Venue & Date for 2020 event to be confirmed

resources

The preliminary results of the differences in craniofacial
and airway morphology between preterm and
full-term children with obstructive sleep apnea

article

Yun-Chia Lian a,b, Yu-Shu Huang c,d, Christian Guilleminault e, Kuang-Tai Chen c, Miche`le Hervy-Auboiron f, Li-Chuan Chuang a,b*, Aileen I. Tsai a,b

a Department of Pediatric Dentistry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
b Graduate Institute of Craniofacial and Dental Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
c Department of Child Psychiatry and Sleep Center, Chang Gung Memorial Hospital and College of Medicine, Taoyuan, Taiwan
d Craniofacial Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 
e Stanford University Sleep Medicine Division, Stanford, CA, USA
f Orthodontic Institute, Noisy-Lesec, France 

Received 15 March 2017; Final revision received 22 March 2017
Available online 12 May 2017

KEYWORDS
preterm children; obstructive sleep apnea; craniofacial and airway morphology

Abstract
Background/purpose:
The prematurely born and obstructive sleep apnea (OSA) could affect craniofacial and airway growth. The purpose of this study is to compare the differences in craniofacial and airway morphology between preterm and full-term children both with OSA problem.

Materials and methods:
The differences in craniofacial and airway morphology between preterm children and full-term children both with OSA problem during the prepubertal (age 6e10) and pubertal (age 11e14) period were measured using lateral cephalometric radiograph.

Results:
In the prepubertal period, effective maxillary length, and length from Go to Gn were smaller in the preterm group (n Z 6) compared to the full-term (n Z 8). The length of the soft palate was smaller and the distance soft palate-posterior side of nasopharynx was longer in preterm children. During puberty, (1) position of maxilla relative to cranial base: there was an anteroposterior maxilla and a mandibular discrepancy, a convexity of facial profile, (2) the distance from point A to nasion perpendicular, the distance from Pog to nasion perpendicular, and the ratio of effective maxillary length/effective mandibular length were smaller in the preterm group (n Z 5) compare to the full-term (n Z 6).

Conclusion:
During prepuberty, the preterm children had a significantly shorter effective maxillary and mandibular length but the catch up growth resulted during the pubertal period in reduction in facial profile convexity and more important mandibular vertical growth toward a dolichocephalic profile. Due to preterm birth, OSA children have a different craniofacial morphology compared to the full-term. When using an oral device for passive myofunctional therapy, the treatment outcome maybe different.

ª 2017 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

INTRODUCTION
Pediatric sleep-disordered-breathing (SDB) is a common health problem in children and adolescents,1e3 which includes upper airway resistance syndrome (UARS) and obstructive sleep apnea syndrome (OSA). OSA is the most prevalent clinical syndrome when considering SDB.4 OSA may have a very negative impact on children’s systemic health and development.3,5,6 The pathophysiology of pediatric OSA is unclear, but craniofacial anomalies and abnormal anatomic development have been reported: Nasal obstruction with retrognathism and deformities of craniofacial structures, micrognathia, short and narrow cranial base, midfacial hypoplasia, macroglossia and hypotonia are all highly associated with pediatric OSA.7e10
Preterm children have both a 70% incidence of OSA and a high rate of craniofacial anomalies such as shorter anterior cranial base, less convex skeletal profile, shorter maxillary length, oral defects such as high and narrow hard palate and dental arch, and significant growth failure compared to full-term children.11e18 Most premature infants will have “catch-up growth” during adolescence, however.13,16,19,20 Even though the incidence of OSA in preterm children is high, no associated study has investigated whether the craniofacial anomalies seen in premature children may relate to the incidence of OSA and the craniofacial change noted during the pubertal period.

The purpose of this study was to compare the differences in craniofacial and airway morphology between preterm children and full-term children both with OSA problems during the pre-pubertal and pubertal periods.

