ORIGINAL ARTICLE
Prediction of the Need for Orthognathic Surgery in Patients With Cleft Lip and/or Palate Heon-Mook Park, DDS, Pil-Jong Kim, BA, MS,y Hong-Gee Kim, MS, PhD,y Sukwha Kim, MD, PhD,z and Seung-Hak Baek, DDS, MSD§ Abstract: The purpose of this study was to determine the cephalometric variables that can predict the future need for orthognathic surgery or distraction osteogenesis in Korean male patients with nonsyndromic cleft lip and alveolus (CLA) and unilateral (UCLP) and bilateral cleft lip and palate (BCLP). A total of 131 patients who were treated by one surgeon and one orthodontist using identical protocol were divided into CLA group (n ¼ 35), UCLP group (n ¼ 56), and BCLP group (n ¼ 40). Lateral cephalograms were taken before secondary alveolar bone graft (T0; mean age, 9.3 years) and at the minimum of 15 years of age (T1; mean age, 17.3 years). The cephalometric variables of these cephalograms were measured. At T1 stage, 3 cephalometric criteria were used to divide the subjects into surgery and nonsurgery groups (ANB 3 degrees; Wits appraisal 5 mm; Harvold unit difference 34 mm for surgery group). The feature wrapping method was used to determine the cephalometric variables at T0 stage for a prediction model. At T1 stage, 27 (20.6%) of 131 subjects required surgical intervention to correct their sagittal skeletal discrepancies. Frequency was significantly different among the CLA, UCLP, and BCLP groups (8.5%, 21.4%, and 30.0%, respectively; P < 0.05; [CLA, UCLP] < [UCLP, BCLP]). A total of 10 cephalometric variables of T0 stage were selected as predictors, and weighted classification accuracy was 77.3%. The frequency of surgical intervention increased with cleft severity. Ten cephalometric variables might be regarded as effective predictors of the future need for surgery to correct their sagittal skeletal discrepancies. Key Words: Cleft lip and palate, need for orthognathic surgery, feature wrapping method (J Craniofac Surg 2015;26: 1159–1162)
From the Department of Orthodontics, School of Dentistry; yBiomedical Knowledge Engineering Laboratory, School of Dentistry; zDepartment of Plastic and Reconstructive Surgery, College of Medicine; and §Department of Orthodontics, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, South Korea. Received August 23, 2014. Accepted for publication January 21, 2015. Address correspondence and reprint requests to Seung-Hak Baek, DDS, Department of Orthodontics, School of Dentistry, Dental Research Institute, Seoul National University, 101 Daehakno, Jongno-gu, Seoul, 110-768, South Korea; E-mail: [email protected] Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jcraniofacialsurgery.com). The authors report no conflict of interest. Copyright # 2015 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001605
The Journal of Craniofacial Surgery
P
atients with cleft lip and/or palate often develop maxillary hypoplasia owing to inherited growth deficiencies and/or scar formation after cheiloplasty/palatoplasty.1,2 Although several treatment protocols have been used to minimize the amount of maxillary hypoplasia,2,3 some patients still need orthognathic surgery or distraction osteogenesis (DO) to correct the sagittal skeletal discrepancy (Fig. 1). Parents of patients with cleft lip and/or palate usually want to know the percentage of patients needing surgical correction of the sagittal skeletal discrepancy after a child’s growth is complete. Previous studies suggest that a wide range from 25% to 76.5% of patients with unilateral (UCLP) and bilateral cleft lip and palate (BCLP) need correction with either orthognathic surgery or DO.4– 6 Therefore, it is necessary to confine the samples using relatively strict inclusion and exclusion criteria for increasing the sample purity as follows: (1) The cleft samples should be divided into cleft lip and alveolus (CLA) and cleft lip and palate (CLP) groups according to the etiology of oral clefting; (2) The growth difference between male and female patients should be considered; (3) Treatment protocol with respect to timing and methods of surgical repair (cheiloplasty/palatoplasty) and orthodontic/orthopedic treatment should be identical to avoid bias from difference in treatment; and (4) The racial and ethnic backgrounds of the samples should be identical.7,8 There are 2 methods to predict the future need for a surgical intervention. One method is conventional statistical analysis of the cephalometric variables such as discrimination or regression analysis. The other method involves computational analysis of the cephalometric variables. Numerous studies using conventional statistical analyses have reported that diverse cephalometric variables such as ANB, Wits appraisal, gonial angle, total mandibular length (Co-Pog), mandibular ramus length, A to N perpendicular, and AB to mandibular plane angle might be valuable prognostic indicators for class III treatment.9–13 However, common decisive predictors were not identified. Moreover, the results from these studies cannot be directly applied to patients with cleft lip and/or palate because the samples were class III patients rather than patients with cleft lip and/or palate. Among computational analysis methods, the feature wrapping (FW) method uses a learning algorithm that evaluates every set of features generated from the subject’s original characteristics and can select the subset of features that shows the highest classification accuracy. Given this ability, the FW method was used to predict prognosis for class III treatment.14 Concurrent use of the sequential forward search and support vector machine algorithms with the FW method can minimize the empirical classification, maximize the geometric margin, and ultimately increase the classification accuracy.14– 16 There have been a few studies that investigate the cephalometric variables to predict the surgical need for patients with cleft lip and/ or palate using statistical or computational analysis. Therefore, the purpose of this retrospective study was to determine the cephalometric variables that can predict the future need for orthognathic
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Park et al
FIGURE 1. Comparison of lateral cephalograms taken immediately before the secondary ABG (T0; mean age, 9.3 years) and at a minimum of 15 years of age (T1; mean age, 17.3 years; a proper age to judge the need for orthognathic surgery). A, An example of a favorable prognosis. B, An example of a poor prognosis.
