ± 2.8 GP2: 6.5 ± 3 NO Removable retainer • 2.09 ± 1.39 • 2.02 ± 1.67 Janson et al. 2006 (38) • Longitudinal (pre-post) study • University clinics 66 (29/37) NR 21 E NE • 3.9 • 3.1 NO L3-3 • 0.98 ± 1.28 • 0.55 ± 1.48 Kahl-Nieke et al 1995 (2) • Longitudinal (pre-post) study • University clinics 226 (NR) NR 31.2 ± 4.8 E NE 15.7 ± 4.4 NO NR • 1.8 ± 2 • 2.3 ± 2.1 Little et al. 1990 (42) • Longitudinal (pre-post) study • University clinics and private practice 30 (6/24) 14 y 4 m (12 y 7 m–17 y) 29 y 1 m (24 y 3 m–42 y 3 m) E 11.25 (9.3–22.6) NO NR • 2.59 ± 1.32 Little et al. 1981 (43) • Longitudinal (pre-post) study • University clinics and private practice 65 (24/41) 15 y 2 m (12 y 6 m–19 y 11 m) 30 y 1 m (25 y– 43 y 4 m) E 12.6 (9.6–23.9) NO NR • 2.9 ± 1.42 Luppanapornlarp and Johnston 1993 (44) • Longitudinal (pre-post) study • University clinics 62 (26/36) 14.8 30.2 E NE 15.3 (10.8– 22.5) NR NR • 2.6 ± 3.38 • 3.1 ± 3.38 McReynolds and Little 1991 (45) • Longitudinal (pre-post) study • University clinics and private practice 46 (11/35) 15.3 30 y 8 m E • 14.4 • 16.6 NO L3-3 • 2 ± 1.09 • 2.6 ± 1.27 Miyazaki et al. 1997 (46) • Longitudinal (pre-post) study • University clinics 48 (NR) GP1: 22 y 4 m (18 y 1 m–28 y 5 m) GP2: 14 y (12 y 2 m–16) GP1: 26 y 7 m (20 y 7 m–33 y 4 m) GP2: 18 y 6 m (15 y 6 m–22 y 10 m) E ≥ 1 NO Removable retainer • Adults: 1.28 ± 1.17 • Adolescents: 2.36 ±1 .1 Moussa et al. 1995 (47) • Longitudinal (pre-post) study • Private practice 55 (16/39) 15.7 ± 2.6 30.2 ± 5.3 (20.8–51.1) NE 8 ± 3.1 NO L3-3 • 0.8 ± 1.2 Rossouw et al. 1999 (50) • Longitudinal (pre-post) study • NR 88 (NR) 14.7 (11.1–24.2) 21.5 (16.2–33.5) E NE 5 NO NR • 1.2 ± 1.3 • 1.4 ± 1.11 Vaden et al. 1997 (52) • Longitudinal (pre-post) study • Private practice 36 (7/29) 15.3 ± 1.95 30.5 ± 2.84 E 15 NO Either L3-3 or removable retainer • 1.44 ± 1.38 Yavari et al. 2000 (53) • Longitudinal (pre-post) study • Private practice 31 (NR) NR NR NE ≥2 NO L4-4 • 0 ± 1.1 Study ID (author and date) Study design and clinical setting Sample size, n (M/F) Age at T1 (y) Age at T2 (y) Intervention Post-treatment follow-up (y) Adjunctive procedure use Retention type T2-T1 LII mean and SD (mm) Artun et al. 1996 (19) • Longitudinal (pre-post) study • University clinics 78 (33/45) NR 31.1 ± 5 E NE 14 ± 4.6 NO NR • 3.15 ± 1.5 • 2.55 ± 1.42 Boley et al. 2003 (20) • Longitudinal (pre-post) study • Private practice 32 (9/23) 15.5 (12.8–41.7) 31.6 (24.3–51.1) E ≥5 IPR L3-3 • 0.7 ± 1.1 Canut and Arias 1999 (22) • Longitudinal (pre-post) study • NR 30 (10/20) 15.14 ± 2.99 22.1 ± 3.59 NE 7 ± 2.8 NO NR • 2.24 ± 2.6 de Freitas et al. 2006 (24) • Longitudinal (pre-post) study • University clinics 94 (50/44) NR NR E 5.3 ± 1.6 NO L3-3 • 1 ± 1.15 de la Cruz et al. 1995 (26) • Longitudinal (pre-post) study • University clinics and private practice 87 (31/56) 15 y 8 m 33 y 7 m E ≥10 NO L3-3 • CL I: 2.3 ± 1.6 • CL II Div1: 2.9 ± 1.9 Driscoll-Gilliland et al. 2001 (28) • Longitudinal (pre-post) study • Private practice 43 (21/22) 15.2 ± 1.1 28.9 ± 3.6 E ≥5 NO L3-3 • 1.3 ± 1.9 Dugoni et al. 1995 (29) • Longitudinal (pre-post) study • Private practice 25 (8/17) 13 y 7 m ± 1 y 6 m 27 y 11 m ± 4 y 9 m NE 9.5 CSF, IPR L3-3 • 1.61 ±1.77 Dyer et al. 2012 (1) • Longitudinal (pre-post) study • Private practice 52 (0/52) NR 39.4 E 24.7 NO Either L3-3 or removable retainer • 1.1 ± 1.05 Tynelius et al. 2015 (4) • Randomized control trial (RCT) • Private practice 49 (16/33) 14.3 ± 1.5 21 E (5–9) IPR in one group Lower 3-3, IPR, positioner • 1.7 ± 0.67 • 1.7 ± 1.38 • 3.1 ± 1.51 Elms et al. 1996 (30) • Longitudinal (pre-post) study • Private practice 42 (8/34) 14.5 (12.1–17.6) 23.1 (18.2–28) NE 6.5 IPR L3-3 • 0.4 ± 1 Erdinc et al. 2006 (31) • Longitudinal (pre-post) study • NR 96 (38/60) 16 y 3 m 20 y 11 m E NE 4.6 NO Removable retainer • 0.97 ±1.4 • 0.99 ± 1.16 Freitas et al. 2004 (5) • Longitudinal (pre-post) study • University clinics 40 (16/24) 15 y 7 m 20 y 5 m NE 5 NO L3-3 • 1.08 ± 0.96 de Freitas et al. 2006 (25) • Longitudinal (pre-post) study • University clinics 56 (29/27) NR NR E 5.1 NO L3-3 • 1 ± 1.15 Glenn et al. 1987 (33) • Longitudinal (pre-post) study • Private practice 28 (NR) 14 y 9 m 26 y 7 m NE 8 NO NR • 1.2 ± 1.25 Goldberg et al. 2013 (7) • Longitudinal (pre-post) study • Private practice 75 (31/44) 15.4 (14.8–16.3) 32 (26.9–36.7) E 16.5 NO L3-3 • 0.9 ± 0.89 Hagler et al. 1998 (34) • Longitudinal (pre-post) study • NR 60 (13/47) 18.2 25.9 E NE 7.8 NR NR • 1.5 ± 3.28 • 0.8 ± 3.28 Harris and Vaden 1994 (36) • Longitudinal (pre-post) study • Private practice 74 (NR) GP1: 15.1± 1.53 GP2: 32.2 ± 5.85 GP1: 21.7 ± 2.08 GP2: 36.2 ± 5.72 E GP1: 6.6 ± 1.3 GP2: 4.1 ± 2.7 NO Hawley retainer • Early treatment 0.41 ± 0.87 • Late treatment 0.54 ± 0.54 Haruki and Little 1998 (8) • Longitudinal (pre-post) study • University clinics and private practice 83 (19/64) 15 y 5 m ± 19.98 m 31 y 5 m ± 5.6 E 15.9 ± 5 NO L3-3 • Early treatment 1.53 ± 1.14 • Late treatment 2.75 ± 1.95 Heiser et al 2008 (37) • Longitudinal (pre-post) study • Private practice 60 (12/48) GP1: 14.13 ± 3.78 GP2: 15.1 ± 4.38 GP1: 21.7 ± 4.16 GP2: 22.4 ± 6.4 E NE GP1: 6.3 ± 2.8 GP2: 6.5 ± 3 NO Removable retainer • 2.09 ± 1.39 • 2.02 ± 1.67 Janson et al. 2006 (38) • Longitudinal (pre-post) study • University clinics 66 (29/37) NR 21 E NE • 3.9 • 3.1 NO L3-3 • 0.98 ± 1.28 • 0.55 ± 1.48 Kahl-Nieke et al 1995 (2) • Longitudinal (pre-post) study • University clinics 226 (NR) NR 31.2 ± 4.8 E NE 15.7 ± 4.4 NO NR • 1.8 ± 2 • 2.3 ± 2.1 Little et al. 1990 (42) • Longitudinal (pre-post) study • University clinics and private practice 30 (6/24) 14 y 4 m (12 y 7 m–17 y) 29 y 1 m (24 y 3 m–42 y 3 m) E 11.25 (9.3–22.6) NO NR • 2.59 ± 1.32 Little et al. 1981 (43) • Longitudinal (pre-post) study • University clinics and private practice 65 (24/41) 15 y 2 m (12 y 6 m–19 y 11 m) 30 y 1 m (25 y– 43 y 4 m) E 12.6 (9.6–23.9) NO NR • 2.9 ± 1.42 Luppanapornlarp and Johnston 1993 (44) • Longitudinal (pre-post) study • University clinics 62 (26/36) 14.8 30.2 E NE 15.3 (10.8– 22.5) NR NR • 2.6 ± 3.38 • 3.1 ± 3.38 McReynolds and Little 1991 (45) • Longitudinal (pre-post) study • University clinics and private practice 46 (11/35) 15.3 30 y 8 m E • 14.4 • 16.6 NO L3-3 • 2 ± 1.09 • 2.6 ± 1.27 Miyazaki et al. 1997 (46) • Longitudinal (pre-post) study • University clinics 48 (NR) GP1: 22 y 4 m (18 y 1 m–28 y 5 m) GP2: 14 y (12 y 2 m–16) GP1: 26 y 7 m (20 y 7 m–33 y 4 m) GP2: 18 y 6 m (15 y 6 m–22 y 10 m) E ≥ 1 NO Removable retainer • Adults: 1.28 ± 1.17 • Adolescents: 2.36 ±1 .1 Moussa et al. 1995 (47) • Longitudinal (pre-post) study • Private practice 55 (16/39) 15.7 ± 2.6 30.2 ± 5.3 (20.8–51.1) NE 8 ± 3.1 NO L3-3 • 0.8 ± 1.2 Rossouw et al. 1999 (50) • Longitudinal (pre-post) study • NR 88 (NR) 14.7 (11.1–24.2) 21.5 (16.2–33.5) E NE 5 NO NR • 1.2 ± 1.3 • 1.4 ± 1.11 Vaden et al. 1997 (52) • Longitudinal (pre-post) study • Private practice 36 (7/29) 15.3 ± 1.95 30.5 ± 2.84 E 15 NO Either L3-3 or removable retainer • 1.44 ± 1.38 Yavari et al. 2000 (53) • Longitudinal (pre-post) study • Private practice 31 (NR) NR NR NE ≥2 NO L4-4 • 0 ± 1.1 CSF: circumferential supracrestal fibrotomy; CL: class; GP: group; NO: not used. Open in new tab Risk of bias within studies The randomized control trial (4) was judged to have a high risk of bias (Supplementary Table 5), because of 34% of the sample having been lost to follow-up. In addition, compliance with the retention protocol was unclear. Of the 42 longitudinal observational studies, the quality of 31 (1, 2, 5–8, 19, 20, 22, 24–26, 28–31, 33, 34, 36–38, 42–47, 49, 50, 52, 53) was judged to be fair and 12 (21, 23, 27, 32, 35, 39–41, 48, 51, 54, 55) were judged to be poor (Supplementary Table 6). Risk of bias across studies There was a significant risk of publication bias among the studies. The funnel plot (Supplementary Figure 1) showed an asymmetrical distribution of studies, which was confirmed by the Begg’s (P = 0.006) and Egger’s (P = 0.024) tests. Results of individual studies, meta-analyses, and additional analyses A total of 30 