Burden of Care Analysis of Various Infant Orthopedic Protocols … · 2012-11-27 · ii Abstract Burden of Care Analysis of Various Infant Orthopedic Protocols for Improvement of
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Burden of Care Analysis of Various Infant Orthopedic Protocols for Improvement of Nasolabial Aesthetics in Patients with Complete Unilateral Cleft Lip and Palate
by
Emily Singer D.D.S.
A thesis submitted in conformity with the requirements for the degree of Master of Science (Orthodontics), Graduate Department of
palate (Moore, 1982; Melnick, 1990). By the end of the fourth week, bilateral swellings,
the nasal placodes, develop on the lower part of the frontonasal prominence. The
medial and lateral nasal prominences develop as peripheral thickenings of the
mesenchymal tissue of the nasal placodes, producing two central depressions, the
nasal pits (Ten Cate, 1998). Failure of the nose to develop completely is associated
with failure of the nasal placodes to develop.
Between the fourth and eighth weeks, the paired medial nasal prominences fuse with
each other, with the paired lateral nasal prominences, and with cells in the maxillary
prominences. Successful fusion of the medial nasal and maxillary prominences is
essential for continuity of the upper lip and primary palate. Failure of fusion of one or
both medial nasal and maxillary prominences results in unilateral or bilateral cleft lip,
respectively.
As the face nears the completion of the “developmental critical period”, from
approximately the end of the sixth to the eighth intrauterine week, the lateral palatine
processes grow out from the walls of the still common oronasal cavity. Growth of these
paired processes is initially medial, but continues inferolaterally to lie on either side of
the developing tongue. Nearing the eighth week, palatal shelf elevation begins while
the tongue is depressed downward and forward. Once in contact, epithelial cells of the
palatal shelves degenerate by programmed cell death uniting the paired processes in a
process known as fusion. Once fusion of the shelves of the secondary palate occurs,
the mesenchymal cells differentiate and become osteogenic cells contributing to the
bony development of the premaxillary, maxillary and palatine portions of the palate
6
(Berkowitz, 2006). Cleft palate results from the failure of fusion of these paired lateral
palatine processes as a result of a defect in any of the three major stages of palatal
formation – palatal shelf outgrowth, elevation, or fusion (Kaartinen et al., 1995).
Figure 1. Schematic diagrams of the development of the lip and palate in humans. a. The developing frontonasal prominence, paired maxillary processes and paired mandibular processes surround the primitive oral cavity by the fourth week of development. b. By the fifth week, the nasal pits have formed, leading to the formation of the paired medial and lateral nasal processes. c. The medial nasal processes have merged with the maxillary processes to form the upper lip and primary palate by the end of the sixth week. The lateral nasal processes form the nasal alae and the mandibular processes fuse to form the mandible d. During the sixth week, the secondary palate develops as bilateral outgrowths from the maxillary processes, which grow vertically down the side of the tongue. e. Subsequently, the palatal shelves elevate to a horizontal position above the tongue, contact one another and commence fusion. f. Fusion of the palatal shelves ultimately divides the oronasal space into separate oral and nasal cavities. (Adapted from Dixon et al., 2011)
7
2. Classification of Cleft Lip and Palate
Numerous methods have been proposed for the classification and recording of CLP
deformities. None, however, have been universally accepted due to limitations
including inadequate descriptions of the deformities of the cleft in some classification
systems and unnecessarily onerous complexities of more sophisticated methods (Liu et
al., 2007). A simplified approach focuses on the distinction between clefts involving the
lip, palate or a combination thereof, with reference to the extent of the cleft (complete or
incomplete); between unilaterally or bilaterally occurring anomalies; and between those
occurring in conjunction with or in the absence of an associated syndrome.
Nonsyndromic CUCLP may therefore be defined as a continuous cleft extending from
the nasal sill through the upper lip and alveolar process on one side up to the incisive
foramen and posteriorly from the incisive foramen to include both the hard and soft
palates, in the absence of a concomitant syndrome. (Figure 2d)
Figure 2. Illustrative drawings of types of CL&P. a and e show unilateral and bilateral clefts of the soft palate; b, c and d show degrees of unilateral cleft lip and palate; f, g and h show degrees of bilateral cleft lip and palate. (Adapted from Dixon et al. 2011)
8
3. Nasolabial Morphology in Infants with Unrepaired CUCLP
Bilateral dysmorphology of the nasolabial region is often demonstrated in patients with
CUCLP. The nasolabial region is largely asymmetric with deviation towards the non-
cleft side as aberrant muscle insertions and tongue protrusion cause the non-cleft side
of the maxilla to deviate and rotate away from the cleft. The perioral musculature
overpowers the inadequately supported bone and pulls the nose and nasal septum to
the non-cleft side, yet the alar base on the side of the cleft remains in about the same
position. As a result, the cleft side nostril becomes abnormally stretched and flattened
(Ross, 2002). These abnormal muscle insertions lead to displacement of the non-cleft
side tissues vertically, laterally and anteriorly, with lateral and vertical displacement of
the cleft side. The columella on the cleft side is shortened significantly, as compared
with the non-cleft side and is oriented obliquely, with its base deviated toward the non-
cleft side, away from the midline. The alar bases are asymmetric, with the cleft side alar
base displaced inferiorly and posteriorly (Lo, 2006).
Figure 3. Typical nasolabial morphology in patients with unrepaired CUCLP (Adapted from http://dentistry.ouhsc.edu/os_cleft-craniofacial.php)
9
4. Primary Surgical Repair of CUCLP
Primary cheilorhinoplasty, surgical repair of the lip and nasal deformity, involves
reconstruction of the musculoaponeurotic complex of the cleft to place the muscles in
their proper anatomic and physiologic orientation through careful identification,
dissection, and mobilization of the paranasal and labial tissues. The cleft repair is
essentially a muscle repair to enhance the establishment of a normal nasolabial
complex. Accurate repositioning of the lower alar cartilages (Thomas, 2009) and the
orbicularis oris muscles (Farmand, 2002) during the primary lip repair is thought to aid in
establishing a normal nasal shape.
Chinese physicians, as early as the fourth century AD, were the first to describe a
technique to repair the cleft lip by simple excision of the cleft margins and suturing of
the opposing segments (Wong and Wu, 1932). While some form of this technique was
utilized by most surgeons until the early 19th century, it was later abandoned because it
led to the formation of a vertical scar that invariably resulted in an unaesthetic
shortening of the lip. In 1844, Germanicus Mirault devised a method to circumvent this
problem by introducing a triangular flap that was brought from the lateral side into a gap
created by a horizontal incision on the medial side. This not only eliminated the linear
scar by adding extra tissue to help lengthen the lip, but it also helped to recreate a
nostril floor (Bhattacharya et al., 2009). The triangular flap repair was later modified by
Tennison (Tennison, 1952) and by Randall (1959), who described the geometry of the
technique; and, today, the Tennison-Randall triangular flap repair is still utilized by
several cleft centres worldwide.
10
Along with the Tennison-Randall repair, the Millard rotation-advancement repair has
become part of the mainstay of primary CLP surgery and is thought to be a reliable and
versatile method for repair of the unilateral cleft lip deformity (Millard, 1976; Skyes,
2001). This technique allows for an anatomic lip repair and tip rhinoplasty while
camouflaging the scars in the nasal creases and newly formed philtral border (Kirschner
and LaRossa, 2000; Skyes, 2001; Arosarena, 2007).
Despite advancements in surgical techniques and attempts to reestablish normal
anatomy both immediately post surgically and during early growth, repair of a CUCLP
rarely produces ideal facial aesthetics. While satisfactory functional results can be
achieved after primary repair in the majority of patients with unilateral clefts,
morphologic results tend to be less ideal (Bilswatch et al., 2009). Patients generally
demonstrate some degree of deformation of the upper lip and nose with variable nasal
asymmetry, scarring of the philtral area, or an uneven vermillion border. The resultant
craniofacial impairments may have significant negative psychological consequences,
ranging from low self-esteem to the risk of social rejection (Tobiasen 1987, Broder and
Strauss, 1989; Fudalej et al., 2009).
11
5. Methods of Assessment of the Cleft-Related Facial Deformity
The ultimate objective of all CLP treatment modalities is to restore acceptable form and
function and to minimize the visible stigmata of the cleft related facial deformity.
Assessment of the appearance of the repaired deformity is a crucial component in
quality of life outcome measures in this patient population. Although international ratings
of attractiveness of individuals without clefts have been explored, a conclusive definition
of attractiveness in terms of facial features has not been agreed upon in the literature.
The measurement of facial aesthetics continues to be a complex and subjective process
that is dependent on a number of variables (Patzer, 1984; Al-Omari et al., 2005).
A review of the literature by Al-Omari et al. in 2005 identified the stimulus media,
scoring systems, characteristics of the raters and regions of interest most commonly
used in assessment of the appearance of the cleft-related facial deformity.
Stimulus Media
Stimulus media for the assessment of the cleft related deformity can be categorized into
direct clinical assessment of live subjects or facial casts, two- or three-dimensional
media or a comparative combination of clinical assessment with two- or three-
dimensional media.