MATERIALS AND METHODS
The study protocol was approved by the Institutional Review Board (IRB 104-9308A3) of the Human Investigation Committee of Chang Gung Memorial Hospital and Chang Gung University. This study included 25 children with pediatric OSA (mean age, 9.8  2.5 years; age range, 6e14 years; Table 1) diagnosed with OSA based on the results of polysomnography (PSG) in the Sleep Center at the Medical Center in northern Taiwan. The selection criteria obtained from the PSG results were as follows: (1) oxygen level in children: <94% during sleep; (2) Respiratory Disturbance Index [including apnea-hypopnea and respiratory-eventrelated- arousals] (RDI): 5 events/hr; and (3) Apnea-Hypopnea Index (AHI): 1 events/hr. Children were
divided into two groups with two different ages (pre-pubertal {age 6e10} and pubertal {age 11e14}), and, based on their gestational ages, in “preterm “ (less than 37 weeks) and “full-term”. Children with epilepsy, head injury, severe developmental delay and mental retardation, schizophrenia, severe depression, and with in-ability to cooperate with the PSG-testing were excluded.

Differences in craniofacial morphology between OSA preterm and full-term children

Before conducting the study, the informed consent form had been signed by every participant and their parents. One lateral cephalometric radiograph was taken for each child. The participants had their heads kept in the natural position with Frankfort horizontal plane paralleled to the floor, teeth in centric occlusion and the lips closed in a relaxed position. Cephalograms were obtained on the same machine by the same operator. All cephalometric radiographs were hand-traced by a single investigator and another experienced dentist verified the cephalometric
radiographs. The definitions of landmarks and reference lines used to perform the cephalometric analysis are provided in Table 2 and Figs. 1e3.21 We assessed the error of the method by tracing and measuring 10 randomly selected radiographs one more time under the same conditions and performed calculations by using the intra class correlation
coefficient. The average measure of intra class correlation coefficient was 0.78. 

Statistical analyses were performed using the statistical software package SPSS- Released 2009. (PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc.). Descriptive statistics were presented as means and standard deviations. The chi-square test was used to test whether there were sex differences between full-term and preterm groups, while the ManneWhitney test was used to test whether there were significance differences in cephalometric measurements among full-term and preterm groups.

The level of significance was set at P < 0.05.

RESULTS
Twenty-five children were involved in this study and the demographic data of full-term and preterm children are shown in Table 1. There were no significant differences in age, body weight and body height distributions between the groups. Also no significant difference was shown in PSG
data (AHI and RDI). The preterm group had significantly smaller gestational age and birth body weight. 

Prepubertal subgroup (age 6e10): 8 children were fullterms and 6 children were premature-born (mean age, 9.7  1.5 years; age range, 6e10 years; Table 3). There were no significant differences in age, PSG data (AHI and RDI), birth body weight and body height distributions between groups. The preterm group had significantly smaller gestational age and body weight. Pubertal group: (age 11e14), 6 children were full terms and 5 children premature-born (mean age, 12.2  1.1 years; age range, 11e14 years; Table 4). There were again no significant differences in age, PSG data (AHI and RDI), body weight, or body height distributions between the groups. The preterm group had significantly smaller gestational age and birth body weight.

The results of cephalometric analysis between preterm and full-term groups are shown in Table 5 and Figs. 4 and 5. In the pre-pubertal group the effective maxillary length (Ar-A), and length from Go to Gn (Go-Gn) were smaller in preterm than in full-term children (P < 0.05). Also the length of the soft palate (LSP) was smaller and the distance soft palate-posterior side of nasopharynx (PMm-NPh) was longer in preterm children (P < 0.05). In the pubertal children, the position of the maxilla relative to cranial base (SNA), the anteroposterior maxilla and mandible discrepancy (ANB), the facial profile convexity (N-A-Pg), the distance from point A to nasion perpendicular (A-Nv), the distance from Pog to nasion perpendicular (Pg-Nv), and the
ratio of effective maxillary length/effective mandibular length (Ar-A/Ar-Gn)were smaller in preterms compared to full-term children (P < 0.05). There were no significant differences in airway morphology during the pubertal period.

DISCUSSION
Our results showed significantly more changes in preterm children during the pre-pubertal period, but a catch-upgrowth of maxillary length, mandibular length and soft tissue occurs during puberty. But during the pubertal period, the preterm children have still less facial profile convexity and more mandibular vertical growth like dolichocephalic profile compared to the full-term children. Our full-term children with have more of a class II pattern of growth with a retrusive mandible, where the distance (Ar-Gn) has not grown as much compared to preterms.