studies were included in the meta-analysis, including a total of 1859 orthodontic patients (1, 2, 4, 5, 7, 8, 19, 20, 22, 24–26, 28–31, 33, 34, 36–38, 42–47, 50, 52, 53). The studies that reported subgroups of extraction and non-extraction treatment were analysed separately. There were 30 (66.6%) extraction studies or subgroups, and 15 (33.3%) non-extraction studies or subgroups (Figure 2). The SMD between T1 and T2 irregularity for the extraction group was 1.22; (95% CI, 1.04–1.40), compared to 0.85; (95% CI, 0.63–1.07) for the non-extraction group. There was a statistically significant (P = 0.026) difference between extraction and non-extraction groups. Figure 2. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.026) difference in irregularity change between extraction and non-extraction treatment. The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. Figure 2. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.026) difference in irregularity change between extraction and non-extraction treatment. The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. The heterogeneity was substantial for both the extraction (Q-test = 116.7df 29, P < 0.001, Tau2 = 0.18, I2 = 75.2%) and non-extraction (Q-test = 46.9df 14, P < 0.001, Tau2 = 0.13, I2 = 70.1%) studies (Figure 2). Owing to the high heterogeneity, meta-regression analysis was conducted to determine how the study characteristics influenced effect size, and to evaluate their contributions (Table 2). Approximately 33% of the between-study variance (heterogeneity) was explained by follow-up duration (1–10 versus 10–20 years). Treatment protocol (extraction versus non-extraction) explained 9.9% of the heterogeneity, and study design (interventional versus observational studies) explained 9.2% of the heterogeneity. The type of retention used, the adjunctive procedures used, pre-treatment irregularity, and clinical setting did not significantly influence the estimated alignment changes. Table 2. Meta-regression table of potential explanatory factors of variation in the effect size estimate Characteristics No. of observations Constant Effect Tau2 I2 residual Adjusted R2 Estimate Probability Estimate Probability (%) (%) Follow-up duration (1–10 versus 10–20 y) 45 0.89 <0.001 0.49 0.002 0.138 67.9 32.8 Treatment protocol (extraction versus non-extraction) 45 0.85 <0.001 0.37 0.026 0.185 73.7 9.9 Study design 45 1.05 <0.001 0.83 0.029 0.186 73.6 9.2 Retention type (fixed versus removable) 27 1.05 <0.001 0.11 0.65 0.228 74.8 5.5 Adjunctive procedures use 41 0.75 0.008 0.42 0.14 0.191 73.8 4.7 Pre-treatment irregularity index 41 0.68 0.032 0.08 0.15 0.215 75.7 4.0 Clinical setting (academic versus private) 31 1.09 <0.001 −0.15 0.41 0.157 68.2 1.7 Characteristics No. of observations Constant Effect Tau2 I2 residual Adjusted R2 Estimate Probability Estimate Probability (%) (%) Follow-up duration (1–10 versus 10–20 y) 45 0.89 <0.001 0.49 0.002 0.138 67.9 32.8 Treatment protocol (extraction versus non-extraction) 45 0.85 <0.001 0.37 0.026 0.185 73.7 9.9 Study design 45 1.05 <0.001 0.83 0.029 0.186 73.6 9.2 Retention type (fixed versus removable) 27 1.05 <0.001 0.11 0.65 0.228 74.8 5.5 Adjunctive procedures use 41 0.75 0.008 0.42 0.14 0.191 73.8 4.7 Pre-treatment irregularity index 41 0.68 0.032 0.08 0.15 0.215 75.7 4.0 Clinical setting (academic versus private) 31 1.09 <0.001 −0.15 0.41 0.157 68.2 1.7 Tau2: estimate of between-study variance; I2 residual: % residual variation due to heterogeneity; Adjusted R2: Proportion of between-study variance explained. Open in new tab Table 2. Meta-regression table of potential explanatory factors of variation in the effect size estimate Characteristics No. of observations Constant Effect Tau2 I2 residual Adjusted R2 Estimate Probability Estimate Probability (%) (%) Follow-up duration (1–10 versus 10–20 y) 45 0.89 <0.001 0.49 0.002 0.138 67.9 32.8 Treatment protocol (extraction versus non-extraction) 45 0.85 <0.001 0.37 0.026 0.185 73.7 9.9 Study design 45 1.05 <0.001 0.83 0.029 0.186 73.6 9.2 