Midpalatal Suture Maturation Method for the Assessment of Maturation before Maxillary Expansion: A Systematic Review

Assessment of midpalatal suture maturation is crucial before deciding which type of maxillary expansion technique will be performed to treat transverse discrepancies. In 2013, Angelieri et al. proposed a new method to evaluate midpalatal maturation using cone-beam computed tomography. The aim of this study was to systematically identify, evaluate, and provide a synthesis of the existing literature about this new method and to rigorously assess the methodological quality of these articles. A bibliographic search was carried out using PubMed, Cochrane Library, SciELO, LILACS, Web of Science, and Scopus using the terms midpalatal suture, cranial sutures, palate, maturation, interdigitation, ossification, maxillary expansion, evaluation, assessment, and assess. Quality assessment was performed using the Observational Cohort and Cross-Sectional Studies tool developed by the National Heart, Lung, and Blood Institute. Hence, 56 articles were obtained, of which only 10 met the selection criteria. We could not include any of the data into an analysis because of the large variation of the data collected and high methodological heterogeneity found among studies. Of all the studies included, 10% had poor quality, 70% fair, and 20% good quality, respectively. Even though age and sex play a role in midpalatal suture obliteration, there is a poor correlation between these variables. Thus, every patient should be assessed individually before choosing the best protocol for maxillary expansion. The midpalatal suture maturation method has the potential to be used for diagnostic purposes, but clinicians should be cautious of routinely using it because an extensive training and calibration program should be performed prior.


Introduction
The maxillary deficiency in the transverse plane is called maxillary constriction. The main etiologic factors of this deficiency are mouth breathing, harmful habits, like thumb sucking and/or pacifiers, and atypical phonation and swallowing. The poor positioning of the tongue, the imbalance of perioral muscles, the lack of lip seal, together with the labial hypotonicity, contribute to maxillary constriction [1][2][3][4].
Transverse maxillary deficiency is a relatively frequently encountered orthodontic problem, with a prevalence of approximately 10% in adults, and is often characterized by a unilateral or bilateral posterior crossbite [5,6].
The orthodontic procedure used to achieve the correction of maxillary transverse deficiency is called maxillary expansion. The main goal of this treatment is to widen the maxilla by accomplishing the separation of the midpalatal suture (MPS), maximizing skeletal expansion, and minimizing dentoalveolar expansion [7]. This occurs by the stretching Since the creation of this method, some systematic revisions have been performed [45][46][47], but this is the first article to systematically assess and standardize the calibration, training, blinding processes, and randomization of the images that each one of the articles used. This is of vital importance to ensure the internal validity of each study.
Therefore, the present systematic review aimed to critically appraise the available literature on the assessment of maturation of the midpalatal suture before maxillary expansion, using the method proposed by Angelieri et al. [27], with a two-fold focus: (1) to summarize and (2) to assess the methodological quality of evidence.

Protocol and Registration
The systematic review was conducted and written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [48,49]. The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42022307742).

Eligibility Criteria
A PICOS (population, intervention, comparator, outcomes, and study design) question was established as an inclusion criteria: Population (P): human subjects of any gender without restriction of ethnicity or age. Intervention (I): midpalatal suture maturation method proposed by Angelieri et al. [27] (Table 1). Table 1. Skeletal maturation stages of the MPS proposed by Angelieri et al. [27].

Stage Description
A Represents the earliest maturation stage of the suture, and in this stage the suture was identified as a relatively straight high-density line at the midline B The suture presents an irregular shape and was identified as a scalloped high-density line at the midline C The suture is seen as two parallel, scalloped, high-density lines close to each other and separated in some areas by small low-density spaces D The complete fusion of the suture has occurred in the palatine bone and the radiographic image of the suture was identified as two scalloped, high-density lines at the midline on the maxillary portion of the palate that were not visible in the palatine bone E Fusion of the suture has occurred in the maxilla. It is not possible to identify the MPS. As to bone density, it is the same as in other parts of the palate Condition (C): not having used another method to assess midpalatal suture maturation. Outcome (O): degree of ossification-maturation-interdigitation of midpalatal suture before maxillary expansion treatment.
Study design (S): observational studies (cohort studies either prospective or retrospective and cross-sectional studies).
Articles including subjects who had undergone any type of orthodontic or orthopedic treatment, nonhuman studies, syndromic conditions, case reports, cleft lip, and palate, and review articles were excluded.