For the assessment of live subjects or facial casts, both quantitative and qualitative
means have been employed. A number of studies have utilized anthropometry to
quantitatively analyze the extent of the abnormal morphology and degree of
disproportion and asymmetry of the repaired nasolabial region using direct linear and
12
proportional measurements (Lindsey and Farkas, 1972; Farkas et al. 1993). Friede et
al. (1980) measured angular, linear and surface measurements of plaster casts of the
midfacial regions of patients with clefts to evaluate various surgical techniques.
Qualitative visual evaluation of live subjects and clinical photographs was utilized by
Assuncao (1992), who employed a subjective “V.L.S.” classification system of the labial
deformity by the assessment of three components: the vermillion border, the lip and the
scar.
Qualitative and quantitative assessments of two-dimensional media, i.e. clinical
photographs and video recordings, are, by far, the most frequently used methods for
rating the cleft-related deformity. Subjective assessments of black and white
photographs (Glass et al., 1981), colour photographs (Asher-McDade et al. 1991;
Eliason et al. 1991; Roberts-Harry et al, 1991; Brattström et al. 1992; Mercado et al.
2011), projected colour transparancies (Tobiasen et al. 1991; Cussons et al., 1993;
Feragen et al., 1999; Al-Omari et al. 2003; Johnson and Sandy, 2003), and on-screen
digital photographs (Becker et al. 1998) have all been employed, as have quantitative
objective measures of various features of the nasolabial complex (Kohout et al., 1998;
Heller et al. 2011). Acceptable reliability and reproducibility from ratings of standardized
facial photographs (Asher-McDade et al., 1991) and direct measurements of on-screen
digital images (Becker et al., 1998) have been demonstrated. Several studies have also
shown good intra- and inter-examiner reliability scores between judgements of facial
appearance made from live stimuli and those from colour photographs (Becker et al.
1998; Johnson and Sandy, 2003; Al-Omari et al. 2003). While video recording has
been used to assess both the form and function of patients with cleft lip and palate
13
(Morrant and Shaw, 1996; Frey et al., 1999; Russell et al., 2000, 2001), a large range in
the reliability of ratings of video recordings has been observed (Morrant and Shaw,
1996) and attempts at digitizing soft tissue outlines from video imaging have not been
shown consistently to be valid or reproducible (Benson and Richmond, 1997).
Three-dimensional imaging techniques to assess the cleft deformity have included laser
scanning (Foong et al., 1999; Duffy et al. 2000), computer-aided tomography (CT)
(Fisher et al., 1999, Miyamoto et al. 2012), three-dimensional morphoanalysis (Ras et
al. 1994) and stereophotogrammetry (Al-Omari et al. 2003; Krimmel et al., 2006;
Nakamura et al., 2010; Sander et al., 2011). While the reliability and accuracy of 3-D
assessment media is promising, limitations including radiation exposure of CT imaging,
cooperation of young patients during prolonged image acquisition periods and limited
access to equipment across centres have prohibited widespread use, especially in
multicentre outcome studies.
Scoring Systems
Scoring methods to measure facial attractiveness have included ordinal scales based
on distinct categories of classification, rankings in order from best to worst for the
chosen features, or the use of visual analogue scales. The possibility of systematic bias
is recognized considering that raters may differ in their interpretation of a scoring
system. Several suggestions to overcome this limitation have been proposed. The use
of objective standards in conjunction with qualitative assessments, such as the
distribution of a written set of criteria for each index category, has been advocated
(Vegter and Hage, 2001; Johnson and Sandy, 2003). A visual yardstick to supplement
14
the Asher-McDade rating system (Asher-McDade et al., 1991), based on a set of
photographs that demonstrated the highest agreement among observers in the study,
has recently been published to facilitate the use of this commonly used 5 point ordinal
scale (Kuijpers-Jagtman et al., 2009).
Raters
In addition to the stimulus media and scoring systems selected, the composition of the
group of raters has been shown to have a large impact on the outcome of any study
assessing facial appearance. Researchers have attempted to determine whether
clinicians, patients, and laypersons agree in their perception of acceptable facial
attractiveness in patients with CLP. Studies comparing ratings of professionals and
laypersons have revealed inconsistent results, with some showing good agreement
(Coghlan et al. 1987; Cussons et al., 1993; Roberts-Harry and Stephens, 1991), and
others demonstrating discrepancies between expert and nonexpert groups (Eliason et
al., 1991). While some studies show that professionals tended to be more critical in
their assessments (Eliason et al. 1991), a recent study evaluating the relation between
professional and lay ratings of nasolabial appearance in CUCLP showed that the
professionals consistently gave higher scores for nasolabial appearance than did the lay
panel. In the same investigation, a self-assessment of nasolabial appearance by the
patients did not correlate with the judgement of either the lay or professional panels.
(Mani et al., 2010). Despite the inconsistent results regarding which group provides the
most reliable and clinically relevant outcome measure, most studies have concluded
15
that increasing the number of assessors should minimize interexaminer bias and
improve reliability (Asher-McDade et al., 1991).
Region of Interest
Since the ultimate aesthetic goals of a restored cleft deformity are to improve social
acceptance and reduce the visible stigmata associated with the malformation, many
studies have advocated assessment of the global facial appearance for ratings of
attractiveness, as would be perceived in social interactions (Tobiasen et al., 1991; Al-
Omari et al. 1993; Johnson and Sandy, 2003). Conversely, it has been demonstrated
that judgement of the cleft area is likely to be affected by surrounding features of the
face (Asher-McDade et al., 1991; Tobiasen and Hiebert, 1993) which may confound the
aesthetic assessments of various interventions or surgical techniques. Both Asher-
McDade et al. (1991) and Tobiasen et al. (1991) were able to demonstrate high
correlations between full-face ratings and ratings of the nasolabial area and photos
cropped just below the eyes, respectively, and both advocate using views that only
depict the nasolabial region for unbiased rating assessments.
16
6. Development of Presurgical Infant Orthopedics
Successful management of the functional and aesthetic demands of CLP repair requires
precise manipulation of the soft and hard tissues of the lip, nose and alveolus. It has
been theorized that favourable alignment of the alveolar segments of the cleft prior to
primary cheilorhinoplasty using non-surgical techniques can provide a foundation upon
which the results of primary lip and nasal surgery can be built.
Presurgical infant orthopedics has been employed in the treatment of CLP patients for
centuries. Early techniques included retraction of the protruding premaxilla using
elastics in patients with BCLP; facial binding to narrow the cleft and prevent postsurgical
dehiscence; the use of a bonnet and strapping to stabilize the premaxilla after surgical
retraction; or the passing of a silver wire through the two ends of the cleft followed by
progressive tightening to approximate the alveolar segments before lip repair (Grayson
and Shetye, 2009).
The modern school of infant orthopedic treatment was introduced by McNeil who used a
series of intraoral appliances to actively mold the alveolar segments into the desired
position presurgically (McNeil, 1950). The cleft is thereby narrowed and additional soft
and hard tissue is available for surgical repair (Ross and Johnston,1972). Hotz later
described the use of a passive orthopedic appliance to slowly align the cleft segments
(Hotz, 1969). Continued wear of the appliance prevented the tongue from entering the
cleft, allowing the palatal shelves to grow medially. The appliance is a compound
soft/hard acrylic resin which obturates the full extent of the cleft down to the tip of the
uvula, normalizing tongue posture and swallowing. Manipulation of the appliance
17
permits the deviated maxillary segments to lengthen and spontaneously assume a more
normal position. The results of the “growth-guidance” effect of the appliance are
uprighting the deviated greater segment and narrowing of the cleft (Hotz and Gnoinski
1976, Hotz et al. 1978). The McNeil and Hotz appliances, or various modifications
thereof, are still utilized by several CLP centres today.
In 1975, Georgiade and Latham introduced a pin-retained active appliance for patients
with BCLP to simultaneously retract the premaxilla and expand the posterior segments
over a period of several days (Georgiade and Latham, 1975). Similarly, the Latham
dentomaxillary alignment (DMA) appliance for UCLP advances and expands the lesser
segment of the unilateral cleft and retracts the greater segment posteromedially by daily
activation for 3 to 4 weeks (Latham, 1980). The use of the Latham appliance has been
controversial. Evidence has been accumulating that the pin-retained DMA appliance
may have detrimental effects on dental arch relationships and facial growth (Ross,
1987; Brattström et al., 1991; Chan et al., 2003; Berkowitz et al., 2004).
Motivated by research on the plasticity of neonatal auricular cartilage (Matsuo et al.
1984), Grayson and Cutting proposed that active molding and repositioning of the nasal
cartilages in patients with CLP may take advantage of the temporary plasticity of the
nasal cartilage of the newborn infant, thought to arise from high levels of hyaluronic acid
circulating for weeks after birth (Grayson et al. 1993, Cutting et al. 1998, Grayson et al.