Retention type (fixed versus removable) 27 1.05 <0.001 0.11 0.65 0.228 74.8 5.5 Adjunctive procedures use 41 0.75 0.008 0.42 0.14 0.191 73.8 4.7 Pre-treatment irregularity index 41 0.68 0.032 0.08 0.15 0.215 75.7 4.0 Clinical setting (academic versus private) 31 1.09 <0.001 −0.15 0.41 0.157 68.2 1.7 Characteristics No. of observations Constant Effect Tau2 I2 residual Adjusted R2 Estimate Probability Estimate Probability (%) (%) Follow-up duration (1–10 versus 10–20 y) 45 0.89 <0.001 0.49 0.002 0.138 67.9 32.8 Treatment protocol (extraction versus non-extraction) 45 0.85 <0.001 0.37 0.026 0.185 73.7 9.9 Study design 45 1.05 <0.001 0.83 0.029 0.186 73.6 9.2 Retention type (fixed versus removable) 27 1.05 <0.001 0.11 0.65 0.228 74.8 5.5 Adjunctive procedures use 41 0.75 0.008 0.42 0.14 0.191 73.8 4.7 Pre-treatment irregularity index 41 0.68 0.032 0.08 0.15 0.215 75.7 4.0 Clinical setting (academic versus private) 31 1.09 <0.001 −0.15 0.41 0.157 68.2 1.7 Tau2: estimate of between-study variance; I2 residual: % residual variation due to heterogeneity; Adjusted R2: Proportion of between-study variance explained. Open in new tab Subgroup analyses have shown a significant influence of follow-up duration (1–10 versus 10–20 years) and study design (interventional versus observational studies) on the irregularity changes. The SMD of the 1–10 years follow-up group was 0.89 (95% CI, 0.73–1.05), compared to 1.39 (95% CI, 1.18–1.60) for the 10–20 years follow-up group (Figure 3).The SMD was 1.90 (95% CI, 1.13–2.67) and 1.05 (95% CI, 0.91–1.19) for the interventional and observational studies, respectively (Figure 4). Figure 3. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.002) difference in irregularity change between follow-up durations (1-10 versus 10-20 years). The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. Figure 3. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.002) difference in irregularity change between follow-up durations (1-10 versus 10-20 years). The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. Figure 4. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.02) difference in irregularity change between study designs (observational versus interventional). The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. Figure 4. Open in new tabDownload slide Forest plot of summary effect size (ES, quantified as standardized mean difference) showing statistically significant (P = 0.02) difference in irregularity change between study designs (observational versus interventional). The vertical red dotted line (---) indicates the overall estimate, and the highlighted black diamond shapes ( ¨ ) indicate individual study estimates. The open diamonds indicate the subtotal and overall estimates, along with predictive intervals. Discussion Summary of evidence Both SMDs and unstandardized mean differences (UMDs) of post-treatment irregularity are important and need to be reported. The SMDs, which were reported in the results, provide better control of the outcome variable’s variance, resulting in smaller confidence intervals. For example, the 95% CI of the SMDs in the present study ranged from 0.95 to 1.23 (Figure 2), compared to 1.39–1.86 for the UMDs (Table 3). The UMDs are necessary because they maintain the measurement’s unit (e.g. millimetre) and make the results of this meta-analysis more easily understood and interpreted (56, 57). Table 3 summarizes the SMD and UMD of long-term irregularity changes, along with the 95% confidence intervals, in different clinical comparisons. Table 3. Summary of standardized mean difference (SMD) and unstandardized mean difference (UMD) of post-treatment irregularity changes in different clinical comparisons. CI: confidence interval Comparison SMD of irregularity change (95% CI) P-value I2 (%) MD of irregularity change (mm) (95% CI) P-value I2 (%) Overall 1.09 (0.95-1.23) <0.001 74.7 1.63 (1.39-1.86) <0.001 91.1 Treatment approach  Extraction  Non-extraction 1.22 (1.04-1.40) 0.85 (0.63-1.07) <0.001 <0.001 75.2 70.1 1.74 (1.46-2.02) 1.40 (0.96-1.85) <0.001 <0.001 90.2 92.9 Follow-up duration  1–10 y  10–20 y 0.89 (0.73-1.05) 1.39 (1.18-1.60) <0.001 <0.001 65.1 71.8 1.22 (1.01-1.44) 2.25 (1.91-2.60) <0.001 <0.001 81.2 89.9 Study design  Interventional  Observational 1.90 (1.13-2.67) 1.05 (0.91-1.19) <0.001 <0.001 74.7 74.1 2.16 (1.25-3.07) 1.60 (1.35-1.84) <0.001 <0.001 71.7 91.5 Retention methods  Fixed  Removable 1.04 (0.82-1.27) 1.15 (0.82-1.48) <0.001 <0.001 76.3 71.0 1.42 (1.06-1.79) 1.48 (0.96-1.99) <0.001 <0.001 91.0 88.2 Clinical setting  Private  Academic 0.94 (0.69-1.17) 1.08 (0.89-1.27) <0.001 <0.001 70.2 65.7 1.21 (0.87-1.55) 1.81 (1.43-2.20) <0.001 <0.001 85.1 91.8 Adjunctive procedure use  Used  Not used 0.71 (0.38-1.04) 1.18 (1.02-1.33) <0.001 <0.001 32.1 75.1 1.06 (0.43-1.70) 1.65 (1.39-1.90) 0.001 <0.001 81.3 91.0 Comparison SMD of irregularity change (95% CI) P-value I2 (%) MD of irregularity change (mm) (95% CI) P-value I2 (%) Overall 1.09 (0.95-1.23) <0.001 74.7 1.63 (1.39-1.86) <0.001 91.1 Treatment approach  Extraction  Non-extraction 1.22 (1.04-1.40) 0.85 (0.63-1.07) <0.001 <0.001 75.2 70.1 1.74 (1.46-2.02) 1.40 (0.96-1.85) <0.001 <0.001 90.2 92.9 Follow-up duration  1–10 y  10–20 y 0.89 (0.73-1.05) 1.39 (1.18-1.60) <0.001 <0.001 65.1 71.8 1.22 (1.01-1.44) 2.25 (1.91-2.60) <0.001 <0.001 81.2 89.9 Study design  Interventional  Observational 1.90 (1.13-2.67) 1.05 (0.91-1.19) <0.001 <0.001 74.7 74.1 2.16 (1.25-3.07) 1.60 (1.35-1.84) <0.001 <0.001 71.7 91.5 Retention methods  Fixed  Removable 1.04 (0.82-1.27) 1.15 (0.82-1.48) <0.001 <0.001 76.3 71.0 1.42 (1.06-1.79) 1.48 (0.96-1.99) <0.001 <0.001 91.0 88.2 Clinical setting  Private  Academic 0.94 (0.69-1.17) 1.08 (0.89-1.27) <0.001 <0.001 70.2 65.7 1.21 (0.87-1.55) 1.81 (1.43-2.20) <0.001 <0.001 85.1 91.8 Adjunctive procedure use  Used  Not used 0.71 (0.38-1.04) 1.18 (1.02-1.33) <0.001 <0.001 32.1 75.1 1.06 (0.43-1.70) 1.65 (1.39-1.90) 0.001 <0.001 81.3 91.0 I2: measure of heterogeneity. P-value: probability of post-treatment change. Open in new tab Table 3. Summary of standardized mean difference (SMD) and unstandardized mean difference (UMD) of post-treatment irregularity changes in different clinical comparisons. CI: confidence interval Comparison SMD of irregularity change (95% CI) P-value I2 (%) MD of irregularity change (mm) (95% CI) P-value I2 (%) Overall 1.09 (0.95-1.23) <0.001 74.7 1.63 (1.39-1.86) <0.001 91.1 Treatment approach  Extraction  Non-extraction 1.22 (1.04-1.40) 0.85 (0.63-1.07) <0.001 <0.001 75.2 70.1 1.74 (1.46-2.02) 1.40 (0.96-1.85) <0.001 <0.001 90.2 92.9 Follow-up duration  1–10 y  10–20 y 0.89 (0.73-1.05) 1.39 (1.18-1.60) <0.001 <0.001 65.1 71.8 1.22 (1.01-1.44) 2.25 (1.91-2.60) <0.001 <0.001 81.2 89.9 Study design  Interventional  Observational 1.90 (1.13-2.67) 1.05 (0.91-1.19) <0.001 <0.001 74.7 74.1 2.16 (1.25-3.07) 1.60 (1.35-1.84) <0.001 <0.001 71.7 91.5 Retention methods  Fixed  Removable 1.04 (0.82-1.27) 1.15 (0.82-1.48) <0.001 <0.001 76.3 71.0 1.42 (1.06-1.79) 1.48 (0.96-1.99) <0.001 <0.001 91.0 88.2 Clinical setting  Private  Academic 0.94 (0.69-1.17) 1.08 (0.89-1.27) <0.001 <0.001 70.2 65.7 1.21 (0.87-1.55) 1.81 (1.43-2.20) <0.001 <0.001 85.1 91.8 Adjunctive procedure use  Used  Not used 0.71 (0.38-1.04) 1.18 (1.02-1.33) <0.001 <0.001 32.1 75.1 1.06 (0.43-1.70) 1.65 (1.39-1.90) 0.001 <0.001 81.3 91.0 Comparison SMD of irregularity change (95% CI) P-value I2 (%) MD of irregularity change (mm) (95% CI) P-value I2 (%) Overall 1.09 (0.95-1.23) <0.001 74.7 1.63 (1.39-1.86) <0.001 91.1 Treatment approach  Extraction  Non-extraction 1.22 (1.04-1.40) 0.85 (0.63-1.07) <0.001 <0.001 75.2 70.1 1.74 (1.46-2.02) 1.40 (0.96-1.85) <0.001 <0.001 90.2 92.9 Follow-up duration  1–10 y  10–20 y 0.89 (0.73-1.05) 1.39 (1.18-1.60) <0.001 <0.001 65.1 71.8 1.22 (1.01-1.44) 2.25 (1.91-2.60) <0.001 <0.001 81.2 89.9 Study design  Interventional  Observational 1.90 (1.13-2.67) 1.05 (0.91-1.19) <0.001 <0.001 74.7 74.1 2.16 (1.25-3.07) 1.60 (1.35-1.84) <0.001 <0.001 71.7 91.5 Retention methods  Fixed  Removable 1.04 (0.82-1.27) 1.15 (0.82-1.48) <0.001 <0.001 76.3 71.0 1.42 (1.06-1.79) 1.48 (0.96-1.99) <0.001 <0.001 91.0 88.2 Clinical setting  Private  Academic 0.94 (0.69-1.17) 1.08 (0.89-1.27) <0.001 <0.001 70.2 65.7 1.21 (0.87-1.55) 1.81 (1.43-2.20) <0.001 <0.001 85.1 91.8 Adjunctive procedure use  Used  Not used 0.71 (0.38-1.04) 1.18 (1.02-1.33) <0.001 <0.001 32.1 75.1 1.06 (0.43-1.70) 1.65 (1.39-1.90) 0.001 <0.001 81.3 91.0 I2: measure of heterogeneity. P-value: probability of post-treatment change. Open in new tab Importantly, post-treatment changes of mandibular irregularity are less than commonly thought. The average overall post-treatment irregularity change in this meta-analysis was 1.63 mm. On the basis of the estimated confidence interval (95% CI, 1.39–1.86 mm), average irregularity changes greater than 2 mm are unlikely to occur. Approximately 93% of the studies in this review reported changes less than 3 mm. The difference in the amount of irregularity reported in this study and previous studies might be related to statistical power. This meta-analysis was based on 1859 patients, whereas previous reports typically used small samples, which can bias estimates of variation. Large sample size enhances statistical power, limits the influence of outliers, and provides a more representative estimate of the target population. In addition, this meta-analysis used post-treatment changes (T2-T1) in irregularity rather than post-retention (T2) irregularity, which often includes irregularities that remain after treatment. Assuming little or no post-treatment irregularity, the changes estimated are not clinically significant, being less than the 3.5 mm suggested as minimally acceptable (43). The limited irregularity changes that occur post-treatment are probably not treatment-related because similar changes have been previously reported for untreated individuals (28, 58, 59). In this review the average age at the end of treatment (T1) was 15.8 years, and the average age at follow-up (T2) was 27 years. Crowding of untreated individuals has been shown to increase maximally during the teen years, with rates decreasing thereafter through the twenties (58). The average irregularity change reported in this review is slightly less than changes reported over comparable time periods for untreated individuals (28, 59), suggesting greater stability in orthodontic patients than in untreated individuals. Orthodontic patients might be expected to be more stable because they were treated and retained throughout the critical growth ages, when the greatest irregularity changes normally occur. Mandibular anterior teeth exhibit greater post-treatment irregularity in patients whose premolars were extracted than in patients whose premolars were not extracted. The long-term changes in irregularity were 1.74 mm (95% CI, 1.46–2.02) after extraction treatments and 1.40 mm (95% CI, 0.96–1.85) after non-extraction treatments (Table 3). Primary studies comparing extraction and non-extraction treatments have also reported greater post-treatment malalignment after extraction than non-extraction treatments, with differences ranging from 0.2 to 0.8 mm (6, 19, 50, 60). Higher dental crowding has been reported in individuals with narrower arches (61, 62), suggesting that the difference between two treatments approaches might be related to the shape of dental arch rather than the type of treatment. The difference could also be related to the major tooth movements that are usually required during extraction treatment. Regardless, differences in long-term irregularity changes between the extraction and non-extraction treatment were small, 0.34 mm, and clinically negligible. The longer the post-treatment follow-up, the greater the irregularity, with most of the irregularity changes occurring during the earlier years. The irregularity index was 1.22 mm for studies reporting up to 10-year follow-up and 2.25 mm for studies reporting up to 20-year follow-up (Table 3). A similar pattern of change has been reported for patients