Keywords craniofacial phenotype - pediatric - obstructive sleep apnea - phenotyping methods
Introduction
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or
complete upper airway obstruction during sleep leading to episodes of hypopnea and/or
apnea and sleep disruption. In pediatric patients, these lead to daytime symptoms
such as hypersomnolence, mood changes, enuresis, hyperactivity, trouble focusing,
and poor performance in school. This represents a significant health concern in the
growing patients as it may negatively impact neurocognitive development, cardiovascular
health, and overall quality of life later in adulthood.[1 ]
[2 ] The cause of OSA in pediatric patients is commonly associated with abnormalities
in the anatomical form of the upper airway.[3 ]
[4 ] Several craniofacial features of the developing patients were found to play a crucial
role in the pathophysiology of pediatric OSA.[5 ]
[6 ]
[7 ] Identifying these factors would give some guidance to frontline clinicians, such
as family physicians, dentists, and other healthcare practitioners, to detect and
screen for OSA risks. This allows for an early interceptive intervention before using
more complex or invasive diagnostic approaches, like polysomnography (PSG) or drug-induced
sleep endoscopy (DISE).
One of the main objectives of phenotyping is to minimize and manage the heterogeneity
of presenting symptoms, etiopathophysiology, diagnostic variations, and treatment
outcomes in pediatric OSA associated with craniofacial phenotypes. Classifying the
disorder into a systematic characterization of craniofacial morphology will provide
a more homogenous phenotype.[8 ]
[9 ] This phenotyping has emerged as a valuable tool in pediatric OSA research and clinical
practice which can provide insights into the underlying mechanisms of airway obstruction
and facilitate risk stratification, diagnosis, and treatment planning. Given the crucial
role of dental surgeons and orthodontists in addressing the craniofacial phenotype
associated with pediatric OSA, it is imperative for medical professionals across disciplines
to adeptly identify patients who stand to benefit from early interceptive dental treatments
through comprehensive craniofacial phenotyping.[10 ]
[11 ]
[12 ]
[13 ]
Current methods in identifying craniofacial phenotypes for pediatric OSA encompass
a range of approaches aimed at characterizing anatomical features of the hard and
soft tissues in terms of size, shape, and position, that may contribute to airway
obstruction during sleep. These features involve graded and structured clinical assessment
of the facial structures, such as Mallampati score and the Friedman tongue position,
Brodsky grading and nasofiberendoscopy (NFE) scoring of the adenotonsils,[14 ]
[15 ]
[16 ]
[17 ]
[18 ] the dentofacial relationship and morphology,[19 ]
[20 ]
[21 ] as well as the adipose tissue under the chin. Other important craniofacial assessment
includes a comprehensive dental and occlusal assessment with classification of dental
occlusion, arch width, and palatal vault. Recent studies found that malocclusion with
restricted maxilla, retruded mandible, and distal molar occlusion were predictive
factors of OSA in children.[22 ]
[23 ]
Several imaging techniques were also employed in craniofacial phenotyping to accurately
assess craniofacial morphology and its relationship to OSA risk. Lateral cephalometric
analysis evaluates the cranial base angle, mandibular plane angle, and pharyngeal
airway dimensions through several landmarks in the cephalogram.[24 ]
[25 ]
[26 ]
[27 ] Current technology of imaging such as cone-beam computed tomography and surface-based
3D imaging (photometry /3D photographic analysis) can provide detailed representation
of the craniofacial morphology allowing precise quantification of landmarks and volumes
that may predispose to OSA.[17 ]
[28 ]
[29 ]
[30 ]
Despite the wealth of available methods, there exists a notable lack of standardization
of methods across studies, in particular, the research methodology, and the data collection
such as appropriate cephalometric measurements leading to variability and inconsistency
in phenotypic assessment.[5 ]
[7 ]
[31 ] The importance of standardization in these assessment methods for craniofacial phenotyping
in pediatric OSA cannot be overstated. Standardization refers to the establishment
of uniform protocols, criteria, and measurement techniques to ensure consistency,
reproducibility, and comparability of results across studies and clinical settings.[32 ] Multiple benefits can be achieved in standardizing the assessment of craniofacial
phenotyping methods in pediatric OSA.[8 ]
[9 ]
[33 ] Of paramount advantage is the ability of these phenotyping methods to increase the
statistical power, as well as reduce the risk of measurement error and bias, thereby
facilitating comparison across studies. These attempts lay the groundwork to establish
craniofacial phenotypes in OSA while advancing precision medicine in pediatric OSA.
