The Cleft Palate–Craniofacial Journal 53(6) pp. e198–e207 November 2016 Ó Copyright 2016 American Cleft Palate–Craniofacial Association
ORIGINAL ARTICLE Preoperative Cleft Lip Measurements and Maxillary Growth in Patients With Unilateral Cleft Lip and Palate Gregory S. Antonarakis, D.D.S., M.Sc., Ph.D., Bryan D. Tompson, D.D.S., D. Paedo., D. Ortho., David M. Fisher, M.B. B.Ch., F.R.C.S.C., F.A.C.S. Objective: Maxillary growth in patients with cleft lip and palate is highly variable. The authors’ aim was to investigate associations between preoperative cleft lip measurements and maxillary growth determined cephalometrically in patients with complete unilateral cleft lip and palate (cUCLP). Design: Retrospective cross-sectional study. Patients: Children with cUCLP. Methods: Preoperative cleft lip measurements were made at the time of primary cheiloplasty and available for each patient. Maxillary growth was evaluated on lateral cephalometric radiographs taken prior to any orthodontic treatment and alveolar bone grafting (8.5 6 0.7 years). The presence of associations between preoperative cleft lip measurements and cephalometric measures of maxillary growth was determined using regression analyses. Results: In the 58 patients included in the study, the cleft lateral lip element was deficient in height in 90% and in transverse width in 81% of patients. There was an inverse correlation between cleft lateral lip height and transverse width with a b coefficient of 0.382 (P ¼ .003). Patients with a more deficient cleft lateral lip height displayed a shorter maxillary length (b coefficient ¼ 0.336; P ¼ .010), a less protruded maxilla (b coefficient ¼ .334; P ¼ .008), and a shorter anterior maxillary height (b coefficient ¼ 0.306; P ¼ .020) than those with a less deficient cleft lateral lip height. Conclusions: Patients with cUCLP present with varying degrees of lateral lip hypoplasia. Preoperative measures of lateral lip deficiency are related to later observed deficiencies of maxillary length, protrusion, and height. KEY WORDS:
cleft lip anthropometry, maxillary growth, unilateral cleft lip and palate
The two principal factors are intrinsic developmental deficiency and iatrogenic (Ross, 1987). Whatever the mechanism, maxillary growth impairment becomes progressively apparent as patients reach maturity (Semb and Shaw, 1998). Despite growth impairment being present in all cUCLP patients, considerable interpatient variation is present with a mix of good, medium, and poor facial growth. Intercenter collaborative efforts, including the Eurocleft and Americleft studies, have shown that large differences exist between centers with regard to midface growth (Brattstrom ¨ et al., 2005; Daskalogiannakis et al., 2011). A certain percentage of cUCLP patients will go on to require orthognathic surgery at the end of their active growth to correct their midface deficiency. These rates of orthognathic surgery range from approximately one in eight to one in two patients (Ross, 1987; Rosenstein et al., 1991, 2003; Cohen et al., 1995; DeLuke et al., 1997; Schnitt et al., 2004; Good et al., 2007; Daskalogiannakis and Mehta, 2009; Oberoi et al., 2012; Meazzini et al., in press). Midface growth deficiency is multifactorial. Surgical technique and experience are often implicated in the variation seen among patients in the severity of maxillary
INTRODUCTION Craniofacial growth deficiencies in individuals with complete unilateral cleft lip and palate (cUCLP) are widely recognized and have been reported for more than half a century (Graber, 1954). Midface growth deficiency may include reduced maxillary length and height as well as maxillary retrusion. Different etiological factors have been suggested to be responsible for these growth deficiencies.
Dr. Antonarakis is Orthodontist, Department of Orthodontics, Faculty of Dentistry, University of Geneva, Switzerland. Dr. Tompson is Head, Division of Orthodontics, The Hospital for Sick Children, and Associate Professor and Head, Department of Orthodontics, Faculty of Dentistry, University of Toronto, Toronto Ontario, Canada. Dr. Fisher is Medical Director, Cleft Lip and Palate Program, Division of Plastic Surgery, The Hospital for Sick Children, and Associate Professor, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Submitted September 2014; Revised November 2014, December 2014; Accepted December 2014. Address correspondence to: Gregory S. Antonarakis, Department of ´ Orthodontics, University of Geneva, 19 rue Barthelemy-Menn, 1205 Geneva, Switzerland. E-mail [email protected]. DOI: 10.1597/14-274 e198
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
hypoplasia (Shaw et al., 1992). However, even when considering cUCLP patients treated by the same surgeon using the same surgical protocol (minimizing variation due to iatrogenic factors), varying outcomes are observed with respect to maxillary hypoplasia (Nakamura et al., 2005; Meazzini et al., 2011). This suggests that individual intrinsic factors may play an important role in maxillofacial growth potential. One intrinsic factor possibly responsible for maxillofacial growth variation in cUCLP patients is the initial severity of the cleft. Within a particular cleft type, such as cUCLP, there is large phenotypic variation, defined in part by the severity of the deformity. The severity at birth may reflect differing contributions of tissue deficiency and/or tissue displacement. If initial severity and maxillary skeletal growth are linked, it is plausible to assume that the midface growth problem associated with tissue deficiency will play a role throughout the postnatal growth period (Peltomaki ¨ et al., 2001). The relationship between cleft severity and maxillofacial growth in cUCLP patients is still unresolved, although many studies support the claim that the more severe the cleft deformity at birth, the greater the amount of maxillary growth disturbance. Several studies have suggested that patients with more severe palatal or alveolar clefts or greater palatal tissue deficiency exhibit less favorable maxillary growth and poorer dental arch relationships (Schwartz et al., 1984; Suzuki et al., 1993; Peltomaki ¨ et al., 2001; Honda et al., 2002; Liao and Mars, 2005; Liao et al., 2010; Chiu et al., 2011; Chiu and Liao, 2012; Hsieh et al., 2012; Tomita et al., 2012). However, other studies do not support this idea (Johnson et al., 2000; Meazzini et al., 2008, 2011; Reiser et al., 2010; Wiggman et al., 2013). Measuring cleft severity based on cleft or palate or alveolar size, however, carries certain limitations. Factors such as infant orthopedics, aberrant function such as tongue force (Delestan et al., 2014), sleeping position (Huang et al., 1994), or the general size of the infant can influence these severity measurements. Liao et al. (2010) postulated that the cleft size reflects primarily tissue displacement, mainly through tongue force, rather than tissue deficiency. Cleft severity in cUCLP individuals at the level of the lip as opposed to the palate is something that has not attracted much attention in this respect. Nakamura et al. (2005) nevertheless found that a more deficient cleft lip tissue volume shows worse maxillary growth. Patients with unilateral clefts have been shown to exhibit large variability in preoperative lip measurements (Boorer et al., 2011), with a wide variety of growth asymmetry observed between the cleft and noncleft sides (Chou et al., 2013). We hypothesize that the dimensions of the cleft lateral lip element are associated with subsequent maxillary growth. The aim of the current study was to investigate the presence of associations between the severity of the unilateral cleft lip deficiency and maxillary growth using cephalometry.
MATERIALS
AND
e199
METHODS
The current study design was retrospective and crosssectional in nature and approved by our institution’s Research Ethics Board. A chart review was carried out to identify Caucasian children born with cUCLP between 2000 and 2007. Inclusion criteria comprised the following: primary unilateral cheiloplasty and palatoplasty carried out by the senior author and lateral cephalometric radiographs available at the approximate age of 9 years (62 years) before any orthodontic treatment or alveolar bone grafting. The following were our exclusion criteria: children whose cleft was part of a craniofacial syndrome, children who had secondary surgical treatment prior to the taking of the lateral cephalometric radiograph, children who had a history of dental or facial trauma, and lateral cephalometric radiographs of insufficient diagnostic quality. All children had been treated according to the following treatment protocol: presurgical infant orthopedics using the nasoalveolar molding technique (Grayson et al., 1999) for a period of approximately 12 to 24 weeks (until primary cheiloplasty), primary cheiloplasty at approximately 3 to 6 months of age using the technique of Fisher (2005), and primary palatoplasty at approximately 12 months of age using the hybrid palatoplasty technique (Gillet and Clarke, 1996). Determination of Cleft Phenotype Determination of cUCLP phenotype was based on clinical diagnosis. All diagnoses were made by the senior author at or soon after birth and confirmed at the time of primary cheiloplasty. Laterality of the cleft (left or right sided) was also recorded. Preoperative Lip Measurements The senior author performed all preoperative lip measurements, with calipers, at the time of primary cheiloplasty with the patient under general anesthesia. This ensured that the underlying muscles and overlying skin surfaces were in complete relaxation and thus that all soft tissues were at rest. Height and transverse width measurements of both the cleft and the noncleft lateral lip element were recorded to the nearest 0.5 mm. The landmarks used for measurements are shown in Figure 1. Lateral lip height of the noncleft side was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. Lateral lip height of the cleft side was measured from subalare to the proposed peak of Cupid’s bow. The proposed peak of Cupid’s bow was defined, according to Noordhoff (1997), as the point along the vermilion-cutaneous junction where the cutaneous roll and red line (vermilion-mucosal junction) begin to converge medially. Lateral lip transverse width
e200
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
FIGURE 1 The noncleft side lateral lip height (A) was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The cleft side lateral lip height (B) was measured from subalare to the proposed peak of Cupid’s bow. The noncleft side lateral lip transverse width (C) was measured from the oral commissure to the peak of Cupid’s bow. The cleft side lateral lip transverse width (D) was measured from the oral commissure to the proposed peak of Cupid’s bow (reproduced with permission from Boorer et al., 2011).
