Protocol and Registration

The study protocol was registered on PROSPERO (CRD42020189139). For reporting, this systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.¹²

Eligibility Criteria

A PICOS acronym was established as an inclusion criterion:

• Population (P): children and adolescents in the mixed or early permanent dentition.

• Interventions (I): orthodontic treatment with appliances that maintained or increased the perimeters of the mandibular dental arch prior to M2 eruption: lingual arch, lip bumper, Schwarz appliances, Arnold appliances, or others appliances described by authors.

• Comparison (C): individuals who were not subjected to orthodontic treatment or available data from individuals treated prior to arch perimeter management.

• Outcomes (O): primary: prevalence and odds of M2 eruption disturbances; secondary: identified possible predictive risk factors.

• Study-design (S): randomized clinical trial (RCT) or non-RCT.

The exclusion criteria were: case reports, editorials, animal and in vitro studies, descriptions of clinical techniques, studies with orthodontic/orthopedic approaches performed concomitantly, treatment with mandibular tooth extractions or any other surgical procedure, and studies evaluating individuals with craniofacial deformities/syndromes or cleft lip/palates.

Information Sources and Search Strategy

An electronic search was conducted in MedLine (via PubMed), Web of Science, Cochrane Library, Scopus, Embase, and Lilacs up to June 22, 2020. Google Scholar (first 200 references) was investigated to partially access the gray literature. Detailed search strategies were developed appropriately for each database (Appendix). To check the possibility of unpublished and ongoing studies, the Clinical Trials-US National Institutes of Health (http://www.clinicaltrials.gov) was consulted. Additionally, manual searches in the reference lists of the articles included were also carried out. No restrictions on language, year, or status of publication for inclusion were applied.

Study Selection

Two authors (LGS and KA) independently and in duplicate screened the titles/abstracts of the reference lists. The full text of those references that met the eligibility criteria or with insufficient information in the title/abstract for a decision on inclusion or exclusion was retrieved. The same authors assessed independently the full text, and those studies that met the eligibility criteria were included. In both phases, any disagreements were resolved by consensus.

Data Extraction and Items Extracted

The data were collected with a standardized table. The following data were extracted: authors, year of publication, study design, characteristics of participants, description of groups, description of intervention (appliance use, treatment duration/time of records uptake), and outcomes. Data were compared for accuracy, and any discrepancy was resolved through reexamination of the original study.

Assessment of Bias Risk Within Studies

The revised Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used to assess the risk of bias in non-RCTs.¹³ The bias due to confounding factors, selecting participants for the study, classifying the interventions, deviations from the intended intervention, missing data, measuring outcomes, and selective reported results were graded after answering the signaling questions following the recommendations of the Cochrane Handbook 6.0 (https://training.cochrane.org/handbook).¹⁴ The risk of overall bias for the non-RCT was judged as low, moderate, serious, critical, or no information.

If RCTs were included, the use of the revised Cochrane Collaborations-2 tool to assess the risk of bias was planned.

Summary Measurements and Synthesis of Results

Measurements were based on continuous (units) or dichotomous data from clinical indices, radiographs, or cone beam computed tomography. A meta-analysis was carried out with studies that reported comparable outcomes. When reported by the studies in percentage, the occurrence of events was converted into units to be grouped in the meta-analysis.

Data were analyzed with RevMan 5.4 software (Cochrane, London, UK). The effect measure odds ratio (OR) and the corresponding 95% confidence intervals (CI) were calculated for the occurrence of M2 eruption disturbances. A random effect was applied due to variations in terms of the implementation of interventions, design, and conduct of studies. Heterogeneity was assessed using the I² test, with guide for interpretation as follows: 0 to 30%, not important; 31%–50%, moderate; 51%–80%, substantial; 81%–100%, considerable.¹⁴ Sensitivity analysis was performed based on results of subgroup analysis comparing passive appliances (that maintain the arch perimeter) and active appliances (that maintain or increase the arch perimeter). The outcomes that were not included in the meta-analysis were discussed qualitatively.