A one-treatment-fits-all approach of CPAP in the management of OSA should not be the
standard approach in pediatric OSA.
Considering the benefits, the standardization of phenotyping methods for craniofacial
assessment in pediatric OSA represents a critical imperative for advancing research,
clinical practice, and patient care in this field. This systematic review aims to
1) explore the current landscape of phenotyping methods, 2) identify existing gaps
and challenges in standardization efforts, and 3) provide recommendations for future
research and clinical practice to promote uniformity and consistency in craniofacial
phenotyping approaches for pediatric OSA.
Methods
This systematic review protocol on the methods of craniofacial phenotyping in pediatric
OSA was developed following PRISMA reporting guidelines.[34 ]
Search Strategy and Eligibility Criteria
A comprehensive search strategy using multiple databases was employed to find relevant
studies up to the year 2023. A consultation with a specialized health-sciences librarian
was done to ensure resources were suitable. Electronic searches using a series of
keywords and keyword combinations based on the knowledge of the subject-area controlled
vocabulary, free-text terms, and use of Medical Subject Headings were done. Reference
lists in the selected articles were also reviewed during the article screening process.
The databases searched include MEDLINE via PubMed, the Cochrane Central Register of
Controlled Trials, BMJ Online Journals, ScienceDirect, and Scopus. The search syntax
consisted of three concepts: obstructive sleep apnea (OSA), pediatric population,
and craniofacial phenotype. The MeSH term used for OSA included “sleep apnea, obstructive,”
“obstructive sleep apnea” and “obstructive sleep apnea syndrome”; for the pediatric
population included “child” and “adolescent” and for craniofacial phenotype included
“craniofacial abnormalities” and “facial bones.” These concepts were used during the
search by adding the Boolean operator AND. [Table 1 ] shows the search strategy with the MeSH and terms used.
Table 1
Concepts, MeSH terms and Keywords used for search strategy
Concept
MeSH Term
Keywords
Obstructive sleep apnea
“Sleep Apnea, Obstructive” [MeSH]
“Obstructive Sleep Apneas” [MeSH]
“Obstructive Sleep Apnea Syndrome” [MeSH]
“Obstructive Sleep Apnea”[tiab]
OSA[tiab]
OSAHS[tiab]
“Syndrome, Sleep Apnea, Obstructive”[tiab]
“Sleep Apnea Syndrome, Obstructive”[tiab]
“Apnea, Obstructive Sleep”[tiab]
“Sleep Apnea Hypopnea Syndrome”[tiab]
“Syndrome, Obstructive Sleep Apnea”[tiab]
“Upper Airway Resistance Sleep Apnea Syndrome”[tiab]
“Syndrome, Upper Airway Resistance, Sleep Apnea”[tiab]
Pediatric population
“Child”[MeSH]
“Adolescent”[Mesh]
Adolescen*[tiab]
Teen*[tiab]
Teenage*[tiab]
Youth*[tiab]
“Adolescent*, Female”[tiab]
“Female Adolescent*”[tiab]
“Adolescent*, Male”[tiab]
“Male Adolescent*”[tiab]
Preschool[tiab]
Child*[tiab]
Craniofacial phenotype
“craniofacial abnormalities” [MeSH]
“Facial bones” [MeSH]
“Craniofacial morpholog*”[tiab]
“Craniofacial featur*”[tiab]
Dentofacial[tiab]
“Facial skeletal”[tiab]
“Maxillomandibular”[tiab]
“Jaw*”[tiab]
The inclusion and exclusion of articles were guided by the PICO question: “In nonsyndromic
pediatric patients diagnosed with obstructive sleep apnea, how are the craniofacial
and dental phenotypes being assessed?” The articles focused on (P) nonsyndromic pediatric
patients below the age of 18, (I) who were diagnosed with obstructive sleep apnea,
with their craniofacial phenotypes identified, and (C) compared with the non-obstructive
sleep apnea pediatric patients as control, evaluating the (O) variations in the method
of assessment of the craniofacial and dental features through clinical and imaging
([Table 2 ]).