surgery or DO in Korean male patients with nonsyndromic CLA, UCLP, and BCLP using the FW method.
MATERIALS AND METHODS The samples consisted of 131 Korean male patients with nonsyndromic CLA (n ¼ 35), UCLP (n ¼ 56), or BCLP (n ¼ 40) who were treated at the Department of Orthodontics at Seoul National University Hospital (SNUH) and Dental Hospitals (SNUDH). This retrospective study was reviewed and approved by the Institutional Review Board of SNUDH (CRI 14008). Inclusion criteria for sampling of nonsyndromic CLA, UCLP, and BCLP were as follows: (1) To avoid bias from developmental differences between male and female and from ethnic background, only Korean male patients were selected; (2) To eliminate the influences of different surgical and orthodontic treatment, patients who were treated with the same protocol by a single surgeon (S.K.) and a single orthodontist (S.H.B.) were recruited; (3) To minimize the effects of surgical treatment after cheiloplasty and palatoplasty, patients whose lateral cephalogram was taken just before secondary alveolar bone graft (ABG) (T0; mean age, 9.3 years) were included; (4) To judge the need for future orthognathic surgery or DO, patients whose lateral cephalogram was taken at minimum 15 years of age (T1; mean age, 17.3 years) were enlisted. In addition, patients who had syndromic cleft including Van der Woude syndrome and Pierre Robin sequence or other craniofacial anomalies were excluded. The treatment protocol used in XNUH and XNUDH is summarized below: (1) Primary cheiloplasty (Millard rotation and advancement flap) between 3 and 5 months of age; (2) Palatoplasty (Furlow double opposing Z-plasty for one-stage palatorrhaphy) between 12 and 18 months of age; (3) No primary gingivoperiosteoplasty; (4) If needed, the maxillary arch was expanded before secondary ABG was performed; (5) During the mixed dentition stage, secondary ABG with particulate cancellous bone and marrow
FIGURE 2. Comparison of the frequency of orthognathic surgery or DO among groups 1, 2, and 3. Fisher exact test was performed. P < 0.05.
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from the iliac crest was conducted; (6) During the pubertal growth period, a facemask was used for orthopedic maxillary protraction; and (7) Fixed orthodontic treatment was performed during the permanent dentition stage. The cephalometric variables of lateral cephalograms taken at the T0 and T1 stages were measured by a single operator (H.M.P.). At T1 stage, the subjects were divided into surgery and nonsurgery groups according to 2 criteria: (1) If patients met the cephalometric criteria with ANB 3 degrees, Wits appraisal 5 mm, and Harvold unit difference (CoGn-CoSn0 ) 34 mm, they were classified into the surgery group.3,7,17,18 (2) The patients had been treated with preoperative orthodontic treatment or had already undergone orthognathic surgery or DO, they were automatically classified into the surgery group.3,7 A total of 40 subjects (n ¼ 20 in the surgery group and n ¼ 20 in the nonsurgery group) were reassessed by a single operator (H.M.P.) at one-month interval. Intraclass correlation coefficients were used to verify intraexaminer reliability. Because there were significant correlations between the first and second measurements (see Supplemental Digital Content, Table 1, http://links.lww.com/ SCS/A119), the first set of measurement was used. One-way analysis of variance, Fisher exact test, and independent t test were used for statistical analysis. For the prediction model, the cephalometric variables at the T0 stage were determined using the FW method with support vector machine /sequential forward search algorithms (see Supplemental Digital Content, Appendix, http://links.lww.com/SCS/A125).14–16 Classification accuracy was verified with a 10-fold cross-validation test.19
RESULTS There were no significant differences in age at each stage (T0 and T1) and duration (T0-T1) among CLA, UCLP, and BCLP groups (see Supplemental Digital Content, Table 2, http://links.lww.com/ SCS/A120). At T1 stage, a total of 27 (20.6%) of 131 subjects required orthognathic surgery or DO to correct their sagittal skeletal discrepancies (see Supplemental Digital Content, Table 3, http:// links.lww.com/SCS/A121). There were significant differences in the frequency of surgical intervention among CLA, UCLP, and BCLP groups (8.5%, 21.4%, and 30.0%, respectively; P < 0.05; (CLA, UCLP) < (UCLP, BCLP); see Supplemental Digital Content, Table 3, http://links.lww.com/SCS/A121 and, Fig. 2).