Additionally, insufficient sagittal development and more vertical mandibular growth was also noted in the preterm children. Similar results were shown in studies comparing craniofacial structures growth between preterm and fullterm children regardless of OSA problem.12e14,16,18e20 The

differences may be related to a lower growth rate in preterm children. Preterm children showed significant growth failure in their early childhood as is well-documented in many studies: smaller head circumference, shorter height, lower body weight have been reported in preterm compared with full-term children.11,13 High incidences of oral defects including high-arched and narrowing palate, prenormal occlusion, and palatal asymmetry have also been reported in preterm children.13 The smaller cephalometric data of our preterm children compared to those in full-term children found in this study may thus be explained. These traits also are found in children with OSA.22 Preterm OSA children have a significantly shorter cranial base and maxillary length. The cranial base may significantly influence a large amount of the craniofacial dimensions23,24; the decreased cranial base dimensions are associated with a decrease in pharyngeal airway size.25 Therefore, it is possible that the smaller cranial base dimensions may have important implications in the pathogenesis of OSAS,24 noted particularly in the preterm children.

In the OSA full-term group, normal SNA with small SNB and large ANB suggests that the mandible is more retrusive than the maxilla in relation to anterior cranial base; higher mandibular angle (SN-MP), longer anterior face height (NMe) and smaller ratio of anterior and posterior face height
(S-Go/N-Me) are associated with vertical growth skeletal type, which represents a more clock-wise rotation of the mandible as seen in adults with OSA.26,27 Reduced intermaxillary relationship and longer soft palate have been reported in many previous studies related to children with OSA problems.22,26,28,29 Craniofacial morphology can be one of the predictors of the treatment outcome of oral appliance with mandible advancement in adult OSA patients.

27 Narrow minimal retroglossal airways, mandibular retrusion and short anterior face heights have better treatment outcome with oral appliances.
27 Due to premature birth, preterm OSA children (dolichocephalic profile) have a totally different craniofacial morphology compared to full-term individuals (class II profile with retrognathic mandible), and the treatment outcome of oral appliance could be different for full-term individuals. Further studies will be needed to compare the treatment outcome of oral appliance between these two groups of children.

There are some limitations to our study. First, we had few girls. Second, the sample size was small and could not be matched year-by-year for age. However, this study is the first to report different craniofacial findings for preterm and full-term children with OSA during the pre-pubertal and
pubertal periods.

In conclusion, during pre-puberty, the preterm children had a significantly shorter effective maxillary (Ar-A) and mandibular length (Go-Gn), but the catch-up growth resulted during the pubertal period in reduction in facial profile convexity (ANB, N-A-Pg) and more importantly, mandibular vertical growth toward a dolichocephalic profile. Also the full-term children tended to be more mandibular retrognathic during puberty relative to those who had preterm births. Due to preterm birth, OSA children have a different craniofacial morphology compared to the full-term children with OSA. When using an oral device for a passive myofunctional therapy, the treatment outcome maybe different.

Conflict of interest

The authors have no conflicts of interest relevant to this article.

Acknowledgment

This research was supported by Chang Gung Memorial Hospital grant #: CRRPG5C0172 and 173 to YS Huang. We thank Prof. FM Hwang for help with statistical analysis.