Table 2
PICO Strategy for eligibility criteria
PICO
Description
Population
Non-syndromic pediatric patients, below 18 years
Intervention/Exposure
Diagnosed with OSA
Comparison
Non OSA as control
Outcome
Method of assessment of craniofacial and dental assessment
Study Selection
The review process for the searched articles involved two phases and two reviewers
(I.N.I and N.D.I). Initially, the articles underwent evaluation based on their titles
and abstracts. Subsequently, those selected proceeded to a thorough examination of
their full texts. Following these stages, further citations were identified by analyzing
the reference lists of all previously chosen articles. The articles identified went
through a similar review process for the selection. Lastly, the eligibility criteria,
which encompassed the specified PICO strategy and study types, were meticulously applied
during the analysis of articles.
Data Extraction and Outcome Synthesis
Data extraction was conducted meticulously to assess various types of phenotyping
methods employed across studies which was represented in a table together with other
important details such as the author, year of publication, and demographic features,
as well as their main results ([Table 3 ]). To ensure consistency and comparability across studies, rigorous standardization
measures were implemented during data extraction, encompassing predefined criteria
for inclusion, data abstraction protocols, and quality assessment tools. This extraction
was performed by 2 reviewers (I.N.I and N.D.I). The outcome synthesis involved a comprehensive
analysis of the extracted data, synthesizing findings across studies to elucidate
trends, patterns, and discrepancies in phenotyping methodologies and their respective
outcomes.
Table 3
Study Characteristics
Authors, Year, Type of Study
Age in Range or (Mean ± SD)
Body mass index (BMI)
Ethnicity
Control group
Criteria adopted to define or diagnose OSA
Methods used to assess craniofacial features
Manrikyan, 2023, CS
(35)
Mean 15.8 (1.08)
22.49 ± 4.25
(5 cases BMI >30)
Indo-European and Armenian
Nil
PSG (AHI ≥ 5)
Lateral cephalometry
Adenotonsillar assessment
Nasal septum
Oral breathing
Xu, 2023, CC
(38)
5–7 years and 8–10 years
BMI z-score 0.29 ± 1.03 and 0.92 ± 0.20 (OSA vs control)
Chinese
Low risk of PSQ and underwent lateral cephalogram
Pediatric Sleep Questionnaire (PSQ) >8
PSG (AHI >1)
Lateral cephalometry
Wang, 2023, CC (39)
5–12 years
BMI z score (0.88 OSA group*)
significant
Chinese
No snoring and OAHI ≤ 1/h
PSG (AHI >1)
OSA-18 questionnaire
Friedman tongue position
Brodsky tonsil grading
NFE adenoid grading
Craniofacial photogrammetry
Bozzini, 2022, CS (36)
4–9 years
BMI z-score categorization
Brazilians
Mild OSA
Level 2 PSG (AHI >1)
SDSC Questionnaire
Nasopharynx obstruction
Tonsil enlargement (Brodsky's grades 2, 3, 4)
Orthodontic assessment
Lateral cephalometry
Emsaeili, 2022, CC (40)
8–12 years (9.25 ± 1.08)
NR
Iranian
Healthy subject
Berlin questionnaire
CBCT Assessment
Lumbau, 2021, CS (37)
3–8 years
NR
Italian
PSG revealed no OSAS
Clinical sleep record
PSG
Dental assessment
Marino, 2021, OS (44)
5.2 - 6.1 years (5.8 ± 0.2)
NR
Caucasian
Nil
PSG with AHI >1
Dental impressions for dental assessments
Murakami, 2021, CC (41)
(10 ± 2.1)
BMI 17.4 ± 2.6
Japanese
ANB > 4 (mandibular retrusion vs normal)
Basal arch <65 (narrow vs normal)
Out-of-center sleep testing REI >1 and 3% ODI
Lateral cephalograms
Dental models
Hsu, 2021, CC (17)
4–16 years (7.9 ± 2.8)
18.4 ± 4.4
Taiwanese
No OSA with AHI ≤ 1
PSG with AHI > 5
CBCT Parameters
Lee, 2020, CC (28)
(5.14 ± 0.79)
15.38 ± 2.24
Taiwanese
Normal (AHI < 1)
PSG (Mild OSA =
< 5 (AHI) >1)
Digital measurements of scanned model
Lateral cephalometry
Ahmad, 2020, CC (42)
10–19 years
NR
Indians
Non OSA risk (STOP BANG≤2)
STOP-BANG 3–8
Extra and intra-oral examination
Lateral cephalometry
Inoshita, 2018, RS (18)
3–15 years
BMI and BMI z-score
Japanese
Gender comparison
PSG with AHI > 1
Tonsillar size
Lateral neck radiographs
Smith, 2016, CC (43)
2–12 years (4.7 ± 2.1)
BMI z score (0.45 ± 1.7 vs 0.37 ± 0.7)
Mixed ethnicities (White, Black, Hispanic, Asian, Mixed)
Healthy subjects, non-snoring
PSQ
PSG (AHI > 1)
Dental casts
Abbreviations: CC, case control; CS, cross sectional; NR, not recorded; OS, observational
study.