of the noncleft side was measured from the oral commissure to the peak of Cupid’s bow. Lateral lip transverse width of the cleft side was measured from the oral commissure to the proposed peak of Cupid’s bow at Noordhoff’s point. Lateral Cephalometric Analysis All lateral cephalometric radiographs had been taken on the same cephalostat according to standardized cephalometric guidelines with natural head position, the teeth in occlusion, and the lips at rest. The magnification ratio was 9.66%, and necessary adjustments were made when linear measurements were being made. All radiographs were traced by hand on a 0.003-inch matte acetate sheet (GAC International Inc., Bohemia, NY), using a 0.3-mm 2H lead pencil and a protractor (3M Unitek, Monrovia, CA) by one investigator. No more
than 10 radiographs were traced in a single day to minimize errors due to investigator fatigue (Erkan et al., 2012). A total of six cephalometric landmarks were located on each radiograph, and a resulting seven variables were measured (four linear and three angular; Fig. 2). Traditional landmarks for the anterior nasal spine, posterior nasal spine, and point A were used instead of constructed alternatives for these landmarks proposed for patients with clefts since it has been found that constructed landmarks are no more reliable than the traditional ones (Bongaarts et al., 2008). Selected variables were measured representing the maxilla (Table 1), based on recent published studies investigating cleft severity and maxillary growth (Chiu et al., 2011; Wiggman et al., 2013). Variables were divided into length, height, protrusion, and inclination.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
e201
FIGURE 2 Cephalometric landmarks and measured variables on the tracing of a lateral cephalometric radiograph. Cephalometric landmarks: A ¼ cephalometric A point; ANS ¼ anterior nasal spine; N ¼ nasion; PNS ¼ posterior nasal spine; R ¼ registration point (point of crossing of the greater wing of the sphenoid and the planum sphenoidale); S ¼ sella turcica. Cephalometric measurements: ANS-PNS ¼ basal maxillary length; A-PNS ¼ alveolar maxillary length; S-N-ANS ¼ basal maxillary protrusion; S-N-A ¼ alveolar maxillary protrusion; N-ANS ¼ anterior maxillary height; R-PNS ¼ posterior maxillary height; S-N/ANS-PNS ¼ maxillary plane angle.
Statistical Analysis All data were analyzed using the Statistical Package for Social Sciences Version 21.0 for Windows (SPSS Inc., Chicago, IL). Statistical significance was set at the P , .05 level. Preoperative lip measurements and all lateral cephalometric measurements were initially tested for normality visually based on plots (histograms and TABLE 1
normal Q-Q plots) as well as statistically using the Shapiro-Wilks test. All data were found to be normally distributed, and thus parametric statistics were used throughout. Descriptive statistics (mean, standard deviation, and range) were calculated for the preoperative lip measurements, and independent-sample t tests were used to investigate the presence of statistically significant
Selected Variables Measured Representing the Maxilla
Measurement
Landmark Measures*
Similar to
Maxillary length Basal maxillary length Alveolar maxillary length
ANS-PNS (linear) A-PNS (linear)
Chiu et al. (2011); Wiggman et al. (2013) Chiu et al. (2011)
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
S-N-ANS (angular) S-N-A (angular)
Chiu et al. (2011) Chiu et al. (2011); Wiggman et al. (2013)
Maxillary height Anterior maxillary height Posterior maxillary height
N-ANS (linear) R-PNS (linear)
Chiu et al. (2011) Chiu et al. (2011)
Maxillary inclination Maxillary plane angle
S-N/ANS-PNS (angular)
Wiggman et al. (2013)
* A ¼ cephalometric A point; ANS ¼ anterior nasal spine; N ¼ nasion; PNS ¼ posterior nasal spine; R ¼ registration point; S ¼ sella.
e202
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
TABLE 2
TABLE 3
Summary of Preoperative Lip Measurements
Measurement
Mean (SD)*
Range†
Lateral lip height Noncleft side (mm) Cleft side (mm) Difference (mm) Cleft side/noncleft side (%)
11.1 8.4 2.8 76
(1.7) (1.8) (2.0) (16)
7–15.5 5.5–17 4–6.5 46–131
Lateral lip transverse width Noncleft side (mm) Cleft side (mm) Difference (mm) Cleft side/noncleft side (%)
17.3 15.4 1.9 90
(2.4) (1.8) (1.8) (9)
13–26 11–22 2–10 58–114
* SD ¼ standard deviation. † Negative values in range indicate cleft side greater than noncleft side measurement.
differences between lip measurements and sex or laterality. Descriptive statistics were also calculated for the various lateral cephalometric measurements. The presence of associations between preoperative lip measurements and lateral cephalometric measurements was subsequently examined using linear regression analysis. Possible confounding determinants of facial growth, including sex, laterality, age at primary cheiloplasty, age at primary palatoplasty, age at which the lateral cephalometric radiographs were taken, and surgeon’s experience, were first investigated using bivariate analysis to identify the possible presence of any statistically significant association between these factors and any of the lateral cephalometric measurements. When a significant association was found, the variables were then incorporated in the final linear regression model as covariates. Error of the Method Analysis The error of the method was calculated by performing duplicate tracings on 20 lateral cephalometric radiographs 2 to 4 weeks later by the same investigator. Systematic error was assessed by using one-sample t tests comparing the duplicate lateral cephalometric tracings (Houston, 1983). Random error was assessed using Dahlberg’s (1940) formula (SE ¼ =Rd2/2n), where n ¼ the number of patients undergoing repeated measurements and d ¼ the difference in measurements.
Summary of Lateral Cephalometric Measurements Measurement*
Mean (SD)†
Range
Maxillary length Basal maxillary length (mm) Alveolar maxillary length (mm)
46.8 (4.0) 43.2 (4.0)
38–55 35.5–51
Maxillary protrusion Basal maxillary protrusion (deg) Alveolar maxillary protrusion (deg)
81.7 (5.1) 77.0 (5.0)
70.5–93.5 64–90
Maxillary height Anterior maxillary height (mm) Posterior maxillary height (mm)
46.7 (3.4) 41.4 (3.9)
38–55 33–52
Maxillary inclination Maxillary plane angle (deg)
9.0 (4.0)
1–20.5
* deg ¼ degrees; mm ¼ millimeters. † SD ¼ standard deviation.
total patient sample, or 8.5 6 0.7 years for the males and 8.6 6 0.9 years for the females. Preoperative Lip Measurements Mean height and transverse width measurements, as well as differences between the cleft and noncleft sides, for the total study sample are shown in Table 2. The same table also presents the cleft side lip measurements as a percentage of the same measurements on the noncleft side. No sex or cleft side differences were found for the lip measurements. A total of 52 of 58 (90%) patients had a cleft lateral lip height deficiency, while 47 of 58 (81%) had a cleft lateral lip transverse width deficiency. Severe cleft lateral lip height deficiency (defined as .1 standard deviation from the mean) was seen in 11 patients. Severe cleft lateral lip transverse width deficiency was observed in four patients. A combined cleft lateral lip element deficiency (both height and transverse width) was found in 41 of 58 (71%) patients, but a combined severe cleft lateral lip element (.1 standard deviation for both height and width) was not found in any of the patients. There was an inverse correlation between cleft lateral lip height and transverse width (b coefficient ¼ 0.382; P ¼ .003). Lateral Cephalometric Analysis
RESULTS Sample Fifty-eight cUCLP children fit the predefined inclusion and exclusion criteria. The sample comprised 44 males (30 left- and 14 right-sided clefts) and 14 females (11 left- and 3 right-sided clefts). The overall left:right ratio was 41:17. The mean age at which the lateral cephalometric radiographs were taken was 8.5 6 0.7 years (minimum 7.1 years; maximum 10.7 years) for the
The lateral cephalometric variables measured are presented in Table 3. No significant differences were found when comparing males to females or left- to rightsided clefts. Using repeated measurements for detection of systematic error, there was no statistically significant difference, at the 5% level, between the first and second measurements. With regard to random error, for linear measurements the error did not exceed 1.0 mm, while for angular measurements this did not exceed 1.4 degrees.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
TABLE 4
e203
Associations Between Lip and Cephalometric Measurements Univariable Estimates
Measurement
a Coefficient
b Coefficient
Adjusted Estimates
95% CI*
P Value
Adjusted Coefficient
Confounder
P Value
0.004 0.008
Lateral Lip Height† Maxillary length Basal maxillary length Alveolar maxillary length
8.093 8.634
0.336 0.358
2.028; 14.158 2.610; 14.659
0.010 0.006
0.428 0.403
Age‡ Age‡
11.415 10.662
0.334 0.358
3.625; 19.206 3.059; 18.266
0.008 0.006
— —
— —
— —
Maxillary height Anterior maxillary height Posterior maxillary height
6.299 3.835
0.306 0.161
1.047; 11.550 2.472; 10.143
0.020 0.228 (ns)
— —
— —
— —
Maxillary inclination Maxillary plane angle
1.447
0.059
5.067; 7.960
0.658 (ns)
—
—
—
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
Lateral Lip Transverse Width Maxillary length Basal maxillary length Alveolar maxillary length
11.645 16.159
0.268 0.373
22.808; 0.483 26.935; 5.383
0.041 0.004
0.374 0.459
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
18.508 21.003
0.323 0.339
32.729; 4.287 34.493; 7.512
0.013 0.009
— —
— —
— —
Maxillary height Anterior maxillary height Posterior maxillary height
6.768 6.873
0.183 0.160
16.527; 2.991 18.225; 4.478
0.170 (ns) 0.230 (ns)
— —
— —
— —
Maxillary inclination Maxillary plane angle
2.976
0.068
14.690; 8.739
0.613 (ns)
—
—
—
Age‡ Age‡
0.016 0.001
* CI ¼ confidence interval; ns ¼ nonsignificant correlation found. † Lip heights or widths refer to cleft/noncleft side ratios. ‡ ¼ Age at which the lateral cephalometric radiograph was taken.
Associations Bivariate analyses investigating the possible confounding determinants of facial growth showed significant associations between the age at which the lateral cephalometric radiograph was taken and the basal maxillary length (b coefficient ¼ 0.282; P ¼ .032) as well as alveolar maxillary length (b coefficient ¼ 0.298; P ¼ .023). No other significant covariates (sex, laterality, age at primary repair, surgeon’s experience) were found. When performing the linear regression analysis between lip measurements and these cephalometric variables, the age at which the lateral cephalometric radiograph was taken was controlled for by including it as a covariate in the analysis. Correlations were observed as shown in Table 4. Children with a more deficient preoperative cleft lateral lip height showed a shorter maxillary length, a less protruded maxilla, and a shorter anterior maxillary height than those with a less deficient cleft lateral lip height. Inversely, children with a more deficient preoperative cleft lateral lip transverse width showed a longer maxillary length and a more protruded maxilla than those with a less deficient cleft lateral lip transverse width.