FIGURE 3. Superimposition of T0 stage profilograms using sella with the Frankfort horizontal plane. A 9-year-old boy without cleft lip and palate represents normal findings. Cleft-OS, a patient with cleft lip and/or palate who was treated with or needed orthognathic surgery or DO; Cleft-NOS, a patient with cleft lip and/or palate who was not treated with or did not need orthognathic surgery or DO.
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2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery
Volume 26, Number 4, June 2015
At T1 stage, 13 variables were significantly different between the surgery and nonsurgery groups (gonial angle, SNA, ANB, IMPA, interincisal angle, A to N perpendicular, AB to mandibular plane, ODI, APDI, Wits, overbite, overjet, and Harvold unit difference; all P < 0.001; see Supplemental Digital Content, Table 4, http://links.lww.com/SCS/A122). However, at the T0 stage, only 7 cephalometric variables demonstrated significant differences between the surgery and nonsurgery groups (ANB, IMPA, AB to mandibular plane, APDI, Wits, overjet, and Harvold unit difference; all P < 0.05; see Supplemental Digital Content, Table 4, http:// links.lww.com/SCS/A122). Superimposition of the T0 profilograms between the surgery group and the nonsurgery group revealed differences in the amount of maxillary hypoplasia and clockwise rotation of the mandible (Fig. 3). In addition, when the T0 profilograms of each group were compared to that of a norsmal 9-year-old Korean boy, there were differences in the amount of maxillary hypoplasia and clockwise rotation of the mandible (Fig. 3). A total of 10 cephalometric variables (APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA) of the T0 stage were selected as predictors with an adjusted classification accuracy of 77.3% (see Supplemental Digital Content, Table 5, http://links.lww.com/SCS/A123). The prediction model is uploaded on the following Web site (http://bikechild.iptime.org:8838/orthodontics/). If the values of these 10 variables are inserted, prognosis prediction results for surgery and nonsurgery is generated. The sensitivity and specificity of this model were 99.0% and 74.1%, respectively (see Supplemental Digital Content, Table 6, http:// links.lww.com/SCS/A124).
DISCUSSION The finding that the frequency of orthognathic surgery or DO was increased with cleft severity (8.5% in CLA, 21.4% in UCLP, 30.0% in BCLP; see Supplemental Digital Content, Table 3, http:// links.lww.com/SCS/A121) was similar with the results from previous studies (12%–40% in UCLP, 13%–70% in BCLP).3,7,17,18 When considering that the subjects of these studies consisted of white population only or a diverse mixture of ethnic backgrounds, the effect of ethnic difference between Asian and white populations might not be greater than other factors such as the surgical timing and techniques of cheiloplasty, palatoplasty, and secondary ABG and the methods and duration of orthopedic/orthodontic treatment. However, well-designed, prospective, and controlled studies would be needed to perform the objective evaluation of the effects of the timing and techniques of the aforementioned surgery on the future needs of surgical intervention for correction of skeletal sagittal discrepancy.20 In addition, it would be appropriate to investigate long-term follow-up results of a facemask therapy in reduction of the need for surgical intervention and/or the amount of Le Fort I advancement of the maxilla by orthognathic surgery or DO. Antonarakis et al3 and Meazzini et al,8 in their conventional statistical analysis studies, suggest that ANB would be a powerful predictor in cleft patients at the age of 5–6 years. Because the permanent maxillary incisors are not completely erupted at that age, accurate tracing and cephalometric analysis of the anterior maxilla (including point A) might be difficult. However, the present study measured the T0 stage lateral cephalograms taken immediately before secondary ABG (at the mean age of 9.3 years). At this age, the permanent maxillary incisors are completely erupted, possibly making tracing and cephalometric analysis more accurate than in previous studies.3,8 When compared to previous studies that recommended ANB as a powerful predictor in cleft patients,3,8 the present study selected #
2015 Mutaz B. Habal, MD
Prediction of Surgery Need for Cleft Patients
