Protocol and Registration

This systematic review was written as closely as possible according to the PRISMA guidelines and recommendations.¹⁹ The protocol of this systematic review was registered in PROSPERO (CRD42019127386) and can be accessed at https://www.crd.york.ac.uk/prospero/.

Eligibility Criteria

The eligibility criteria were articles without restriction of language and year of publication; prospective studies and randomized controlled trials (RCTs); studies involving patients in the primary, mixed, or early permanent dentitions who underwent conventional RME; studies that analyzed the influence of RME on NE in the short (until 1 year of follow-up) or long term (more than 1 year of follow-up); and studies that analyzed the primary and secondary outcomes using questionnaires, laboratory tests, and/or medical examinations.

Exclusion criteria consisted of retrospective studies, studies that treated patients with history of previous orthodontic treatment, studies that associated RME with other orthodontic or medical treatment modalities; studies including patients diagnosed with urological, nephrologic, endocrine or neurologic disorders, cleft lip and palate, and/or craniofacial syndromes; and case reports, case series, expert opinions, literature reviews, and animal model experimental studies.

Information Sources

An extensive search of the available scientific literature was carried out both electronically and manually until March 2020. The electronic search was performed with the assistance of a librarian specialized in searches in the health sciences area databases. The databases searched included PubMed/MEDLINE, Cochrane library, Scopus, Science Direct, Google Scholar, and LILACS. Unpublished literature was also searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database.

The references of each selected study were searched manually to identify articles that were not found by the electronic search. Contact with study authors was not necessary.

Search

The search strategy used in all databases included the combination of the following MeSH terms and synonyms: “palatal expansion technique”, “palatal expansion technic”, “maxillary expansion”, “enuresis”, and “nocturnal enuresis”. The search methodology is listed in Table 1.

Table 1. Search Methodology for Electronic Systematic Review

View Fullscreen

Study Selection

Evaluation of the selected articles was staged in a two-step process to determine eligibility. First, two reviewers (Dr Padilha and Dr Barbalho) independently and blindly selected the studies by reading the title and abstract. Then, decisions for final eligibility were made based on full-text assessments by the same reviewers. Any disagreements between reviewers were solved by discussion or by introduction of a third reviewer (Dr Alves) to mediate when deemed necessary.

Data Collection Process

Data collection was done in duplicate. Key features of eligible articles were documented by each reviewer. Kappa tests were used to analyze interexaminer concordance level both after the selection of the articles and the quality assessment of the final studies.

Data Items

The primary data extracted from each study were as follows: author, year of publication, study design, sample size, study groups, dentition stage, type of expander, amount of expansion, follow-up period, respiratory disorders, and methods of assessment of respiratory disorders and NE. The characteristics of the included studies are summarized in Table 2.

Table 2. Summary of Study Characteristics and Results of the Included Studies

View Fullscreen

Table 2. Extended

View Fullscreen

Risk of Bias in Individual Studies

The non-randomized studies that met the inclusion criteria were assessed qualitatively using the Risk Of Bias In Non-randomized Studies for Intervention tool (ROBINS-I),²⁰ which is an updated version of the ACROBAT-NRSI.²¹

For the overall risk of bias, these studies were categorized according to the following: low risk of bias (the study was comparable with a well-performed randomized trial), moderate risk of bias (the study was sound for a non-randomized study but cannot be considered comparable with a well-performed randomized trial), serious risk of bias (the study had important problems), critical risk of bias (the study was too problematic to provide any useful evidence on the effects of the intervention), or no information (no information on which to base a judgement of risk of bias).

On the other hand, the Revised Cochrane Risk-of-Bias tool (RoB 2)²² was used to qualitatively assess the selected randomized controlled clinical trial. The study could be categorized as “low” risk of bias, “some concerns,” or “high” risk of bias.

Risk of Bias Across Studies

The level of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).²³ For the outcome examined, the GRADE assesses the study design, risk of bias, inconsistency, indirectness, imprecision, and publication bias. Based on this assessment, the certainty of the evaluation of the outcome could be very low, low, moderate, or high quality.

Summary Measures

The main summary measures were the mean difference and the relative and absolute frequencies of the NE episodes recorded during the pre-expansion and postexpansion periods.