evaluated longitudinally after orthodontic treatment (39, 63). Untreated individuals also exhibit the same pattern (64, 65). These findings support the notion that the factors that cause irregularity, especially growth and the anterior component of force, have a major impact on mandibular alignment after orthodontic treatment. This emphasizes how important it is for orthodontic patients and clinicians to understand these effects and to maintain their retention protocol indefinitely. Informing the patients of possible minor irregularity changes after retention should help motivate them to use their retainers long term and increase their awareness of possible corrections later. Even though the study design showed a significant effect, the design itself probably plays no role in explaining the difference. In this study there were two main designs, with greater irregularities in the interventional than observational studies (Table 3). The greater irregularity changes identified in the interventional study was probably related to the use of positioners, which required patient compliance (66). Whether the patients are given fixed or removable retainers has no effect on post-treatment alignment changes that occur. In this study, the irregularity changes were 1.42 mm with fixed and 1.48 mm with removable retention. Currently, there is no consensus among orthodontists concerning the best retention protocol to use. Retention depends on multiple factors, including the type of malocclusion, periodontal status of patients, amount of subsequent growth, patient compliance, and patient preference (67). Several types of retainers were included in each category, which makes the comparison less accurate. In addition, compliance with removable retainers use, operators’ skills, and failure rates with fixed retainers could have increased the variation and made differences difficult to detect. The amount of pre-treatment irregularity was also unrelated to the long-term changes in alignment that occurred. The meta-regression showed that amount of pre-treatment irregularity explained an insignificant 4% of the variability in the long-term irregularity changes that occur. This agrees with previous studies that found no association between pre-treatment irregularity and long-term irregularity changes of mandibular anterior teeth (43, 45). No relation between the pre-treatment irregularity and post-retention malalignment should be expected. The teeth do not have any preordained positions to which they return if properly treated and retained. Although no significant effect was shown in this study, the ability of adjunctive procedures (i.e. the use of supra-crestal fiberotomy, inter-proximal enamel reduction, or both) performed at the end of orthodontic treatment or retention to enhance long-term mandibular alignment cannot be ruled out. In this review, the irregularity changed 1.06 mm for the studies using adjunctive procedures and 1.65 mm for those not using adjunctive procedures (Table 3). The lack of significant difference could have been due to insufficient power, as only a small number of studies used adjunctive procedures. Similar amounts of irregularity change have been reported for patients who had IPR during treatment and evaluated up to 9 years out of retention (68). The difference in irregularity is probably related to the broader contacts that could prevent mandibular incisors contact slippage (69). The clinical setting of orthodontic treatment probably does not affect post-treatment alignment changes (Table 3). The 0.6 mm difference in irregularity change reported in this study might be related to follow-up durations, with almost 50% of the university studies reporting individuals followed 10–20 years, compared to only 12% of private practice studies. As shown in this study, follow-up duration has a significant effect on post-treatment alignment changes. Although no previous study has evaluated long-term alignment changes in different clinical settings, it has been shown that both produce