Interceptive treatment with Invisalign® First in moderate and severe cases: a case series

Citation: Pinho, T.; Rocha, D.; Ribeiro, S.; Monteiro, F.; Pascoal, S.; Azevedo, R. Interceptive Treatment with Invisalign®First in Moderate and Severe Cases: A Case Series. Children 2022,9, 1176. https:// doi.org/10.3390/children9081176 Academic Editors: Silvia Caruso, Chiarella Sforza and Roberto Gatto Received: 17 June 2022 Accepted: 2 August 2022 Published: 5 August 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). children Article Interceptive Treatment with Invisalign®First in Moderate and Severe Cases: A Case Series Teresa Pinho 1,2,* , Duarte Rocha 1, Sofia Ribeiro 1, Francisca Monteiro 3,4,5 , Selma Pascoal 1and Rui Azevedo 1,6 1UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), 4585-116 Gandra, Portugal 2IBMC—Instituto Biologia Molecular e Celular, i3S—Instituto de Inovação e Investigação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal 3Center for MicroElectroMechanical Systems (CMEMS), University of Minho, 4800-058 Guimarães, Portugal 4ICVS/3B’s—PT Government Associate Laboratory, University of Minho, 4710-057 Braga, Portugal 5LABBELS—Associate Laboratory, University of Minho, 4800-058 Guimarães, Portugal 6 TOXRUN-Toxicology Research Unit, University Institute of Health Sciences, Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), 4585-116 Gandra, Portugal *Correspondence: ter[email protected] Abstract: The increasing demand for more aesthetic/comfortable orthodontic alternatives fostered the utilization of clear aligners in recent years. However, the efficacy of clear aligners for treating complex malocclusions is often treated with scepticism. This case series aims to evaluate the predictability of the Invisalign ® First system in moderate and severe cases requiring interceptive orthodontic treatments in mixed dentition. A total of 23 patients with 102 interceptive orthodontic malocclusion traits were selected for orthodontic treatment with Invisalign ® First and were examined over 18 months (Phase 1). Clinical assessments included ClinCheck ® predictions, cephalometric measurements, and measuring tools commonly used to quantify tooth movement. Measurements taken at the beginning and end of the treatment were compared. The complexity degree of each case was established based on the set of problems presented by each patient. All treatment objectives were achieved within 18 months, except for two Class II cases, with 69% of them solved with the first set of aligners. Additional aligners were used in the remaining cases. Even though these 23 cases suggest that the Invisalign ® First (Phase 1) may be effective in most interceptive problems, controlled randomized clinical trials are required to evaluate movement predictability and how this relates to the problem complexity and additional aligners required. Keywords: clear aligners; early diagnosis and treatment; interceptive orthodontic treatment; Invisalign®First 1. Introduction Interceptive orthodontic problems include functional oral complications, pathologies, and/or malocclusion traits that usually occur in mixed dentition, at an early age and before growth is complete, and that can evolve into serious and complicated orofacial malocclusion traits in adulthood if not treated in time. Early diagnosis is essential for preventing future extensive orthodontic treatment. Interceptive orthodontic interventions in early mixed dentitions have a common objective of allowing a more favorable functional growth of the jaws and the consequent development of a satisfactory occlusion [ 1 ]. For such treatments, the most common malocclusion traits to intercept are arch constriction, molar rotation, and crowding, which are commonly associated with a posterior crossbite, impacted teeth, and a loss of space for permanent dentition. Additionally, molar sagittal Class II or III and open bite are important to intercept to avoid the progression of skeletal malocclusion traits that may require future surgical intervention [ 2 , 3 ]. Furthermore, the early treatment of midline deviation prevents the development of skeletal and/or dental asymmetries [4–6]. Children 2022,9, 1176. https://doi.org/10.3390/children9081176 https://www.mdpi.com/journal/children Children 2022,9, 1176 2 of 19 Invisalign ® First systems, implemented in 2018 by Align Technology ® , allow an interceptive treatment of 18 months (Phase 1) and the inclusion of an unlimited number of additional aligners planned by the ClinCheck ® software (ClinCheck Pro version 1.10 Align Technolgy Inc. San José, CA, USA). This involves using digital set-ups that allow the pediatric orthodontist to virtually plan each tooth’s movement in 3D [ 7 , 8 ]. Importantly, after ending Phase 1, the orthodontic treatment can be re-activated with a new treatment (Phase 2) with a duration of three years maximum. This could occur within ten years since Phase 1 ends if the malocclusion trait was not resolved or in case of a recurrence. In the present study, the movement predictability was only assessed for Invisalign First during Phase 1. As with any other