Other abbreviations, refer to list of abbreviations.
Results
Study Selection
Following the electronic search across databases and adhering to PRISMA guidelines,
the study selection process generated a total of 462 articles from the year 2004 to
2023. After removing duplicates, 431 articles were subjected to title and abstract
screening, leading to the exclusion of 339 studies deemed irrelevant for data evaluation.
Next, a total of 92 articles were sought for retrieval from the database for full-text
reading. However, 77 articles were not retrieved due to unavailable access to full
text. The remaining 31 articles underwent full-text review, of which 13 met the predefined
eligibility criteria and were incorporated into the systematic review ([Fig. 1 ]).
Fig. 1 Flowchart of study selection according to PRISMA guidelines.
Study Characteristics
[Table 3 ] reported the characteristics of the included studies, with details of the author,
year of publication, and the type of study; the demographic features including age,
body mass index, and ethnicity; control group description, criteria adopted to define
OSA, and methods used to assess the craniofacial features, and the upper airway were
systematically represented.
Among the 13 included studies, 3 presented a cross-sectional design,[35 ]
[36 ]
[37 ] 8 were case-control studies,[17 ]
[28 ]
[38 ]
[39 ]
[40 ]
[41 ]
[42 ]
[43 ] and one was an observational study.[44 ] There was a variability in the age range of patients in the studies, ranging from
2 to 19 years old. 5 articles used BMI z scores to classify the different degrees
of weight status.[18 ]
[36 ]
[38 ]
[39 ]
[43 ] Each of the articles has almost similar comparison groups where children with no
OSA (AHI≤1) were used as control. The criteria for the diagnosis of OSA used include
overnight polysomnography as well as multiple other types of questionnaires. The craniofacial
and airway assessment includes otolaryngological examination, extra-oral and dental
assessment, clinical photos, lateral cephalograms, and CBCT.
Craniofacial Phenotyping Methods
[Table 4 ] describes the clinical assessments done to assess the airway and the skeletal and
dental features that would contribute to OSA. Four studies assessed the airway patency
through adenotonsillar assessment using various scoring and grading scales, e.g.,
Brodsky tonsil grading and nasofiberendoscopy (NFE) adenoid grading.[18 ]
[35 ]
[36 ]
[39 ] Most articles that investigated the adenotonsills had positive significance in the
OSA group. The nasal and nasopharynx features were also recorded but none had any
positive findings that would contribute to OSA in children.[35 ]
[36 ] Tongue position was assessed in one article but did not show any significance in
the pediatric OSA group.[39 ]
Table 4
Clinical assessment of the airway, skeletal and dental
Authors (Year)
Airway Assessment
Skeletal and Dental Assessment
Positive findings
Manrikyan et al. (2023) (35)
Adenotonsillar assessment
Nasal septum
Oral breathing
NI
Tonsillar hypertrophy (14.6%)
Adenoid hypertrophy (51.2%)
Adenotonsillar hypertrophy (7.3%)
Bruxism (22%)
Oral breathing (34.1%)
Wang et al. (2023) (39)
Friedman tongue position
Brodsky tonsil grading
NFE adenoid grading
NI
NFE adenoid grading (0% in grade 1 and 39.6% in grade 4 for OSA group)
Tonsil hypertrophy (64.2%) in OSA group
Bozzini et al. (2022) (36)
Nasopharynx obstruction
Tonsil enlargement (Brodsky's grades 2, 3, 4)
Orthodontic assessment:
Facial profile
Lip seal
Overjet
Distooclusion (Angle Class II)
Crossbites
No significance
Lumbau (2021) (37)
NI
Dental assessment:
Angles classification
Molar relationship
Open bite
Crossbite
Overjet
Narrow palate
Crossbite
Narrow palate
Marino (2021) (44)
NI
Dental models:
Inter-canine and Inter-molar, Arch length on upper and lower arches.