similar quality of treatment outcome (70–72). Clinical setting might affect the duration of treatment, but it plays a limited or no role in long-term mandibular alignment. Finally, mandibular alignment changes following lower incisors extraction have been evaluated in two studies (21, 49). An exploratory meta-analysis showed that irregularity change was limited, with irregularity increasing 0.74 mm (95% CI, −0.05 to 1.52) (Supplementary Figure 2). Importantly, irregularity changes were based on changes of four rather than five contacts. Strengths and limitations This review was able to identify a large number of studies that were systematically reviewed and investigated. It is the first review of long-term mandibular alignment changes. The major limitation of this review pertains to the quality of evidence provided by the studies. The majority of studies were longitudinal and retrospective, which are known to have inherited design issues, and prone to high risk of bias. Because the quality of evidence in this review was low to moderate, the findings should be interpreted carefully. Higher quality studies of mandibular alignment changes after orthodontic treatment are needed to substantiate these finding. The lack of high-quality evidence is probably related to the nature of the phenomenon being investigated. Long-term alignment of mandibular anterior teeth could be affected by multiple factors and designing prospective studies requires time and resources that many might consider impractical. Another limitation of this review is the lack of protocol registration. There was a significant risk of publication bias (Supplementary Figure 1). It is likely that only studies with larger sample size and significant findings were published. There might be unpublished studies that could have affected the irregularity estimates reported in this review. In addition, it is crucial to understand that there are various clinical factors (e.g. arch width manipulation, amount of incisors proclination, the number and experience of treated practitioners and outcome assessors, and possibly the treatment philosophy) that could have affected post-treatment irregularity change, but were not feasible to assess in this article because they are not commonly reported. Therefore, the findings of this review should be interpreted cautiously, and the importance of semi-permanent or permanent retention should not be neglected. This is especially important for patients completing their orthodontic treatment during the critical growth ages (late teens). Conclusions On the basis of 30 studies involving 1859 patients, the following conclusions relating to post-treatment mandibular alignment changes can be drawn: there are only limited amounts of irregularity change after orthodontic treatment. It increases only 1.6 mm, over an average of 9.3 post-treatment years. There is a statistically significant difference in post-treatment irregularity changes between mandibular premolars extraction and non-extraction treatments. There are greater irregularity changes in orthodontic patients who are followed up for longer periods of time. Meta-regression analysis showed that pre-treatment irregularity, the clinical setting, the type of retention, and adjunctive procedures have no significant effects on post-treatment irregularity changes. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest None declared. Acknowledgements We are very grateful for the help of Professor Gilbert Ramirez, from Texas A&M University, Public Health School, in demonstrating the use of Stata® 14.2 software in meta-analysis. 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TI - Mandibular alignment changes after full-fixed orthodontic treatment: a systematic review and meta-analysis
JO - The European Journal of Orthodontics
DO - 10.1093/ejo/cjz004
DA - 2019-11-15
UR - https://www.deepdyve.com/lp/oxford-university-press/mandibular-alignment-changes-after-full-fixed-orthodontic-treatment-a-uk0fh07Gwm
SP - 609
VL - 41
IS - 6
DP - DeepDyve
ER -