Information Sources and Search Strategy
Electronics searches in MEDLINE (via PubMed), Web of Science, Cochrane Library, Scopus, LILACS and SciELO were conducted up to July 2022. Google Scholar was investigated to partially access the gray literature.
Finally, manual searches in the reference list of included articles were also carried out. There was no restriction of language, year, or status of publication for inclusion.

Selection of Sources of Evidence
Study selection was performed in three phases. First, the main researcher (A.S) excluded the duplicate articles using the Reference Manager EndNote X9 (Clarivate Analytics, Philadelphia, Pa). Secondly, two reviewers (A.S and P.S.V) blindly assessed the titles and abstracts of identified records. Then, the same reviewers separately applied eligibility criteria to the full-text studies using the systematic review web application Rayyan [50] (rayyan.qcri.org). Information was cross-checked in a consensus meeting in which disagreements were solved between them. If there was no consensus, a third reviewer was consulted to make a final decision (I.G.C).

Data Charting Process and Data Items
The data was extracted independently by two reviewers (A.S and P.S.V) using a data extraction sheet designed in Microsoft Excel (Redmond, Wash), and any differences were resolved by discussion and consensus with a third reviewer (I.G.C). The following data were extracted from each included study: first author, publication year, study design, sample size, sex distribution, objectives, inclusion criteria, equipment used, number of examiners, calibration, training, and blinding process, inter and intra-evaluator agreement, statistical analysis used, and the author's conclusion.

Quality Assessment of Included Studies Synthesis of Results
As suggested by Ma et al. [51], the Observational Cohort and Cross-Sectional Studies tool developed by the National Heart, Lung, and Blood Institute [52] was used to assess the quality of the articles that met the inclusion criteria.
Two reviewers independently assessed the articles and subsequently discussed the quality of each study (A.S and P.S.V.). In case of discrepancy, a third author was consulted for further evaluation (I.G.C.).

Results
A total of 56 studies were identified by electronic searches, and 36 studies remained after removing duplicates. After initial screening, a total of 31 studies met the predetermined inclusion criteria. After the full text review, nine studies were included for this review. In addition, 1 eligible study was identified via hand searches. As a result, 10 studies were included in this systematic review ( Figure 1). A summary of the characteristics of each included study is presented in Table 3. Angelieri et al. [27] assessed midpalatal suture maturation in 140 subjects between the ages of 5-58. Stages A and B were mainly observed up to 13 years of age (55 subjects), whereas stage C was noted primarily from 11 to 17 years of age but occasionally in younger and older age groups (two subjects under 11 years and four over 18 years old). Fusion of the palatine (stage D) and maxillary (stage E) regions of the midpalatal suture was completed after 11 years only in girls (six subjects). From ages 14 to 17 (no years here), three of 13 (23%) boys showed fusion only in the palatine bone (stage D).

Tonello et al. 2017
Tonello et al. [53] evaluated midpalatal suture maturation in 84 children 11-15 years old. Stage A was only found in one 11-year-old girl. In the age group 11-13 years, it was observed that the unfused stages (A, B, and C) were seen in 90.3% of the subjects.
Stage D was present in six girls and five boys (13.1% of the sample). Stage E was found in 10.7% of the sample. Almost all subjects (eight of nine) were 14 or 15 years of age, except for a 12-year-old girl.