Evaluation of the Level Evidence

The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool.¹⁵ The certainty of evidence level was generated using online software (GRADEpro, available online at gradepro.org) based on assessment of the study design, risk of bias, inconsistency, indirectness, and other considerations (such as publication bias). Based on this assessment, the certainty of the evaluation of the outcome could be very low, low, moderate, or high quality.

If a sufficient number (n > 10) of trials were included, it was planned to assess the publication bias visually through the level of funnel plot asymmetry.

Study Selection

The search strategy yielded a total of 877 studies (Figure 1). After the removal of duplicates and screening the tittle/abstract, 22 references were obtained for the full-text evaluation. Among them, 17 were excluded and the reasons are provided in Table 1. Finally, five studies^{5,10,11,16,17} met the eligibility criteria and were included in this systematic review.

View Figure

• Download as Powerpoint
• Download Figure

Table 1. List of Excluded Studies With Reasons After Full-Text Evaluation

View Fullscreen

Study Characteristics

Table 2 provides the descriptive characteristics of the studies included. All of them were non-RCT, three^5,11,16 were retrospective, and two studies^10,17 were prospective studies, of which three^5,10,11 were clinically controlled. Sample sizes ranged from 67¹⁶ to 260⁵ individuals per study group, and the mean age of participants at baseline ranged from 8^10,11 to 11¹⁷ years.

Table 2. Summary of Study Characteristics and Results of the Included Studies^a–d

View Fullscreen

Regarding the type of orthodontic appliance, two studies^5,16 used a lip bumper appliance, and another two studies^11,17 used a passive mandibular lingual arch. One study¹⁰ compared groups of individuals treated with a Schwarz appliance, individuals treated with a mandibular lingual arch, and individuals treated with a combination of both appliances. The mean time interval between onset and the end of the therapy varied substantially from 10 months¹⁶ to 4.6 years.¹⁰

Concerning the measures used to verify the M2 eruption disturbances, in two studies^10,11 the diagnosis of impaction¹¹ and eruption difficulties¹⁰ was defined when the root of the M2 was formed by at least 75% but the tooth remained unerupted. In one study⁵ it was necessary for the apices of the M2 to be closed for the diagnosis of impaction or ectopic eruption. In two studies,^16,17 a clinical evaluation of the M2 impaction was based on whether there was eruption into full occlusal contact and whether the mesial cusps were confirmed radiographically to be below the height of the distal surface of the first molar.¹⁷

Risk of Bias Within Studies

The methodological appraisal of the studies included and the reasons for the judgments are reported in Table 3. Overall, one study¹⁰ was classified as having a moderate risk of bias, while four studies^5,11,16,17 were graded as having a serious risk of bias. The items affected by methodological flaws were the domains “confounding,” “classifying the interventions,” and “measuring outcomes.”

Table 3. Evaluation of Risk of Bias of the Included Studies Using ROBINS-I^a–i

View Fullscreen

Data Synthesis

Primary Outcome.

The studies included reported a higher prevalence of M2 eruption disturbances in children and adolescents undergoing arch perimeter management therapy, with a mean frequency ranging from 7%⁵ to 14.7%,¹⁰ while untreated subjects showed a mean frequency of M2 eruption disorders of about 1.5%.

A meta-analysis was carried out regarding the odds ratio of occurrence of M2 eruption disorders (Figure 2). The I² test showed non-significant heterogeneity among the studies. The results showed, with statistical significance, that children and adolescents treated with appliances that maintained or increased mandibular arch perimeter in the mixed dentition were at a greater chance of the occurrence of M2 eruption disorders by 7.57 times compared to untreated individuals (OR: 7.57, 95% CI: 3.72–15.41, I² = 0%, P < .001). Possibility of heterogeneity was explored with subgroup analysis based on the appliance design (Figure 3). The meta-analysis showed that the use of active appliances (that is, those that increased the arch perimeter), such as the lip bumper and Schwarz appliance, lead to greater odds of the occurrence of difficulties in M2 eruption (OR: 10.32, 95% CI: 4.09–26.01, I² = 0%, P < .001) than passive arch perimeter maintainers such as the mandibular lingual arch (OR: 5.24, 95% CI: 1.94–14.16, I² = 0%, P = .001).