10 features including APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA as cephalometric predictors (see Supplemental Digital Content, Table 5, http://links. lww.com/SCS/A123). This finding means that a combination of cephalometric features might have better classification accuracy than did a single decisive predictor. Patients with cleft lip and/or palate usually have a class III malocclusion pattern owing to maxillary hypoplasia as well as hyperdivergent growth pattern due to clockwise rotation of the mandible. The prediction model in the present study also included cephalometric variables related to the sagittal growth difference (ANB, APDI, Wits appraisal, Harvold unit difference, and A to N perpendicular) and the vertical growth pattern (ODI and AB to mandibular plane angle). These findings were in accordance with Seo et al,21 which also found that patients with cleft lip and/or palate had a more hyperdivergent growth pattern and clockwise rotation of the mandible compared to patients without cleft lip and/or palate. In addition, the predictors related to the mandibular morphology (gonial angle) and the dental compensation (overjet and IMPA) were included. Therefore, this combination of cephalometric variables might accurately predict the growth of cleft subjects who will need a surgical intervention. The sensitivity of classification model (the proportion of actual nonsurgery patients that were correctly predicted as nonsurgery patients) was higher than was the specificity (the proportion of actual surgery patients that were correctly predicted as surgery patients) (99.0% vs. 74.1%; see Supplemental Digital Content, Table 6, http://links.lww.com/SCS/A124). We found that 26% of actual patients who underwent surgery (7 of 27) were predicted as patients who did not undergo surgery (see Supplemental Digital Content, Table 6, http://links.lww.com/SCS/A124). These false negatives might reflect a physician’s subjective decision for orthognathic surgery or DO and/or a patient’s desire for facial esthetics.6 Therefore, further studies would be needed to find a method to improve the low specificity of this prediction model. The findings from this study might provide helpful information for management of patients with cleft lip and/or palate and their parents about possible surgical interventions. However, there are some limitations in the present study such as a relatively small sample size and short-term observation period. To establish a more accurate and objective prediction model, the effects of diverse surgical timing and method for cheiloplasty and palatoplasty and different technique and duration of maxillary protraction on the amount of maxillary hypoplasia would be investigated. In addition, further studies would be needed to identify the percentage of patients with cleft lip and/or palate with transverse discrepancy between the maxilla and the mandible and/or facial asymmetry that requires surgical correction.
CONCLUSIONS
The frequency of surgical intervention increased with cleft severity. A total of 10 cephalometric variables including APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA might be regarded as effective predictors of the future need for surgery to correct their sagittal skeletal discrepancies in Korean patients with cleft lip and/or palate.
REFERENCES 1. Baek SH, Moon HS, Yang WS. Cleft type and Angle’s classification of malocclusion in Korean cleft patients. Eur J Orthod 2002;24:647–653
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2. da Silva Filho OG, Valladares Neto J, Capelloza Filho L, et al. Influence of lip repair on craniofacial morphology of patients with complete bilateral cleft lip and palate. Cleft Palate Craniofac J 2003;40:144–153 3. Antonarakis GS, Watts G, Daskalogiannakis J. The need for orthognathic surgery in nonsyndromic patients with repaired isolated cleft palate. Cleft Palate Craniofac J 2015;52:e8–e13 4. Ross RB. Treatment variables affecting facial growth in complete unilateral cleft lip and palate. Cleft Palate J 1987;24:5–77 5. Schnitt DE, Agir H, David DJ. From birth to maturity: a group of patients who have completed their protocol management. Part I. Unilateral cleft lip and palate. Plast Reconstr Surg 2004;113:805–817 6. Good PM, Mulliken JB, Padwa BL. Frequency of LeFort I osteotomy after repaired cleft lip and palate or cleft palate. Cleft Palate Craniofac J 2007;44:396–401 7. Daskalogiannakis J, Mehta M. The need for orthognathic surgery in patients with repaired complete unilateral and complete bilateral cleft lip and palate. Cleft Palate Craniofac J 2009;46:498–502 8. Meazzini MC, Capello AV, Ventrini F, et al. Long-term follow-up of UCLP patients: surgical and orthodontic burden of care during growth and final orthognathic surgery need. Cleft Palate Craniofac J [published online ahead of print July 23, 2013]. doi: 10.1597/12-211 9. Ferro A, Nucci LP, Ferro F, et al. Long-term stability of skeletal Class III patients treated with splints, class III elastics, and chincup. Am J Orthod Dentofacial Orthop 2003;123:423–434 10. Ko YI, Baek SH, Mah J, et al. Determinants of successful chincup therapy in skeletal class III malocclusion. Am J Orthod Dentofacial Orthop 2004;126:33–41 11. Moon YM, Ahn SJ, Chang YI. Cephalometric predictors of long-term stability in the early treatment of class III malocclusion. Angle Orthod 2005;75:747–753