1999). The technique, known as nasoalveolar molding (NAM), combines presurgical
alveolar molding with nasal molding through the incorporation of an acrylic nasal stent
to the labial vestibular flange of a conventional intraoral molding appliance. The nasal
18
stent and intraoral component are adjusted gradually, usually at weekly intervals over a
three-to-four -month period, to achieve nasal and alveolar symmetry, nasal tip projection
and contact of the cleft alveolar segments just prior to primary repair. According to
Grayson, presurgical reduction in the soft tissue and cartilaginous deformities allows for
repair under minimal tension, optimizing conditions for scar formation and improving
nasal symmetry in the long term (Grayson and Cutting, 2001).
The inclusion of PSIO of any kind in primary infant management is variable across CLP
centres. Proponents advocate its employment to facilitate surgical repair, improve
feeding, guide growth of the developing maxilla and provide psychological benefit to the
parents. Adversaries quote the potential inhibition of future maxillary growth and the
unnecessary added expense and burden of care for minimal, if any, long-term benefit
(Ross, 1987; Prahl et al. 2006).
19
7. PSIO for Improvement of Nasolabial Aesthetics in CUCLP
Despite its long standing history in CLP treatment and a recent resurgence with the
advent of NAM, the inclusion of PSIO in infant management protocols for patients with
CUCLP is still highly controversial. Alleged benefits of orthopedic appliances include
facilitation of feeding, guidance of growth, development of the maxillary segments,
normalization of tongue function, facilitation of surgery, better speech, and a positive
psychological effect on the parents (Prahl-Andersen, 2000).
In addition, it has been suggested that proper presurgical alignment of the cleft
segments with an intraoral appliance will provide a foundation upon which the results of
surgery can be built, allowing for a more esthetic repair under minimal tension (Grayson
et al., 1999). The incorporation of the nasal stent in the NAM appliance further aims to
improve nasolabial aesthetics by shaping and remodeling the nasal cartilages before
primary cheilorhinoplasty. The NAM technique is aimed at elevating the wing and tip of
the nose to improve nasal tip projection, expanding the nasal mucosal lining and
straightening the columella that has deviated towards the noncleft side. The result is
thought to be a more symmetric nose in the long term, with improved rounding of the
nostril on the cleft side and reduced alar flattening (Grayson and Cutting, 2001; Jaeger
et al., 2006; Shetye, 2010) .
The proposed benefits of PSIO, in general, and NAM, in particular, on improvement of
nasolabial aesthetics in patients with CUCLP have been examined in a number of
studies with conflicting results.
20
Traditional IO (infant orthopedics), generally involving an active or passive intraoral
appliance without the incorporation of a nasal stent, is thought by some to improve
facial appearance in unilateral cleft patients by facilitating lip surgery and stimulating a
favourable direction of maxillary growth (Graf-Pinthus and Bettex, 1974; Hotz and
Gnoinski, 1976). Others have refuted this claim, suggesting that similar effects could be
obtained with lip surgery alone (Ross, 1987; Asher-McDade et al., 1992; Winters and
Hurwitz, 1995).
To address the uncertainty surrounding the effects of IO, a prospective randomized
controlled trial (RCT), the Dutchcleft study, was conducted in three CLP centres in the
Netherlands (Prahl et al., 2006). The aim was to investigate the effect of IO using a
passive intraoral appliance in children with CUCLP. Early results showed that IO had a
temporary effect on maxillary arch dimensions, which did not last beyond surgical soft
palate closure (Prahl et al., 2001; Bongaarts et al., 2006). Results of aesthetic ratings in
the first two years of life using visual analogue scales and reference scores to assess
facial appearance showed no effect of IO on facial appearance in this study (Prahl et al.,
2006).
A later study by the same group evaluated the facial appearance at ages 4 and 6 in a
randomized clinical trial involving two of the three original Dutchcleft centres. Twenty-
seven patients were treated with a passive appliance until the time of soft palate closure
and 27 were treated with surgical repair alone. Twenty-six observers, 16 professionals
with experience in cleft care and 10 laypersons, were asked to evaluate photographs
(full facial photos and cropped photos of the nasolabial region alone) relative to a
21
reference photo of “average” CLP appearance. The results showed that while IO had a
positive effect on the full facial appearance of children with UCLP at the age of 4 years,
by the age of 6, only professionals saw a positive effect of IO which was limited to the
cropped nasolabial photographs. The authors concluded that the results at age 6, and
thus the influence of IO, were insignificant for patients with UCLP since they deal with
laypersons in their day to day lives (Bongaarts et al., 2008).
In another multicentre outcome assessment study, the Americleft group of researchers
examined nasolabial aesthetic outcomes of four centres each employing different early
management protocols. The subjects, totaling 124 patients across the four centres,
presented with repaired, nonsyndromic complete unilateral cleft lip and palate and were
between the ages of 5 and 12 years. Preorthodontic frontal and profile patient images
were scanned and cropped to show the nose and upper lip, and were evaluated by five
examiners using the rating system reported by Asher-McDade et al. (1991). No
statistically significant differences among centres were detected for either total aesthetic
scores or for any of the individual aesthetic components. Overall fair-to-good nasolabial
aesthetic results were achieved by all four North American centres despite using
different early treatment protocols (Mercado et al., 2011).
The past decade has seen a renaissance in the use of PSIO in CLP treatment with the
introduction and popularization of NAM. While early results showing immediate
postoperative improvements in nasal form following NAM were promising, a number of
studies have demonstrated variable degrees of relapse in the postoperative period (Liou
et al., 2004; Pai et al., 2005). As a result, a number of researchers have attempted to
22
address the controversy surrounding the long-term improvement in nasolabial
aesthetics proposed by Grayson and other advocates of the NAM technique.
In a systematic review by Uzel and Alparslan (2011), the authors aimed to assess the
scientific evidence on the efficiency of presurgical infant orthopedic appliances in
patients with cleft lip and palate and to address the controversy regarding whether these
appliances have any long-term advantages with respect to treatment outcomes. Two
literature surveys from five electronic databases were performed with a one-month
interval to identify RCTs and controlled clinical trials (CCTs), where the controls had no
PSIO. Studies with a follow up period of a minimum of six years were included in the
review with the exception of the outcome measures of feeding and motherhood
satisfaction, which are considered most important in the first year of life. Of the 319
articles retrieved in the literature surveys, 12 qualified for final analysis based on the
inclusion criteria. Eight RCTs and four CCTs were available on eight treatment
Within the category “vermillion border”, pairwise comparisons revealed significant
differences between Centre 1 and the TIO sample from Centre 3 (p=0.003) and
between Centre 1 and NAM sample from Centre 3 (p<0.001), with both samples from
Centre 3 exhibiting superior nasolabial aesthetic scores.
Within the category “nasolabial frontal”, significant differences were detected between
Centres 1 and 2 (p<0.001) with Centre 2 exhibiting the greater (less favourable) score
and between Centres 2 and Centre 3 (TIO) with the TIO sample demonstrating superior
ratings.
When the three categories were averaged to determine an overall cumulative score,
statistically significant differences were revealed between Centre 2 and the TIO sample
from Centre 3 (p <0.001) with the TIO group exhibiting improved overall aesthetics.
57
The median values for each sample across the aesthetic categories and the results of
the Kruskal Wallis multiple and pairwise comparisons are summarized in Table 8.
Vermillion
Border
Nasolabial
Frontal
Nasolabial
Profile
Cumulative
Score
Centre 1 3.39a,b 2.93c 2.71 3.00
Centre 2 3.07 3.36c,d 2.82 3.21e
Centre 3 (TIO) 2.79a 2.82d 2.86 2.82e
Centre 3 (NAM) 2.36b 3.00 3.07 2.86
Kruskal-Wallis
(Multiple
Comparisons)
p < 0.001 p = 0.002 p > 0.05 p = 0.007
Table 8. Median values of nasolabial aesthetics ratings using the modified Asher-
McDade method. [Pairwise comparison significant differences: a (p = 0.003); b, c, d, e
(p < 0.001)]
58
Discussion
A number of publications reporting immediate postsurgical improvements in nasal
symmetry following NAM therapy (Grayson et al. 1999, 2001, Maull et al. 1999; Liou et
al. 2004) have led advocates of the technique to call for a “paradigm shift” in infant CLP
management from more traditional methods of PSIO (Grayson and Maull, 2004).
However, as has previously been stated, the mounting evidence and enthusiasm
surrounding short-term benefits of NAM must be balanced against the increased burden
of care due to the multiple clinic visits and treatment costs necessary to institute such
care. Even more importantly, long-term outcome assessment is necessary before the
various proposed benefits of presurgical orthopedics and nasal molding can be claimed
(Wyszynski, 2002; Long, 2011).
In this study, a significant increase in the burden of orthodontic care of NAM over TIO
was identified, both with respect to the number of days in treatment and the number of
appointments required to implement care. However, no significant differences in the
nasolabial aesthetic outcomes of these subjects could be identified by orthodontists with
experience in cleft care. In short, with respect to nasolabial aesthetics, an increased
burden of care was identified when using NAM over TIO, without a measurable
associated benefit.