DISCUSSION The preoperative physical dimensions of the cleft lip in cUCLP patients show some associations with subsequent maxillary growth, in both sagittal and vertical dimensions, as suggested by the present study. Children with a more deficient cleft lateral lip height and a less deficient cleft lateral lip transverse width are more likely to demonstrate a shorter maxillary length, a less protruded maxilla, and a shorter anterior maxillary height. However, associations, albeit present, were not very strong. The majority of previous studies looking into associations between cleft severity and maxillary growth have focused on measuring initial cleft severity based on the palatal or alveolar cleft despite its complexity and possible inaccuracies. Seckel et al. (1995) illustrated the difficulties in measuring initial cleft severity in this way and stated that reproducible landmark positioning on the infant maxilla can be a reality only with optimal cast quality and an experienced investigator. In the present study, maxillary length was found to be partly dependent on cleft severity as defined by preoperative cleft lip measurements. The fact that cleft lateral lip height and transverse width were inversely correlated in our sample explains why both of these measurements displayed associations with maxillary
* Note that the specific cephalometric landmarks used to make the above measurements may not have been identical to the ones used in the present study. Yes ¼ an association/correlation was found between cleft severity and the cephalometric measurement; X ¼ no association/correlation was found; — ¼ not reported.
— Yes Yes — — Yes — — X — X X Maxillary inclination Maxillary plane angle
—
— — — — X Yes — — X X Yes X — — Yes X X Yes Yes Yes X X Yes X Maxillary height Anterior maxillary height Posterior maxillary height
— —
— Yes — X — X — X X Yes Yes Yes — X — X Yes Yes — — — Yes Yes Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
— Yes
— — X — X — — — X X Yes Yes — — — X Yes Yes — Yes X — Yes Yes
Yes Yes
France Sweden/Norway Japan Italy Taiwan Taiwan Italy Japan Sri Lanka Japan United States Japan Canada
Patient origin Maxillary length Basal maxillary length Alveolar maxillary length
Liao and Mars (2005) Honda et al. (2002) Peltomaki ¨ et al. (2001) Suzuki et al. (1993) Present Study
Comparison of the Present Findings to Other Studies (in Chronological Order)*
Nakamura et al. (2005)
Meazzini et al. (2008)
Liao et al. (2010)
Chiu et al. (2011
Meazzini et al. (2011)
Tomita et al. (2012)
Wiggmann et al. (2013)
Doucet et al. (2014)
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
TABLE 5
e204
length. From the other studies that examined maxillary length in relation to initial cleft severity (Table 5), four were in line with our results (Peltomaki et al., 2001; ¨ Honda et al., 2002; Liao and Mars, 2005; Liao et al., 2010), while five did not find significant associations (Suzuki et al., 1993; Nakamura et al., 2005; Chiu et al., 2011; Tomita et al., 2012; Wiggman et al., 2013). Maxillary protrusion was also found to be partly dependent on cleft severity as defined by preoperative cleft lip measurements in this study. Both cleft lateral lip height and transverse width were found to be correlated with maxillary protrusion. Among the other studies examining cephalometric variables representing maxillary protrusion (Table 5), four found positive associations with initial cleft severity (Peltomaki ¨ et al., 2001; Liao and Mars, 2005; Liao et al., 2010; Doucet et al., 2014), while Chiu et al. (2011) found an association with alveolar but not basal maxillary protrusion. On the other hand, five studies found no such associations (Nakamura et al., 2005; Meazzini et al., 2008, 2011; Tomita et al., 2012; Wiggman et al., 2013). With regard to maxillary height, our study found positive associations with cleft severity. More precisely, this held true for anterior but not posterior maxillary height. Other studies examining maxillary height were conflicting (Table 5). Three studies found significant associations between cleft severity and anterior maxillary height (Honda et al., 2002; Nakamura et al., 2005; Liao et al., 2010), while four did not (Suzuki et al., 1993; Liao and Mars, 2005; Chiu et al., 2011; Tomita et al., 2012). Three studies found significant associations with posterior maxillary height (Honda et al., 2002; Liao and Mars, 2005; Tomita et al., 2012), while four did not (Suzuki et al., 1993; Nakamura et al., 2005; Liao et al., 2010; Chiu et al., 2011). One must be aware that the different maxillary measurements that were undertaken on the lateral cephalometric radiographs are inherently correlated to some extent. Different cephalometric measurements with at least one similar cephalometric landmark can be influenced by differences in that specific landmark in any direction. For example, the location of the anterior nasal spine can influence basal maxillary length, basal maxillary protrusion, anterior maxillary height, and maxillary plane angle. The associations between initial cleft severity and maxillofacial growth are usually attributed to an intrinsic growth potential. One cannot overlook, however, the possibility that cleft severity may have an indirect influence on outcome following surgical cleft repair. The extent of the cleft lip may affect the difficulty of surgical repair, thereby ultimately influencing outcome via greater generation of scar tissue or amount of surgical tissue movement. Lateral lip element hypoplasia, used as an indicator of cleft severity, may suggest that the amount of palatal or alveolar tissue deficiency is also great, thereby leading to a more difficult palatal surgical repair, again indirectly affecting outcome.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
Tension from scar tissue arising from lip and palate repair may show adverse effects on maxillary growth. Delestan et al. (2014) advocate that a more detailed analysis of the different cleft subtypes within a cUCLP population is necessary to distinguish between the role of treatment and the inherent growth potential. This highlights the importance of establishing a precise initial evaluation of the malformation to avoid comparing different entities and making flawed assumptions (Meazzini et al., in press). Cleft subtypes within a population could be established using clinical criteria, such as cleft lip hypoplasia (Cosman and Crikelair, 1965; Boorer et al., 2011), cleft palate severity (Suzuki et al., 1993; Peltomaki ¨ et al., 2001; Chiu et al., 2011), or nasolabial deformity (Lindsay and Farkas, 1972; Fisher et al., 2008). The heterogeneity of cUCLP and its characterization by subtype or initial cleft severity can have important clinical implications. Favorable or unfavorable maxillary growth (and potentially other treatment outcomes) can be anticipated according to cleft severity, directing cUCLP children with different cleft severities to a different treatment protocol (Peltomaki et al., 2001). Individual treatment ¨ planning based on presenting morphology could be adopted for every cUCLP-affected child rather than conforming to predetermined surgical treatment protocols (Reiser et al., 2010). For example, in the case of a child with severe cUCLP, prone sleep positioning and delayed or staged palate closure might be preferred (Hsieh et al., 2012). This information, if available at birth, can help both parents and those involved in the care of children with clefts better prepare themselves for the eventual outcomes. If growth prognosis is identified early, those with worst prognoses may receive special attention to allocate appropriate and well-timed treatment protocols (Chiu et al., 2011; Doucet et al., 2014). One of the main limitations of the present study was its design, being retrospective and cross-sectional in nature. However, the presurgical measurements were obtained in a prospective fashion with this study in mind. A prospective longitudinal study would be able to provide a more superior level of evidence, and these types of well-designed studies should be planned for future investigations into the association of maxillary growth and cleft severity. The sample size, though small, did allow us to observe statistical significance. A larger sample size, however, would have been better able to demonstrate statistical significance given its improved power. In addition, maxillary growth disturbances in cUCLP patients may be expressed in three dimensions, and no data were available in the current study that allowed an assessment of maxillary growth in the transverse dimension. Lateral cephalometric radiographs allow an assessment of the sagittal and vertical but not the transverse plane. A postero-anterior cephalometric radiograph or a cone-beam–computed tomographic image would have been suited to allow an assessment of the
e205
transverse dimension. These modalities were not available for the present patient sample. The choice of using Noordhoff’s point as the proposed peak of Cupid’s bow on the cleft lateral lip element was made, as this is a reference surgical point. One could have also used a true anatomical point instead in the hope that this may provide a better basis for correlations. Furthermore, the finding that the cleft lateral lip height was inversely correlated to the transverse width may have been related to the use of this point. All lip measurements in the present patient sample were done after nasoalveolar molding, which included lip taping. The force of the lip taping needs to be recognized as having a potential effect on the soft tissues. Flattening and other effects may alter the dimensions of the lip elements. The ideal timing for the lip measurements could have been immediately after birth and prior to nasoalveolar molding treatment, but this would have the disadvantage that the measurements would not be carried out under general anesthesia. The measurements were chosen to be undertaken at the time of lip repair so that any inaccuracies of the measurements could be minimized. Unfortunately, repeated measurements to assess the error of the method were not possible due to the subsequent lip repair, but all measurements were carried out by one experienced operator. Moreover, nasoalveolar molding will have affected all patients and both sides of the lip, making results comparable. Lip repair was undertaken anywhere from 3 to 6 months of age, depending on factors such as the readiness of the infant for surgery, family constraints, and operating room schedules. This variation in age at surgery can affect lip dimensions, as growth will affect lip measurements. For this reason, proportions were used instead of absolute lip measurements. The impact of the original condition of the cleft on final outcome deserves special attention, as it is a complex issue. The present study highlights the variation seen in cleft lateral lip element deficiency, both in the vertical and in the transverse dimensions, and the potential correlations that this deficiency may have with maxillary growth and position. Certainly, cleft lip severity is not an isolated prognostic factor for maxillary growth, and its use as a sole factor is insufficient. The present data, however, suggest that within the spectrum of the deformity for patients with cUCLP, the degree of lateral lip element hypoplasia is one of the factors associated with the resulting maxillary growth potential. Our findings may have implications in the design of future research protocols for growth studies in cUCLP children. Children with cUCLP could be ranked by severity before correlating specific treatment variables and outcomes, moving away from the traditional pooling of patients (Peltomaki ¨ et al., 2001). Severity could be based on infant parameters, such as the relative size of the cleft lip, alveolar and palatal cleft widths, the area and inclination of the palatal shelves, the nasal deformity, and missing teeth,
