Accepted Manuscript

Efficacy of rapid maxillary expansion in the treatment of Obstructive Sleep Apnea

Syndrome: a systematic review with meta-analysis

Francisco Vale, Professor and Department chair, Mariana Albergaria, Post-graduate

student, Eunice Carrilho, Full Professor, Inês Francisco, Post-graduate student,
Adriana Guimarães, Post-graduate student, Francisco Caramelo, Professor, Luísa
Maló, Professor

PII: S1532-3382(17)30030-1
DOI: 10.1016/j.jebdp.2017.02.001
Reference: YMED 1173

To appear in: The Journal of Evidence-Based Dental Practice

Received Date: 6 February 2017

Accepted Date: 6 February 2017

Please cite this article as: Vale F, Albergaria M, Carrilho E, Francisco I, Guimarães A, Caramelo F,
Maló L, Efficacy of rapid maxillary expansion in the treatment of Obstructive Sleep Apnea Syndrome:
a systematic review with meta-analysis, The Journal of Evidence-Based Dental Practice (2017), doi:
10.1016/j.jebdp.2017.02.001.

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 ACCEPTED MANUSCRIPT
Efficacy of rapid maxillary expansion in the treatment of Obstructive Sleep

Apnea Syndrome: a systematic review with meta-analysis

Francisco Valea , Mariana Albergaria b, Eunice Carrilhoc, Inês Francisco b, Adriana

Guimarães b, Francisco Caramelod, Luísa Maló e

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a
Professor and Department chair, Department of Orthodontics, Faculty of Medicine,

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University of Coimbra, Coimbra, Portugal
b
Post-graduate student, Department of Orthodontics, Faculty of Medicine, University of

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Coimbra, Coimbra, Portugal
c
Full Professor, Department of Dentistry and IBILI, Faculty of Medicine, University of

Coimbra, Coimbra, Portugal

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d
Professor, Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine,
University of Coimbra, Portugal
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e
Professor, Department of Orthodontics, Faculty of Medicine, University of Coimbra,

Coimbra, Portugal
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Corresponding author: Professor Francisco do Vale, Department of Orthodontics,

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Faculty of Medicine, University of Coimbra, Avenida Bissaya Barreto, Blocos de Celas,

3000-075 Coimbra, Portugal

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fvale@fmed.uc.pt
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franciscofvale@gmail.com
 ACCEPTED MANUSCRIPT
Efficacy of rapid maxillary expansion in the treatment of Obstructive Sleep Apnea
Syndrome: a systematic review with meta-analysis

ABSTRACT

Background: OSAS (Obstructive Sleep Apnea Syndrome) is a sleep-related

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breathing disorder with a peak of prevalence in pre-school age children. There are
several factors that determine its origin, among which are anatomic alterations such as

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maxillary constriction.

Objective: To conduct a systematic review with meta-analysis to assess the

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efficacy of RME (Rapid Maxillary Expansion) in treatment of OSAS in children and
adolescents.

Search methods: A literature search was performed using the electronic

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databases PubMed, Web of Science, LILACS, EMBASE and Cochrane Library.
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Selection criteria: Randomized controlled trials, nonrandomized controlled trials,
cohort studies, and systematic reviews published in English, Spanish, or Portuguese
between January 2000 and December 2016, performed on children and adolescents
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under 18 years old with OSAS who underwent RME and assessing RME efficacy in
AHI (Apnea-Hypopnea Index) normalization were included. The qualitative assessment
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of the selected studies was performed using CASP (Critical Appraisal Skills
Programme) checklists. Statistic evaluation included two meta-analysis based on a
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random effect model and Cochran’s Q test and I2 statistic to assess heterogeneity
across publications.
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Data collection: Electronic searches identified 84 publications. Five publications

were considered valid and included in this systematic review.
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Results: Results from the meta-analysis show an overall reduction in AHI

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(apnea-hypopnea index) after RME therapy.