Interestingly, when comparing these two groups of subjects who underwent PSIO
during infancy to two groups of subjects from centres that performed surgical repair of
the cleft without PSIO, significant differences in scores for the categories of vermillion
59
border, nasolabial frontal and overall nasolabial aesthetics were elucidated. The
analysis demonstrated more favourable outcomes in the groups of subjects that
underwent either TIO or NAM. This finding is inconsistent with previous studies in
which centres with the highest intensity of early treatment achieved the lowest rankings
for eventual outcome (Shaw et al., 2005). Moreover, an RCT designed to assess this
very topic failed to show an effect of traditional infant orthopedics on facial appearance
in the long term (Prahl et al. 2006).
Results of retrospective multicentre investigations must always be interpreted with
caution as “a fundamental limitation of intercenter comparisons is that they cannot
distinguish between the influence of different individual elements of a center's protocol
on its outcomes nor between its protocols and the influence of the personnel who
deliver that protocol.” (Shaw et al., 2005)
In this study, the assessment of nasolabial aesthetics is performed at the age of 5 and
not later, in an attempt to minimize the compounded effect of every individual procedure
or component of the protocol, a concern that would have been greater, the later the age
of the subjects at the time of evaluation. By rating photographs taken at approximately
age five and excluding subjects that had undergone any additional treatment beyond
primary lip and palate repair and PSIO, if applicable, this study attempted to focus on
the influence of a single variable, the employment of either TIO or NAM.
The influence of additional variables, such as genetic variability, the type of surgical
repair and the personnel delivering the protocol, were the obvious limitations of this
investigation. The WHO (2004) referred to the confounding effect of discrepancies in
60
surgical skill and technique as proficiency bias, stating that it confounds any attempt at
comparisons of outcomes, except within randomized trials. Within the four samples in
this study, primary repair was performed by anywhere between one and five surgeons
with varying surgical experience and methods of repair. While the NAM and TIO
samples were treated by a number of the same surgeons, the distribution was not
uniform between the two groups. This proficiency bias makes it impossible to draw
definitive conclusions regarding whether any observed differences in aesthetic
outcomes truly reflect the influence of the PSIO procedure or are merely a reflection of
the technical skills of different operators within and across samples.
Another challenge in performing intercentre collaborative studies, or even intracentre
studies in centres serving modern urban communities that are ethnically and racially
diverse, is the enormous heterogeneity in the original cleft deformity and underlying
craniofacial form that exists among subjects. Even in children born with the same type
of cleft and treated by identical procedures, outcomes can differ considerably due to the
great genetic variability observed in individuals born with CLP (Mølsted, 1999). An
attempt was made to minimize this heterogeneity to the extent possible, by limiting the
inclusion in this investigation to subjects with non-syndromic CUCLP patients of
Caucasian background.
In its original articles, the Eurocleft group stated that ideal sample sizes for
assessments of cephalometric soft- and hard-tissue measurements and for ratings of
dental arch relationships using the Goslon yardstick, should comprise between 30 and
40 subjects per sample. No recommendations were given for ideal sample sizes for
61
assessment of nasolabial appearance (Shaw et al., 1992). When the same group
conducted its own intercentre assessments of nasolabial appearance, sample sizes of
fewer than 20 subjects in most groups were used with large variability in sample sizes
among centres, due to inadequate available records (Asher-McDade et al., 1992).
When the Americleft group examined the nasolabial appearance of subjects from four
centres, sample sizes were increased slightly (ranging between 21 to 37 subjects per
centre), but with the largest group of 37 subjects limited to just 6 profile images of the
affected side for ratings of profile aesthetics (Mercado et al., 2011). These reduced
sample sizes are indicative of the difficulties encountered in investigations of this type,
mainly owing to the inadequacies of record keeping.
To address the issue of sample size determination in the assessment of the aesthetic
outcomes of cleft lip repair, Power and Matic (2012) conducted a study to determine the
ideal sample size required to critically analyze consecutive unilateral cleft lip repairs and
to determine the number of consecutive cases that represent average outcomes.
Consecutive pre-operative and two-year post-operative photographs of CUCLP subjects
were randomized and evaluated by craniofacial surgeons. Results showed that
calculations for 10 consecutive cases demonstrated wide 95% confidence intervals,
spanning two points on the post-operative grading scales, however the confidence
intervals narrowed within one qualitative grade (±0.30) and one point (±0.50) on the ten-
point scale when a sample size increased to 27 consecutive cases. The authors
concluded that increasing numbers of consecutive cases (n>27) are increasingly
representative of average results.
62
In the present investigation, sample sizes between 33 and 40 subjects were obtained
from each centre; however, similar to Mercado et al. (2011), several profile images of
the nonaffected side had to be excluded in the final analysis from the two centres not
employing PSIO. The residual samples sizes of 16 and 31 subjects for profile
assessments in these two groups were still equal to or greater than previous studies of
this nature. It should be noted that while statistically significant differences were
observed between centres that did and did not employ PSIO for the categories
vermillion border and nasolabial frontal, no significant differences were detected
between samples for the nasolabial profile category. The inability to detect significant
differences for this variable may reflect that, in fact, no differences in aesthetic
outcomes exist, or, may simply be the result of reduced power from decreasing sample
sizes.
Aesthetic outcome assessments inevitably carry a high degree of subjectivity.
Moreover, the use of still photographic images has many limitations (Tobiasen, 1988;
Asher-McDade et al., 1992; Morrant and Shaw, 1996). While results of studies using 3-
dimensional assessments are becoming rapidly available and may represent the future
of cleft deformity analysis, digital 2-dimensional photographs are still the most widely
available, economical and accessible clinical records for use in intercentre collaborative
studies. Recognizing the inherent limitations, the Asher-McDade method has been
shown to be reliable and reproducible and has been used in similar multicentre
assessments of nasolabial aesthetics in the past; it was therefore selected for use in
this study (Brattström et al., 2005; Williams et al., 2001; Mercado et al., 2011).
63
A criticism of this method is that it does not take into account more characteristics of the
repaired lip, such as the scar, contour of the philtrum and the white roll. Evaluation of
this kind of detail requires images of high resolution under standardized lighting and
precise patient positioning, a virtual impossibility in a retrospective intercentre
comparison. In this study, some images were scanned from printed photos, others from
slides and others were obtained directly from digital cameras with high resolution.
While variations in image quality can be overcome in the gross evaluation of the
continuity of the vermillion border, shape of the nose, and profile using the Asher-
McDade method, evaluation of the upper lip in greater objective detail would require live
subjects or highly standardized images at the same resolution (Mercado et al., 2011).
A further criticism of the method used to assess nasolabial appearance in this study is
that it did not include a worm’s-eye view photograph that is thought, by some, to be the
best angle to assess nostril symmetry and deviations in nasal form. Conversely,
although the worm’s-eye view may, in fact, be the best angle to assess symmetry of the
nostrils from a professional point of view, this angle is rarely shown in social
circumstances and may be an unrealistic measure of attainment of the ultimate goal of
cleft surgery, that being the reduction of visible social stigmata (Kuijpers-Jagtman et al.,
2009). Regardless, the worm’s eye view, like the affected-side profile view, was not
consistently available from the centres in this study. A consideration for future research
endeavors is the creation of a method for standardized record taking, both with respect
to image quality and to which views should be included in a standard photographic
series.
64
With respect to the reliability of the method for rating nasolabial aesthetics, an overall
substantial intrarater reliability was achieved (mean 0.747), while moderate interrater
reliabilities were observed (mean 0.565). While these results are similar to previous
studies employing this rating method (Asher-McDade et al. 1992; Williams et al. 2001;
Brattström et al. 2005; Mercado et al. 2011), ideally more standardized, objective
assessment methods should be developed to improve the reliability and accuracy of the
evaluation of nasolabial aesthetic outcomes in this patient population.
In the first part of this study, comparisons were made between the burden of orthodontic
care of two groups of subjects at the same centre treated during different time periods
with two types of PSIO, TIO or NAM. For the purposes of calculation in this study the
time of initial lip repair was taken as the endpoint of PSIO treatment. Since these
samples were drawn from two different time periods, it is important to note that
variations in surgical wait times may have confounded the difference in the results
between the two groups. While this centre's patient population has been steadily
increasing with time, available operating room time has been slowly decreasing. This
could mean that the more recent sample may have had to endure a longer wait for a
surgical date for cheilorhinoplasty. It is conceptually possible that PSIO treatment
objectives for a specific patient can be met, but because a surgical date is not
immediately available, the orthodontist might elect to continue to see the patient on a
maintenance basis, thereby artificially inflating the calculated burden of care. A recent
prospective study was conducted to determine the duration of wait times for surgery for
children and youth at Canadian pediatric academic health institutions and to determine
the percentage of patients receiving surgery after a predetermined acceptable target
65
waiting period. Overall, 27% of pediatric patients from across Canada received their
surgery beyond their standardized target waiting period. Dentistry, ophthalmology,
plastic surgery for cleft lip and palate and cancer surgery showed the highest
percentages of surgeries completed past target (Wright and Menaker, 2011). Due to
the retrospective nature of this study, data on patients’ wait times for surgery after
completion of PSIO could not be obtained, as this type of information was not recorded
in the orthodontic or surgical records. Any assumptions made about the potential
confounding effect of surgical wait times on the results are merely speculative.
