Three-dimensional assessment of the nasopharyngeal airway in Down syndrome during the mixed dentition period: a case-control study

Down syndrome (DS) is the most common chromosomal condition and has various clinical manifestations.¹  It occurs in approximately 1 per 800 births worldwide. In Japan, DS occurs in approximately 2200 live births annually, approximately 22 per 10,000.²  The potential for development and socialization of patients with DS has increased in recent years. Patients with DS often have congenital heart disease, infections caused in part by immunodeficiencies, neurodevelopmental disorders, and orthopedic problems.³  Sleep disorders, thyroid abnormalities, and dysphagia are also symptoms related to DS.³ 

It has been reported that obstructive sleep apnea (OSA) sometimes occurs in children from the neonatal stage to adolescence,^4,5  and children with DS have higher prevalence rates of OSA (32–66%).^6–11  The pathophysiology of pediatric OSA is often associated with upper airway collapsibility, anatomic narrowing of the nasopharyngeal airway, neuropsychological dysfunction, or a combination of these.^4,5  Anatomic narrowing of the airway in children is caused by adenotonsillar hypertrophy, obesity, inflammation of the upper airways, micrognathia, macroglossia, nasal obstruction, and craniofacial anomalies.^4,5  Particularly in children with DS, it is known that OSA is associated with anatomic and physiologic factors, such as midfacial and mandibular hypoplasia with relative macroglossia, a high-arched and narrow palate, adenoid and tonsil hypertrophy, incomplete tracheal rings, muscular hypotonia, and obesity.^12,13 

Various factors that cause airway obstruction also affect craniofacial growth.¹⁴  Airway obstruction can cause skeletal alterations during the growth period, and this condition is commonly known as “long adenoid facies.” Characteristics of the long adenoid face include increased lower facial height and mandibular plane angle and constriction of the maxillary dental arch.¹⁵  Therefore, improvement of airway obstruction at an early growing stage is a key strategy for achieving correct craniofacial development.

Three-dimensional (3D) assessment of the nasopharyngeal airway, including volumetric analysis, allows a more detailed understanding of the anatomical differences of each individual. Cone-beam computed tomography (CBCT) facilitates accurate craniomaxillofacial assessment¹⁶  and has recently been used as an effective tool to evaluate the nasopharyngeal airway.^17–20  Although the anatomical difference in the nasopharyngeal airway is known to be a risk factor for OSA, few authors have measured and assessed the nasopharyngeal airway in patients with DS.²¹  In addition, no authors have used CBCT to evaluate the nasopharyngeal airway in patients with DS during the growing stage.

The aim of the present study was to assess the nasopharyngeal airway volume and potential anatomic risk of OSA in children with DS and compare the findings with those of control participants well matched for sex and age.

This retrospective, cross-sectional study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The participants included 15 children with DS (mean age = 9.43 ± 0.38 years; 8 boys, 7 girls) and 15 non-DS children (mean age = 9.51 ± 0.40 years; 8 boys, 7 girls) who visited the Department of Orthodontics, Showa University Dental Hospital, from August 2016 to August 2020. Participants with a history of cleft lip and palate, tracheomalacia, laryngomalacia, tonsillectomy, adenoidectomy, or previous orthodontic treatment were excluded. Participants in the control group were age and sex matched to the DS participants. The participants were classified according to their anteroposterior skeletal pattern using the ANB angle: Class I = −1° ≤ ANB < 4°; Class II = ANB ≥ 4°; and Class III = ANB < −1°.^22,23  Vertical skeletal patterns were classified using the angle of the Frankfort horizontal (FH) plane to the mandibular plane (MP; FH/MP): hypodivergent = FH/MP < 22°; normodivergent = 22° ≤ FH/MP < 30°; and hyperdivergent = FH/MP ≥ 30°.²³  Patient demographics are shown in Tables 1 through 3 and Figure 1. Written informed consent was obtained from all participants and/or their parents, and the study was approved by the Ethics Committee of Showa University Dental Hospital (Approval No. SUDH0077).

CBCT examination was carried out for all participants to evaluate skeletal malocclusion and deformity, the skeletal relationship between the maxilla and mandible, impacted permanent teeth, the size of the permanent teeth to calculate arch length discrepancy, congenitally missing teeth, and condition of the temporomandibular joint. CBCT images were taken with a KaVo 3DeXam (KaVo Dental, Biberach, Germany). The scanning conditions were set at 120 kV and 5 mA, the voxel size was 0.4 mm, and the scanning time was 8.9 seconds. Participants were seated comfortably, with a natural head position after adjustment of the chin rest, and were asked to bite but not move or swallow during the scan. The CBCT images were saved in Digital Imaging and Communication in Medicine format.