Conclusions: There is increasing evidence that RME devices reduce AHI in

children with OSAS. RME therapy can help in the treatment of children with OSAS.
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INTRODUCTION

Obstructive sleep apnea syndrome (OSAS) is a sleep-related breathing disorder

caused by partial (hypopnea) or complete (apnea) recurrent upper airway obstruction
that disrupts the normal sleep pattern and ventilation [1, 2, 3]. This condition induces
intermittent hypoxia and hypercapnia, leading to increased respiratory effort and
changes in the intrathoracic pressures, with subcortical or cortical arousals during

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sleep [1, 4].

OSAS can occur in children of all ages, from newborns to teenagers [5, 6] Yet,

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the highest prevalence is in pre-school age, in which pharyngeal lymphatic tissues
(such as tonsils and adenoids) are largest when compared to the underlying airway
volume [1]. The peak of prevalence occurs between 2 and 8 years of age, with values

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ranging from 1% to 3% [1, 4].

The aetiology of OSAS is multifactorial, usually arising when exist an imbalance

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between the factors that contribute to the airway patency and those that promote the
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airway collapse [7]. In children, this event may be caused by anatomic alterations and
constriction of the upper airway, or may be originated by hypotonia of the pharyngeal
ring and the muscles of the tongue [8]. Other commonly identified abnormalities are
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mandibular retrusion, placement of the hyoid bone inferiorly to the mandibular plane
and, also, maxillary constriction [9, 10].
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Children with OSAS tend to show some common signs and symptoms, notably
excessive sleepiness during the daytime and atypical behaviour combined with
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morning headaches [4, 11]. In addition to the previous symptoms, these children
frequently present, during the night period, snoring, enuresis, mouth breathing,
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witnessed apnea and disturbed sleep with frequent awakenings and parasomnias
(night terrors, nightmares) [1, 12].

OSAS is usually diagnosed based on the evidence collected from different

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sources, generally combining the information reported by the caregivers, data from a
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physical examination and parameters given by polysomnographic studies (PSG), which

is considered the gold-standard method for diagnosing OSAS [1, 13]. The PSG test
consists in recording both chest and abdominal movements during sleep and other
sleep-related parameters, such as the apnea-hypopnea index (AHI) per hour of sleep.
The parameters recorded permit to distinguish simple snoring from OSAS [1, 14], and
also provide quantified information about the severity of sleep disruption [12]. AHI
measures the number of apneas and hypopneas per hour of sleep which is directly
related to OSAS [3].

PSG findings are considered normal as long as AHI is below one respiratory
event per hour and the duration of the apnea episode is less than 5 seconds and the
oxyhemoglobin saturation is over 90% and less than 10% of carbon dioxide at the end
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of expiration. However, AHI less than 5 might also be accepted as normal but is
commonly categorized as mild [2,15].

Another measure often related with OSAS is the Mallampati test, which is
usually associated to a higher risk for OSAS worsening [16]. The Mallampati score is
determined after careful examination of the oropharyngeal region aiming at detecting
intubation difficulties [17]. Patients with a high Mallampati score tend to have airway
obstruction especially due to macroglossia [16].

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The treatment strategy of OSAS, in children, depends on several factors which
include the severity of the syndrome, the obstruction etiology and patients’ compliance

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[8]. The most frequent treatment options for OSAS include adenotonsillectomy,
ventilation by continuous positive airway pressure (CPAP) and oral appliances [10, 18]

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The most common cause of OSAS in children is adenotonsillar hypertrophy that
can be correct recurring to adenotonsillectiomy, however this surgical technique
presents several risks and in some patients there is a high probability of relapse [19,

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20].
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Another possibility for treating OSAS, as stated above, is the use of oral
appliances that is considered to be an important option in the case of mild OSAS and
represents a viable alternative to CPAP [21]. For example, rapid maxillary expansion
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(RME) devices are used in children with maxillary constriction and posterior crossbite
making possible to broaden the maxillary arch and widen the nasal vault [10, 22].
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Hence, the space gained improves nasal and oropharyngeal patency within a relatively
short period (a few weeks), thereby helping solve nasal airway and naso-respiratory
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problems [8, 9, 23]. Figure 1 shows the increase of the upper airways after RME
treatment.
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OBJECTIVE

The aim of this systematic review with meta-analysis was to answer the
following clinical question according the PICO model (P – population; I – intervention; C
– comparative intervention; O – outcome):

Considering children and adolescents under 18 years with OSAS does RME

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treatment result in AHI normalization?”