While prolonged surgical wait times may have resulted in the overestimation of the
burden of care in one or both samples, the magnitude of the burden of either sample
may have been underestimated by cancelled or missed appointments. Again, as a
result of the retrospective nature of this study, it was only possible to record the number
of appointments actually attended by the subject, rather than scheduled by the
practitioner. Patient burnout is a well-documented phenomenon in the literature of
organizational behaviour and industrial psychology. Orthodontics is known to be a
dental specialty in which long-term patient cooperation and attendance at appointments
is a major factor influencing treatment success (Brezniak and Ben-Ya’ir, 1989). It has
been shown that patients with CLP may be considered at a particular risk of burnout
and poor attendance with clinic appointments as a result of considerable demands on
the family to attend an extraordinary number of outpatient appointments, and because
many multidisciplinary cleft lip and palate clinics are regional, necessitating
considerable travel (Rivkin et al., 2000; Rodd et al., 2007). It is likely that as the burden
of care and demand on parents’ schedules increase, appointment failure rates may
66
follow. Failure to schedule or keep appointments may account for why, despite being
statistically significant, the magnitude of the difference in the number of appointments
between the TIO and NAM groups was minimal (mean of 3.3 visits) and smaller than
one might expect knowing the suggested protocol for each technique.
Finally, while in this study no benefit was found to justify the added burden when
comparing NAM and TIO, it is important to realize that these findings addressed only
one aspect of the burden against one of the proposed benefits of the technique. It has
been suggested that in addition to long term improvements in aesthetics, NAM therapy
facilitates and shortens the primary surgical repair and reduces the number of surgical
revisions performed to correct excessive scar tissue and nasal and labial deformities
(Maull et al.,1999; Grayson and Shetye, 2009). These additional claimed advantages of
NAM could not be assessed by the present investigation. Future prospective studies
should assess these variables to allow for a more comprehensive comparison of the
overall burden of care with each intervention.
67
Conclusions
Under the conditions of this investigation the following conclusions can be drawn:
1. Significant differences exist in the burden of orthodontic care when it involves NAM
as compared to TIO for the treatment of patients with non-syndromic CUCLP, with NAM
patients requiring more appointments and a greater number of days wearing the
appliance.
2. No significant differences exist in the nasolabial aesthetics of patients who have
received NAM as compared to TIO for the initial repair of non-syndromic CUCLP at age
4-6 years.
3. Significant differences exist in the nasolabial aesthetics between centres that utilize
PSIO and those that do not, with centres not employing PSIO demonstrating poorer
nasolabial aesthetics across several categories.
68
Clinical Significance & Future Directions
It is incumbent upon health care professionals providing any treatment for a patient to
perform a risk- and cost-benefit analysis of any intervention to enable them to make
sound, scientific, evidence-based decisions regarding patient care. The burden of CLP
treatment to the individual patients, their families and the health care system is known to
be quite significant. Streamlining treatment protocols and eliminating unnecessary
procedures should be a focus of every CLP centre when evaluating existing protocols
for potential modifications.
The present investigation was conducted with the hope to shed light on the increased
burden imposed on patients undergoing NAM over traditional IO in the absence of
noticeable benefits with respect to nasolabial aesthetics. Furthermore, studies like this
one, along with similar intercentre investigations, like the Eurocleft and Americleft
projects, should alert the CLP community to the concern regarding the lack of standards
in recording and reporting outcomes, and the absence of quality evidence upon which
centres can base their current protocols. It is hoped that results obtained from
retrospective, cross-sectional comparisons such as this one can be used to design
future RCTs to objectively assess outcomes of interventions for patients with CLP more
objectively, so that clinicians may maximize treatment benefits while minimizing burden.
69
References
Al-Omari I, Millett DT, Ayoub A, Bock M, Ray A, Dunaway D, et al. An appraisal of three methods of rating facial deformity in patients with repaired complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 2003 Sep;40(5):530-7.
Al-Omari I, Millett DT, Ayoub AF. Methods of assessment of cleft-related facial deformity: a review. Cleft Palate Craniofac J. 2005 Mar;42(2):145-56.
Arosarena OA. Cleft lip and palate. Otolaryngol Clin North Am. 2007 Feb;40(1):27,60, vi.
Asher-McDade C, Brattström V, Dahl E, McWilliam J, Mølsted K, Plint DA, et al. A six-center international study of treatment outcome in patients with clefts of the lip and palate: Part 4. Assessment of nasolabial appearance. Cleft Palate Craniofac J. 1992 Sep;29(5):409-12.
Asher-McDade C, Roberts C, Shaw WC, Gallager C. Development of a method for rating nasolabial appearance in patients with clefts of the lip and palate. Cleft Palate Craniofac J. 1991 Oct;28(4):385,90; discussion 390-1.
Assuncao AG. The V.L.S. classification for secondary deformities in the unilateral cleft lip: clinical application. Br J Plast Surg. 1992 May-Jun;45(4):293-6.
Barillas I, Dec W, Warren SM, Cutting CB, Grayson BH. Nasoalveolar molding improves long-term nasal symmetry in complete unilateral cleft lip-cleft palate patients. Plast Reconstr Surg. 2009 Mar;123(3):1002-6.
Becker M, Svensson H, Jacobsson S. Clinical examination compared with morphometry of digital photographs for evaluation of repaired cleft lips. Scand J Plast Reconstr Surg Hand Surg. 1998 Sep;32(3):301-6.
Benson PE, Richmond S. A critical appraisal of measurement of the soft tissue outline using photographs and video. Eur J Orthod. 1997 Aug;19(4):397-409.
Berkowitz S. Cleft Lip and Palate. 2nd ed. Spring Publishing Group; 2006.
Berkowitz S, Mejia M, Bystrik A. A comparison of the effects of the Latham-Millard procedure with those of a conservative treatment approach for dental occlusion and facial aesthetics in unilateral and bilateral complete cleft lip and palate: part I. Dental occlusion. Plast Reconstr Surg. 2004 Jan;113(1):1-18.
Bhattacharya S, Khanna V, Kohli R. Cleft lip: The historical perspective. Indian J Plast Surg. 2009 Oct;42 Suppl:S4-8.
Bilwatsch S, Kramer M, Haeusler G, Schuster M, Wurm J, Vairaktaris E, et al. Nasolabial symmetry following Tennison-Randall lip repair: a three-dimensional
approach in 10-year-old patients with unilateral clefts of lip, alveolus and palate. J Craniomaxillofac Surg. 2006 Jul;34(5):253-62.
Bongaarts CA, Kuijpers-Jagtman AM, van 't Hof MA, Prahl-Andersen B. The effect of infant orthopedics on the occlusion of the deciduous dentition in children with complete unilateral cleft lip and palate (Dutchcleft). Cleft Palate Craniofac J. 2004 Nov;41(6):633-41.
Bongaarts CA, Prahl-Andersen B, Bronkhorst EM, Prahl C, Ongkosuwito EM, Borstlap WA, et al. Infant orthopedics and facial growth in complete unilateral cleft lip and palate until six years of age (Dutchcleft). Cleft Palate Craniofac J. 2009 Nov;46(6):654-63.
Bongaarts CA, Prahl-Andersen B, Bronkhorst EM, Spauwen PH, Mulder JW, Vaandrager JM, et al. Effect of infant orthopedics on facial appearance of toddlers with complete unilateral cleft lip and palate (Dutchcleft). Cleft Palate Craniofac J. 2008 Jul;45(4):407-13.
Bongaarts CA, van 't Hof MA, Prahl-Andersen B, Dirks IV, Kuijpers-Jagtman AM. Infant orthopedics has no effect on maxillary arch dimensions in the deciduous dentition of children with complete unilateral cleft lip and palate (Dutchcleft). Cleft Palate Craniofac J. 2006 Nov;43(6):665-72.
Boulet SL, Grosse SD, Honein MA, Correa-Villasenor A. Children with orofacial clefts: health-care use and costs among a privately insured population. Public Health Rep. 2009 May-Jun;124(3):447-53.
Brattström V, McWilliam J, Larson O, Semb G. Craniofacial development in children with unilateral clefts of the lip, alveolus, and palate treated according to four different regimes. I. Maxillary development. Scand J Plast Reconstr Surg Hand Surg. 1991;25(3):259-67.
Brattström V, McWilliam J, Semb G, Larson O. Craniofacial development in children with unilateral clefts of the lip, alveolus, and palate treated according to four different regimes. II. Mandibular and vertical development. Scand J Plast Reconstr Surg Hand Surg. 1992;26(1):55-63.
Brattström 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 Jan;42(1):69-77.
Brezniak N, Ben-Ya'ir S. Patient burnout - behaviour of young adults undergoing orthodontic treatment. Stress Med. 1989;5:183-187.
Centers for Disease Control and Prevention (CDC). Economic costs of birth defects and cerebral palsy--United States, 1992. MMWR Morb Mortal Wkly Rep. 1995 Sep 22;44(37):694-9.