Reduced upper inter-canine and inter-molar distance
Murakami (2021) (41)
NI
Dental models:
Based on Enoki and Motohashi measuring points (cite Enoki 1974)
Mandibular retrusion (ANB <4)
Reduced transverse maxillary dimensions
Lee et al (2020) (28)
NI
Digital measurements of scanned model (3shape Dental System D640, 3shapre A/S, Copenhagen,
Denmark)
Molar relation, Inter-canine width, Intermolar width, Upper arch length, Lower arch
length, Palatal height
No significance
Ahmad (2020) (42)
NI
Facial profile
Facial height
Mandibular plane
Faucial pillars and soft palate
Shape of upper and lower arch
Molar classification
Convex profile
Steep mandibular plane
Type 3 and 4 faucial pillars
Class II molar relationship
Ovoid upper arch form
Inoshita (2018) (18)
Tonsillar size
NI
Nil significance
Smith (2016) (43)
NI
Dental measurements:
Inter-tooth distance at D, E and 6
Palate height
Reduced inter-tooth distances for D, E, 6
Abbreviations: 6, first permanent molar; D, first primary molar; E, second primary
molar; NI, not indicated.
Other abbreviations, refer to list of abbreviations.
Skeletal and dental assessment was mainly assessed by dentists and orthodontists.
Seven articles investigated the orthodontic aspects of the OSA in children.[28 ]
[36 ]
[37 ]
[41 ]
[42 ]
[43 ]
[44 ] The extraoral skeletal examination involved the clinical assessment from the frontal
and profile, which includes anterior facial height, facial convexity on profile, and
the mandibular plane angle. Cumulatively, a convex profile with a steep mandibular
plane angle showed significance in the OSA group. Four studies used the dental models
for the accurate assessment of the dentition, measuring the horizontal distances between
teeth across the arch.[28 ]
[41 ]
[43 ]
[44 ] It was found that a reduced intermaxillary distance showed positive significance
toward pediatric OSA in four studies.
[Table 5 ] summarizes the imaging techniques used, the hardware and software involved, the
landmarks used for the assessment, and the significant positive findings that showed
statistical significance when comparing OSA children with the control group.