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MATERIALS AND METHODS

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A standardized literature search was performed in electronic bibliographic
databases (PubMed, Web of Science, LILACS, EMBASE and Cochrane Library) and

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by manual search in the references of the articles identified. Our search took place in
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March 2015 and December 2016, using the following key-words:

PubMed: (“Palatal Expansion Technique” [Mesh]) AND (“Sleep Apnea,

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obstructive” [Mesh])

Web of Science and Cochrane Library: (palatal expansion technique OR oral

appliances) AND (sleep apnea, obstructive OR sleep apnea).
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LILACS: (sleep apnea OR apneia do sono) AND (palatal expansion OR

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expansão maxilar).
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EMBASE: ‘palatal expansion technique’ AND ‘sleep apnea’

The inclusion criteria were:
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1. (patients) performed on children or adolescents under 18 years old with

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OSAS

2. (intervention) patients who underwent RME;

3. (endpoint) assessing RME efficacy in AHI normalization;

4. (type of study) randomized controlled trials, nonrandomized controlled

trials, cohort studies and systematic reviews;
5. (language) published in English, Spanish or Portuguese;

6. (period) between 2000 and 2016.

The exclusion criteria were:
1. case reports and case series;
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2. editorials, opinions and studies not specifying the parameters of interest;

3. articles that do not assess AHI;

4. publications not fulfilling the inclusion criteria.

The selected publications were imported to Endnote® software (Thomson

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Reuters Software, USA; http://endnote.com; 2016) and the duplicates were removed.

Quality assessment of included studies

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The qualitative assessment of the selected studies was performed using the

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Critical Appraisal Skills Programme (CASP, Oxford, UK; http://www.casp-uk.net; 2013)
checklists.

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CASP checklists contain several questions, directed to the study type under
evaluation. CASP questions are divided into three sections: internal validity, results
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accuracy and external validity. The presence of one negative answer to the questions
in the first section is sufficient reason to exclude the study under analysis. In all
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sections, several considerations are given in order to elucidate the appraiser about the
importance of each question.
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Statistical analysis
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Mean and standard deviation of the AHI values evaluated before (baseline) and
after the RME treatment were used as the principal outcomes in each study. Although
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the design of the studies is longitudinal we assumed a control-case design to computed

the standardized mean differences (SMD) - considering the baseline group to be
independent from the group after treatment. Two meta-analysis were performed aiming
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at answer two related but different questions. Firstly, a meta-analysis was conducted to
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check if the treatment (RME) produce a meaningful result regarding AHI. Secondly, the
after treatment group was tested in order to evaluate if the apnea-hypopnea index
(AHI) is lower than 5, which can be considered as normal. Both meta-analyses were
performed based on a random effects model; heterogeneity measures and forest plots
were obtained.

The analysis was carry out resorting to the R statistical platform, notably to the
“metaphor” package [34].

RESULTS

The electronic search identified 84 publications (Figure 2). Titles and abstracts
were independently examined by two review authors (MA and AG) and 16 articles were
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considered potentially relevant (Figure 3). Full reports were obtained and assessed
independently by the review authors. After reading these articles, 10 were excluded by
applying the inclusion and exclusion criteria. The main reasons for the exclusion of
those items are detailed in Table I.

The 6 selected studies were subjected to qualitative assessment by two review

authors (MA and AG) and in cases of uncertainty, the main supervisor (FV) was
consulted.