Angelieri et al. 2017
Angelieri et al. [54] assessed midpalatal maturation in 78 adults 18-66 years old. Hence, 19 of the adults presented a fused midpalatal suture in the palatine (Stage D) and/or maxillary bones (50, 42 female and eight male). However, the midpalatal suture was not fused in nine of the subjects (12%) iagnostics 2022, 12, x FOR PEER REVIEW 5 of 18

Results
A total of 56 studies were identified by electronic searches, and 36 studies remained after removing duplicates. After initial screening, a total of 31 studies met the predetermined inclusion criteria. After the full text review, nine studies were included for this review. In addition, 1 eligible study was identified via hand searches. As a result, 10 studies were included in this systematic review ( Figure 1). A summary of the characteristics of each included study is presented in Table 3.

Quality Assessment of Included Studies
The obtained grade of quality assessment for each study is included in Table 4. Grades for the selected studies ranged from 58.3% to 83.3%. One study [59] had poor quality, seven studies [27,[53][54][55][56]58,60] had fair quality, and two studies [57,61] had good quality.

Summary of Evidence
One of the most important factors when making the clinical decision regarding how to deal with a transverse maxillary constriction is defining whether the midpalatal suture is open or closed, thus influencing enormously the treatment that will be given to the patient. This can be especially challenging in late-stage adolescent and young adult patients because there is no consensus in the literature regarding the minimum age for reliable palatal expansion [57].
Even though RME is a more conservative treatment, if it is indicated in patients with totally or partially closed midpalatal sutures, it can lead to consequences such as significant pain, gingival recession, palatal mucosa ulceration or necrosis, buccal tipping of the posterior teeth, reduction of buccal bone thickness [30,[62][63][64][65][66], alveolar bone bending [67], buccal root resorption [68], fenestration of the buccal cortex [69], and instability of the expansion [70,71]. On the other hand, it is important to mention that even though a surgical expansion with SARPE is possible at any time throughout life, it implies increasing morbidity, cost, risk, and more days required for patient recovery [54]. It has also been reported to be the most unpredictable procedure among all orthognathic surgery modal-ities. This unpredictability of the surgical expansion has to do with its relapse potential [72,73].
A third option mentioned in the scientific literature is the use of micro implants (MARPE) in cases in which the midpalatal suture is in process of closure [74][75][76].
Despite the unquestionable success of the RME protocol in clinical practice, there is still no consensus regarding the age limit for palatal expansion. This is mainly due to the great physiologic variability, among patients with an obliterated palatal suture earlier or at a more advanced age, without a precise diagnostic [77]. This has been confirmed by histologic studies that have shown the same variability in the maturation of the midpalatal suture [35][36][37][38].
As mentioned above, a lot of uncertainty and doubt exists in scientific literature because of contradictory information in relation to which is the best clinical approach when performing maxillary expansion.
Within this frame of reference, a diagnostic method in which it is possible to evaluate the maturation of the palatal suture with safety and reliability before maxillary expansion becomes important [53].
The individual evaluation of midpalatal suture maturation on CBCT scans has been proposed by Angelieri et al. [27], to identify the morphology of the midpalatal suture prior to maxillary expansion, trying to guide clinicians in choosing the best clinical procedure to accomplish a successful treatment.
Two important factors mentioned in literature are age and sex. They play an essential role in finding midpalatal suture opening but are not crucial in the decision making because they are not reliable parameters to determine if the MPS is merged or not [35]. Angelieri et al. [27] mention that chronologic age is unreliable for determining the developmental status of the suture during growth, even though it has been suggested that gradual obliteration of MPS occurs as patients get older.
Related to age, an interesting event that occurs is related to studies that included adults. In them, it is possible to appreciate subjects that, despite having passed their growth phase, still have an open or partially obliterated midpalatal suture [27,53,54,[56][57][58][59][60][61] (Table 5).  (4) Were all the subjects selected or recruited from the same or similar populations? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? (5) Was a sample size justification, power description or variance and effect estimates provided? (6) For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? (7) Was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed? (8) For exposures that can vary in amount or level. did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure or exposure measured as continuous variable)? (9) Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? (10) Was the exposure(s) assessed more than once over time? (11) Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? (12) Were the outcome assessors blinded to the exposure status of participants? (13) Was loss to follow-up after baseline 20 % or less? (14) Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?
Even though the advent of CBCT has brought many benefits to the field of orthodontics, allowing the clinician to three-dimensionally visualize the maxillary anatomy [94] and evaluate the MPS maturation without the overlap of the surrounding structures [38], we have to remember that radiological assessment is not a risk-free procedure, especially when children are involved, and there is a growing concern of radiation dose [95,96].
The existing guidelines about the use of CBCT in orthodontics have emphasized the need of a stronger justification when prescribing CBCT examinations. Children or young adults should undergo a CBCT examination only when the benefits of the diagnosis or treatment plan outweigh the potential risks of radiation exposure [97]. Jimenez et al. [57] mention that the need for a tomographic examination should be reduced to avoid the load of ionizing radiation in the patient. In this regard, it is an essential clinical procedure to follow the guidelines of imaging proposed by the American Academy of Oral and Maxillofacial Radiology appropriately [97], according to the clinical condition and assessing the radiation dose risk.
When assessing the reliability and reproducibility of the method proposed by Angelieri et al. [27], we were able to find contradictory information. Some authors mentioned that the method presents a substantial reliability and reproducibility as evaluated through the intraexaminer and interexaminer reliability calculation [27,52], while other authors emphasized the low reproducibility of the method [47,98], describing it as nonintuitive and requiring major training for operator calibration. Vieira Barbosa et al. [55] mention that whenever proposing a new diagnostic method examiner's agreement plays an important role. Methods that are considered highly reproducible are also considered reliable. Reliability is the capacity of a method to result in identical or similar outcomes in different clinical or statistical experiments. More specifically, any test or procedure considered reliable will always result in similar outcomes regardless of the time, environment, or examiner. This reliability helps reduce the occurrence of diagnostic errors.
Apart from reliability and reproducibility of a method, validation of a diagnostic method is also necessary, with this method being validated in the literature [77]. Specifically, the individual assessment of midpalatal suture maturation was compared with hand-wrist and cervical vertebrae maturation and showed strong statistical association.