71
Chan KT, Hayes C, Shusterman S, Mulliken JB, Will LA. The effects of active infant orthopedics on occlusal relationships in unilateral complete cleft lip and palate. Cleft Palate Craniofac J. 2003 Sep;40(5):511-7.
Coghlan BA, Matthews B, Pigott RW. A computer-based method of measuring facial asymmetry. Results from an assessment of the repair of cleft lip deformities. Br J Plast Surg. 1987 Jul;40(4):371-6.
Cordero DR, Brugmann S, Chu Y, Bajpai R, Jame M, Helms JA. Cranial neural crest cells on the move: their roles in craniofacial development. Am J Med Genet A. 2011 Feb;155A(2):270-9.
Cussons PD, Murison MS, Fernandez AE, Pigott RW. A panel based assessment of early versus no nasal correction of the cleft lip nose. Br J Plast Surg. 1993 Jan;46(1):7-12.
Cutting C, Grayson B, Brecht L, Santiago P, Wood R, Kwon S. Presurgical columellar elongation and primary retrograde nasal reconstruction in one-stage bilateral cleft lip and nose repair. Plast Reconstr Surg. 1998 Mar;101(3):630-9.
Daskalogiannakis J, Mercado A, Russell K, Hathaway R, Dugas G, Long RE,Jr, et al. 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 May;48(3):252-8.
Dixon M, Marazita M, Beaty T, Murray J. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews Genetics. 2011;12:167-178.
Duffy S, Noar JH, Evans RD, Sanders R. Three-dimensional analysis of the child cleft face. Cleft Palate Craniofac J. 2000 Mar;37(2):137-44.
Eliason MJ, Hardin MA, Olin WH. Factors that influence ratings of facial appearance for children with cleft lip and palate. Cleft Palate Craniofac J. 1991 Apr;28(2):190,3;193-4.
Ezzat CF, Chavarria C, Teichgraeber JF, Chen JW, Stratmann RG, Gateno J, et al. Presurgical nasoalveolar molding therapy for the treatment of unilateral cleft lip and palate: a preliminary study. Cleft Palate Craniofac J. 2007 Jan;44(1):8-12.
Farkas LG, Hajnis K, Posnick JC. Anthropometric and anthroposcopic findings of the nasal and facial region in cleft patients before and after primary lip and palate repair. Cleft Palate Craniofac J. 1993 Jan;30(1):1-12.
Farmand M. Lip repair techniques and their influence on the nose. Facial Plast Surg. 2002 Aug;18(3):155-64.
Feragen KJ, Semb G, Magnussen S. Asymmetry of left versus right unilateral cleft impairments: an experimental study of face perception. Cleft Palate Craniofac J. 1999 Nov;36(6):527-32.
72
Fisher DM, Lo LJ, Chen YR, Noordhoff MS. Three-dimensional computed tomographic analysis of the primary nasal deformity in 3-month-old infants with complete unilateral cleft lip and palate. Plast Reconstr Surg. 1999 Jun;103(7):1826-34.
Foong KW, Sandham A, Ong SH, Wong CW, Wang Y, Kassim A. Surface laser scanning of the cleft palate deformity--validation of the method. Ann Acad Med Singapore. 1999 Sep;28(5):642-9.
Frey M, Giovanoli P, Gerber H, Slameczka M, Stussi E. Three-dimensional video analysis of facial movements: a new method to assess the quantity and quality of the smile. Plast Reconstr Surg. 1999 Dec;104(7):2032-9.
Friede H, Lilja J, Johanson B. Lip-nose morphology and symmetry in unilateral celft lip and palate patients following a two-stage lip closure. Scand J Plast Reconstr Surg. 1980;14(1):55-64.
Fudalej P, Katsaros C, Hozyasz K, Borstlap WA, Kuijpers-Jagtman AM. Nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate. Br J Oral Maxillofac Surg. 2012 Jan 13 (Epub ahead of print).
Georgiade NG, Latham RA. Maxillary arch alignment in the bilateral cleft lip and palate infant, using pinned coaxial screw appliance. Plast Reconstr Surg. 1975 Jul;56(1):52-60.
Glass L, Starr CD, Stewart RE, Hodge SE. Indentikit Model II--a potential tool for judging cosmetic appearance. Cleft Palate J. 1981 Apr;18(2):147-51.
Graf-Pinthus B, Bettex M. Long-term observation following presurgical orthopedic treatment in complete clefts of the lip and palate. Cleft Palate J. 1974 Jul;11(0):253-60.
Grayson BH, Cutting C, Wood R. Preoperative columella lengthening in bilateral cleft lip and palate. Plast Reconstr Surg. 1993 Dec;92(7):1422-3.
Grayson BH, Cutting CB. Presurgical nasoalveolar orthopedic molding in primary correction of the nose, lip, and alveolus of infants born with unilateral and bilateral clefts. Cleft Palate Craniofac J. 2001 May;38(3):193-8.
Grayson BH, Maull D. Nasoalveolar molding for infants born with clefts of the lip, alveolus, and palate. Clin Plast Surg. 2004 Apr;31(2):149,58, vii.
Grayson BH, Santiago PE, Brecht LE, Cutting CB. Presurgical nasoalveolar molding in infants with cleft lip and palate. Cleft Palate Craniofac J. 1999 Nov;36(6):486-98.
Grayson BH, Shetye PR. Presurgical nasoalveolar moulding treatment in cleft lip and palate patients. Indian J Plast Surg. 2009 Oct;42 Suppl:S56-61.
Hathaway R, Daskalogiannakis J, Mercado A, Russell K, Long RE,Jr, Cohen M, et al. The Americleft study: an inter-center study of treatment outcomes for patients with
73
unilateral cleft lip and palate part 2. Dental arch relationships. Cleft Palate Craniofac J. 2011 May;48(3):244-51.
Heller M, Schmidt M, Mueller CK, Thorwarth M, Schultze-Mosgau S. Clinical-anthropometric and aesthetic analysis of nose and lip in unilateral cleft lip and palate patients. Cleft Palate Craniofac J. 2011 Jul;48(4):388-93.
Hotz M, Gnoinski W. Comprehensive care of cleft lip and palate children at Zurich university: a preliminary report. Am J Orthod. 1976 Nov;70(5):481-504.
Hotz M, Gnoinski W. The determining role of gnatho-orthopedics in modern treatment of cleft lip-palate (surgical-orthopedic coordinated technique). Mondo Ortod. 1976 Oct-Nov;18(5):25-41.
Hotz MM. Pre- and early postoperative growth-guidance in cleft lip and palate cases by maxillary orthopedics (an alternative procedure to primary bone-grafting). Cleft Palate J. 1969 Oct;6:368-72.
Hotz MM, Gnoinski WM, Nussbaumer H, Kistler E. Early maxillary orthopedics in CLP cases: guidelines for surgery. Cleft Palate J. 1978 Oct;15(4):405-11.
Jaeger M, Braga-Silva J, Gehlen D, Sato Y, Zuker R, Fisher D. Correction of the alveolar gap and nostril deformity by presurgical passive orthodontia in the unilateral cleft lip. Ann Plast Surg. 2007 Nov;59(5):489-94.
Johnson N, Sandy J. An aesthetic index for evaluation of cleft repair. Eur J Orthod. 2003 Jun;25(3):243-9.
Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, et al. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat Genet. 1995 Dec;11(4):415-21.
Kirschner RE, LaRossa D. Cleft lip and palate. Otolaryngol Clin North Am. 2000 Dec;33(6):1191,215, v-vi.
Kohout MP, Aljaro LM, Farkas LG, Mulliken JB. Photogrammetric comparison of two methods for synchronous repair of bilateral cleft lip and nasal deformity. Plast Reconstr Surg. 1998 Oct;102(5):1339-49.
Konst EM, Prahl C, Weersink-Braks H, De Boo T, Prahl-Andersen B, Kuijpers-Jagtman AM, et al. Cost-effectiveness of infant orthopedic treatment regarding speech in patients with complete unilateral cleft lip and palate: a randomized three-center trial in the Netherlands (Dutchcleft). Cleft Palate Craniofac J. 2004 Jan;41(1):71-7.
Konst EM, Rietveld T, Peters HF, Kuijpers-Jagtman AM. Language skills of young children with unilateral cleft lip and palate following infant orthopedics: a randomized clinical trial. Cleft Palate Craniofac J. 2003 Jul;40(4):356-62.
74
Krimmel M, Kluba S, Bacher M, Dietz K, Reinert S. Digital surface photogrammetry for anthropometric analysis of the cleft infant face. Cleft Palate Craniofac J. 2006 May;43(3):350-5.
Kuijpers-Jagtman AM, Nollet PJ, Semb G, Bronkhorst EM, Shaw WC, Katsaros C. Reference photographs for nasolabial appearance rating in unilateral cleft lip and palate. J Craniofac Surg. 2009 Sep;20 Suppl 2:1683-6.
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977 Mar;33(1):159-74.
Latham RA. Orthopedic advancement of the cleft maxillary segment: a preliminary report. Cleft Palate J. 1980 Jul;17(3):227-33.