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The Pirelli28 article presented a negative response to the first section of the
quality assessment, and therefore it was automatically excluded from the analysis.

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Miano11, Pirelli29, Pirelli30, Villa9 and Villa19 were considered valid and included in this
systematic review. The detailed results of the accepted publications are explained in
Table II.

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Studies description

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The five studies resulting from the systematic review account for 137 subjects
submitted to RME and evaluated at least 4 months after the treatment. The RME
procedure adopted in each study is unequal concerning the appliance, the anchorage
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and the activation protocol. Two studies (Milano2009 and Villa2007) used fixed two
band appliance with an expansion screw whereas the other reported the use of one
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fixed band only (Table II). Regarding the anchorage, Pirelli2005 and Pirelli2010
described the use of the first molars and premolars or the second deciduous molars
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whereas the others preferred the anchorage only on the second deciduous molars of
the upper jaw (Table II). Finally, concerning the activation all the studies refer to used 2
turns a day excepting that both Pirelly2005 and Pirelly2010 indicated 6 turns in the first
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day. Due to all these different approaches there is a high degree of heterogeneity
across studies regarding AHI improving (I2 = 98.02%; Q(4) = 183.55; p < 0.0001) and
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AHI normalization (I2 = 95.53%; Q(4) = 91.09; p < 0.0001).

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Meta-analysis

All the studies present values for AHI before the RME treatment and after the
RME treatment. Thus, the effect of the RME treatment in the AHI values was measure
by standardized mean difference (SMD) computed between the two measures. Figure
4 shows the forest plot concerning the SMD for the five studies and the global result
obtained from a random effects model (restricted maximum-likelihood estimator -
RMEL). RME has a significant effect on diminishing the AHI values; the standardized
mean decrease of AHI values is 3.24 (IC95% [0.34, 6.15]).
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Besides the global effect of RME on AHI, also the capacity for the AHI
normalization was analysed. Figure 5, presents the forest plot for the AHI
normalization. In this case only the values after treatment were studied and compared
to the value 5, which is considered as a threshold for normalization. Once again, the
SMD was computed and it can be observed that the standardized mean difference is -
2.91 (IC95% [-4.80, -1.20]), which means that there is normalization of the AHI values.

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DISCUSSION

In the present review we defined very strict inclusion and exclusion criteria,

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which may have contributed to limitations in its results. Firstly, the five accepted and
included publications consist only of three authors (Miano, Pirelli and Villa), which

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might bring some bias caused for selection criteria of samples. Also, the AHI index
choice excluded several papers found in the search, as they evaluated the efficacy of
treatment resorting mostly to nasal cavity volume increasing, measured from

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radiographic images. According to Pirelli, 28 radiographic images are the most
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accurate method for measuring the increase of the transverse maxillary section.
However, several other authors including Ruehlan3 elect AHI as the preferred method
for assessing the effectiveness of RME in the treatment of OSAS. Baratieri33 explains
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that the transverse maxillary section increase and the consequent gain in nasal cavity
volume cannot be assessed by itself as an OSAS improvement and should not be used
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alone as a method of gauging the effectiveness of RME. Another reason given by

these authors is that radiographic methods do not allow to quantify the evolution of the
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respiratory function, namely the change on pressure and rate of air flow.

Despite the lack of quantity and quality of articles that assess the efficacy of
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RME in children and adolescents with OSAS it was possible to carried out a meta-
analysis that confirmed the effect of RME to reduce and normalize the AHI values.

Only 84 articles were identified and, in addition, 60% were not relevant, 13%
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were ineligible by applying the inclusion and exclusion criteria and due to a negative
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quality evaluation no more than 7% were considered for analysis.