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12. Tahmina K, Tanaka E, Tanne K. Craniofacial morphology in orthodontically treated patients of class III malocclusion with stable and unstable treatment outcomes. Am J Orthod Dentofacial Orthop 2000;117:681–690 13. Fudalej P, Dragan M, Wedrychowska-Szulc B. Prediction of the outcome of orthodontic treatment of class III malocclusions—a systematic review. Eur J Orthod 2011;33:190–197 14. Kim BM, Kang BY, Kim HG, et al. Prognosis prediction for class III malocclusion treatment by feature wrapping method. Angle Orthod 2009;79:683–691 15. Sahiner B, Chan HP, Petrick N, et al. Feature selection and classifier performance in computer-aided diagnosis: the effect of finite sample size. Med Phys 2000;27:1509–1522 16. Ceden˜o W, Agrafiotis DK. Using particle swarms for the development of QSAR models based on K-nearest neighbor and kernel regression. J Comput Aided Mol Des 2003;17:255–263 17. Linton JL. Comparative study of diagnostic measures in borderline surgical cases of unilateral cleft lip and palate and noncleft class III malocclusions. Am J Orthod Dentofacial Orthop 1998;113:526–537 18. Oberoi S, Chigurupati R, Vargervik K. Morphologic and management characteristics of individuals with unilateral cleft lip and palate who required maxillary advancement. Cleft Palate Craniofac J 2008;45: 42–49 19. McLachlan GJ, Do KA, Ambroise C. Analyzing microarray gene expression data. New York: Wiley;; 2004 20. Liao YF, Mars M. Hard palate repair timing and facial growth in cleft lip and palate: a systematic review. Cleft Palate Craniofac J 2006;43:563– 570 21. Seo YJ, Park JW, Kim YH, et al. Initial growth pattern of children with cleft before alveolar bone graft stage according to cleft type. Angle Orthod 2011;81:1103–1110
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2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
Prediction of the Need for Orthognathic Surgery in Patients With Cleft Lip and/or Palate Heon-Mook Park, DDS, Pil-Jong Kim, BA, MS,y Hong-Gee Kim, MS, PhD,y Sukwha Kim, MD, PhD,z and Seung-Hak Baek, DDS, MSD§ Abstract: The purpose of this study was to determine the cephalometric variables that can predict the future need for orthognathic surgery or distraction osteogenesis in Korean male patients with nonsyndromic cleft lip and alveolus (CLA) and unilateral (UCLP) and bilateral cleft lip and palate (BCLP). A total of 131 patients who were treated by one surgeon and one orthodontist using identical protocol were divided into CLA group (n ¼ 35), UCLP group (n ¼ 56), and BCLP group (n ¼ 40). Lateral cephalograms were taken before secondary alveolar bone graft (T0; mean age, 9.3 years) and at the minimum of 15 years of age (T1; mean age, 17.3 years). The cephalometric variables of these cephalograms were measured. At T1 stage, 3 cephalometric criteria were used to divide the subjects into surgery and nonsurgery groups (ANB 3 degrees; Wits appraisal 5 mm; Harvold unit difference 34 mm for surgery group). The feature wrapping method was used to determine the cephalometric variables at T0 stage for a prediction model. At T1 stage, 27 (20.6%) of 131 subjects required surgical intervention to correct their sagittal skeletal discrepancies. Frequency was significantly different among the CLA, UCLP, and BCLP groups (8.5%, 21.4%, and 30.0%, respectively; P < 0.05; [CLA, UCLP] < [UCLP, BCLP]). A total of 10 cephalometric variables of T0 stage were selected as predictors, and weighted classification accuracy was 77.3%. The frequency of surgical intervention increased with cleft severity. Ten cephalometric variables might be regarded as effective predictors of the future need for surgery to correct their sagittal skeletal discrepancies. Key Words: Cleft lip and palate, need for orthognathic surgery, feature wrapping method (J Craniofac Surg 2015;26: 1159–1162)
From the Department of Orthodontics, School of Dentistry; yBiomedical Knowledge Engineering Laboratory, School of Dentistry; zDepartment of Plastic and Reconstructive Surgery, College of Medicine; and §Department of Orthodontics, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, South Korea. Received August 23, 2014. Accepted for publication January 21, 2015. Address correspondence and reprint requests to Seung-Hak Baek, DDS, Department of Orthodontics, School of Dentistry, Dental Research Institute, Seoul National University, 101 Daehakno, Jongno-gu, Seoul, 110-768, South Korea; E-mail: [email protected] Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jcraniofacialsurgery.com). The authors report no conflict of interest. Copyright # 2015 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001605
The Journal of Craniofacial Surgery
P