Study Selection

A total of 488 articles were found with the initial electronic search. After reading the titles and abstracts of these studies, 26 articles were selected. Only eight articles remained after removal of duplicates. No additional articles were found after the manual search in the references of those studies. Considering eight articles met the inclusion criteria, all were analyzed in this systematic review. The search process is illustrated in the flowchart (Figure 1). Kappa test was performed after article selection and showed an almost perfect interexaminer agreement of 0.85.²⁴

View Figure

• Download as Powerpoint
• Download Figure

Study Characteristics

The characteristics of each included study are summarized in Table 2. In general, the selected articles were published between 1990 and 2020 in medical and dental journals and consisted of seven non-randomized prospective studies^{10–13,25–27} and one randomized controlled trial.²⁸

The sample sizes of the studies were quite variable, and only one article¹³ showed control group composed of untreated patients. The patients were either in the mixed or early permanent dentitions.^10–13,26 Separation of midpalatal suture was accomplished in all patients. The most widely used expander was the Hyrax-type.^{12–14,28–30} The amount of expansion obtained ranged from 4 mm²⁵ to 8.2 mm,¹³ and the reduction of NE episodes was analyzed in both the short (6 months²⁸ and 8 months²⁵) and the long term (13 months,^26,27 36 months,^12,13 48 months,¹⁰ and 120 months¹¹) by means of questionnaires,^11–13 interviews with patients' parents,^10,25–27 registration of NE episodes on a voiding chart,²⁸ registration of daytime voided volumes and nocturnal urine production via weighing of diapers or sheet covers,²⁸ polysomnography examinations,²⁷ and laboratory tests of osmolality of the blood plasma to quantify the level of ADH.¹²

Finally, participants of all studies were diagnosed with at least one of the following respiratory disorders: mouth breathing,^{10,11,13,25,28} mixed breathing,²⁵ respiratory tract infections,¹³ snoring,^13,26,28 adenoid hypertrophy,^10,24 amygdala hypertrophy,^10,13,25 nasal septum deviation,²⁵ and/or nasal obstruction.^25–27 The methods used for diagnosis were medical examinations,^{10–12,25,26,28} rhinomanometry,^{10–12,25,27} acoustic rhinomanometry,^26,27 polysomnography,^26,27 cone-beam computed tomography,¹² and/or anamnestic questionnaire.¹³

Risk of Bias Within Studies

The risk of bias of individual studies is shown in Table 3 and Figure 2. Kappa tests were performed after the quality assessment of the studies and showed an almost perfect interexaminer agreement of 0.83.²⁴

Table 3. Assessment of Risk of Bias Using ROBINS-I

View Fullscreen

Table 3. Extended

View Fullscreen

View Figure

• Download as Powerpoint
• Download Figure

Risk of Bias Across Studies

The certainty of evidence was evaluated according to the GRADE approach. The level of evidence for influence of RME on reduction of NE was graded as low, and the strength of recommendation was weak. Reasons for downgrading the evidence are detailed in Table 4.

Table 4. GRADE Evidence Profile About the Outcome Influence of Rapid Maxillary Expansion on Reduction of Nocturnal Enuresis Episodes

View Fullscreen

Results of Individual Studies

Eight studies were selected in this systematic review, and the results were described in Table 2.

Synthesis of Results

A meta-analysis was not possible. Methodologies of the selected studies were highly heterogeneous, posing a challenge for combining results together. In addition, some authors did not clearly describe the number of episodes of NE of patients during the pre-expansion and postexpansion phases.

Summary of Evidence

NE is considered a chronic health problem that compromises quality of life of children.²⁹ Therefore, it must be appropriately treated when diagnosed during childhood and adolescence.²⁹ A recent study found that children who responded successfully to medical treatment of NE showed significant improvement in quality of life and behavior compared with patients who did not.³⁰ In general, medical treatment of NE involves behavioral therapy, psychotherapy, use of urinary alarms, and/or drug therapy with desmopressin, anticholinergics, or tricyclic antidepressants.³¹ The etiology of NE is still unclear and has been associated with genetic, psychological, and physiological factors, such as delay in normal bladder control, sleep apnea, and upper airway obstruction.^15–18 Considering RME significantly reduces nasal airway resistance, it has been suggested as a complementary alternative to NE treatment.¹¹

In the 1990s, orthodontists suggested for the first time that RME might reduce NE episodes in mouth-breathing children with maxillary constriction.⁹ Although some clinical studies have been performed over the past decades,^{10–13,25–27} the present systematic review showed only one randomized controlled clinical trial²⁸ investigating this issue. It showed a low risk of bias for all domains assessed (Figure 2). It is important to highlight that scientific community encourages researchers to develop RCTs because that is the experimental study design in humans that shows the greatest scientific evidence.³²

The non-randomized prospective studies^{10–12,25–27} analyzed in this systematic review showed risk of bias that varied from low to moderate (Table 3), resulting in a low level of certainty that weakens the recommendation of RME as an auxiliary treatment for NE (Table 4). Thus, the results of the selected studies must be interpreted with caution. However, the elaborate efforts in searching an unusually large number of databases provided some safeguard against missing relevant studies. Thus, the evidence summarized in this review is likely to be as good as it will get for the foreseeable future.