e206
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
that would allow associations between cleft severity and outcome to be elucidated. CONCLUSIONS In patients with cUCLP, there is wide variability in the degree of deficiency of the cleft lateral lip element in both height and width. We have demonstrated that the extent of lateral lip hypoplasia is one of the factors that may be predictive of later maxillary growth deficiencies as determined by maxillary sagittal and vertical dimensions and maxillary position. REFERENCES Bongaarts CA, van’t Hof MA, Prahl-Andersen B, Kuijpers-Jagtman AM. Identification of cephalometric landmarks in unilateral cleft lip and palate patients: are there alternatives for point A, ANS, and PNS? Cleft Palate Craniofac J. 2008;45:81–86. Boorer CJ, Cho DC, Vijayasekaran VS, Fisher DM. Presurgical unilateral cleft lip anthropometrics: implications for the choice of repair technique. Plast Reconstr Surg. 2011;127:774–780. Brattstrom ¨ V, Mølsted K, Prahl-Andersen B, Semb G, Shaw WC. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 2: craniofacial form and nasolabial appearance. Cleft Palate Craniofac J. 2005;42:69–77. Chiu YT, Liao YF. Is cleft severity related to maxillary growth in patients with unilateral cleft lip and palate? Cleft Palate Craniofac J. 2012;49:535–540. Chiu YT, Liao YF, Chen PK. Initial cleft severity and maxillary growth in patients with complete unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2011;140:189–195. Chou PY, Lou CC, Chen PK, Chen YR, Noordhoff MS, Lo LJ. Preoperative lip measurements in patients with complete unilateral cleft lip/palate and its comparison with norms. J Plast Reconstr Aesthet Surg. 2013;66:513–517. Cohen SR, Corrigan M, Wilmot J, Trotman CA. Cumulative operative procedures in patients aged 14 years and older with unilateral or bilateral cleft lip and palate. Plast Reconstr Surg. 1995;96:267–271. Cosman B, Crikelair GF. The shape of the unilateral cleft lip defect: a speculative report. Plast Reconstr Surg. 1965;35:484–493. Dahlberg G. Statistical Methods for Medical and Biological Students. New York: Interscience Publications; 1940. 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. Daskalogiannakis J, Mercado A, Russell K, Hathaway R, Dugas G, Long RE Jr, Cohen M, Semb G, Shaw W. The Americleft study: an inter-center study of treatment outcomes for patients with unilateral cleft lip and palate part 3. Analysis of craniofacial form. Cleft Palate Craniofac J. 2011;48:252–258. Delestan C, Montoya P, Doucet JC, Bigorre M, Baumler C, Herlin C, ¨ Daures JP, Captier G. New neonatal classification of unilateral cleft lip and palate—part 1: to predict primary lateral incisor agenesis and inherent tissue hypoplasia. Cleft Palate Craniofac J. 2014;51:392–399. DeLuke DM, Marchand A, Robles EC, Fox P. Facial growth and the need for orthognathic surgery after cleft palate repair: literature review and report of 28 cases. J Oral Maxillofac Surg. 1997;55:694– 697. Doucet JC, Delestan C, Montoya P, Matei L, Bigorre M, Herlin C, Baumler C, Daures JP, Captier G. New neonatal classification of ¨ unilateral cleft lip and palate—Part 2: to predict permanent lateral
incisor agenesis and maxillary growth. Cleft Palate Craniofac J. 2014;51:533–539. Erkan M, Gurel HG, Nur M, Demirel B. Reliability of four different computerized cephalometric analysis programs. Eur J Orthod. 2012;34:318–321. Fisher DM. Unilateral cleft lip repair: an anatomical subunit approximation technique. Plast Reconstr Surg. 2005;116:61–71. Fisher DM, Tse R, Marcus JR. Objective measurements for grading the primary unilateral cleft lip nasal deformity. Plast Reconstr Surg. 2008;122:874–880. Gillet DA, Clarke HM. The hybrid palatoplasty: a preliminary report. Canadian J Plast Surg. 1996;4:157–160. Good PM, Mulliken JB, Padwa BL. Frequency of Le Fort I osteotomy after repaired cleft lip and palate or cleft palate. Cleft Palate Craniofac J. 2007;44:396–401. Graber TM. The congenital cleft palate deformity. J Am Dent Assoc. 1954;48:375–395. Grayson BH, Santiago PE, Brecht LE, Cutting CB. Presurgical nasoalveolar molding in infants with cleft lip and palate. Cleft Palate Craniofac J. 1999;36:486–498. Honda Y, Suzuki A, Nakamura N, Ohishi M. Relationship between primary palatal form and maxillofacial growth in Japanese children with unilateral cleft lip and palate: infancy to adolescence. Cleft Palate Craniofac J. 2002;39:527–534. Houston WJ. The analysis of errors in orthodontic measurements. Am J Orthod. 1983;83:382–390. Hsieh YJ, Liao YF, Shetty A. Predictors of poor dental arch relationship in young children with unilateral cleft lip and palate. Clin Oral Invest. 2012;16:1261–1266. Huang CS, Cheung HC, Chen YR, Noordhoff MS. Maxillary dental arch affected by different sleep positions in unilateral complete cleft lip and palate infants. Cleft Palate Craniofac J. 1994;31:179–184. Johnson N, Williams A, Singer S, Southall P, Sandy J. Initial cleft size does not correlate with outcome in unilateral cleft lip and palate. Eur J Orthod. 2000;22:93–100. Liao YF, Mars M. Long-term effects of palate repair on craniofacial morphology in patients with unilateral cleft lip and palate. Cleft Palate Craniofac J. 2005;42:594–600. Liao YF, Prasad NK, Chiu YT, Yun C, Chen PK. Cleft size at the time of palate repair in complete unilateral cleft lip and palate as an indicator of maxillary growth. Int J Oral Maxillofac Surg. 2010;39:956–961. Lindsay WK, Farkas LG. The use of anthropometry in assessing cleftlip nose. Plast Reconstr Surg. 1972;49:286–293. Meazzini MC, Capello AV, Ventrini F, Autelitano L, Morabito A, Garattini G, Brusati R. Long-term follow-up of UCLP patients: surgical and orthodontic burden of care during growth and final orthognathic surgery need. Cleft Palate Craniofac J. In press. Meazzini MC, Donati V, Garattini G, Brusati R. Maxillary growth impairment in cleft lip and palate patients: a simplified approach in the search for a cause. J Craniofac Surg. 2008;19:1302–1307. Meazzini MC, Tortora C, Morabito A, Garattini G, Brusati R. Factors that affect variability in impairment of maxillary growth in patients with cleft lip and palate treated using the same surgical protocol. J Plast Surg Hand Surg. 2011;45:188–193. Nakamura N, Suzuki A, Takahashi H, Honda Y, Sasaguri M, Ohishi M. A longitudinal study on influence of primary facial deformities on maxillofacial growth in patients with cleft lip and palate. Cleft Palate Craniofac J. 2005;42:633–640. Noordhoff MS. The Surgical Technique for the Unilateral Cleft LipNasal Deformity. Taipei: Noordhoff Craniofacial Foundation; 1997. Oberoi S, Hoffman WY, Chigurupati R, Vargervik K. Frequency of surgical correction for maxillary hypoplasia in cleft lip and palate. J Craniofac Surg. 2012;23:1665–1667. Peltomaki T, Vendittelli BL, Grayson BH, Cutting CB, Brecht LE. ¨ Associations between severity of clefting and maxillary growth in
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
patients with unilateral cleft lip and palate treated with infant orthopedics. Cleft Palate Craniofac J. 2001;38:582–586. Reiser E, Skoog V, Gerdin B, Andlin-Sobocki A. Association between cleft size and crossbite in children with cleft palate and unilateral cleft lip and palate. Cleft Palate Craniofac J. 2010;47:175–181. Rosenstein SW, Grasseschi M, Dado DV. A long-term retrospective outcome assessment of facial growth, secondary surgical need, and maxillary lateral incisor status in a surgical-orthodontic protocol for complete clefts. Plast Reconstr Surg. 2003;111:1–13. Rosenstein S, Kernahan D, Dado D, Grasseschi M, Griffith BH. Orthognathic surgery in cleft patients treated by early bone grafting. Plast Reconstr Surg. 1991;87:835–892. Ross RB. Treatment variables affecting facial growth in complete unilateral cleft lip and palate. Cleft Palate J. 1987;24:5–77. Seckel NG, van der Tweel I, Elema GA, Specken TF. Landmark positioning on maxilla of cleft lip and palate infant—a reality? Cleft Palate Craniofac J. 1995;32:434–441. 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. Schwartz BH, Long RE Jr, Smith RJ, Gipe DP. Early prediction of posterior crossbite in the complete unilateral cleft lip and palate. Cleft Palate J. 1984;21:76–81.
e207
Semb G, Shaw WC. Facial growth after different methods of surgical intervention in patients with cleft lip and palate. Acta Odontol Scand. 1998;56:352–355. Shaw WC, Dahl E, Asher-McDade C, Brattstrom V, Mars M, ¨ McWilliam J, Mølsted K, Plint DA, Prahl-Andersen B, Roberts C, et al. The RP. A six-center international study of treatment outcome in patients with clefts of the lip and palate: part 5. General discussion and conclusions. Cleft Palate Craniofac J. 1992;29:413– 418. Suzuki A, Mukai Y, Ohishi M, Miyanoshita Y, Tashiro H. Relationship between cleft severity and dentocraniofacial morphology in Japanese subjects with isolated cleft palate and complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 1993;30:175–181. Tomita Y, Kuroda S, Katsura T, Watanabe T, Watanabe K, Fujihara S, Tanaka E. Severity of alveolar cleft before palatoplasty affects vertical maxillofacial growth in 6-year-old patients with complete unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2012;141:S102–S109. Wiggman K, Larson M, Larson O, Semb G, Brattstrom V. The ¨ influence of the initial width of the cleft in patients with unilateral cleft lip and palate related to final treatment outcome in the maxilla at 17 years of age. Eur J Orthod. 2013;35:335–340.