View Figure

• Download as Powerpoint
• Download Figure

View Figure

• Download as Powerpoint
• Download Figure

Secondary Outcome

Regarding the investigation of predictive risk factors for eruption difficulties, an initial mesioangulation of M2 in relation to the first molar was a determining factor for the risk of impaction in two studies using passive lingual arch¹⁷ arch and lip bumper⁵ (mesial inclination greater than 24° and 30°, respectively). However, one study¹⁰ found no statistically significant association for this variable. In one study,⁵ treatment time greater than 2 years increased the risk of ectopic eruptions by 2.6 times in individuals treated with a lip bumper. Likewise, another study¹⁰ reported that patients with M2 eruption difficulties wore the appliance, on average, 4 months longer than patients with normal eruption (P < .001); however, it is important to note that the authors did not analyze the effects of this outcome separately according to the type of appliance.

The initial variables of age at onset of treatment,^5,10,11,17 gender,^5,10,17 first molar/M2 spacing,¹⁷ retromolar space,¹⁰ crowding in mm,⁵ and third molar presence¹⁷ were not significant predictors of disturbances in the eruption of M2.

Certainty Levels and Strength of the Evidence

The certainty of evidence for the outcome prevalence of M2 eruption disorders and the odds that arch perimeter maintainers lead to eruption disorders was classified as low level. Reasons for judgment and downgrading the evidence are detailed in Table 4. The risk of bias, inconsistency, indirectness, and imprecision were the main items that affected the quality of the evidence.

Table 4. GRADE Evidence Profile^a–f

View Fullscreen

Summary of Evidence

Although widely used in orthodontic practice for its immediate effectiveness in relieving crowding in the transition from the mixed to permanent dentition,^2,3 the results of this review and meta-analysis were consistent in reporting that preserving/increasing the mandibular arch perimeter by controlling the E-space increased the prevalence and lead to a greater chance of M2 eruption disorders compared to the untreated population. Lack of space is one of the main hypothesized causes to explain eruption difficulties of the M2. In this sense, late mesial migration of the first molars into the E-space during normal growth was associated with a decrease in the anterior length of the mandibular arch by approximately 4 mm¹ and, consequently, with an increase in retromolar space.⁷ Therefore, appliances that act passively to prevent the migration of the first molar or that also act by distal tipping or translation of the first molar³ could reduce the retromolar space and increase the chance of adverse effects in M2 eruption.

However, it is important to note that the evidence for the association of lack of retromolar space as a predictive factor leading to the occurrence of M2 eruption disorders after arch perimeter therapy is weak. Only one study¹⁰ evaluated this variable and the survey method was used using two-dimensional images; however, the molars and the mandibular ramus are not situated in the same transverse plane. The other variable investigated related to space ratio, spacing of the M2 in relation to the first molar, was also not associated with impaction.¹⁷

Several other variables were also investigated by the studies included to provide predictive factors for M2 eruption disturbances. Pretreatment intermolar angulation (M2 mesioangulation > 24°) and treatment time (>2 years) were considered the main issues. As the initial mesioangulation suggests the M2 eruption pathway angled toward the surface of the first molar, the assessment of the prior M2/first molar angulation and the follow-up of the eruption pathway are important and should be included in the planning of any orthodontic treatment as supplementary information for making a clinical decision about the use of these appliances. In addition, a concern was the possible increase in the intermolar angle due to distal tipping of the first molar caused by these appliances.^4,16 Previous studies suggested that active appliances, such as the lip bumper, could lead to the first molar tipping distally by approximately 6°–8°³ while, with a passive lingual arch, this value was 0.5°.¹⁸ In this sense, the subgroup analysis confirmed increased odds of M2 eruption disorders in individuals treated with active appliances. However, even with first molar distal tipping, the risk of eruption disorders appeared to be minimal when the initial M2 mesiangulation was less than 10°. In cases where the intermolar angulation is a concern, the use of passive appliances seems to be the most suitable.