atients with cleft lip and/or palate often develop maxillary hypoplasia owing to inherited growth deficiencies and/or scar formation after cheiloplasty/palatoplasty.1,2 Although several treatment protocols have been used to minimize the amount of maxillary hypoplasia,2,3 some patients still need orthognathic surgery or distraction osteogenesis (DO) to correct the sagittal skeletal discrepancy (Fig. 1). Parents of patients with cleft lip and/or palate usually want to know the percentage of patients needing surgical correction of the sagittal skeletal discrepancy after a child’s growth is complete. Previous studies suggest that a wide range from 25% to 76.5% of patients with unilateral (UCLP) and bilateral cleft lip and palate (BCLP) need correction with either orthognathic surgery or DO.4– 6 Therefore, it is necessary to confine the samples using relatively strict inclusion and exclusion criteria for increasing the sample purity as follows: (1) The cleft samples should be divided into cleft lip and alveolus (CLA) and cleft lip and palate (CLP) groups according to the etiology of oral clefting; (2) The growth difference between male and female patients should be considered; (3) Treatment protocol with respect to timing and methods of surgical repair (cheiloplasty/palatoplasty) and orthodontic/orthopedic treatment should be identical to avoid bias from difference in treatment; and (4) The racial and ethnic backgrounds of the samples should be identical.7,8 There are 2 methods to predict the future need for a surgical intervention. One method is conventional statistical analysis of the cephalometric variables such as discrimination or regression analysis. The other method involves computational analysis of the cephalometric variables. Numerous studies using conventional statistical analyses have reported that diverse cephalometric variables such as ANB, Wits appraisal, gonial angle, total mandibular length (Co-Pog), mandibular ramus length, A to N perpendicular, and AB to mandibular plane angle might be valuable prognostic indicators for class III treatment.9–13 However, common decisive predictors were not identified. Moreover, the results from these studies cannot be directly applied to patients with cleft lip and/or palate because the samples were class III patients rather than patients with cleft lip and/or palate. Among computational analysis methods, the feature wrapping (FW) method uses a learning algorithm that evaluates every set of features generated from the subject’s original characteristics and can select the subset of features that shows the highest classification accuracy. Given this ability, the FW method was used to predict prognosis for class III treatment.14 Concurrent use of the sequential forward search and support vector machine algorithms with the FW method can minimize the empirical classification, maximize the geometric margin, and ultimately increase the classification accuracy.14– 16 There have been a few studies that investigate the cephalometric variables to predict the surgical need for patients with cleft lip and/ or palate using statistical or computational analysis. Therefore, the purpose of this retrospective study was to determine the cephalometric variables that can predict the future need for orthognathic
Volume 26, Number 4, June 2015
1159
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery
Park et al
FIGURE 1. Comparison of lateral cephalograms taken immediately before the secondary ABG (T0; mean age, 9.3 years) and at a minimum of 15 years of age (T1; mean age, 17.3 years; a proper age to judge the need for orthognathic surgery). A, An example of a favorable prognosis. B, An example of a poor prognosis.
surgery or DO in Korean male patients with nonsyndromic CLA, UCLP, and BCLP using the FW method.
MATERIALS AND METHODS The samples consisted of 131 Korean male patients with nonsyndromic CLA (n ¼ 35), UCLP (n ¼ 56), or BCLP (n ¼ 40) who were treated at the Department of Orthodontics at Seoul National University Hospital (SNUH) and Dental Hospitals (SNUDH). This retrospective study was reviewed and approved by the Institutional Review Board of SNUDH (CRI 14008). Inclusion criteria for sampling of nonsyndromic CLA, UCLP, and BCLP were as follows: (1) To avoid bias from developmental differences between male and female and from ethnic background, only Korean male patients were selected; (2) To eliminate the influences of different surgical and orthodontic treatment, patients who were treated with the same protocol by a single surgeon (S.K.) and a single orthodontist (S.H.B.) were recruited; (3) To minimize the effects of surgical treatment after cheiloplasty and palatoplasty, patients whose lateral cephalogram was taken just before secondary alveolar bone graft (ABG) (T0; mean age, 9.3 years) were included; (4) To judge the need for future orthognathic surgery or DO, patients whose lateral cephalogram was taken at minimum 15 years of age (T1; mean age, 17.3 years) were enlisted. In addition, patients who had syndromic cleft including Van der Woude syndrome and Pierre Robin sequence or other craniofacial anomalies were excluded. The treatment protocol used in XNUH and XNUDH is summarized below: (1) Primary cheiloplasty (Millard rotation and advancement flap) between 3 and 5 months of age; (2) Palatoplasty (Furlow double opposing Z-plasty for one-stage palatorrhaphy) between 12 and 18 months of age; (3) No primary gingivoperiosteoplasty; (4) If needed, the maxillary arch was expanded before secondary ABG was performed; (5) During the mixed dentition stage, secondary ABG with particulate cancellous bone and marrow
FIGURE 2. Comparison of the frequency of orthognathic surgery or DO among groups 1, 2, and 3. Fisher exact test was performed. P < 0.05.