Table 5
Imaging techniques
Imaging techniques
Author
Hardware and software
Landmarks
Positive findings
Lateral cephalometry
Manrikyan et al. (2023) (35)
Planmeca ProMax Type 3D+ (Planmeca) set at 12mA, 90 kV, and exposure time of 0.30 minute
at natural head position
Romexis viewer 5.4.1 with manual tracing
Angles:
SNA, SNB, ANB, BaSN, ArGoGn, MxPl/MdPl
Linear:
Hyoid and C3 (horizontal distance)
Mandibular plane and hyoid (vertical distance)
Vertical position of tongue, U1NA, L1NB, OJ, OB, Posterior airway space (PAS)1, PAS2,
PAS3, PASmin
SNB 79.4 ± 3.1 (distal position of mandible relative to anterior cranial base)
ANB 4.3 ± 1.9
ArGoGn 130.47 ± 8.99
AH-C3H 32.69 ± 5.8
Xu et al (2023) (38)
ORTHOPHOS XG 3D Ceph, Sirona Dental Systems GmbH
Digital cephalometric analysis
Skeletal variables:
SNA, SNB , ANB, SN, S-Ar, Ar-Go , Go-Me, NSAr, SArGo, NMeGo, SumAngles
Upper airwar, adenoid and hyoid:
NP space , OP space , A-B Absolute value of adenoid , Linear dimension of bony nasopharynx , Ratio A-N (relative adenoid size) , Distance hypoid-RGn, H-FP
SNB, Ar-Go (ramus height)
NP, OP, A(absolute value of adenoid), N (linear dimension of bony nasopharynx),
Relative adenoid size
Bozzini et al (2022) (36)
Orthophos XG 5 DS Ceph, Sirona, Brazil regulated to 12mA, 90kV and 0.30 second of
time exposure at natural head position
Easy Ceph (Anne Solutions ®Brazil)
Rickets's cephalometric analysis:
Facial axis
Facial depth
Mandibular plane angle
Lower facial height
Mandibular arch
Jarabak's analysis:
Posterior and anterior facial height
Facial depth angle on Ricketts (87 ± 2.8 vs 84.1 ± 4.6)
Murakamai et al (2021) (41)
Not mentioned
Lateral cephalograms
SNA, SNB, ANB, FMPA, UIA, LIA
Nasopharyngeal and oropharyngeal airway dimension
Mandibular retrusion (ANB <4)
Lower pharynx
Lee et al (2020) (28)
Hardware not mentioned
PACS software
Lateral cephalometry:
Skeletal: SNA, SNB, ANB, SN-PP, SN-MP, AFH
Teeth: OJ, OB
Upper Airway: MinRPA, MinRGA
Soft palate: SPL, MPT
Tongue: TGL, TGH
Hyoid bone: MPH
SNB, ANB, Overjet
Ahmad (2020) (42)
CS 2200-Carestream Health® machine at 30mA, 70 kVp
Manual tracing with RK LED X-Ray View
Cephalometric analysis
SNA, SNB, ANB, SN-MP, BaSN, PNS-AD1, PNS-AD2
ANB, SN-MP, BaSN, PNS-AD1, PNS-AD2
Inoshita et al (2018) (18)
NI
Lateral neck radiographs:
Airway area,
Diameter of adenoids and nasopharynx
Ratio of adenoids and nasopharynx (A/N)
ANS, PNS, H, Eb, TAA, UNG,
Upper airway area
A/N ratio
Craniofacial photogrammetry
Wang et al (2022) (39)
Smartphone camera to photograph frontal and profile with a scale plate.
Image analysis software (Image J version 1.8.0, NIH, Bethesda, Maryland, United States)
Facial landmarks:
Facial heights and widths
Facial convexity angle,
Eyes and Nose:
Inner and outer canthus width
Nose width
Nasal convexity angle
Mouth:
Lip width and height
Maxilla and mandible:
Maxillary length, mandibular length, Posterior mandibular height, Maxillomandibular angle , Mandibular angle
Upper face width, lower face width, lower facial height, maxillary-mandibular relationship
angle effective and sensitive in predicting OSA in children
CBCT Assessment
Emsaili (2022) (40)
NewTom VGi cone-beam CT unit (Verona/Italy)
NNT Viewer software version 2.21
SNA, SNB, ANB, SN-MP, PP-MP, BaSN, PNS-AD1, PNS-AD2
UA width, UA AP dimension, SNB, Shortest distance between PNS-Ad1
Hsu et al (2021) (17)
i-CT (Imaging Sciences International, LLC, Hatfield, PA) regulated at 120kV, 5mA,
0.25mm voxel size, scanning time of 20 seconds.
Dolphin Imaging, Chatsworth, CA
Nasopharyngeal, oropharyngeal volume,
Airway length
Minimal airway locus – AP and lateral distances
Adenoid and tonsil size
Nasopharynx:
Volume, Minimal airway area, AP distance, Mean airway area
Oropharynx:
Volume, Minimal airway area, Lateral distance, airway length, mean airway area
Abbreviations: AP, anteroposterior; NI, not indicated.
Other abbreviations, refer to list of abbreviations.