REFERENCES

1. Huynh NT, Desplats E, Almeida FR. Orthodontics treatments for managing obstructive sleep apnea syndrome in children: a systematic review and meta-analysis. Sleep Med Rev 2016;25: 84e94.
2. Katyal V, Pamula Y, Martin AJ, Daynes CN, Kennedy JD,Sampson WJ. Craniofacial and upper airway morphology in pediatric sleep-disordered breathing: systematic review and
meta-analysis. Am J Orthod Dentofac Orthop 2013;143:20e30.
3. Capua M, Ahmadi N, Shapiro C. Overview of obstructive sleep apnea in children: exploring the role of dentists in diagnosis and treatment. J Can Dent Assoc 2009;75:285e9.
4. Elden LM, Wetmore RF, Potsic WP, Fairbanks D, Mickelson S, Woodson B. Snoring and obstructive sleep apnea in children. In:Fairbanks DNF, ed. Snoring and obstructive sleep apnea, 3rd ed. USA: Philadelphia: Lippincott Williams & Wilkins, 2003: 246e7.
5. Bahammam A. Obstructive sleep apnea: from simple upper airway obstruction to systemic inflammation. Ann Saudi Med 2011;31:1e2.
6. Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest 2012;141:1601e10.
7. Zucconi M, Caprioglio A, Calori G, et al. Craniofacial modifications in children with habitual snoring and obstructive sleep apnoea: a case-control study. Eur Respir J 1999;13:411e7.
8. Lo¨fstrand-Tidestro¨m B, Thilander B, Ahlqvist-Rastad J, Jakobsson O, Hultcrantz E. Breathing obstruction in relation to craniofacial and dental arch morphology in 4-year-old children. Eur J Orthod 1999;21:323e32.
9. Zang YH, Chen J. Study on differences among sagittal facial types, upper airway width and hyoid position of children with mixed dentition. Med J Qilu 2009;24:340e2.
10. Wei Y, Cai Z, Qian Y. Cephalometry study of craniofacial and upper airway in boys with OSAS. Shanghai Kou Qiang Yi Xue 2003;12:3e6.
11. Huang YS, Guilleminault C. Pediatric obstructive sleep apnea and the critical role of oral-facial growth: evidences. Front Neurol 2012;3:1e7.
12. Paulsson L, Bondemark L, So¨derfeldt B. A Systematic Review of the consequences of premature Birth on palatal morphology, dental occlusion, tooth-crown dimensions, and Tooth maturity and eruption. Angle Orthod 2004;74:269e79.
13. Paulsson L, Bondemark L. Craniofacial morphology in prematurely born children. Angle Orthod 2009;79:276e83.
14. Paulsson L, So¨derfeldt B, Bondemark L. Malocclusion traits and orthodontic treatment needs in prematurely born children. Angle Orthod 2008;78:786e92.
15. Zettergren-Wijk L, Forsberg CM, Linder-Aronson S. Changes in dentofacial morphology after adeno-/tonsillectomy in young children with obstructive sleep apnoeaea 5-year follow-up study. Eur J Orthod 2006;28:319e26.
16. Farooqi A, Ha¨gglo¨f B, Sedin G, Gothefors L, Serenius F. Growth in 10- to 12-year-old children born at 23 to 25 weeks gestation in the 1990s: a Swedish national prospective follow-up study. Pediatrics 2006;118:1452e65. 17. Korobkin R, Guilleminault C. Neurologic abnormalities in nearmiss for sudden infant death syndrome infants. Pediatrics 1979;64:369e74.
18. Daily DK, Kilbride HW, Wheeler R, Hassanein R. Growth patterns for infants weighing less than 801 grams at birth to 3 years of age. J Perinatol 1994;14:454e60.
19. Stjernqvist K, Svenningsen N. Ten-year follow-up of children born before 29 gestational weeks: health, cognitive development, behaviour and school achievement. Acta Paediatr 1999; 88:557e62. 
20. Ford GW, Doyle LW, Davis NM, Callanan C. Very low birth weight and growth into adolescence. Arch Pediatr Adolesc 2000;154:778e84.
21. Tanon-Anoh MJ, Kouassi YM, Yoda M, et al. Craniofacial modifications in Ivorian melanoderm children with chronic retronasal obstruction. Int J Pediatr Otorhinolaryngol 2014;78:588e92. 
22. Pirila-Parkkinen K, Pirttiniemi P, Nieminen P, Tolonen U, Pelttari U, Lopponen H. Dental arch morphology in children with sleep-disordered breathing. Eur J Orthod 2009;31:160e7.
23. Enlow DH, Kuroda T, Lewis AB. The morphological and morphogenetic basis for craniofacial form and pattern. Angle Orthod 1971;41:161e88.
24. Li KK, Kushida C, Powell NB, Riley RW, Guilleminault C. Obstructive sleep apnea syndrome: a comparison between Far- East Asian and white men. Laryngoscope 2000;110:1689e93.
25. Steinberg B, Fraser B. The cranial base in obstructive sleep apnea. J Oral Maxillofac Surg 1995;53:1150e4. 
26. Kapsimalis F, Kryger M. Gender and obstructive sleep apnea syndrome, Part 1 clinical features. Sleep 2002;25:409e16. 
27. Shen HL, Wen YW, Chen NH, Liao YF. Craniofacial morphologic predictors of oral appliance outcomes in patients with obstructive sleep apnea. J Am Dent Assoc 2012;143:
1209e17.
28. Katyal V, Pamula Y, Daynes CN, et al. Craniofacial and upper airway morphology in pediatric sleep-disordered breathing and changes in quality of life with rapid maxillary expansion. Am J Orthod Dentofac Orthop 2013;144:860e71. 
29. Deng J, Gao X. A case-control study of craniofacial features of children with obstructed sleep apnea. Sleep Breath 2012;16: 1219e27.