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from the iliac crest was conducted; (6) During the pubertal growth period, a facemask was used for orthopedic maxillary protraction; and (7) Fixed orthodontic treatment was performed during the permanent dentition stage. The cephalometric variables of lateral cephalograms taken at the T0 and T1 stages were measured by a single operator (H.M.P.). At T1 stage, the subjects were divided into surgery and nonsurgery groups according to 2 criteria: (1) If patients met the cephalometric criteria with ANB 3 degrees, Wits appraisal 5 mm, and Harvold unit difference (CoGn-CoSn0 ) 34 mm, they were classified into the surgery group.3,7,17,18 (2) The patients had been treated with preoperative orthodontic treatment or had already undergone orthognathic surgery or DO, they were automatically classified into the surgery group.3,7 A total of 40 subjects (n ¼ 20 in the surgery group and n ¼ 20 in the nonsurgery group) were reassessed by a single operator (H.M.P.) at one-month interval. Intraclass correlation coefficients were used to verify intraexaminer reliability. Because there were significant correlations between the first and second measurements (see Supplemental Digital Content, Table 1, http://links.lww.com/ SCS/A119), the first set of measurement was used. One-way analysis of variance, Fisher exact test, and independent t test were used for statistical analysis. For the prediction model, the cephalometric variables at the T0 stage were determined using the FW method with support vector machine /sequential forward search algorithms (see Supplemental Digital Content, Appendix, http://links.lww.com/SCS/A125).14–16 Classification accuracy was verified with a 10-fold cross-validation test.19
RESULTS There were no significant differences in age at each stage (T0 and T1) and duration (T0-T1) among CLA, UCLP, and BCLP groups (see Supplemental Digital Content, Table 2, http://links.lww.com/ SCS/A120). At T1 stage, a total of 27 (20.6%) of 131 subjects required orthognathic surgery or DO to correct their sagittal skeletal discrepancies (see Supplemental Digital Content, Table 3, http:// links.lww.com/SCS/A121). There were significant differences in the frequency of surgical intervention among CLA, UCLP, and BCLP groups (8.5%, 21.4%, and 30.0%, respectively; P < 0.05; (CLA, UCLP) < (UCLP, BCLP); see Supplemental Digital Content, Table 3, http://links.lww.com/SCS/A121 and, Fig. 2).
FIGURE 3. Superimposition of T0 stage profilograms using sella with the Frankfort horizontal plane. A 9-year-old boy without cleft lip and palate represents normal findings. Cleft-OS, a patient with cleft lip and/or palate who was treated with or needed orthognathic surgery or DO; Cleft-NOS, a patient with cleft lip and/or palate who was not treated with or did not need orthognathic surgery or DO.
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2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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Volume 26, Number 4, June 2015
At T1 stage, 13 variables were significantly different between the surgery and nonsurgery groups (gonial angle, SNA, ANB, IMPA, interincisal angle, A to N perpendicular, AB to mandibular plane, ODI, APDI, Wits, overbite, overjet, and Harvold unit difference; all P < 0.001; see Supplemental Digital Content, Table 4, http://links.lww.com/SCS/A122). However, at the T0 stage, only 7 cephalometric variables demonstrated significant differences between the surgery and nonsurgery groups (ANB, IMPA, AB to mandibular plane, APDI, Wits, overjet, and Harvold unit difference; all P < 0.05; see Supplemental Digital Content, Table 4, http:// links.lww.com/SCS/A122). Superimposition of the T0 profilograms between the surgery group and the nonsurgery group revealed differences in the amount of maxillary hypoplasia and clockwise rotation of the mandible (Fig. 3). In addition, when the T0 profilograms of each group were compared to that of a norsmal 9-year-old Korean boy, there were differences in the amount of maxillary hypoplasia and clockwise rotation of the mandible (Fig. 3). A total of 10 cephalometric variables (APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA) of the T0 stage were selected as predictors with an adjusted classification accuracy of 77.3% (see Supplemental Digital Content, Table 5, http://links.lww.com/SCS/A123). The prediction model is uploaded on the following Web site (http://bikechild.iptime.org:8838/orthodontics/). If the values of these 10 variables are inserted, prognosis prediction results for surgery and nonsurgery is generated. The sensitivity and specificity of this model were 99.0% and 74.1%, respectively (see Supplemental Digital Content, Table 6, http:// links.lww.com/SCS/A124).
DISCUSSION The finding that the frequency of orthognathic surgery or DO was increased with cleft severity (8.5% in CLA, 21.4% in UCLP, 30.0% in BCLP; see Supplemental Digital Content, Table 3, http:// links.lww.com/SCS/A121) was similar with the results from previous studies (12%–40% in UCLP, 13%–70% in BCLP).3,7,17,18 When considering that the subjects of these studies consisted of white population only or a diverse mixture of ethnic backgrounds, the effect of ethnic difference between Asian and white populations might not be greater than other factors such as the surgical timing and techniques of cheiloplasty, palatoplasty, and secondary ABG and the methods and duration of orthopedic/orthodontic treatment. However, well-designed, prospective, and controlled studies would be needed to perform the objective evaluation of the effects of the timing and techniques of the aforementioned surgery on the future needs of surgical intervention for correction of skeletal sagittal discrepancy.20 In addition, it would be appropriate to investigate long-term follow-up results of a facemask therapy in reduction of the need for surgical intervention and/or the amount of Le Fort I advancement of the maxilla by orthognathic surgery or DO. Antonarakis et al3 and Meazzini et al,8 in their conventional statistical analysis studies, suggest that ANB would be a powerful predictor in cleft patients at the age of 5–6 years. Because the permanent maxillary incisors are not completely erupted at that age, accurate tracing and cephalometric analysis of the anterior maxilla (including point A) might be difficult. However, the present study measured the T0 stage lateral cephalograms taken immediately before secondary ABG (at the mean age of 9.3 years). At this age, the permanent maxillary incisors are completely erupted, possibly making tracing and cephalometric analysis more accurate than in previous studies.3,8 When compared to previous studies that recommended ANB as a powerful predictor in cleft patients,3,8 the present study selected #