There may be a perception that early perimeter management results in more effective relief of crowding. However, longer treatments should be discouraged as they have been shown to increase M2 eruption disturbances.^5,10 In cases where there was no premature loss of deciduous teeth, the ideal time for placing the appliance in the mandibular arch seems to be just before the loss of the deciduous second molars.^1–3

Implications for Practice

Clinicians should carefully evaluate the cases in which arch perimeter management therapy will be used, considering, in addition to relieving the current space problem, the possibility of adverse effects in the medium to long term. Specifically, they should consider how treatment might affect eruption of the M2. Measurement of the intermolar angle must be performed during the diagnostic process for making appropriate clinical decisions regarding the use of this therapy. Mesioangular eruption of the M2 is often related to genetic issues of dentition development. Thus, prior identification of hereditary problems for the development of malocclusions can lead to more effective treatment strategies.¹⁹ In addition, the optimal duration for wear of the appliance and timely removal are equally important.

Often, the absence of painful symptoms and the posterior location within the dental arch make it difficult for parents to identify the absence of a posterior tooth compared to an anterior tooth. Thus, due to the significant increase in the chance of the occurrence of M2 eruption disorders subsequent to arch perimeter management therapy in the mixed dentition, it is essential that clinicians follow these patients even in cases where other treatment will not be necessary. An early diagnosis of M2 eruption disturbances results in a better outcome, regardless of the method of treatment used.²⁰

In cases where there is no monitoring of the M2 eruption process,²⁰ approaches involving orthodontic uprighting, surgical exposure or replacement, transplantation, or tooth extractions may be necessary.^21–23 In these cases, the early therapy with arch perimeter management that aimed to reduce the complexity of future treatment with fixed appliances may, in fact, result in the requirement for additional orthodontic intervention. This would ultimately decrease treatment efficiency and effectiveness.²⁰ Likewise, the initial option for a non-extraction orthodontic treatment may not always be a final non-extraction approach.

Strengths, Limitations, and Future Directions

Possible selection bias was avoided by extensive searches in several electronic databases and by access to partial gray literature without language restrictions or publication status. Other sources of gray literature, such as OpenGrey and Proquest, were not accessed for this review. Additionally, the risks of non-inclusion of unpublished trials were partially overcome by checking on a trial registration platform.

For rare outcomes such as M2 eruption disorders, meta-analysis may be the best way to obtain reliable evidence of the effects of healthcare interventions. Individual studies are usually underpowered to detect differences in rare outcomes. Therefore, a meta-analysis may have adequate power to investigate whether interventions do have an impact on the incidence of a rare event.¹⁴ Although the mathematical synthesis did not demonstrate heterogeneity between studies, there are concerns about the weak estimate of I² when there are a small number of studies.²⁴ Therefore, the implementation of a random-effects model seemed more appropriate in this meta-analysis, as this model addressed the inherent diversity of the retrospective studies that used different appliance designs.^24,25

The lack of RCTs was a weakness that affected the certainty of the evidence on the outcomes assessed. Even in observational studies, future trials should be performed/reported according to guidelines such as STROBE (Strengthening the Reporting of Observational Studies in Epidemiology)²⁶ to increase evidence-based practice information about this topic. Finally, other outcomes, such as the identification of negative predictive factors, should be included in trials in addition to frequency and the risk of M2 eruption disorders. These factors are possibly more relevant and can be determinant for the successful management of arch perimeter in the mixed dentition.