ORIGINAL ARTICLE Preoperative Cleft Lip Measurements and Maxillary Growth in Patients With Unilateral Cleft Lip and Palate Gregory S. Antonarakis, D.D.S., M.Sc., Ph.D., Bryan D. Tompson, D.D.S., D. Paedo., D. Ortho., David M. Fisher, M.B. B.Ch., F.R.C.S.C., F.A.C.S. Objective: Maxillary growth in patients with cleft lip and palate is highly variable. The authors’ aim was to investigate associations between preoperative cleft lip measurements and maxillary growth determined cephalometrically in patients with complete unilateral cleft lip and palate (cUCLP). Design: Retrospective cross-sectional study. Patients: Children with cUCLP. Methods: Preoperative cleft lip measurements were made at the time of primary cheiloplasty and available for each patient. Maxillary growth was evaluated on lateral cephalometric radiographs taken prior to any orthodontic treatment and alveolar bone grafting (8.5 6 0.7 years). The presence of associations between preoperative cleft lip measurements and cephalometric measures of maxillary growth was determined using regression analyses. Results: In the 58 patients included in the study, the cleft lateral lip element was deficient in height in 90% and in transverse width in 81% of patients. There was an inverse correlation between cleft lateral lip height and transverse width with a b coefficient of 0.382 (P ¼ .003). Patients with a more deficient cleft lateral lip height displayed a shorter maxillary length (b coefficient ¼ 0.336; P ¼ .010), a less protruded maxilla (b coefficient ¼ .334; P ¼ .008), and a shorter anterior maxillary height (b coefficient ¼ 0.306; P ¼ .020) than those with a less deficient cleft lateral lip height. Conclusions: Patients with cUCLP present with varying degrees of lateral lip hypoplasia. Preoperative measures of lateral lip deficiency are related to later observed deficiencies of maxillary length, protrusion, and height. KEY WORDS:
cleft lip anthropometry, maxillary growth, unilateral cleft lip and palate
The two principal factors are intrinsic developmental deficiency and iatrogenic (Ross, 1987). Whatever the mechanism, maxillary growth impairment becomes progressively apparent as patients reach maturity (Semb and Shaw, 1998). Despite growth impairment being present in all cUCLP patients, considerable interpatient variation is present with a mix of good, medium, and poor facial growth. Intercenter collaborative efforts, including the Eurocleft and Americleft studies, have shown that large differences exist between centers with regard to midface growth (Brattstrom ¨ et al., 2005; Daskalogiannakis et al., 2011). A certain percentage of cUCLP patients will go on to require orthognathic surgery at the end of their active growth to correct their midface deficiency. These rates of orthognathic surgery range from approximately one in eight to one in two patients (Ross, 1987; Rosenstein et al., 1991, 2003; Cohen et al., 1995; DeLuke et al., 1997; Schnitt et al., 2004; Good et al., 2007; Daskalogiannakis and Mehta, 2009; Oberoi et al., 2012; Meazzini et al., in press). Midface growth deficiency is multifactorial. Surgical technique and experience are often implicated in the variation seen among patients in the severity of maxillary
INTRODUCTION Craniofacial growth deficiencies in individuals with complete unilateral cleft lip and palate (cUCLP) are widely recognized and have been reported for more than half a century (Graber, 1954). Midface growth deficiency may include reduced maxillary length and height as well as maxillary retrusion. Different etiological factors have been suggested to be responsible for these growth deficiencies.
Dr. Antonarakis is Orthodontist, Department of Orthodontics, Faculty of Dentistry, University of Geneva, Switzerland. Dr. Tompson is Head, Division of Orthodontics, The Hospital for Sick Children, and Associate Professor and Head, Department of Orthodontics, Faculty of Dentistry, University of Toronto, Toronto Ontario, Canada. Dr. Fisher is Medical Director, Cleft Lip and Palate Program, Division of Plastic Surgery, The Hospital for Sick Children, and Associate Professor, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Submitted September 2014; Revised November 2014, December 2014; Accepted December 2014. Address correspondence to: Gregory S. Antonarakis, Department of ´ Orthodontics, University of Geneva, 19 rue Barthelemy-Menn, 1205 Geneva, Switzerland. E-mail [email protected]. DOI: 10.1597/14-274 e198
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
hypoplasia (Shaw et al., 1992). However, even when considering cUCLP patients treated by the same surgeon using the same surgical protocol (minimizing variation due to iatrogenic factors), varying outcomes are observed with respect to maxillary hypoplasia (Nakamura et al., 2005; Meazzini et al., 2011). This suggests that individual intrinsic factors may play an important role in maxillofacial growth potential. One intrinsic factor possibly responsible for maxillofacial growth variation in cUCLP patients is the initial severity of the cleft. Within a particular cleft type, such as cUCLP, there is large phenotypic variation, defined in part by the severity of the deformity. The severity at birth may reflect differing contributions of tissue deficiency and/or tissue displacement. If initial severity and maxillary skeletal growth are linked, it is plausible to assume that the midface growth problem associated with tissue deficiency will play a role throughout the postnatal growth period (Peltomaki ¨ et al., 2001). The relationship between cleft severity and maxillofacial growth in cUCLP patients is still unresolved, although many studies support the claim that the more severe the cleft deformity at birth, the greater the amount of maxillary growth disturbance. Several studies have suggested that patients with more severe palatal or alveolar clefts or greater palatal tissue deficiency exhibit less favorable maxillary growth and poorer dental arch relationships (Schwartz et al., 1984; Suzuki et al., 1993; Peltomaki ¨ et al., 2001; Honda et al., 2002; Liao and Mars, 2005; Liao et al., 2010; Chiu et al., 2011; Chiu and Liao, 2012; Hsieh et al., 2012; Tomita et al., 2012). However, other studies do not support this idea (Johnson et al., 2000; Meazzini et al., 2008, 2011; Reiser et al., 2010; Wiggman et al., 2013). Measuring cleft severity based on cleft or palate or alveolar size, however, carries certain limitations. Factors such as infant orthopedics, aberrant function such as tongue force (Delestan et al., 2014), sleeping position (Huang et al., 1994), or the general size of the infant can influence these severity measurements. Liao et al. (2010) postulated that the cleft size reflects primarily tissue displacement, mainly through tongue force, rather than tissue deficiency. Cleft severity in cUCLP individuals at the level of the lip as opposed to the palate is something that has not attracted much attention in this respect. Nakamura et al. (2005) nevertheless found that a more deficient cleft lip tissue volume shows worse maxillary growth. Patients with unilateral clefts have been shown to exhibit large variability in preoperative lip measurements (Boorer et al., 2011), with a wide variety of growth asymmetry observed between the cleft and noncleft sides (Chou et al., 2013). We hypothesize that the dimensions of the cleft lateral lip element are associated with subsequent maxillary growth. The aim of the current study was to investigate the presence of associations between the severity of the unilateral cleft lip deficiency and maxillary growth using cephalometry.
MATERIALS
AND
e199
METHODS
The current study design was retrospective and crosssectional in nature and approved by our institution’s Research Ethics Board. A chart review was carried out to identify Caucasian children born with cUCLP between 2000 and 2007. Inclusion criteria comprised the following: primary unilateral cheiloplasty and palatoplasty carried out by the senior author and lateral cephalometric radiographs available at the approximate age of 9 years (62 years) before any orthodontic treatment or alveolar bone grafting. The following were our exclusion criteria: children whose cleft was part of a craniofacial syndrome, children who had secondary surgical treatment prior to the taking of the lateral cephalometric radiograph, children who had a history of dental or facial trauma, and lateral cephalometric radiographs of insufficient diagnostic quality. All children had been treated according to the following treatment protocol: presurgical infant orthopedics using the nasoalveolar molding technique (Grayson et al., 1999) for a period of approximately 12 to 24 weeks (until primary cheiloplasty), primary cheiloplasty at approximately 3 to 6 months of age using the technique of Fisher (2005), and primary palatoplasty at approximately 12 months of age using the hybrid palatoplasty technique (Gillet and Clarke, 1996). Determination of Cleft Phenotype Determination of cUCLP phenotype was based on clinical diagnosis. All diagnoses were made by the senior author at or soon after birth and confirmed at the time of primary cheiloplasty. Laterality of the cleft (left or right sided) was also recorded. Preoperative Lip Measurements The senior author performed all preoperative lip measurements, with calipers, at the time of primary cheiloplasty with the patient under general anesthesia. This ensured that the underlying muscles and overlying skin surfaces were in complete relaxation and thus that all soft tissues were at rest. Height and transverse width measurements of both the cleft and the noncleft lateral lip element were recorded to the nearest 0.5 mm. The landmarks used for measurements are shown in Figure 1. Lateral lip height of the noncleft side was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. Lateral lip height of the cleft side was measured from subalare to the proposed peak of Cupid’s bow. The proposed peak of Cupid’s bow was defined, according to Noordhoff (1997), as the point along the vermilion-cutaneous junction where the cutaneous roll and red line (vermilion-mucosal junction) begin to converge medially. Lateral lip transverse width
e200
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
FIGURE 1 The noncleft side lateral lip height (A) was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The cleft side lateral lip height (B) was measured from subalare to the proposed peak of Cupid’s bow. The noncleft side lateral lip transverse width (C) was measured from the oral commissure to the peak of Cupid’s bow. The cleft side lateral lip transverse width (D) was measured from the oral commissure to the proposed peak of Cupid’s bow (reproduced with permission from Boorer et al., 2011).
of the noncleft side was measured from the oral commissure to the peak of Cupid’s bow. Lateral lip transverse width of the cleft side was measured from the oral commissure to the proposed peak of Cupid’s bow at Noordhoff’s point. Lateral Cephalometric Analysis All lateral cephalometric radiographs had been taken on the same cephalostat according to standardized cephalometric guidelines with natural head position, the teeth in occlusion, and the lips at rest. The magnification ratio was 9.66%, and necessary adjustments were made when linear measurements were being made. All radiographs were traced by hand on a 0.003-inch matte acetate sheet (GAC International Inc., Bohemia, NY), using a 0.3-mm 2H lead pencil and a protractor (3M Unitek, Monrovia, CA) by one investigator. No more
than 10 radiographs were traced in a single day to minimize errors due to investigator fatigue (Erkan et al., 2012). A total of six cephalometric landmarks were located on each radiograph, and a resulting seven variables were measured (four linear and three angular; Fig. 2). Traditional landmarks for the anterior nasal spine, posterior nasal spine, and point A were used instead of constructed alternatives for these landmarks proposed for patients with clefts since it has been found that constructed landmarks are no more reliable than the traditional ones (Bongaarts et al., 2008). Selected variables were measured representing the maxilla (Table 1), based on recent published studies investigating cleft severity and maxillary growth (Chiu et al., 2011; Wiggman et al., 2013). Variables were divided into length, height, protrusion, and inclination.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
e201
FIGURE 2 Cephalometric landmarks and measured variables on the tracing of a lateral cephalometric radiograph. Cephalometric landmarks: A ¼ cephalometric A point; ANS ¼ anterior nasal spine; N ¼ nasion; PNS ¼ posterior nasal spine; R ¼ registration point (point of crossing of the greater wing of the sphenoid and the planum sphenoidale); S ¼ sella turcica. Cephalometric measurements: ANS-PNS ¼ basal maxillary length; A-PNS ¼ alveolar maxillary length; S-N-ANS ¼ basal maxillary protrusion; S-N-A ¼ alveolar maxillary protrusion; N-ANS ¼ anterior maxillary height; R-PNS ¼ posterior maxillary height; S-N/ANS-PNS ¼ maxillary plane angle.