technology, the number of Invisalign ® aligners prescribed depends on several factors, such as dental malposition type, location, and complexity [ 7 ], and sometimes the way the case evolves is unpredictable by itself independent of the approach. Currently, there is sparse scientific knowledge and research about the predictability and effectiveness of Invisalign ® systems as corrective treatments in later mixed or adult dentition [ 9 – 12 ]. To the best of our knowledge, there is only one study evaluating the efficacy of dentoalveolar expansion movement with Invisalign ® First technology in mixed dentition [ 13 ]. Hence, there are no proven data about the predictability and effectiveness of interceptive treatments requiring other types of problems/movements. Therefore, this case series intends to compare and retrospectively evaluate the predictability and effectiveness of the Invisalign ® First system in orthodontic treatments in children with early mixed dentition. In addition, the system effectiveness was analyzed as a function of the malocclusion traits and complexity degree. The guardians and children filled out short questionnaires to ascertain if the treatment met their expectations in different domains. 2. Materials and Methods 2.1. Case Series This study comprised a sample of 23 Caucasian children (13 female and 10 male) having 102 interceptive malocclusion traits. The children were recruited in two independent clinics of orthodontics—Clínica Médico Dentária de São João da Madeira and Clínica de Medicina Dentária Dr. Manuel Neves—from October 2018 to October 2019. All patients were treated with Invisalign ® First for 18 months (Phase 1) by an Invisalign ® Diamond provider and double specialist in Orthodontics and Odontopediatrics (TP). Patients were selected according to the following inclusion criteria: individuals with early mixed dentition treated with Invisalign ® First who underwent treatment in both arches; children who completed an initial and final intraoral digital scan; and cases requiring at least one movement with intermediate to high complexity based on an adaptation of the Align ® protocol, the Invisalign ® evaluation tool. Children with previous/concomitant orthodontic treatments and having craniofacial malformations (including cleft lip or palate), history of dental trauma, oral neoformations, or other oral cavity pathologies were excluded. 2.2. Ethical Considerations The study was accepted by the Ethics Committee of the University Institute of Health Sciences (reference 11/CE-IUCS/2020). 2.3. Orthodontic Intervention The children were instructed to use each aligner for as many hours as possible ( 20–22 h/day ) and to only remove them to eat and during oral hygiene practices. Each aligner is designed to produce a 0.25-mm translation and 1 ◦ of rotation movement for standard forces (Align 2022) [ 14 ]. The aligners were changed every seven days at the beginning of the treatments, as recommended by Align ® protocols. In more complex cases with more sequenced movements and more than 50 aligners on the first set, the change was Children 2022,9, 1176 3 of 19 performed twice a week (only if the patient revealed compliance and if the aligners were adjusted). The control consultations were carried out every four weeks (shorter intervals compared with the same treatment in adults). Elastics were used as auxiliaries from the beginning of the treatment in moderate and complex cases of posterior crossbite, as well as in complex Class II or Class III relations. However, in Class II division 2 situations, these were only used when an overjet was created. Additional aligners were only required at the final stage of this study period (just closing of Phase 1) to conclude the active phase in specific cases (e.g., when the objectives were not achieved yet, to perform overcorrections, or to work as a retention method). Additional aligners were only used during sleep. 2.4. Clinical Assessment The interceptive orthodontic malocclusion traits described here were classified as predictable, intermediate, or difficult corrections based on the Align ® recommendations adapted for children’s growth (see the classification criteria described in Table 1). Table 1. Reference values for the classification of the malocclusion traits into predictable, intermediate, or difficult corrections based on Align ® recommendations, with the respective alterations described below. Malocclusion Traits /Required Movements Type of Measurement Predictability with Aligners Predictable (1) Intermediate (2) Difficult (3) Molar derotation (teeth 16 & 26) Initially planned by ClinCheck®15–30◦>30–40◦>40◦ Dentoalveolar Expansion (teeth 16–26) Difference between the initially ClinCheck® planned and experimentally measured & visual interpretation of the initial intraoral photographs 3–4 mm and Negative molar torque >4–6 mm and Negative molar torque >6 mm or >4 mm and Positive molar torque and Skeletal compression Space to recover (teeth 12, 22, 32, 42, 15, 25, 33, & 43) Difference between the initially planned by ClinCheck®and experimentally measured 2–4 mm >4–6 mm >6 mm Molar