Seven studies evaluated craniofacial and airway features through lateral cephalometry
with similar measuring instruments (Maxilla and mandible position about the anterior
cranial base: SNA, SNB, ANB, BaSN, ArGo, SnMP, MMPA; Facial height; Airway dimension:
PAS, NP space, OP space, linear distance between hyoid and spine, and tongue and pharynx).[18 ]
[28 ]
[35 ]
[36 ]
[38 ]
[41 ]
[42 ] Craniofacial features that yielded significant findings in pediatric obstructive
sleep apnea include the retrusive mandible, the high maxillomandibular plane angle,
the adenoid size, and the posterior airway space. One study assessed the craniofacial
features through photogrammetry and looked at the facial heights, convexity, and maxillomandibular
angle.[39 ] This method produced similar positive findings to pediatric OSA. Two studies assessed
the craniofacial features using CBCT with similar landmarks for assessing the airway
space and volume.[17 ]
[40 ]
Discussion
Obstructive sleep apnea (OSA) is a multifactorial disorder influenced by a complex
interplay of genetic, anatomical, and physiological factors. Understanding the craniofacial
phenotype is crucial for identifying individuals at higher risk, as specific anatomical
features can significantly contribute to the development and severity of OSA. Accurate
detection of these phenotypic characteristics enhances early diagnosis and personalized
treatment strategies. The key findings from this qualitative examination of 13 articles
highlighted the diversity in methodologies and variables employed in appraising craniofacial
attributes among pediatric patients with obstructive sleep apnea. While both clinical
examination and imaging techniques for evaluating craniofacial features exhibit similarities,
the specific criteria and landmarks utilized vary significantly across methodologies.
Despite these methodological differences, certain variables demonstrate consistent
significance in pediatric OSA. Notably, these craniofacial characteristics encompass
a convex facial profile associated with a downward rotation of the maxillomandibular
complex, resulting in mandibular retrusion and an elevated maxillomandibular plane
angle.[41 ]
[42 ] These skeletal morphological features contributed to the constriction in the pharyngeal
space, evident through diminished horizontal distances between the base of the tongue
to the posterior pharynx, and the hyoid bone to the cervical vertebra. Furthermore,
dental characteristics predisposing children to OSA include a narrow maxillary arch,
with or without crossbite.[37 ]
[41 ]
[43 ]
[44 ] The validity of these findings has been reinforced by several systematic reviews
and meta-analyses, as documented by Fagundes[5 ] and Brockman.[45 ]
The importance of standardizing methodologies to identify and screen for risks of
pediatric obstructive sleep apnea (OSA) through craniofacial phenotyping cannot be
overstated. While numerous studies have delineated craniofacial phenotypes associated
with pediatric OSA, recent meta-analyses[5 ]
[24 ] have failed to detect significant differences in six skeletal features between OSA
and non-OSA patients in lateral cephalometry, including SNA, SNB, ANB, BaSN, U1-L1,
and U1-SN. This could be attributed to the fact that these 2-dimensional images represent
a single static snapshot of the dynamic upper airway structure and did not reflect
adequate anatomical contributions that could risk for OSA. For example, the tongue
position when standing or lying supine during cephalometric assessment via CBCT or
CT may greatly influence the upper airway space.[46 ] Therefore, a definitive diagnosis of obstructive sleep apnea (OSA) should not be
based solely on this single radiographic assessment, as it only suggests potential
risks for OSA. Further investigation to show the dynamic function of the upper airway
during sleep is indicated to confirm the presence of OSA. Similarly, other associated
craniofacial features of pediatric OSA, such as cranial base length,[11 ] adenotonsillar hypertrophy,[21 ]
[47 ] and lateral pharyngeal wall thickness[9 ] have not demonstrated a strong association with pediatric OSA. The authors suggest
that the inconsistencies in the literature could be due to the varying methodologies
used in different studies, making it difficult to conduct reliable qualitative and
quantitative analyses.
Given the diversity in methodologies, variables, and instruments used for the assessment
of craniofacial morphology, the initial set of craniofacial phenotypes was found to
be extremely broad.[7 ]
[8 ]
[9 ]
[24 ] Nonetheless, the significant craniofacial morphologies from the skeletal, dental,
and pharyngeal assessment ultimately contributed to the narrowing of the pharyngeal
space. From here, identifying the key craniofacial parameters or measurements that
led to this finding should be standardized across studies. Clinical examination of
the facial profile, facial height, and lateral cephalometric analysis which would
determine the position of the mandible about the cranial base, the pattern of growth,
and the angle of the maxillomandibular complex are important parameters to be assessed.