Statistical Analysis All data were analyzed using the Statistical Package for Social Sciences Version 21.0 for Windows (SPSS Inc., Chicago, IL). Statistical significance was set at the P , .05 level. Preoperative lip measurements and all lateral cephalometric measurements were initially tested for normality visually based on plots (histograms and TABLE 1
normal Q-Q plots) as well as statistically using the Shapiro-Wilks test. All data were found to be normally distributed, and thus parametric statistics were used throughout. Descriptive statistics (mean, standard deviation, and range) were calculated for the preoperative lip measurements, and independent-sample t tests were used to investigate the presence of statistically significant
Selected Variables Measured Representing the Maxilla
Measurement
Landmark Measures*
Similar to
Maxillary length Basal maxillary length Alveolar maxillary length
ANS-PNS (linear) A-PNS (linear)
Chiu et al. (2011); Wiggman et al. (2013) Chiu et al. (2011)
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
S-N-ANS (angular) S-N-A (angular)
Chiu et al. (2011) Chiu et al. (2011); Wiggman et al. (2013)
Maxillary height Anterior maxillary height Posterior maxillary height
N-ANS (linear) R-PNS (linear)
Chiu et al. (2011) Chiu et al. (2011)
Maxillary inclination Maxillary plane angle
S-N/ANS-PNS (angular)
Wiggman et al. (2013)
* A ¼ cephalometric A point; ANS ¼ anterior nasal spine; N ¼ nasion; PNS ¼ posterior nasal spine; R ¼ registration point; S ¼ sella.
e202
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
TABLE 2
TABLE 3
Summary of Preoperative Lip Measurements
Measurement
Mean (SD)*
Range†
Lateral lip height Noncleft side (mm) Cleft side (mm) Difference (mm) Cleft side/noncleft side (%)
11.1 8.4 2.8 76
(1.7) (1.8) (2.0) (16)
7–15.5 5.5–17 4–6.5 46–131
Lateral lip transverse width Noncleft side (mm) Cleft side (mm) Difference (mm) Cleft side/noncleft side (%)
17.3 15.4 1.9 90
(2.4) (1.8) (1.8) (9)
13–26 11–22 2–10 58–114
* SD ¼ standard deviation. † Negative values in range indicate cleft side greater than noncleft side measurement.
differences between lip measurements and sex or laterality. Descriptive statistics were also calculated for the various lateral cephalometric measurements. The presence of associations between preoperative lip measurements and lateral cephalometric measurements was subsequently examined using linear regression analysis. Possible confounding determinants of facial growth, including sex, laterality, age at primary cheiloplasty, age at primary palatoplasty, age at which the lateral cephalometric radiographs were taken, and surgeon’s experience, were first investigated using bivariate analysis to identify the possible presence of any statistically significant association between these factors and any of the lateral cephalometric measurements. When a significant association was found, the variables were then incorporated in the final linear regression model as covariates. Error of the Method Analysis The error of the method was calculated by performing duplicate tracings on 20 lateral cephalometric radiographs 2 to 4 weeks later by the same investigator. Systematic error was assessed by using one-sample t tests comparing the duplicate lateral cephalometric tracings (Houston, 1983). Random error was assessed using Dahlberg’s (1940) formula (SE ¼ =Rd2/2n), where n ¼ the number of patients undergoing repeated measurements and d ¼ the difference in measurements.
Summary of Lateral Cephalometric Measurements Measurement*
Mean (SD)†
Range
Maxillary length Basal maxillary length (mm) Alveolar maxillary length (mm)
46.8 (4.0) 43.2 (4.0)
38–55 35.5–51
Maxillary protrusion Basal maxillary protrusion (deg) Alveolar maxillary protrusion (deg)
81.7 (5.1) 77.0 (5.0)
70.5–93.5 64–90
Maxillary height Anterior maxillary height (mm) Posterior maxillary height (mm)
46.7 (3.4) 41.4 (3.9)
38–55 33–52
Maxillary inclination Maxillary plane angle (deg)
9.0 (4.0)
1–20.5
* deg ¼ degrees; mm ¼ millimeters. † SD ¼ standard deviation.
total patient sample, or 8.5 6 0.7 years for the males and 8.6 6 0.9 years for the females. Preoperative Lip Measurements Mean height and transverse width measurements, as well as differences between the cleft and noncleft sides, for the total study sample are shown in Table 2. The same table also presents the cleft side lip measurements as a percentage of the same measurements on the noncleft side. No sex or cleft side differences were found for the lip measurements. A total of 52 of 58 (90%) patients had a cleft lateral lip height deficiency, while 47 of 58 (81%) had a cleft lateral lip transverse width deficiency. Severe cleft lateral lip height deficiency (defined as .1 standard deviation from the mean) was seen in 11 patients. Severe cleft lateral lip transverse width deficiency was observed in four patients. A combined cleft lateral lip element deficiency (both height and transverse width) was found in 41 of 58 (71%) patients, but a combined severe cleft lateral lip element (.1 standard deviation for both height and width) was not found in any of the patients. There was an inverse correlation between cleft lateral lip height and transverse width (b coefficient ¼ 0.382; P ¼ .003). Lateral Cephalometric Analysis
RESULTS Sample Fifty-eight cUCLP children fit the predefined inclusion and exclusion criteria. The sample comprised 44 males (30 left- and 14 right-sided clefts) and 14 females (11 left- and 3 right-sided clefts). The overall left:right ratio was 41:17. The mean age at which the lateral cephalometric radiographs were taken was 8.5 6 0.7 years (minimum 7.1 years; maximum 10.7 years) for the
The lateral cephalometric variables measured are presented in Table 3. No significant differences were found when comparing males to females or left- to rightsided clefts. Using repeated measurements for detection of systematic error, there was no statistically significant difference, at the 5% level, between the first and second measurements. With regard to random error, for linear measurements the error did not exceed 1.0 mm, while for angular measurements this did not exceed 1.4 degrees.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
TABLE 4
e203
Associations Between Lip and Cephalometric Measurements Univariable Estimates
Measurement
a Coefficient
b Coefficient
Adjusted Estimates
95% CI*
P Value
Adjusted Coefficient
Confounder
P Value
0.004 0.008
Lateral Lip Height† Maxillary length Basal maxillary length Alveolar maxillary length
8.093 8.634
0.336 0.358
2.028; 14.158 2.610; 14.659
0.010 0.006
0.428 0.403
Age‡ Age‡
11.415 10.662
0.334 0.358
3.625; 19.206 3.059; 18.266
0.008 0.006
— —
— —
— —
Maxillary height Anterior maxillary height Posterior maxillary height
6.299 3.835
0.306 0.161
1.047; 11.550 2.472; 10.143
0.020 0.228 (ns)
— —
— —
— —
Maxillary inclination Maxillary plane angle
1.447
0.059
5.067; 7.960
0.658 (ns)
—
—
—
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
Lateral Lip Transverse Width Maxillary length Basal maxillary length Alveolar maxillary length
11.645 16.159
0.268 0.373
22.808; 0.483 26.935; 5.383
0.041 0.004
0.374 0.459
Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
18.508 21.003
0.323 0.339
32.729; 4.287 34.493; 7.512
0.013 0.009
— —
— —
— —
Maxillary height Anterior maxillary height Posterior maxillary height
6.768 6.873
0.183 0.160
16.527; 2.991 18.225; 4.478
0.170 (ns) 0.230 (ns)
— —
— —
— —
Maxillary inclination Maxillary plane angle
2.976
0.068
14.690; 8.739
0.613 (ns)
—
—
—
Age‡ Age‡
0.016 0.001
* CI ¼ confidence interval; ns ¼ nonsignificant correlation found. † Lip heights or widths refer to cleft/noncleft side ratios. ‡ ¼ Age at which the lateral cephalometric radiograph was taken.
Associations Bivariate analyses investigating the possible confounding determinants of facial growth showed significant associations between the age at which the lateral cephalometric radiograph was taken and the basal maxillary length (b coefficient ¼ 0.282; P ¼ .032) as well as alveolar maxillary length (b coefficient ¼ 0.298; P ¼ .023). No other significant covariates (sex, laterality, age at primary repair, surgeon’s experience) were found. When performing the linear regression analysis between lip measurements and these cephalometric variables, the age at which the lateral cephalometric radiograph was taken was controlled for by including it as a covariate in the analysis. Correlations were observed as shown in Table 4. Children with a more deficient preoperative cleft lateral lip height showed a shorter maxillary length, a less protruded maxilla, and a shorter anterior maxillary height than those with a less deficient cleft lateral lip height. Inversely, children with a more deficient preoperative cleft lateral lip transverse width showed a longer maxillary length and a more protruded maxilla than those with a less deficient cleft lateral lip transverse width.