sagittal malocclusion Visual interpretation of the initial intraoral photographs and ANB Class II (incomplete or complete due to functional deviation or molar ectopic eruption) Tendency for Class III Class II (complete) or Class III Posterior crossbite Visual interpretation of the initial intraoral photographs Crossbite only on deciduous teeth Crossbite in deciduous/ permanent teeth and Negative molar torque Crossbite in permanent teeth and Positive molar torque and Skeletal compression Open bite Initially planned by ClinCheck®and FMA Posterior intrusion: <0.5 mm and/or Anterior extrusion: <2.5 mm Posterior intrusion: >0.5–1 mm and/or Anterior extrusion: >2.5–3.5 mm Posterior intrusion: >1 mm and/or Anterior extrusion: >3.5 mm Midline discrepancy Initially experimentally measured mm >2 and <3 mm ≥3 mm Crowding Required space initially experimentally measured and required incisor rotation planned by ClinCheck® 3–6 m >6–8 mm or Lateral incisors: 30–40◦or Central incisors 40–50◦ >8 mm or Lateral incisors: >40◦or Central incisors: >50◦ The tool made available by Invisalign ® to classify the cases (i.e., the Invisalign ® evaluation tool) resulted in the same classification obtained in our study. Please note that according to the Invisalign ® criteria, a patient only needs one complex problem to be Children 2022,9, 1176 4 of 19 classified as complex/severe. Because we are dealing with children in mixed dentition, with temporary teeth and whose craniofacial structure will grow and change over time, we believe this is not the best methodology for the classification of our cases of global complexity. Given this, we have considered a combination of factors that together can represent a more realistic classification. This classification was performed based on an adaptation of the Align ® protocol [ 14 ] to consider the potential growth of the children over time. The alterations to the Align classification protocol are described after each malocclusion trait. The following criteria were defined for each interceptive problem: 1. Molar derotation—MDR: This was analyzed using the movement values planned in the initial and final ClinCheck ® data. Only upper first molars were considered in order to uniformize the data. Predictable movements required 15 ◦ to 30 ◦ movements; intermediate malocclusions needed a derotation higher than 30 ◦ till 40 ◦ ; and malocclusion traits demanding more than 40 ◦ derotation were classified as difficult rectifications. Adaptation to the Align ® protocol: An additional margin of 10 ◦ was considered for each range since this movement is considerably easier in mixed dentitions since the second permanent molar has not erupted yet. 2. Dentoalveolar expansion—DAE: This problem was evaluated through the real values of the maxillary first molar transversal distances on the initial and final arch width table on the ClinCheck ® treatment plan. Here, simple tooth expansion (3–4 mm) and negative molar torque is a predictable movement. An expansion movement of > 4 to 6 mm with negative molar torque is considered to be an intermediate correction. Alternatively, difficult movements were considered to be expansions greater than 6 mm or greater than 4 mm, with the treatment having a skeletal component with positive molar torque (normally is associated with transversal skeletal problems). Adaptation to the Align ® protocol: Tooth torque was considered since the children are in a growing stage and the palatal suture is not closed yet. 3. Space recovery—SR: This classification resulted from mesiodistal width measurements and predictions of the space available for missing teeth using a millimetric scale and the initial and final ClinCheck ® scans. Adaptation to the Align ® protocol: This malocclusion trait is not present in the Invisalign ® evaluation tool, but it is important to consider particularly in this stage since permanent teeth are erupting. 4. Molar sagittal malocclusion—MSC II or III: Because cephalometry is bidimensional, having left and right structures superimposed, ClinCheck ® and clinical intraoral photographs images were prioritized. Clinically, according to the Angle classification, we have defined incomplete Class II (half premolar) and complete Class II associated with functional deviation or molar ectopic eruption as predictable movements. Class III tendency was classified as intermediate, whereas complete Class II (one premolar discrepancy) or Class III were considered to be difficult movements (confirmed by ANB cephalometric measures). Adaptation to the Align ® protocol: Align ® uses the mesialization/distalization quantification. Here, as we are dealing with growing patients in mixed dentition, it is more pertinent to evaluate the molar sagittal relation. 