Lee CT, Grayson BH, Cutting CB, Brecht LE, Lin WY. Prepubertal midface growth in unilateral cleft lip and palate following alveolar molding and gingivoperiosteoplasty. Cleft Palate Craniofac J. 2004 Jul;41(4):375-80.
Lindsay WK, Farkas LG. The use of anthropometry in assessing the cleft-lip nose. Plast Reconstr Surg. 1972 Mar;49(3):286-93.
Liou EJ, Subramanian M, Chen PK, Huang CS. The progressive changes of nasal symmetry and growth after nasoalveolar molding: a three-year follow-up study. Plast Reconstr Surg. 2004 Sep 15;114(4):858-64.
Liu Q, Yang ML, Li ZJ, Bai XF, Wang XK, Lu L, et al. A simple and precise classification for cleft lip and palate: a five-digit numerical recording system. Cleft Palate Craniofac J. 2007 Sep;44(5):465-8.
Lo LJ. Primary correction of the unilateral cleft lip nasal deformity: achieving the excellence. Chang Gung Med J. 2006 May-Jun;29(3):262-7.
Long RE,Jr. The Americleft Project: Comparing Treatment Outcomes for Cleft Lip and Palate to Identify Evidence-Based Best Practices of Importance to the Orthodontist. 2011.
Long RE,Jr, Hathaway R, Daskalogiannakis J, Mercado A, Russell K, Cohen M, et al. The Americleft study: an inter-center study of treatment outcomes for patients with unilateral cleft lip and palate part 1. Principles and study design. Cleft Palate Craniofac J. 2011 May;48(3):239-43.
Lukash FN, Schwartz M, Grauer S, Tuminelli F. Dynamic cleft maxillary orthopedics and periosteoplasty: benefit or detriment? Ann Plast Surg. 1998 Apr;40(4): 326-7.
Mani MR, Semb G, Andlin-Sobocki A. Nasolabial appearance in adults with repaired unilateral cleft lip and palate: Relation between professional and lay rating and patients' satisfaction. J Plast Surg Hand Surg. 2010 Nov;44(4-5):191-8.
75
Mars M, Asher-McDade C, Brattström V, Dahl E, McWilliam J, Mølsted K, et al. A six-center international study of treatment outcome in patients with clefts of the lip and palate: Part 3. Dental arch relationships. Cleft Palate Craniofac J. 1992 Sep;29(5):405-8.
Masarei AG, Wade A, Mars M, Sommerlad BC, Sell D. A randomized control trial investigating the effect of presurgical orthopedics on feeding in infants with cleft lip and/or palate. Cleft Palate Craniofac J. 2007 Mar;44(2):182-93.
Maull DJ, Grayson BH, Cutting CB, Brecht LL, Bookstein FL, Khorrambadi D, et al. Long-term effects of nasoalveolar molding on three-dimensional nasal shape in unilateral clefts. Cleft Palate Craniofac J. 1999 Sep;36(5):391-7.
McNeil C. Orthodontic procedures in the treatment of congenital cleft palate. Dent Records. 1950;70:126-132.
Melnick M. Cleft lip and cleft palate. Etiology and pathogenesis. In: Kernahan DA, Rosenstein SW, Dado DV, editor. Cleft Lip and Palate. A System of Management. Baltimore: Williams & Wilkins.; 1990. p.3.
Mercado A, Russell K, Hathaway R, Daskalogiannakis J, Sadek H, Long RE,Jr, et al. The Americleft study: an inter-center study of treatment outcomes for patients with unilateral cleft lip and palate part 4. Nasolabial aesthetics. Cleft Palate Craniofac J. 2011 May;48(3):259-64.
Millard DJ. Cleft Craft: The Evolution of Its Surgery. Vol 1 ed. Boston: Little Brown; 1976.
Miyamoto J, Miyamoto S, Nagasao T, Nakajima T, Kishi K. Anthropometric evaluation of bilateral cleft lip nose with cone beam computed tomography in early childhood: Estimation of nasal tip collapse. J Plast Reconstr Aesthet Surg. 2012 Feb;65(2):169-74.
Mølsted K. Treatment outcome in cleft lip and palate: issues and perspectives. Crit Rev Oral Biol Med. 1999;10(2):225-39.
Mølsted K, Asher-McDade C, Brattström V, Dahl E, Mars M, McWilliam J, et al. A six-center international study of treatment outcome in patients with clefts of the lip and palate: Part 2. Craniofacial form and soft tissue profile. Cleft Palate Craniofac J. 1992 Sep;29(5):398-404.
Moore KL. The Developing Human. WB Saunders Co, editor. Philadelphia; 1982.
Morrant DG, Shaw WC. Use of standardized video recordings to assess cleft surgery outcome. Cleft Palate Craniofac J. 1996 Mar;33(2):134-42.
Nakamura N, Okawachi T, Nishihara K, Hirahara N, Nozoe E. Surgical technique for secondary correction of unilateral cleft lip-nose deformity: clinical and 3-dimensional
76
observations of preoperative and postoperative nasal forms. J Oral Maxillofac Surg. 2010 Sep;68(9):2248-57.
Pai BC, Ko EW, Huang CS, Liou EJ. Symmetry of the nose after presurgical nasoalveolar molding in infants with unilateral cleft lip and palate: a preliminary study. Cleft Palate Craniofac J. 2005 Nov;42(6):658-63.
Patzer G. The Physical Attractiveness Phenomena. New York: Plenum Press; 1984.
Pfeifer TM, Grayson BH, Cutting CB. Nasoalveolar molding and gingivoperiosteoplasty versus alveolar bone graft: an outcome analysis of costs in the treatment of unilateral cleft alveolus. Cleft Palate Craniofac J. 2002 Jan;39(1):26-9.
Pope AW, Tillman K, Snyder HT. Parenting stress in infancy and psychosocial adjustment in toddlerhood: a longitudinal study of children with craniofacial anomalies. Cleft Palate Craniofac J. 2005 Sep;42(5):556-9.
Power SM, Matic DB. Critical Analysis of Consecutive Unilateral Cleft Lip Repairs: Determining Ideal Sample Size. Cleft Palate Craniofac J. 2012 Mar 19 (Epub ahead of print).
Prahl C, Kuijpers-Jagtman AM, Van 't Hof MA, Prahl-Andersen B. Infant orthopedics in UCLP: effect on feeding, weight, and length: a randomized clinical trial (Dutchcleft). Cleft Palate Craniofac J. 2005 Mar;42(2):171-7.
Prahl C, Kuijpers-Jagtman AM, Van 't Hof MA, Prahl-Andersen B. A randomized prospective clinical trial of the effect of infant orthopedics in unilateral cleft lip and palate: prevention of collapse of the alveolar segments (Dutchcleft). Cleft Palate Craniofac J. 2003 Jul;40(4):337-42.
Prahl C, Kuijpers-Jagtman AM, van't Hof MA, Prahl-Andersen B. A randomised prospective clinical trial into the effect of infant orthopaedics on maxillary arch dimensions in unilateral cleft lip and palate (Dutchcleft). Eur J Oral Sci. 2001 Oct;109(5):297-305.
Prahl C, Prahl-Andersen B, van 't Hof MA, Kuijpers-Jagtman AM. Infant orthopedics and facial appearance: a randomized clinical trial (Dutchcleft). Cleft Palate Craniofac J. 2006 Nov;43(6):659-64.
Prahl C, Prahl-Andersen B, Van't Hof MA, Kuijpers-Jagtman AM. Presurgical orthopedics and satisfaction in motherhood: a randomized clinical trial (Dutchcleft). Cleft Palate Craniofac J. 2008 May;45(3):284-8.
Prahl-Andersen B. Dental treatment of predental and infant patients with clefts and craniofacial anomalies. Cleft Palate Craniofac J. 2000 Nov;37(6):528-32.
Randall P. A triangular flap operation for the primary repair of unilateral clefts of the lip. Plastic and reconstructive surgery.1959; 23:331-347.
77
Ras F, Habets LL, van Ginkel FC, Prahl-Andersen B. Three-dimensional evaluation of facial asymmetry in cleft lip and palate. Cleft Palate Craniofac J. 1994 Mar;31(2):116-21.
Rivkin CJ, Keith O, Crawford PJ, Hathorn IS. Dental care for the patient with a cleft lip and palate. Part 2: The mixed dentition stage through to adolescence and young adulthood. Br Dent J. 2000 Feb 12;188(3):131-4.
Rodd HD, Clark EL, Stern MR, Baker SR. Failed attendances at hospital dental clinics among young patients with cleft lip and palate. Cleft Palate Craniofac J. 2007 Jan;44(1):92-4.
Ross R. Midfacial and mandibular dysmorphology and growth in facial clefting: clinical implications. In: Mooney M SM, editor. Understanding craniofacial anomalies: the etiopathogenesis of craniosynostoses and facial clefting. Toronto: Wiley-Liss Inc.
Ross R, Johnston M. Cleft Lip and Palate. Baltimore: Williams and Wilkins; 1972.
Ross RB. Treatment variables affecting facial growth in complete unilateral cleft lip and palate. Cleft Palate J. 1987 Jan;24(1):5-77.