To evaluate the nasopharyngeal structures, the CBCT images were examined using Invivo5 dental radiology software (Anatomage, San Jose, Calif). The images were reoriented, using the FH plane as a reference plane to standardize the measurements and to minimize errors (Figure 2).^19,20  The FH plane was defined by right and left porions (the most laterosuperior point of the external auditory meatus) and the right and left orbitales (the most inferior point of the lower margin of the bony orbit). Five cross-sectional planes: the anterior nasal plane (Ana), posterior nasal plane (Pna), upper pharyngeal plane (Uph), middle pharyngeal airway (Mph), inferior pharyngeal airway (Iph), and five volumes of the pharyngeal airway were configured (Table 4). The five cross-sectional planes were defined as Ana was perpendicular to the FH plane through the anterior nasal spine; Pna was perpendicular to the FH plane through the posterior nasal spine; Uph was parallel to the FH plane through the posterior nasal spine; Mph was parallel to the FH plane through the caudal margin of the soft palate; and lph was parallel to the FH plane through the superior margin of the epiglottis. The five pharyngeal airway volumes were defined as the nasal airway was the airway formed by the anterior and posterior nasal planes; the superior pharyngeal airway was the airway formed by the posterior nasal plane and the upper pharyngeal plane; the middle pharyngeal airway was the airway formed by the upper and middle pharyngeal planes; the inferior pharyngeal airway was the airway formed by the middle and lower pharyngeal planes; and the total airway was the airway extending from the anterior nasal plane to the lower pharyngeal plane.

To separate and extract the airway space from the craniofacial region, a threshold tool with the histogram adjusted as a guide to −523.9 Hounsfield units was used.^20,24  The defined nasopharyngeal airway volumes were calculated in cubic millimeters, and the airway width, length, and area were measured in the sectional views (frontal and axial) in the cross-sectional lines (Figures 2 and 3). Reconstructed volumes were calculated automatically; lengths in the cross-sectional plane were measured manually; and areas were measured automatically.

Statistical analyses were performed using SPSS Statistics, version 25 (IBM Corp., Armonk, NY). To assess intraoperator error, all measurements on the CBCT images were remeasured at a separate session with a 2-week or greater interval under identical conditions. The measurement error was estimated according to intraclass correlation coefficient (ICC) assessment. The Shapiro-Wilk test and Leven’s test were used to confirm normality and equality of variance among the measurements. Analysis of covariance (ANCOVA) with Bonferroni post hoc pairwise comparison tests for the corrected means were used to compare the 26 measurements of the volume, area, and length of the nasopharyngeal airway among the groups and between individual differences, with body height and body weight as covariates. Additionally, as covariates with the ANB angle and the mandibular plane angle, ANCOVA with Bonferroni post hoc pairwise comparison tests were also conducted. Significance probability adjusted with Bonferroni was set at P < .0019.

Power analyses were performed using G*Power Ver. 3.1.9.4 (Franz Faul, Universität Kiel, Germany) to calculate a priori required sample sizes at a two-sided significance level of 5% and a power of 80%. A sample size of at least 14 patients for each group was calculated to be adequate to detect the difference in total airway volume as a primary measurement between control and DS patients, assuming mean volumes of 21,000 mm³ and 17,000 mm³, respectively, with a common standard deviation of 3600 mm³. Post hoc power analysis was also carried out using G*power version 3.1.9.6 (Franz Faul) for calculation of detection power at a two-sided significance level of 5% and a sample size of 15 in each group.

ICC analyses revealed an average score of 0.94. The random error evaluation according to the ICC indicated that the magnitude of measurement error was sufficiently small.

Table 5 shows the descriptive statistics for the volumetric and two-dimensional measurements of the nasopharyngeal airway for DS and control participants.

Table 6 shows the ANCOVA results adjusted for body height and body weight, and Table 7 shows ANCOVA results adjusted for ANB angle and mandibular plane angle. In the ANCOVA results adjusted for ANB angle and mandibular plane angle, the nasal airway, superior pharyngeal airway, and total airway volumes were significantly smaller in the DS group than in the control group. The ANCOVA results adjusted for ANB angle and mandibular plane angle showed significant differences for the nasal airway (P = .000), superior pharyngeal airway (P = .000), and total airway (P = .000). However, no significant differences were found in the volume measurements in the ANCOVA results adjusted for body height and body weight. The post hoc detection powers were 100.0%, 100.0%, 100.0%, 27.4%, and 100.0% for the nasal pharyngeal airway, superior pharyngeal airway, middle pharyngeal airway, inferior pharyngeal airway, and total airway volumes, respectively.