5. Posterior crossbite—PCB: PCB classification was done based on ClinCheck ® treatment plan images and intraoral photographs. Movements were classified as predictable when we have crossbite only on deciduous teeth. Intermediate movements were considered to be PCB presenting a dental component (i.e., negative torque) on the first permanent molar (as an end tooth position). Difficult movements were associated with PCB accompanied by positive torque on first permanent molar (as an end tooth position) and skeletal compression. Adaptation to the Align ® protocol: Align ® evaluates the complexity of the cases according to the number of teeth involved (if one, it is mild, if two, it is moderate, and if three or more, it is severe). Here, in addition to permanent teeth, patients also presented deciduous teeth with the first molar as an end tooth; therefore, these cases cannot be compared with (or classified as) adult dentition. As such, we have classified the cases differently if the tooth in crossbite is Children 2022,9, 1176 5 of 19 permanent or deciduous. We have also considered the necessity of torque movement, as described for dentoalveolar expansion. 6. Open bite—OP: OP was assessed based on the initial and final cephalometry, the ClinCheck ® images, and the presence of dental or skeletal components. The planned amount of posterior intrusion and/or anterior extrusion was also considered, as recommended by the Align ® protocol. Due to their skeletal components (confirmed by FMA cephalometric measures), all open bite pathologies were associated with difficult malocclusion traits/movements. Adaptation to the Align ® protocol: This malocclusion trait was assessed as recommended by Align ® , although we considered the presence of skeletal problems. 7. Midline discrepancy—MD: MD was assessed through the millimetric scale obtained from the ClinCheck ® treatment plan. The movement was considered predictable when 1 to 2 mm movement was required. Movements were classified as having intermediate complexity when more than 2 mm and less than 3 mm was prescribed, and teeth needing more than 3 mm movement were considered to be difficult malocclusions. Adaptation to the Align ® protocol: MD is not considered by Align ® . However, the existence of a MD requires an interceptive treatment in order to prevent serious future asymmetries and to understand the amount of space to recover due to the early loss of deciduous teeth. 8. Crowding—CR: This malocclusion was evaluated using the negative dentomaxillary discrepancy (DDM) for early mixed dentition: When the required movement ranged from 3 to 6 mm, the problem was considered to be predictable. When the required translation exceeded 6 mm to 8 mm, it was classified as an intermediate correction. If more than 8 mm of translation was required, the movement was considered to be a difficult rectification. In addition, the need for rotation was considered: Rotations greater than 30 through 40 ◦ on lateral incisors or greater than 40 through 50 ◦ on central incisors were considered to be intermediate CR, while rotations greater than 40 ◦ on lateral incisors or greater than 50 ◦ on central incisors were considered to be difficult corrections. Adaptation to the Align ® protocol: In the early mixed dentition, in addition to the ectopic eruption of the first molars, crowding in the anterior region is highly frequent. Due to this fact, we considered anterior permanent teeth rotation since this is one of the main problems to solve associated with crowding. Thus, it is also important to consider the required tooth rotation since the need for great rotation movements increases the complexity of crowding. Then, based on this qualitative classification, a score of 1, 2 or 3 was respectively assigned for predictable, intermediate or difficult movements, from which a quantitative global complexity classification was obtained for each case (i.e., for each child). The sum of the scores categorizes the cases into mild (scoring lower than 3), moderate (between 3 and 8), or severe (greater than 8) (see the global complexity scale calculation in Table 2, in the Results). For high scores on severe cases, fewer teeth were selected to be moved in each stage, with their movements more sequenced, in order to increase the predictability of the overall movements. The predictability of the Invisalign ® First was assessed by comparing tooth position/movement at the beginning and at the end of the treatment. Two types of data were compared: (i) the planned movement table provided by ClinCheck ® software (ClinCheck Pro version 1.10 Align Technolgy Inc. San José, USA) and the real amount of movement experimentally measured. Children 2022,9, 1176 6 of 19 Table 2. Qualitative evaluations of each objective and the global complexity classification of every case. Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Case 16 Case 17 Case 18 Case 19 Case 20 Case 21 Case 22 Case 23 Age & Sex 9.7 M 8.0 F 9.7 F 9.2 F 8.0 F 9.5 F 8.2 F 8.0 M 9.3 M 8.0 M 10.3 F 9.7 F 9.0 F 8.7 M 8.7 M 7.8 M 10.2 M 9.2 F 7.7 F 7.3 F 9.4 F 9.2 M 6.8 M Molar derotation (N= 9) 0 0 0 1 1 1 0 0 0 0 1 2 0 0 0 0 0 1 0 1 1 1 0 Dentoalveolar Expansion (N= 20) 20102201232221331112123 Space to recover (N= 16) 3 2 1 2 3 1 0 1 2 2 0 3 1 2 0 0 1 3 0 1 0 0 3 Molar sagittal Class (N= 18) 2 0 3 2 1 3 3 2 0 1 3 2 2 3 1 1 0 1 2 0 3 0 3 Posterior crossbite (N= 11) 3 1 0 0 0 2 1 2 2 0 0 0 0 0 2 3 0 0 3 1 0 1 0 Open bite (N= 3) 0 3 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 Midline discrepancy (N= 13) 3 0 0 0 0 3 0 0 3 0 1 3 3 0 2 3 0 3 2 1 3 2 3 Crowding (N= 13) 3 2 1 3 2 0 0 1 3 3 0 1 0 0 0 0 2 3 0 2 0 0 3 Skeletal problem (N= 15) 3 3 3 3 3 0 0 3 0 3 3 3 3 0 0 0 3 0 3 3 3 0 3 TOTAL 19 11 9 11 15 12 4 10 12 12 10 16 11 6 8 10 7 12 11 14 11 6 18 Caption: F: female; M: male; objectives to be achieved: Predictable (1);Intermediate (2), Difficult (3). Case global complexity: Children 2022,9, 1176 7 of 19 In addition, multiple other methods were used to analyze the included cases and to quantify and classify the movements/corrections to be accomplished. This includes the virtual three-dimensional (3D) planning using the ClinCheck ® treatment plan software, intraoral photographs, and digital models obtained with the iTero ® intraoral scanner from each patient. ClinCheck ® measurement tools (i.e., the planned movement table, real measures with the millimetric scale, and arch width) and cephalometric measurements were also conducted. Although not all cases presented skeletal malocclusion traits, the evaluation of cephalometric parameters was conducted in all patients to verify the overall improvement of the malocclusions. ANB (skeletal convexity) and FMA (mandibular plane angle) were used to analyze the sagittal and vertical skeletal components, respectively, while overjet and overbite were selected for the sagittal and vertical dental components, respectively. Signs and symptoms of temporomandibular disorders were also clinically assessed. Questionnaires with five response items were given to the children and their caregivers to demonstrate patients’ cooperation as well as to ascertain if there was an agreement between their responses in order to determine potential treatment compliance flaws. 2.5. Statistical Analysis The statistical analysis was carried out in IBM SPSS ® (IBM SPSS Statistics 28, IBM Corp., Armonk, NY, USA) and R software (R version 4.1.2, R Foundation for Statistical Computing, Vienna, Austria), and Microsoft Excel ® (Microsoft Excel for Microsoft 365 Version 2206, Microsoft Corporation, Redmond, WA, USA) was used for the data organization and graphical reporting. A descriptive analysis of the movement and cephalometry metrics of all children was performed. When comparing achieved goals as a function of the complexity degree per pathology, the one-sided Cochran–Armitage Trend test was used considering a Bonferroni correction on the significance level for multiple testing (standard statistical method for reducing the inflation of type 1 errors, i.e., false positives, with multiple comparisons). The Wilcoxon signed-rank test was used to compare cephalometry metrics (i.e., overjet, overbite, ANB, and FMA), derotation, expansion, and space recovery before and after treatment. All cephalometric measurements were validated by calculating the standard intra-investigator error deviation using the Dahlberg method [ 15 ]. The significance level was set at 0.05. 3. Results Case Series A total of 23 Caucasian children (13 female and 10 male) having 102 interceptive orthodontic malocclusion traits in mixed dentition were included in this case report. The age of the patients ranged from 6.8 to 10.3 years old, with an average age of 8.3 ± 1.0 years old. The desired movements/corrections included molar derotation, dentoalveolar expansion, space recovery, midline discrepancy, molar sagittal malocclusion, posterior crossbite, open bite, and crowding. No signs or symptoms of temporomandibular dysfunctions were observed. All patients complied with the Invisalign ® treatment, and no dropouts were registered. All patients were treated with Invisalign ® First for 18 months (Phase 1). This phase attempts to solve malocclusion traits that would affect function, future occlusion with permanent dentition, and possibly skeletal development as well. Therefore, each patient can have one or more treatment goals with different levels of complexity and, consequently, distinct predictability. The global classification for the treatment complexity for each patient was mild, moderate, or severe based on the discrete interceptive malocclusion traits that the children presented (see Table 2). All the included cases were classified as having moderate (N= 5) or severe (N= 18) complexity. A total of 102 interceptive orthodontic malocclusion traits were found in this sample (see the comprehensive quantitative and qualitative evaluation of the defined objectives in Table 3). Each case is illustrated and briefly characterized in Supplementary Figure S1, Children 2022,9, 1176 8 of 19 which presents the intraoral photographs taken before and after the interceptive treatment as well as the virtual ClinCheck ® predictions for the desired results to be achieved at the end of the treatment. Here, a statistical study of different dental components is presented (see the descriptive analysis of MDR, DAE, SR, and cephalometric data in Table 4, and Supplementary Tables S1–S4 with all measurements). Specifically, the molar derotation metrics of the upper permanent first molars (teeth 16 and 26) from nine patients show that the planned movement