Ross RB, MacNamera MC. Effect of presurgical infant orthopedics on facial esthetics in complete bilateral cleft lip and palate. Cleft Palate Craniofac J. 1994 Jan;31(1):68-73.
Russell K, Long RE,Jr, Hathaway R, Daskalogiannakis J, Mercado A, Cohen M, et al. The Americleft study: an inter-center study of treatment outcomes for patients with unilateral cleft lip and palate part 5. General discussion and conclusions. Cleft Palate Craniofac J. 2011 May;48(3):265-70.
Russell KA, Waldman SD, Lee JM. Video-imaging assessment of nasal morphology in individuals with complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 2000 Nov;37(6):542-50.
Russell KA, Waldman SD, Tompson B, Lee JM. Nasal morphology and shape parameters as predictors of nasal esthetics in individuals with complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 2001 Sep;38(5):476-85.
Sander M, Daskalogiannakis J, Tompson B, Forrest C. Effect of alveolar bone grafting on nasal morphology, symmetry, and nostril shape of patients with unilateral cleft lip and palate. Cleft Palate Craniofac J. 2011 Jan;48(1):20-7.
Schabel BJ, McNamara JA,Jr, Franchi L, Baccetti T. Q-sort assessment vs visual analog scale in the evaluation of smile esthetics. Am J Orthod Dentofacial Orthop. 2009 Apr;135(4 Suppl):S61-71.
78
Semb G, Brattström V, Mølsted K, Prahl-Andersen B, Shaw WC. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 1: introduction and treatment experience. Cleft Palate Craniofac J. 2005 Jan;42(1):64-8.
Semb G, Shaw WC. Facial growth after different methods of surgical intervention in patients with cleft lip and palate. Acta Odontol Scand. 1998 Dec;56(6):352-5.
Severens JL, Prahl C, Kuijpers-Jagtman AM, Prahl-Andersen B. Short-term cost-effectiveness analysis of presurgical orthopedic treatment in children with complete unilateral cleft lip and palate. Cleft Palate Craniofac J. 1998 May;35(3):222-6.
Shaw WC, Asher-McDade C, Brattström V, Dahl E, McWilliam J, Mølsted K, et al. A six-center international study of treatment outcome in patients with clefts of the lip and palate: Part 1. Principles and study design. Cleft Palate Craniofac J. 1992 Sep;29(5):393-7.
Shaw WC, Dahl E, Asher-McDade C, Brattström V, Mars M, McWilliam J, et al. 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 Sep;29(5):413-8.
Shaw WC, Semb G, Nelson P, Brattström V, Mølsted K, Prahl-Andersen B, et al. The Eurocleft project 1996-2000: overview. J Craniomaxillofac Surg. 2001 Jun;29(3):131,40; discussion 141-2.
Shetye PR. Presurgical infant orthopedics. J Craniofac Surg. 2012 Jan;23(1):210-1.
Singh GD, Levy-Bercowski D, Santiago PE. Three-dimensional nasal changes following nasoalveolar molding in patients with unilateral cleft lip and palate: geometric morphometrics. Cleft Palate Craniofac J. 2005 Jul;42(4):403-9.
Sischo L, Chan JW, Stein M, Smith C, van Aalst JA, Broder HL. Nasoalveolar Molding: Prevalence of Cleft Centers Offering NAM and Who Seeks It. Cleft Palate Craniofac J. 2011 Jul 8 (Epub).
Skyes J. Management of the cleft lip deformity. Facial Plastic Surgery Clinics of North America. 2001;9(1):37-50.
Smith K. University of Oklahoma College of Dentistry Cleft Craniofacial Fellowship. http://dentistry.ouhsc.edu/os_cleft-craniofacial.php.; 2012(04/11).
Snowden CB, Miller TR, Jensen AF, Lawrence BA. Costs of medically treated craniofacial conditions. Public Health Rep. 2003 Jan-Feb;118(1):10-7.
Stephenson W. The study of behaviour. Chicago: University of Chicago Press. 1953.
Suri S, Tompson BD. A modified muscle-activated maxillary orthopedic appliance for presurgical nasoalveolar molding in infants with unilateral cleft lip and palate. Cleft Palate Craniofac J. 2004 May;41(3):225-9.
Ten Cate A. Oral Histology: Development, Structure and Function. 5th ed. St. Louis: Mosby-Year Book, Inc; 1998.
Tennison CW. The repair of the unilateral cleft lip by the stencil method. Plast Reconstr Surg (1946). 1952 Feb;9(2):115-20.
Thomas C. Primary rhinoplasty by open approach with repair of unilateral complete cleft lip. J Craniofac Surg. 2009 Sep;20 Suppl 2:1711-4.
Tobiasen JM. Social judgments of facial deformity. Cleft Palate J. 1987 Oct;24(4):323-7.
Tobiasen JM, Hiebert JM. Reliability of esthetic ratings of cleft impairment. Cleft Palate J. 1988 Jul;25(3):313-7.
Tobiasen JM, Hiebert JM, Boraz RA. Development of scales of severity of facial cleft impairment. Cleft Palate Craniofac J. 1991 Oct;28(4):419-24.
Uzel A, Alparslan ZN. Long-term effects of presurgical infant orthopedics in patients with cleft lip and palate: a systematic review. Cleft Palate Craniofac J. 2011 Sep;48(5):587-95.
Vegter F, Hage JJ. Facial anthropometry in cleft patients: a historical appraisal. Cleft Palate Craniofac J. 2001 Nov;38(6):577-81.
Wehby GL, Cassell CH. The impact of orofacial clefts on quality of life and healthcare use and costs. Oral Dis. 2010 Jan;16(1):3-10.
Williams AC, Bearn D, Mildinhall S, Murphy T, Sell D, Shaw WC, et al. Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 2: dentofacial outcomes and patient satisfaction. Cleft Palate Craniofac J. 2001 Jan;38(1):24-9.
Winters JC, Hurwitz DJ. Presurgical orthopedics in the surgical management of unilateral cleft lip and palate. Plast Reconstr Surg. 1995 Apr;95(4):755-64.
Wong K, Wu L. History of Chinese Medicine. Tientsin: Tientsin Press; 1932.
Wood RJ, Grayson BH, Cutting CB. Gingivoperiosteoplasty and midfacial growth. Cleft Palate Craniofac J. 1997 Jan;34(1):17-20.
World Health Organization. Global strategies to reduce the health care burden of craniofacial anomalies: report of WHO meetings on international collaborative research on craniofacial anomalies. Cleft Palate Craniofac J. 2004 May;41(3):238-43.
80
Wright JG, Menaker RJ, Canadian Paediatric Surgical Wait Times Study Group. Waiting for children's surgery in Canada: the Canadian Paediatric Surgical Wait Times project. CMAJ. 2011 Jun 14;183(9):E559-64.
Wyszynski D. Cleft Lip and Palate: From Origin to Treatment. New York: Oxford University Press; 2002.
81
Appendix 1: Abbreviations/Acronyms
ACPA: American Cleft Palate Craniofacial Association
BCLP: Bilateral Cleft Lip and Palate
CA: Coefficient of Asymmetry
CCT: Controlled Clinical Trial
CDC: Centre for Disease Control
CLP: Cleft Lip and Palate
CSAG: Clinical Standards Advisory Group
CT: Computed Tomography
CUCLP: Complete Unilateral Cleft Lip and Palate
DMA: Dentomaxillary Alignment Appliance
GPP: Gingivoperiosteoplasty
IO: Infant Orthopedics
JPEG: Joint Photographic Experts Group
NAM: Nasoalveolar Molding
PSIO: Presurgical Infant Orthopedics
RCT: Randomized Controlled Trial
TIO: Traditional Infant Orthopedics
UCLP: Unilateral Cleft Lip and Palate
US: United States
USB: Universal Serial Bus Drive
WHO: World Health Organization
82
Appendix 2: Sample Demographics & BOC Data
Centre 1
Research Number
Sex Cleft Side Surgeon Code Age at Photo (yrs)
Non Cleft Side Photos
1 F L 2 4.82 Y 2 F L 3 5.01 3 M R 2 4.45 4 F R 3 5.09 Y 5 M L 3 5.1 6 M L 2 5.03 8 F R 2 6.01 Y 9 F L 2 4.39 Y
10 M L 2 5.05 11 F L 2 6.01 12 M R 2 6.07 13 M L 3 6.03 14 M L 2 4.92 Y 15 M L 2 6.03 17 F L 2 6.83 18 F R 2 6.23 19 M L 2 6.18 Y 20 F L 2 6.22 21 F L 3 5.26 23 F L 3 6.01 Y 24 M L 2 6.01 25 M L 2 6.04 Y 26 M L 2 4.76 27 M R 2 5.87 Y 28 M R 3 6.01 29 F L 2 6.05 30 M L 2 4.01 31 M L 4 6.08 32 M R 6 6.2 33 M L 2 5.66 34 F R 6 5.99 35 M L 6 6.33 36 M L 2 6.05 37 F L 2 6.06 38 F L 2 6.06 39 M L 2 6.02 40 M L 3 6.15 41 F L 6 5.96 43 M L 6 5.99 44 F R 6 6.02