Methodological Quality Assessment
Methodological quality (risk of bias) assessment is an important step before study initiation usage. Therefore, accurately judging study type is the first priority, and choosing the proper tool is also important [51]. One of the strengths of this review is that it is the first to assess the methodological quality of the articles related to this topic using the Quality assessment of the included studies using the Observational Cohort and Cross-Sectional Studies tool.
This differentiates this systematic review from another [26] in which a quality review was performed using the STROBE checklist. According to Ma et al. [51], this is not the most suitable tool for quality assessment of cross-sectional studies.
Other points of vital importance are related to the calibration between the observers, the blinding process, and the randomization of the images used to evaluate the intraobserver agreement.

Limitations
A limitation of this study has to do with results not being homogeneous, making it impossible to perform a meta-analysis.
The methodological quality of the studies included was assessed rigorously and many deficiencies were found, such as: lack of randomization, blinding, and sample calculation.
Another limitation has to do with the method itself. Thus, because of its qualitative nature, an extensive calibration and training program is necessary for more reliable and reproducible applications [55].
There is an urgent need for future studies to also include the evaluation of the rest of the circummaxillary sutures. Table 6. Distribution of maturational stages of midpalatal suture by age in the included studies. Angelieri et al. 2013 [27] Age groups 5 < 11 y 11-<14 y 14-18 y

Conclusions
The midpalatal suture maturation method has the potential to be used for diagnostic purposes.
Before using this method, an extensive training and calibration program should be performed.
Even though age and sex play an important role in midpalatal suture obliteration, every patient should be assessed individually before choosing the best protocol for maxillary expansion.