Introducing a framework for conducting craniofacial assessments in the context of
pediatric OSA serves as more than just a mere suggestion; it offers a structured guide
essential for researchers navigating the complexities of pediatric OSA and craniofacial
phenotyping.[5 ]
[7 ]
[48 ] This proposed framework not only outlines standardized parameters but also emphasizes
the importance of consistency and uniformity in research practices. By advocating
for the adoption of this framework among clinicians and researchers, the authors hoped
to ensure a harmonized approach to data collection, analysis, and interpretation across
studies. This not only enhances the credibility and reliability of research findings
but also facilitates meaningful comparisons and meta-analyses
[Fig. 2 ] illustrates the proposed framework of the important parameters that contributed
to the craniofacial phenotyping in pediatric OSA that should be evaluated. Key landmarks
for these parameters include clinical facial convexity, SNA, SNB, ANB, Ar-Go, Ar-Go-Gn,
and MMPA, and therefore need to be included and standardized across studies. Other
studies in adult OSA have also confirmed the significance of these parameters.[49 ]
[50 ]
[51 ] In addition to that, adenotonsillar assessment using Brodsky and NFE grading would
provide more accurate information regarding the pharyngeal space[52 ]
[53 ]
[54 ] than a Mallampati score or the Friedman tongue position. On the other hand, a crucial
characteristic that can often be overlooked is the dental and occlusal status of these
children. It was known that a narrow and high-arched palate would contribute to the
constriction of the airway at the nasal and nasopharyngeal levels. Hence, measurement
of the palate in transverse, vertical, and anteroposterior would benefit the researchers
in confirming this component of the craniofacial phenotype for pediatric OSA.
Fig. 2 Proposed framework for parameters to evaluate pediatric obstructive sleep apnea.
The attempt by the authors to report on the heterogeneity of articles evaluating pediatric
OSA will strengthen the need for standardized methodologies to ensure that clinicians
in the field can consistently identify and diagnose craniofacial features associated
with pediatric OSA while enabling the reproducibility and reliability of results.
The present study has systematically gathered and qualitatively reviewed data concerning
the methodologies employed to ascertain the craniofacial phenotype of pediatric OSA.
The diversity in these methodologies has constrained the ability to establish a uniform
approach. Nevertheless, the framework suggested for standardizing evaluated parameters
was developed by identifying commonalities among the noteworthy positive findings.
Conclusion
In conclusion, this approach to standardization will facilitate comparison across
studies and meta-analyses. Without standardized protocols, variations in methodologies
have led to discrepancies in results, making it challenging to draw meaningful conclusions
or establish consensus in phenotyping pediatric OSA. Moreover, embracing this framework
fosters collaboration and knowledge exchange within the research community, ultimately
advancing our understanding of pediatric OSA and improving clinical outcomes for affected
individuals.
List of Abbreviations
Abbreviation
Description
NFE
Nasofiberendoscopy
CPAP
Continuous positive airway pressure
BMI
Body mass index
AHI
Apnea/Hypopnea Index
CBCT
Cone-beam computed tomography
REI
Respiratory event index
ODI
Oxygen desaturation index
Lateral cephalometric analysis abbreviations and its description
SNA
Angle between the sella/nasion plane and the nasion/A-plane
SNB
Angle between the sella/nasion plane and the nasion/B-plane
ANB
Angle between the A-plane and B-plane
BaSN
Angle between the cranial base and the mid-sagittal plane
ArGo
Line between the condyle and the gonial angle of the mandible
Ar-Go-Gn
Angle between the condyle/gonion plane and the gonion/gnathion plane
SNMP
Angle between the sella/nasion plane and the maxillary plane
MMPA
Angle between the maxillary and mandibular plane
PAS
Posterior airway space
NP
Nasopharynx
OP
Oropharynx
U1-L1
Angle between the upper incisor and lower incisor
U1-SN
Angle between the upper incisor and the sella/nasion plane
Bibliographical Record