at the last ClinCheck ® was greatly reduced compared with the initial ClinCheck ® prediction for both teeth. Additionally, the dentoalveolar expansion initially planned for teeth 16 to 26 in 20 patients was achieved at the end of the orthodontic intervention, as the mean, minimum, and maximum values demonstrate. Similarly, data from 16 patients requiring space opening for teeth 12, 15, 22, 32, 33, and 43 reveal that a great part of the amount of movement initially planned for these teeth was accomplished (more than 98%). Moreover, cephalometric metrics on the entire sample show that overbite and overjet malocclusion traits observed in 23 patients were mitigated by the end of the orthodontic treatment. Overall, this preliminary analysis suggests that the interceptive treatment tended to normalize the dental component of the examined cases (as observed through overbite and overjet data), while ANB values tended to decrease, reflecting the worsening of the skeletal component in Class III situations and improvement in Class II cases. On the other hand, in general, FMA scores did not reveal a tendency to modify the skeletal component in the vertical direction. The intra-operator error associated with the cephalometric measurements was assessed using the Dahlberg method [ 15 ]. As shown in Supplementary Table S5 the intra-operator error was very low for all cephalometric features and time points, reflecting the repeatability of the measurements. After this preliminary descriptive analysis, the most adequate statistical tests were conducted. The Wilcoxon signed-rank test was used to evaluate the progression in the cephalometry parameters, as well as the derotation, expansion, and space recovery metrics, from the beginning to the end of the study (see Table 5). If there was no change in the need for correction between the beginning and the end, it means that there were no improvements (reflected by similar numbers in negative/positive ranks). In Table 5, it is demonstrated that most of the values related to the need for correction decreased significantly (reflected by the predominance of negative ranks). Statistically significant differences were found for all metrics, except for FMA. This means that the tendency for a decrease in ANB data is statistically significant. Furthermore, final and initial FMA scores were not significantly different, which is in line with the data from Table 4. Then, we decided to ascertain if the total number of aligners required by the patients varied depending on the malocclusion trait complexity and the proposed treatment plan. Despite the presence of eruption compensations, which is a valuable tool for these treatments with Invisalign ® in mixed dentition, it is not possible to fully control the permanent teeth eruption, which increased the probability of misaligned aligners. Due to this factor, seven patients had several aligners planned that were never used. After outlier removal, the average difference between the planned and used aligners for these patients was approximately seven. The most frequently diagnosed situation was arch constriction and, consequently, the need for dentoalveolar expansion. The goals defined for the interceptive treatment were achieved, and the malocclusion traits were solved within 18 months for all patients, except for two cases of MSC malocclusion, which was successful in only 89% of the cases. However, only 69% of the interceptive malocclusion traits could be solved with the initial series of aligners (see Figure 1). Children 2022,9, 1176 9 of 19 Table 3. The quantitative and qualitative assessments of the malocclusion traits to be solved for each case. These data were collected/classified at the start of the study. Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Case 16 Case 17 Case 18 Case 19 Case 20 Case 21 Case 22 Case 23 Molar derotation (º) (N= 9) t16 = 17.8 t26 = 10.7 t16 = 16.6 t26 = 17.8 t16 = 22.2 t26 = 22.2 t16 = 24.0 t26 = 20.9 t16 = 35.9 t26 = 10.2 t16 = 10.4 t26 = 17.7 t16 = 23.0 t26 = 13.4 t16 = 25.5 t26 = 14.8 t16 = 10.9 t26 = 16.6 Dentoalveolar expansion (mm) (N= 20) T-- 6.0 3.8 4.2 4.1 3.6 4.1 T+ 4.4 4.9 5.1 5.1 2.7 T+ 4.4 T+ 4.0 3.0 3.0 3.1 4.1 3.2 4.4 T+ 4.1 Space to recover, (mm) N= 16 t12 = 5.5 t12 = 3 t22 = 2.5 t12 = 2 t22 = 2 t12 = 2.5 t22 = 2.5 t12 = 3.5 t22 = 4.5 t33 = 2.5 T22 = 2.5 t33 = 4.5 t15 = 5.5 t12 = 4 t22 = 1.5 t33 = 5 t32 = 2 t43 = 3.5 t15 = 8 t22 = 2.5 t12 = 2.5 t22 = 1T12 = 2 t43 = 6,5 t12 = 2.5 t22 = 2.5 T12 = 1.5 t22 = 2 t12 = 6.5 t22 = 3.5 t33 = 7.5 t43 = 1 Molar sagittal Class, N= 18 Cl III tendency Cl II complete Cl III tendency Cl II incomplete Cl II complete Cl II complete Cl III tendency Cl II complete; Space recovery Cl II complete Cl III tendency Cl III tendency Cl II complete Cl II complete Cl II incomplete Cl II tendency Cl III tendency Cl II complete Cl II complete Posterior crossbite, N= 11 Skeletal t54, t55 , t16 t64, t65 t54, t55 , t16 t54, t55 t26 t26 Tt64, t65, t25 T+ t54, t55 , t15 Skeletal t64, t65, t25 t55/65 t54 Open bite, mm, N= 3 t22 = 4.4E t36 = 1.2I t21 = 2.6E t16/26 = 1.4I t32 = 5.3E t26 = 1.2I Midline discrepancy, mm, N=13 