In the cross-sectional plane, significant differences were found in both the ANCOVA results adjusted for body height and body weight and the ANCOVA results adjusted for ANB angle and mandibular plane angle for the right-side Ana width and the right-side Pna width. Significant differences were also found in the ANCOVA results adjusted for ANB angle and mandibular plane angle in the right-side Ana area, the Ana height on both sides, the left-side Pna width, and the Uph width, but not in the ANCOVA results adjusted for body height and body weight (Tables 6 and 7). The post hoc detection power for the areas in the cross-sectional plane was 95.4% to 100.0%. For differences in the right- and left-side Pna heights, the post hoc power values were 14.5% and 6.7%, respectively. The post hoc power values for other widths and heights were 66.6% to 100.0%.

This was the first study to evaluate the nasopharyngeal airway in children with DS during the mixed dentition period using CBCT and to compare the results with those of control participants who were well matched for age and sex. Although some volumetric analyses and linear and area measurements in the nasopharyngeal airway were not significantly different between the DS and control participants, the results obtained from the analysis and measurements indicated that the nasopharyngeal airway tended to be constricted in children with DS compared with control participants.

Midfacial hypoplasia, high-arched palate, and narrow maxilla are common anatomic abnormalities in nasal airway constriction.^{4,5,13,21,25,26}  These features of patients with DS may be correlated with nasal and nasopharyngeal airway constriction.^27,28  Additionally, micrognathia and the mandibular position affect inferior pharyngeal airway constriction, especially in children with a hyperdivergent, long face (ie, with a higher mandibular plane angle).^4,29  As previously reported, a small mandible is also a feature of patients with DS,²⁵  so it is possible that the micrognathia caused narrowing of the pharyngeal airway. A hypodivergent (ie, brachycephalic) mandibular position with easily enlarged airways is characteristic of patients with DS,^30,31  and two-thirds of the participants with DS in this study were hypodivergent. The results also suggested no significant differences in the middle pharyngeal airway and inferior pharyngeal airway volumes. One possible explanation for these results relates to the characteristics of craniofacial morphology. However, El and Palomo³²  reported no significant differences in middle pharyngeal airway and inferior pharyngeal airway volumes compared with patients who required orthodontic treatment with rapid expansion (ie, patients with a constricted maxillary arch) and a control group without rapid expansion. Patients with DS often need orthodontic treatment with rapid expansion because of a small maxilla. Therefore, the participants in the current study and the study of El and Palomo³²  had similar characteristics. These results indicate that midfacial hypoplasia may not greatly affect the volume of the middle pharyngeal and inferior pharyngeal airways. Craniofacial morphology and position are considered key factors related to the pharyngeal airway volume; however, further verification is required in DS patients.

Although no significant differences were found in the linear and area measurements of the Uph cross-sectional plane in ANCOVA results adjusted for body height and body weight, the results in DS participants were smaller than those of control participants. These results indicate that children with DS may have adenoid and tonsil hypertrophy. In support of these results, authors of previous studies on OSA reported that patients with DS had enlarged adenoids and/or tonsils.^13,33  Adenoid and tonsil hypertrophy might be another risk factor caused by constricted airways in patients with DS.^13,33 

Several studies reported that orthodontic treatment with rapid maxillary expansion and/or acceleration of maxillary growth using a facial protractor was effective in increasing the nasopharyngeal airway volume.^32,34–42  These orthodontic treatments may therefore have potential to relieve pediatric OSA. The management of pediatric OSA is essential for proper craniofacial growth and development during the mixed dentition period.

This study had some limitations. First, the sample size was small, and the detection power of the inferior pharyngeal airway volume and some area and linear measurements was insufficient. Further studies are required with larger sample sizes. Second, the anteroposterior and vertical skeletal pattern was heterogeneous because the control group in the present study was made up of age- and sex-matched individuals. Third, adenoid and tonsil hypertrophy was not considered in these measurements because CBCT does not accurately detect soft tissues. Fibroscopy assessment of the condition of the adenoids and tonsils should be included in further research. The findings of the present study indicate that these conditions are more likely to be potential risk factors for OSA. 3D assessment in the craniofacial region using CBCT is important not only for orthodontic treatment but also to detect potential anatomical risks for OSA.

• The findings of the present study indicate that the nasopharyngeal airway volume of DS participants tended to be smaller than that of control participants.

We express our thanks to the patients, their families, and medical staff members. This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research© (No. 21K10195).