All selected studies showed a reduction in AHI after RME therapy and the
global effect of reduction was found to be significant (Figure 3) With the exception of
Miano11, all publications included in this review had final values compatible with
normal AHI (AHI<5) and the overall effect is compatible to the normalization of AHI
(Figure 4). In Miano11, despite presenting final AHI values lower than baseline values,
the decrease was not enough to reach normal values. On average, the AHI values
obtained in this study were 5.4 ± 6.25, which corresponds to mild apnea.11 These
results may be related to the small sample size of this study and the high drop-out rate
(34%), since only 9 of the 14 children who began the study were evaluated and
considered for study conclusions.
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Regarding the impact of RME on clinical symptoms, only the articles of Villa9
and Villa19 evaluated this parameter. The authors found a reduction in both nighttime
and daytime frequency of respiratory symptoms.9,19 However, these clinical
improvements may not only be related to the maxilla transverse expansion itself.
According to Pirelli,28 in patients with nasal septum deviation, the increase in
transversal maxillary dimension causes a gain in nasal passage size that might result
in nasal septum repositioning. This reduces nasal breath resistance, indirectly

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diminishing OSAS severity.28

All articles analyzed tend to suggest that RME has an interesting and potential
therapeutic rate of success in OSAS treatment and regarding AHI the overall effect

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suggests that there is normalization making RME indeed effective. Currently,
adenotonsillectomy remains the most frequently used treatment, given that the main

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causal factor for OSAS in children is adenotonsilar hypertrophy.18,19 However, several
studies have shown persistent OSAS after tonsillectomy, adenoidectomy, or both, such
as the study of Tauman31. A partial relapse to adenotonsillectomy may be due to other

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causal factors, namely anatomical facial abnormalities such as nasal septum deviation,
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retruded mandibular position or enlarged inferior turbinates. Kim5 suggests that the
presence of grade 3 or 4 Mallampati in individuals with reduced jaw dimensions, often
coupled with a narrow nasomaxillary complex, is directly linked to a short response to
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adenotonsillectomy.

Despite all selected publications agreeing on the potential effectiveness of RME

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in improving OSAS and the meta-analysis performed corroborated this finding, careful
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should be taken due to the considerable heterogeneity across the analysed articles.
The heterogeneity of studies can be explained by important differences in their study
designs, such as sample sizes, intervention protocols, inclusion/exclusion criteria and
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follow-up periods. Although these non-conformities a meta-analysis based on a random

effects model was attempted to compare the results obtained in each study. A
qualitative assessment was also performed using CASP analysis. The CASP analysis
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is advantageous compared to other types of appraisal of articles, since it allows a

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qualitative study evaluation concerning validity, results and relevance. CASP checklists
also allow the assessment of their methodological quality.

An unavoidable methodological problem in all assessed papers was the

absence of a control group and, therefore, the lack of randomization. Villa9 and Villa19
justified it with the ethical difficulty of refraining from treating children with OSAS for 12
months. Pirelli29 explained that the decision was due to the short duration of the
therapy, and therefore the changes in the studied parameters would not have been
significant. However, a control group is not necessarily the absence of treatment, it can
be just a different therapeutic option, namely a different activation schedule.
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Another important limitation on quality assessment was the poor information
presented by the analysed publications regarding the study design, such as how
sample size was determined, the recruitment strategy, etc. Future studies would benefit
if the Consolidated Standards of Reporting Trials (CONSORT) guidelines were used to
orient the research design [32].

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CONCLUSIONS

Despite the limitations related to the heterogeneity found in the review studies, the meta-

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analysis results suggest that the RME has a significant effect on Obstructive Sleep Apnea
Syndrome improving the apnea-hypopnea index. Thus this therapeutic approach may be

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considered as an auxiliary in the treatment of children with OSAS risk factors such as
craniofacial abnormalities.

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Figure legends

Figure 1. Midsagittal plane of oropharyngeal airway before (a) and after (b)

RME

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Figure 2. Diagram of the results of the electronic search by database

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Figure 3. Diagram of the methodology used for selecting the studies

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Figure 4. Forest plot of the comparison between the AHI values before and after

RME therapeutic.