3.3 3 3.5 1.5 3 3 2.5 4 3 2 3 2 3 Crowding, mm, N=13 U=8 L=6.1 U=4 U=5 t22 = 50.3º L=5.9 U=5 L=9 U=9 U=5.9 U = 5.9 t11 = 49.4º L=9 L=5.9 L=9 Skeletal problem N= 15 T S&V ANB: 6.6 FMA: 40 S ANB: 7.8 S ANB: −1.5 T&V FMA: 32.4 S ANB: 0.9 TS ANB: 6.4 S&T ANB: −1.6 T S ANB: −0.1 T V FMA: 31.9 S ANB: 5.1 S&T ANB: 6.2 Caption: Objectives to be achieved Predictable (1);Intermediate (2),Difficult (3); molar derotation values are the ones predicted at the first ClinCheck ® ; dentoalveolar expansion and space to recover values are the difference between the available space (measured) and planned at the first ClinCheck ® ; molar sagittal class malocclusions were classified according to their class; crossbite notes are about the crossed teeth; open bite values are about the intrusion or extrusion movements predicted at the first ClinCheck ® ; midline discrepancy values are the difference between the initial position of the lower and upper midlines; crowding values are the difference between the initially measured and the predicted space; skeletal problem values are the initial cephalometric parameters for the skeletal component; t # —tooth number; I—intrusion; E—extrusion; U—upper; L—lower; M—molar; T + —positive torque; T−—negative torque; S—sagittal; T—transversal; V—vertical; ANB—skeletal convexity; FMA—mandibular plane angle. Children 2022,9, 1176 16 of 19 In our sample, the unerupted second molars contributed to making both movements, the derotation and the distalization of the first molar, easier. Lastly, space recovery was attained in all 34 teeth. Space measurements performed at the end of the study are in line with the desired reference (i.e., initially planned) values. Overall, considering the early mixed dentition, Invisalign ® First was applied in complex (i.e., moderate and severe) cases. We believe that the orthodontic intervention should start with an interceptive treatment (for instance, to promote space recovery, molar derotation, and dentoalveolar expansion, among others). Of course, the orthodontic correction is inherent to the use of the aligner system as well while we are recovering the dental positioning. On the other hand, in cases with a skeletal component where no serious malocclusion traits exist, the orthopedy treatment must be chosen first [29,30]. We cannot forget that these are children with growth potential. If this growth is favorable, everything is easier. Otherwise, in cases of unfavorable growth, all biological possibilities should be considered in a way to correct the functional malocclusion traits that undoubtedly lead to an aggravation of the malocclusion trait and skeletal problems, always having in mind that these are interceptive treatments. Although the findings was not statistically significant, the satisfaction of children relative to the use of aligners is lower than the perception of their guardians. A possible justification may be the children’s experience and adaptation to the aligners as they develop new habits and routines. However, these aligners are more comfortable, aesthetic, and hygienic compared with traditional fixed appliances [ 19 , 26 , 31 ]. This is one of the reasons for the high treatment compliance. To reinforce it, we highlight that these removable devices are particularly dependent upon the child’s collaboration to achieve treatment success. We found no evidence for a sustained rejection of the orientations provided by the orthodontist and supported by the guardians. This article intended to analyze if the system effectiveness is related to the movement type and degree of complexity. Since this study is of a relatively unexplored orthodontic area and also considering that the Invisalign®First modality started just in 2018 and comprises an 18-months interceptive treatment, our sample consisted of 23 children. However, we believe that the number of interceptive malocclusion traits (N= 102) remains the most representative sample for justifying the robustness of our analysis. 5. Study Limitations The convenience sample we used encompasses diverse clinical characteristics. Although the interest in the Invisalign First ® system has been exponentially growing, this is recent technology (available since 2018), and the number of patients with mixed dentitions using this particular system is limited. Future studies with larger sample sizes and with a randomized design are recommended. Further research using the Invisalign ® First system to produce tooth expansion is needed to better understand the behavior of different groups of teeth when submitted to this type of movement, mainly in children with mixed dentition. As we believe that the differential growth potential of the children must be considered when predicting treatment evolution, the methodology employed here cannot be compared with other studies [ 11 , 12 ], such as ClinCheck ® models’ superimposition. A controlledrandomized trial using a classification method accounting for children’s growth should be conducted to evaluate movement predictability in children having mixed dentition undergoing orthodontic treatment with Invisalign First®. The questionnaire used in the present study has not been tested for validity and reliability and could be subject to various forms of bias such as mood bias and false reporting bias among others. It is not unusual for the children to self-report more aligner wear than what occurs in reality (and unfortunately sometimes the same applies to the guardians). 