The lack of randomization and allocation concealment of participants was observed in the non-RCT studies (Table 3). These methodological flaws are commonly associated with increased risk of selection bias. Similarly, the lack of control group was observed in six studies.^{10–12,25–27} A control group with untreated children would be important in these clinical studies to control confounding variables that might have contributed to the improvement of NE and a possible overestimation of RME effects, such as growth, psychological maturation, spontaneous reduction of adenoids, and/or improvement of sleep hygiene. Only one study¹³ had a control group with untreated participants, two^12,27 used the expander passively during the pre-expansion period, and one²⁸ used the sham appliance to simulate a placebo effect.

All selected studies considered NE as the main eligibility criterion for patients' recruitment. However, some of these studies included patients without maxillary constriction in the sample^10,11,27 or did not cite whether patients had transverse malocclusions or normal occlusion.^12,13,25,26 Ideally, the presence of maxillary constriction should also be an eligibility criterion since recent studies have shown a correlation between transverse malocclusions, narrowing of the upper airways, OSAS, and NE.³³ In addition, the studies did not standardize the amount of maxillary expansion performed in the samples. This may be a problem because the minimum amount of expansion necessary to accomplish the skeletal effects on the palate and nasal cavity to improve air permeability and oxygen saturation to significantly reduce episodes of NE remains unknown.³⁴

Only three studies^12,26,28 showed greater credibility regarding the cause and the diagnosis of NE in the sample, since the participants were submitted to previous nephrologic, neurologic, and pediatric evaluations. The participants of the other selected studies underwent only an otorhinolaryngological evaluation to diagnose respiratory disorders. Similarly, evaluations with otorhinolaryngologists are necessary in both the pre-expansion and postexpansion periods to confirm the improvement in patients' nasal breathing. This is important since the reduction of NE episodes seems to be associated with improvement in sleep hygiene consequent to the improvement of nasal breathing after RME.^17,18

The CONSORT statement emphasizes the importance of a detailed description of results to prevent reporting bias in clinical studies.³⁵ Some articles^10,11,13 of this systematic review did not clearly describe the improvement of NE using the mean or the absolute values of episodes observed in both the pre-expansion and postexpansion periods. In some cases, for example, the authors¹⁰ reported that patients had NE episodes occasionally in the posttreatment period. The term occasionally confers subjectivity to the analysis, and the lack of quantification of NE episodes reduced the reliability of the results.

The most commonly used method to analyze the influence of RME on NE was interviews with the patients' parents using questionnaires. The parents were asked to report the daily, weekly, and monthly number of episodes of NE during a follow-up period that varied from 6 months²⁸ to 10 years.¹³ Attention is required to the high risk of data underestimation associated with this method of analysis, because the quantification of NE episodes was dependent on the memory and the notification to parents regarding the occurrence of bedwetting.

Finally, the difficulty in quantifying the number of NE episodes must be recognized since there is no laboratory test that accurately evaluates the improvement of NE. Although the blood plasma osmolality test is a reliable method for analyzing the concentration of antidiuretic hormone,¹² the correlation between ADH secretion and NE is not yet a consensus in the literature. In addition, the improvement in NE should be carefully analyzed, especially in studies assessing the patient during a long follow-up period, since NE has a multifactorial etiology and growth, patient psychological maturation, spontaneous reduction of adenoids, and/or improvement of sleep hygiene might have influenced the reduction of the number of episodes.

Limitations

Limitations are associated with the high risk of bias of the selected studies and the low level of certainty due to the lack of randomization and allocation concealment of participants, the lack of control groups, incomplete description of eligibility and exclusion criteria, the lack of blinding during outcome analysis, and reporting bias. In addition, these results should be generalized only for children with respiratory disorders in the mixed and early permanent dentitions who underwent conventional RME.