DISCUSSION The preoperative physical dimensions of the cleft lip in cUCLP patients show some associations with subsequent maxillary growth, in both sagittal and vertical dimensions, as suggested by the present study. Children with a more deficient cleft lateral lip height and a less deficient cleft lateral lip transverse width are more likely to demonstrate a shorter maxillary length, a less protruded maxilla, and a shorter anterior maxillary height. However, associations, albeit present, were not very strong. The majority of previous studies looking into associations between cleft severity and maxillary growth have focused on measuring initial cleft severity based on the palatal or alveolar cleft despite its complexity and possible inaccuracies. Seckel et al. (1995) illustrated the difficulties in measuring initial cleft severity in this way and stated that reproducible landmark positioning on the infant maxilla can be a reality only with optimal cast quality and an experienced investigator. In the present study, maxillary length was found to be partly dependent on cleft severity as defined by preoperative cleft lip measurements. The fact that cleft lateral lip height and transverse width were inversely correlated in our sample explains why both of these measurements displayed associations with maxillary
* Note that the specific cephalometric landmarks used to make the above measurements may not have been identical to the ones used in the present study. Yes ¼ an association/correlation was found between cleft severity and the cephalometric measurement; X ¼ no association/correlation was found; — ¼ not reported.
— Yes Yes — — Yes — — X — X X Maxillary inclination Maxillary plane angle
—
— — — — X Yes — — X X Yes X — — Yes X X Yes Yes Yes X X Yes X Maxillary height Anterior maxillary height Posterior maxillary height
— —
— Yes — X — X — X X Yes Yes Yes — X — X Yes Yes — — — Yes Yes Maxillary protrusion Basal maxillary protrusion Alveolar maxillary protrusion
— Yes
— — X — X — — — X X Yes Yes — — — X Yes Yes — Yes X — Yes Yes
Yes Yes
France Sweden/Norway Japan Italy Taiwan Taiwan Italy Japan Sri Lanka Japan United States Japan Canada
Patient origin Maxillary length Basal maxillary length Alveolar maxillary length
Liao and Mars (2005) Honda et al. (2002) Peltomaki ¨ et al. (2001) Suzuki et al. (1993) Present Study
Comparison of the Present Findings to Other Studies (in Chronological Order)*
Nakamura et al. (2005)
Meazzini et al. (2008)
Liao et al. (2010)
Chiu et al. (2011
Meazzini et al. (2011)
Tomita et al. (2012)
Wiggmann et al. (2013)
Doucet et al. (2014)
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
TABLE 5
e204
length. From the other studies that examined maxillary length in relation to initial cleft severity (Table 5), four were in line with our results (Peltomaki et al., 2001; ¨ Honda et al., 2002; Liao and Mars, 2005; Liao et al., 2010), while five did not find significant associations (Suzuki et al., 1993; Nakamura et al., 2005; Chiu et al., 2011; Tomita et al., 2012; Wiggman et al., 2013). Maxillary protrusion was also found to be partly dependent on cleft severity as defined by preoperative cleft lip measurements in this study. Both cleft lateral lip height and transverse width were found to be correlated with maxillary protrusion. Among the other studies examining cephalometric variables representing maxillary protrusion (Table 5), four found positive associations with initial cleft severity (Peltomaki ¨ et al., 2001; Liao and Mars, 2005; Liao et al., 2010; Doucet et al., 2014), while Chiu et al. (2011) found an association with alveolar but not basal maxillary protrusion. On the other hand, five studies found no such associations (Nakamura et al., 2005; Meazzini et al., 2008, 2011; Tomita et al., 2012; Wiggman et al., 2013). With regard to maxillary height, our study found positive associations with cleft severity. More precisely, this held true for anterior but not posterior maxillary height. Other studies examining maxillary height were conflicting (Table 5). Three studies found significant associations between cleft severity and anterior maxillary height (Honda et al., 2002; Nakamura et al., 2005; Liao et al., 2010), while four did not (Suzuki et al., 1993; Liao and Mars, 2005; Chiu et al., 2011; Tomita et al., 2012). Three studies found significant associations with posterior maxillary height (Honda et al., 2002; Liao and Mars, 2005; Tomita et al., 2012), while four did not (Suzuki et al., 1993; Nakamura et al., 2005; Liao et al., 2010; Chiu et al., 2011). One must be aware that the different maxillary measurements that were undertaken on the lateral cephalometric radiographs are inherently correlated to some extent. Different cephalometric measurements with at least one similar cephalometric landmark can be influenced by differences in that specific landmark in any direction. For example, the location of the anterior nasal spine can influence basal maxillary length, basal maxillary protrusion, anterior maxillary height, and maxillary plane angle. The associations between initial cleft severity and maxillofacial growth are usually attributed to an intrinsic growth potential. One cannot overlook, however, the possibility that cleft severity may have an indirect influence on outcome following surgical cleft repair. The extent of the cleft lip may affect the difficulty of surgical repair, thereby ultimately influencing outcome via greater generation of scar tissue or amount of surgical tissue movement. Lateral lip element hypoplasia, used as an indicator of cleft severity, may suggest that the amount of palatal or alveolar tissue deficiency is also great, thereby leading to a more difficult palatal surgical repair, again indirectly affecting outcome.
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
Tension from scar tissue arising from lip and palate repair may show adverse effects on maxillary growth. Delestan et al. (2014) advocate that a more detailed analysis of the different cleft subtypes within a cUCLP population is necessary to distinguish between the role of treatment and the inherent growth potential. This highlights the importance of establishing a precise initial evaluation of the malformation to avoid comparing different entities and making flawed assumptions (Meazzini et al., in press). Cleft subtypes within a population could be established using clinical criteria, such as cleft lip hypoplasia (Cosman and Crikelair, 1965; Boorer et al., 2011), cleft palate severity (Suzuki et al., 1993; Peltomaki ¨ et al., 2001; Chiu et al., 2011), or nasolabial deformity (Lindsay and Farkas, 1972; Fisher et al., 2008). The heterogeneity of cUCLP and its characterization by subtype or initial cleft severity can have important clinical implications. Favorable or unfavorable maxillary growth (and potentially other treatment outcomes) can be anticipated according to cleft severity, directing cUCLP children with different cleft severities to a different treatment protocol (Peltomaki et al., 2001). Individual treatment ¨ planning based on presenting morphology could be adopted for every cUCLP-affected child rather than conforming to predetermined surgical treatment protocols (Reiser et al., 2010). For example, in the case of a child with severe cUCLP, prone sleep positioning and delayed or staged palate closure might be preferred (Hsieh et al., 2012). This information, if available at birth, can help both parents and those involved in the care of children with clefts better prepare themselves for the eventual outcomes. If growth prognosis is identified early, those with worst prognoses may receive special attention to allocate appropriate and well-timed treatment protocols (Chiu et al., 2011; Doucet et al., 2014). One of the main limitations of the present study was its design, being retrospective and cross-sectional in nature. However, the presurgical measurements were obtained in a prospective fashion with this study in mind. A prospective longitudinal study would be able to provide a more superior level of evidence, and these types of well-designed studies should be planned for future investigations into the association of maxillary growth and cleft severity. The sample size, though small, did allow us to observe statistical significance. A larger sample size, however, would have been better able to demonstrate statistical significance given its improved power. In addition, maxillary growth disturbances in cUCLP patients may be expressed in three dimensions, and no data were available in the current study that allowed an assessment of maxillary growth in the transverse dimension. Lateral cephalometric radiographs allow an assessment of the sagittal and vertical but not the transverse plane. A postero-anterior cephalometric radiograph or a cone-beam–computed tomographic image would have been suited to allow an assessment of the
e205
transverse dimension. These modalities were not available for the present patient sample. The choice of using Noordhoff’s point as the proposed peak of Cupid’s bow on the cleft lateral lip element was made, as this is a reference surgical point. One could have also used a true anatomical point instead in the hope that this may provide a better basis for correlations. Furthermore, the finding that the cleft lateral lip height was inversely correlated to the transverse width may have been related to the use of this point. All lip measurements in the present patient sample were done after nasoalveolar molding, which included lip taping. The force of the lip taping needs to be recognized as having a potential effect on the soft tissues. Flattening and other effects may alter the dimensions of the lip elements. The ideal timing for the lip measurements could have been immediately after birth and prior to nasoalveolar molding treatment, but this would have the disadvantage that the measurements would not be carried out under general anesthesia. The measurements were chosen to be undertaken at the time of lip repair so that any inaccuracies of the measurements could be minimized. Unfortunately, repeated measurements to assess the error of the method were not possible due to the subsequent lip repair, but all measurements were carried out by one experienced operator. Moreover, nasoalveolar molding will have affected all patients and both sides of the lip, making results comparable. Lip repair was undertaken anywhere from 3 to 6 months of age, depending on factors such as the readiness of the infant for surgery, family constraints, and operating room schedules. This variation in age at surgery can affect lip dimensions, as growth will affect lip measurements. For this reason, proportions were used instead of absolute lip measurements. The impact of the original condition of the cleft on final outcome deserves special attention, as it is a complex issue. The present study highlights the variation seen in cleft lateral lip element deficiency, both in the vertical and in the transverse dimensions, and the potential correlations that this deficiency may have with maxillary growth and position. Certainly, cleft lip severity is not an isolated prognostic factor for maxillary growth, and its use as a sole factor is insufficient. The present data, however, suggest that within the spectrum of the deformity for patients with cUCLP, the degree of lateral lip element hypoplasia is one of the factors associated with the resulting maxillary growth potential. Our findings may have implications in the design of future research protocols for growth studies in cUCLP children. Children with cUCLP could be ranked by severity before correlating specific treatment variables and outcomes, moving away from the traditional pooling of patients (Peltomaki ¨ et al., 2001). Severity could be based on infant parameters, such as the relative size of the cleft lip, alveolar and palatal cleft widths, the area and inclination of the palatal shelves, the nasal deformity, and missing teeth,