6. Conclusions The main points to highlight from this case series are: Children 2022,9, 1176 17 of 19 1. The interceptive treatment with Invisalign ® First system is effective in growing patients, being capable of producing clinical results comparable with what is planned in the ClinCheck®within 18 months, although not always with the first set of aligners. 2. The degree of complexity affects the success in mitigating various malocclusion traits, with more difficult corrections having lower efficiency rates after the first set of aligners. 3. The statistical analysis of the measurements obtained by the ClinCheck ® treatment plan, table tools, millimetric scale, arch width, and cephalometric metrics at the start and end of the intervention clearly demonstrates the high effectiveness of Invisalign ® treatment in all domains. However, the interpretation of the ClinCheck ® predictions is not straightforward. Our methodology of grouping three levels of severity and assessing the percent of corrected cases allows for the extraction of meaningful clinical interpretations 4. High treatment compliance was observed in this study according to children’s and guardians’ feedback. 5. In summary, randomized controlled trials are needed for evaluating movement predictability and how this relates to the problem complexity and the number of additional aligners required in children in early mixed dentition treated with Invisalign®First. 6. Future investigations of growing patients in early mixed dentition should use the classification methodology proposed here that considers the children’s potential growth over time. Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/children9081176/s1, Table S1: Molar derotation planned on the first and last ClinCheck ® scans of teeth 16 and 26, for nine patients; Table S2: Dentoalveolar expansion measured at the first and last ClinCheck ® scans and planned at the last ClinCheck ® between teeth 16 and 26, in 20 patients; Table S3: Space initially available and planned for the teeth. and space obtained at the end of treatment, for 16 patients; Table S4: Initial and final cephalometric measurements according to each of the selected parameters, for all patients; Table S5. Intra-operator error calculation for cephalometric measurements using the Dahlberg method; Figure S1: Twenty-three interceptive treatments cases with the highest complexity degree problem selected from the sample—A/D/G/J before treatment; B/E/H/K predicted using ClinCheck ® simulation; and C/F/I/L at the end of the 18 months, according to the objectives to be achieved. Case 1: Posterior crossbite; Space recovery— severe (3). Case 2: Open bite; Crowding—severe (3). Case 3: Molar sagittal malocclusion II—severe (3). Case 4: Space recovery—Severe (2). Case 5: Open bite—severe (3). Case 6: Molar sagittal malocclusion II; Midline discrepancy—Severe (2). Case 7: Molar sagittal malocclusion II—moderate (2). Case 8: Crowding—Severe (2). Case 9: Midline discrepancy—severe (3). Case 10: Space recovery; Molar sagittal malocclusion II; Crowding—severe (3). Case 11: Midline discrepancy; Molar sagittal malocclusion II—severe (3). Case 12: Space recovery; Molar sagittal malocclusion III—severe (3). Case 13: Midline discrepancy—severe (3). Case 14: Molar sagittal malocclusion II—moderate (2). Case 15: Midline discrepancy—moderate (3). Case 16: Midline discrepancy; Posterior crossbite; Dentoalveolar expansion—severe (3). Case 17: Crowding—moderate (3). Case 18: Crowding; Midline discrepancy; Space recovery—severe (3). Case 19: Midline discrepancy—severe (3). Case 20: Open bite—severe (3). Case 21: Molar sagittal malocclusion II—severe (3). Case 22: Posterior crossbite— moderate (2). Case 23: Crowding; Midline discrepancy; Space recovery; Dentoalveolar expansion; Molar sagittal malocclusion II—severe (3); Figure S2. Initial (A) and Planned (B) ClinCheck ® treatment plans (first set of aligners). Author Contributions: Conceptualization, T.P.; Data curation, S.R., S.P. and R.A.; Formal analysis, T.P., D.R., S.R., F.M. and R.A.; Funding acquisition, T.P. and S.P.; Investigation, T.P., D.R. and S.P.; Methodology, T.P., F.M. and R.A.; Project administration, T.P.; Resources, T.P.; Software, F.M. and R.A.; Supervision, T.P. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by Fundação para a Ciência e Tecnologia, grant number UID/EEA/04436/2021 and 2020.09375.BD and UNIPRO—Oral Pathology and Rehabilitation Research Uni, grant number AlignAgen-GI2-CESPU-2022. Children 2022,9, 1176 18 of 19 Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the University Institute of Health Sciences (protocol code 11/CEIUCS/2020) in April 2020. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. 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