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Figure 5. Forest plot of AHI normalization after RME therapeutic.
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Table legends
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Table I. Reasons for studies exclusion

Table II. Characteristics of included studies

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Potencially relevant studies Main causes for non-selection
ACCEPTED MANUSCRIPT
Carvalho 2007(18) Does not evaluate RME

Cistullli 1996(10) Adult participants

Conley 2011(24) Review article

Eichenberger 2014(22) Review article

Grime 2015(25) Review article

Hultcrantz 2009(26) Does not evaluate RME

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Lim 2006(14) Adult participants

Rose 2006(8)

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Case report article

Tsuiki 2014(23) Letter to the editor

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Villa 2012(27) Does not evaluate RME

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Table I. Reasons for studies exclusion
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Age Methods AHI (no/h)
Follow-
Author mean at Used Follow-up
Study design Participants up Conclusions
year Aim baseline appliance Anchorage Activation Baseline 4 6 12 36
period
(range) months months months months
To assess the outcome on Fixed two-
Second
cardiorespiratory band RME 2 turns a AHI
Nonrandomized 9 6.40 deciduous
Miano parameters. To analyze the appliance day for the 12 17.4 decreased
controlled (6 males and ±1.97 molars of --- --- 5.4 ±6.3 ---
2009 NREM sleep microstructure with an first 10 months ±21.0 significantly
clinical trial 3 females) (4-8) the upper
before and expansion days* (ρ=0.05)
jaw
after RME treatment. screw
To study whether RME Fixed band First molars Most of

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therapy in the upper jaw 42 RME and First day: 6 patients
Nonrandomized
Pirelli could improve both the (26 males 7.3 appliance premolars turns; after: 12 present a
controlled 12.2 ±2.5 --- --- 0.5 ±1.2 ---
2005 patency of the nasal and 16 (6-13) with an or second 2 turns a months normalization
clinical trial

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airways and OSAS. females) expansion deciduous day** of recording
screw molars with AHI
To describe how rapid Fixed band First molars Most of

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maxillary expansion may 60 RME and First day: 6 patients
Nonrandomized
Pirelli improve the patency of the (38 males 7.3 appliance premolars turns; after: 4 present a
controlled 16.3 ±2.5 0.8 ±1.3 --- --- ---
2010 nasal airway and 22 (6-13) with an or second 2 turns a months normalization
clinical trial
and to which extent it may females) expansion deciduous day** of recording

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improve pediatric OSAS. screw molars with AHI
To assess at 12-month
Fixed two-

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follow-up the effectiveness Second AHI
band RME 2 turns a
Nonrandomized of an RME as an early 16 deciduous diminished
Villa 6.9±2.2 appliance day for the 12
controlled orthodontic (9 males and molars of 5.8 ±6.8 --- 2.7±3.5 1.5 ±1.6 --- significantly
2007 (4.5-10.5) with an first 10 months
clinical trial treatment for OSAS in 7 females) the upper (ρ=0.05)
expansion days*

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young children with dental jaw from baseline
screw
malocclusion.
To evaluate the long-term

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outcome in
the same group of young
children (aged 4–10 years) Fixed two- AHI

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Second
with band RME 2 turns a decreased
Nonrandomized 10 deciduous
Villa dental malocclusion appliance day for the 36 significantly
controlled (5 males and 6.6±2.1 molars of 6.3 ±4.7 --- --- 2.4 ±2.0 2.3 ±1.7
2011 successfully treated with with an first 10 months (ρ=0.05)
clinical trial 5 females) the upper
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RME by expansion days* from baseline
jaw
assessing sleep screw to 12 months
respiratory parameters and
the clinical sign
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and symptoms of OSAS

Table II. Characteristics of included studies
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*until the palatal cusp of the upper molar came into contact with the buccal cusp of the lower molar
**active expansion ranges from 10 to 20 days according to individual needs
AHI – Apnea-hipopnea index
NREM – Non-rapid eye movement
RME – Rapid maxillary expansion
OSAS – Obstructive sleep apnea syndrome
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