e206
Cleft Palate–Craniofacial Journal, November 2016, Vol. 53 No. 6
that would allow associations between cleft severity and outcome to be elucidated. CONCLUSIONS In patients with cUCLP, there is wide variability in the degree of deficiency of the cleft lateral lip element in both height and width. We have demonstrated that the extent of lateral lip hypoplasia is one of the factors that may be predictive of later maxillary growth deficiencies as determined by maxillary sagittal and vertical dimensions and maxillary position. REFERENCES Bongaarts CA, van’t Hof MA, Prahl-Andersen B, Kuijpers-Jagtman AM. Identification of cephalometric landmarks in unilateral cleft lip and palate patients: are there alternatives for point A, ANS, and PNS? Cleft Palate Craniofac J. 2008;45:81–86. Boorer CJ, Cho DC, Vijayasekaran VS, Fisher DM. Presurgical unilateral cleft lip anthropometrics: implications for the choice of repair technique. Plast Reconstr Surg. 2011;127:774–780. Brattstrom ¨ V, Mølsted K, Prahl-Andersen B, Semb G, Shaw WC. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 2: craniofacial form and nasolabial appearance. Cleft Palate Craniofac J. 2005;42:69–77. Chiu YT, Liao YF. Is cleft severity related to maxillary growth in patients with unilateral cleft lip and palate? Cleft Palate Craniofac J. 2012;49:535–540. Chiu YT, Liao YF, Chen PK. Initial cleft severity and maxillary growth in patients with complete unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2011;140:189–195. Chou PY, Lou CC, Chen PK, Chen YR, Noordhoff MS, Lo LJ. Preoperative lip measurements in patients with complete unilateral cleft lip/palate and its comparison with norms. J Plast Reconstr Aesthet Surg. 2013;66:513–517. Cohen SR, Corrigan M, Wilmot J, Trotman CA. Cumulative operative procedures in patients aged 14 years and older with unilateral or bilateral cleft lip and palate. Plast Reconstr Surg. 1995;96:267–271. Cosman B, Crikelair GF. The shape of the unilateral cleft lip defect: a speculative report. Plast Reconstr Surg. 1965;35:484–493. Dahlberg G. Statistical Methods for Medical and Biological Students. New York: Interscience Publications; 1940. 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. Daskalogiannakis J, Mercado A, Russell K, Hathaway R, Dugas G, Long RE Jr, Cohen M, Semb G, Shaw W. The Americleft study: an inter-center study of treatment outcomes for patients with unilateral cleft lip and palate part 3. Analysis of craniofacial form. Cleft Palate Craniofac J. 2011;48:252–258. Delestan C, Montoya P, Doucet JC, Bigorre M, Baumler C, Herlin C, ¨ Daures JP, Captier G. New neonatal classification of unilateral cleft lip and palate—part 1: to predict primary lateral incisor agenesis and inherent tissue hypoplasia. Cleft Palate Craniofac J. 2014;51:392–399. DeLuke DM, Marchand A, Robles EC, Fox P. Facial growth and the need for orthognathic surgery after cleft palate repair: literature review and report of 28 cases. J Oral Maxillofac Surg. 1997;55:694– 697. Doucet JC, Delestan C, Montoya P, Matei L, Bigorre M, Herlin C, Baumler C, Daures JP, Captier G. New neonatal classification of ¨ unilateral cleft lip and palate—Part 2: to predict permanent lateral
incisor agenesis and maxillary growth. Cleft Palate Craniofac J. 2014;51:533–539. Erkan M, Gurel HG, Nur M, Demirel B. Reliability of four different computerized cephalometric analysis programs. Eur J Orthod. 2012;34:318–321. Fisher DM. Unilateral cleft lip repair: an anatomical subunit approximation technique. Plast Reconstr Surg. 2005;116:61–71. Fisher DM, Tse R, Marcus JR. Objective measurements for grading the primary unilateral cleft lip nasal deformity. Plast Reconstr Surg. 2008;122:874–880. Gillet DA, Clarke HM. The hybrid palatoplasty: a preliminary report. Canadian J Plast Surg. 1996;4:157–160. Good PM, Mulliken JB, Padwa BL. Frequency of Le Fort I osteotomy after repaired cleft lip and palate or cleft palate. Cleft Palate Craniofac J. 2007;44:396–401. Graber TM. The congenital cleft palate deformity. J Am Dent Assoc. 1954;48:375–395. Grayson BH, Santiago PE, Brecht LE, Cutting CB. Presurgical nasoalveolar molding in infants with cleft lip and palate. Cleft Palate Craniofac J. 1999;36:486–498. Honda Y, Suzuki A, Nakamura N, Ohishi M. Relationship between primary palatal form and maxillofacial growth in Japanese children with unilateral cleft lip and palate: infancy to adolescence. Cleft Palate Craniofac J. 2002;39:527–534. Houston WJ. The analysis of errors in orthodontic measurements. Am J Orthod. 1983;83:382–390. Hsieh YJ, Liao YF, Shetty A. Predictors of poor dental arch relationship in young children with unilateral cleft lip and palate. Clin Oral Invest. 2012;16:1261–1266. Huang CS, Cheung HC, Chen YR, Noordhoff MS. Maxillary dental arch affected by different sleep positions in unilateral complete cleft lip and palate infants. Cleft Palate Craniofac J. 1994;31:179–184. Johnson N, Williams A, Singer S, Southall P, Sandy J. Initial cleft size does not correlate with outcome in unilateral cleft lip and palate. Eur J Orthod. 2000;22:93–100. Liao YF, Mars M. Long-term effects of palate repair on craniofacial morphology in patients with unilateral cleft lip and palate. Cleft Palate Craniofac J. 2005;42:594–600. Liao YF, Prasad NK, Chiu YT, Yun C, Chen PK. Cleft size at the time of palate repair in complete unilateral cleft lip and palate as an indicator of maxillary growth. Int J Oral Maxillofac Surg. 2010;39:956–961. Lindsay WK, Farkas LG. The use of anthropometry in assessing cleftlip nose. Plast Reconstr Surg. 1972;49:286–293. Meazzini MC, Capello AV, Ventrini F, Autelitano L, Morabito A, Garattini G, Brusati R. Long-term follow-up of UCLP patients: surgical and orthodontic burden of care during growth and final orthognathic surgery need. Cleft Palate Craniofac J. In press. Meazzini MC, Donati V, Garattini G, Brusati R. Maxillary growth impairment in cleft lip and palate patients: a simplified approach in the search for a cause. J Craniofac Surg. 2008;19:1302–1307. Meazzini MC, Tortora C, Morabito A, Garattini G, Brusati R. Factors that affect variability in impairment of maxillary growth in patients with cleft lip and palate treated using the same surgical protocol. J Plast Surg Hand Surg. 2011;45:188–193. Nakamura N, Suzuki A, Takahashi H, Honda Y, Sasaguri M, Ohishi M. A longitudinal study on influence of primary facial deformities on maxillofacial growth in patients with cleft lip and palate. Cleft Palate Craniofac J. 2005;42:633–640. Noordhoff MS. The Surgical Technique for the Unilateral Cleft LipNasal Deformity. Taipei: Noordhoff Craniofacial Foundation; 1997. Oberoi S, Hoffman WY, Chigurupati R, Vargervik K. Frequency of surgical correction for maxillary hypoplasia in cleft lip and palate. J Craniofac Surg. 2012;23:1665–1667. Peltomaki T, Vendittelli BL, Grayson BH, Cutting CB, Brecht LE. ¨ Associations between severity of clefting and maxillary growth in
Antonarakis et al., PREOPERATIVE CLEFT LIP MEASUREMENTS AND MAXILLARY GROWTH
patients with unilateral cleft lip and palate treated with infant orthopedics. Cleft Palate Craniofac J. 2001;38:582–586. Reiser E, Skoog V, Gerdin B, Andlin-Sobocki A. Association between cleft size and crossbite in children with cleft palate and unilateral cleft lip and palate. Cleft Palate Craniofac J. 2010;47:175–181. Rosenstein SW, Grasseschi M, Dado DV. A long-term retrospective outcome assessment of facial growth, secondary surgical need, and maxillary lateral incisor status in a surgical-orthodontic protocol for complete clefts. Plast Reconstr Surg. 2003;111:1–13. Rosenstein S, Kernahan D, Dado D, Grasseschi M, Griffith BH. Orthognathic surgery in cleft patients treated by early bone grafting. Plast Reconstr Surg. 1991;87:835–892. Ross RB. Treatment variables affecting facial growth in complete unilateral cleft lip and palate. Cleft Palate J. 1987;24:5–77. Seckel NG, van der Tweel I, Elema GA, Specken TF. Landmark positioning on maxilla of cleft lip and palate infant—a reality? Cleft Palate Craniofac J. 1995;32:434–441. 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. Schwartz BH, Long RE Jr, Smith RJ, Gipe DP. Early prediction of posterior crossbite in the complete unilateral cleft lip and palate. Cleft Palate J. 1984;21:76–81.
e207
Semb G, Shaw WC. Facial growth after different methods of surgical intervention in patients with cleft lip and palate. Acta Odontol Scand. 1998;56:352–355. Shaw WC, Dahl E, Asher-McDade C, Brattstrom V, Mars M, ¨ McWilliam J, Mølsted K, Plint DA, Prahl-Andersen B, Roberts C, et al. The RP. A six-center international study of treatment outcome in patients with clefts of the lip and palate: part 5. General discussion and conclusions. Cleft Palate Craniofac J. 1992;29:413– 418. Suzuki A, Mukai Y, Ohishi M, Miyanoshita Y, Tashiro H. Relationship between cleft severity and dentocraniofacial morphology in Japanese subjects with isolated cleft palate and complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 1993;30:175–181. Tomita Y, Kuroda S, Katsura T, Watanabe T, Watanabe K, Fujihara S, Tanaka E. Severity of alveolar cleft before palatoplasty affects vertical maxillofacial growth in 6-year-old patients with complete unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2012;141:S102–S109. Wiggman K, Larson M, Larson O, Semb G, Brattstrom V. The ¨ influence of the initial width of the cleft in patients with unilateral cleft lip and palate related to final treatment outcome in the maxilla at 17 years of age. Eur J Orthod. 2013;35:335–340.