2015 Mutaz B. Habal, MD
Prediction of Surgery Need for Cleft Patients
10 features including APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA as cephalometric predictors (see Supplemental Digital Content, Table 5, http://links. lww.com/SCS/A123). This finding means that a combination of cephalometric features might have better classification accuracy than did a single decisive predictor. Patients with cleft lip and/or palate usually have a class III malocclusion pattern owing to maxillary hypoplasia as well as hyperdivergent growth pattern due to clockwise rotation of the mandible. The prediction model in the present study also included cephalometric variables related to the sagittal growth difference (ANB, APDI, Wits appraisal, Harvold unit difference, and A to N perpendicular) and the vertical growth pattern (ODI and AB to mandibular plane angle). These findings were in accordance with Seo et al,21 which also found that patients with cleft lip and/or palate had a more hyperdivergent growth pattern and clockwise rotation of the mandible compared to patients without cleft lip and/or palate. In addition, the predictors related to the mandibular morphology (gonial angle) and the dental compensation (overjet and IMPA) were included. Therefore, this combination of cephalometric variables might accurately predict the growth of cleft subjects who will need a surgical intervention. The sensitivity of classification model (the proportion of actual nonsurgery patients that were correctly predicted as nonsurgery patients) was higher than was the specificity (the proportion of actual surgery patients that were correctly predicted as surgery patients) (99.0% vs. 74.1%; see Supplemental Digital Content, Table 6, http://links.lww.com/SCS/A124). We found that 26% of actual patients who underwent surgery (7 of 27) were predicted as patients who did not undergo surgery (see Supplemental Digital Content, Table 6, http://links.lww.com/SCS/A124). These false negatives might reflect a physician’s subjective decision for orthognathic surgery or DO and/or a patient’s desire for facial esthetics.6 Therefore, further studies would be needed to find a method to improve the low specificity of this prediction model. The findings from this study might provide helpful information for management of patients with cleft lip and/or palate and their parents about possible surgical interventions. However, there are some limitations in the present study such as a relatively small sample size and short-term observation period. To establish a more accurate and objective prediction model, the effects of diverse surgical timing and method for cheiloplasty and palatoplasty and different technique and duration of maxillary protraction on the amount of maxillary hypoplasia would be investigated. In addition, further studies would be needed to identify the percentage of patients with cleft lip and/or palate with transverse discrepancy between the maxilla and the mandible and/or facial asymmetry that requires surgical correction.
CONCLUSIONS
The frequency of surgical intervention increased with cleft severity. A total of 10 cephalometric variables including APDI, ODI, Harvold unit difference, Wits appraisal, AB to mandibular plane angle, gonial angle, ANB, overjet, A to N perpendicular, and IMPA might be regarded as effective predictors of the future need for surgery to correct their sagittal skeletal discrepancies in Korean patients with cleft lip and/or palate.
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12. Tahmina K, Tanaka E, Tanne K. Craniofacial morphology in orthodontically treated patients of class III malocclusion with stable and unstable treatment outcomes. Am J Orthod Dentofacial Orthop 2000;117:681–690 13. Fudalej P, Dragan M, Wedrychowska-Szulc B. Prediction of the outcome of orthodontic treatment of class III malocclusions—a systematic review. Eur J Orthod 2011;33:190–197 14. Kim BM, Kang BY, Kim HG, et al. Prognosis prediction for class III malocclusion treatment by feature wrapping method. Angle Orthod 2009;79:683–691 15. Sahiner B, Chan HP, Petrick N, et al. Feature selection and classifier performance in computer-aided diagnosis: the effect of finite sample size. Med Phys 2000;27:1509–1522 16. Ceden˜o W, Agrafiotis DK. Using particle swarms for the development of QSAR models based on K-nearest neighbor and kernel regression. J Comput Aided Mol Des 2003;17:255–263 17. Linton JL. Comparative study of diagnostic measures in borderline surgical cases of unilateral cleft lip and palate and noncleft class III malocclusions. Am J Orthod Dentofacial Orthop 1998;113:526–537 18. Oberoi S, Chigurupati R, Vargervik K. Morphologic and management characteristics of individuals with unilateral cleft lip and palate who required maxillary advancement. Cleft Palate Craniofac J 2008;45: 42–49 19. McLachlan GJ, Do KA, Ambroise C. Analyzing microarray gene expression data. New York: Wiley;; 2004 20. Liao YF, Mars M. Hard palate repair timing and facial growth in cleft lip and palate: a systematic review. Cleft Palate Craniofac J 2006;43:563– 570 21. Seo YJ, Park JW, Kim YH, et al. Initial growth pattern of children with cleft before alveolar bone graft stage according to cleft type. Angle Orthod 2011;81:1103–1110
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2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
