Int. J. Oral Maxillofac. Surg. 2015; 44: 50–56 http://dx.doi.org/10.1016/j.ijom.2014.08.004, available online at http://www.sciencedirect.com
Systematic Review Cleft Lip and Palate
Impact of primary palatoplasty on the maxillomandibular sagittal relationship in patients with unilateral cleft lip and palate: a systematic review and meta-analysis
L. M. Bichara1, R. C. Arau´jo1, C. Flores-Mir2, D. Normando1 1 Orthodontics Department, Federal University of the State of Para´, Bele´m, Para´, Brazil; 2 School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
L. M. Bichara, R. C. Arau´jo, C. Flores-Mir, D. Normando:Impact of primary palatoplasty on the maxillomandibular sagittal relationship in patients with unilateral cleft lip and palate: a systematic review and meta-analysis. Int. J. Oral Maxillofac. Surg. 2015; 44: 50–56. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. The study objective was to evaluate, through a meta-analysis, the impact of primary palatoplasty on the sagittal maxillary and mandibular relationship among patients with complete unilateral cleft lip and palate (UCLP). Electronic database and hand searches were performed. Controlled clinical trials involving non-syndromic UCLP patients were included. Selected papers had to include a group of patients undergoing lip and palate repair and a group undergoing lip repair only. Data heterogeneity was demonstrated and individual means, standard deviations, and sample sizes were collected and summarized using a random effects model meta-analysis. Although six articles were selected for the systematic review, only four were included in the meta-analysis due to large discrepancies in the standard surgical protocol. Only one variable assessing the intermaxillary relationship (A point–nasion–B point; ANB), maxillary position (sella–nasion–A point; SNA), and mandibular position (sella– nasion–B point; SNB) was common among the selected studies. No significant differences in SNA and SNB were indentified between patients undergoing lip surgery alone and those undergoing lip and palate surgery. Evaluation of ANB showed a small statistical standard mean difference of 0.368. Impaired maxillary sagittal growth, observed in patients with UCLP, appears to be a basic consequence of lip surgical repair. Additional changes to the maxilla and mandible produced by palatal repair are minor. Methodologically rigorous controlled studies are needed to provide a stronger evidencebased basis for the surgical management of patients with UCLP.
0901-5027/01050 + 07
Keywords: cleft lip; cleft palate; craniofacial abnormalities; surgery; oral. Accepted for publication 12 August 2014 Available online 10 September 2014
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Primary palatoplasty in cleft lip and palate While primary repair of cleft lip and palate has not been shown to have a significant influence on mandibular morphology,1 maxillary growth deficiencies are very common in patients with unilateral cleft lip and palate (UCLP) who have undergone an early surgical intervention.2–4 The most frequently adopted surgical protocol in the treatment of cleft considers primary palatoplasty to be the major reason for maxillary growth impairment in subjects with UCLP. This is corroborated by several studies that have compared individuals with operated UCLP vs. unoperated patients.2–8 However, some studies4,5 have shown that the cumulative maxillary growth disturbance attributable to lip and palate repair is not significantly worse than that determined by lip repair alone. This suggests that lip repair may be the most important factor in maxillary growth disturbance in patients with UCLP. This comprehensive review was undertaken to review the available evidence regarding which of these surgical procedures has a greater effect on maxillary and mandibular growth. The answer to this clinically relevant question should help us to develop better treatment strategies for patients with cleft lip and palate thereby improving both functional and wellbeing outcomes. Methods
The PRISMA checklist9 was utilized as a reporting guide. This meta-analysis was registered at PROSPERO (the international prospective register of systematic reviews) under registration code CRD 42012003360. For eligibility, all articles had to have compared patients with complete UCLP who had undergone lip repair followed by palate repair to patients who had undergone lip surgery and no palate repair. Information sources
The databases used were PubMed, Cochrane Library, ScienceDirect, SciELO, and BIREME. A partial grey literature search was undertaken using Google Scholar. A hand search of the references of selected articles was also carried out to identify any article that could have been missed in the electronic database searches. Key words ‘cleft lip palate’ were searched in combination with ‘growth’, ‘surgery’, and ‘repair’. All references were managed using reference manager software (RefWorks) and duplicate hits were removed. Search limits were the following: controlled clinical trial, prospective or
51
retrospective, systematic review, metaanalysis, with human samples, no language restriction, from 1960 to the end of the search on 4 September 2013.
software10 was used to perform the statistical analysis. All forest plots and funnel plots, as part of the meta-analysis, were also produced by the software.
Study selection
Risk of bias across studies
The search was performed independently by two researchers (LMB and RCA). If the title and/or abstract appeared to fulfil the inclusion criteria, the article was selected for full retrieval. All abstracts had to mention patients with UCLP and a group of patients undergoing lip surgery only and a group of patients undergoing both lip and palate surgery. Additionally, all studies had to have used a lateral cephalometric analysis. Once full articles were obtained, a second selection stage was executed in which the same set of criteria was applied. Confirmation of inclusion was sought in cases where the title/abstract was misleading due to the limited description contained within them.
A funnel plot was generated using the same software to verify publication bias.
Data collection process
Both researchers retrieved the required information separately. The information selected was then checked jointly and any disagreements resolved. If necessary a third author (DN) was involved in the final decision. The information retrieved from the final selection of articles included the following: author(s), year of publication, recruitment process (random, consecutive, convenience), sample size, inclusion criteria, country of origin, age at the time of surgery, error of method, sample matching (age, gender, origin, type of cleft), surgical technique, confounding factors, analysis, and the pertinent data. Risk of bias in individual studies
A methodology checklist was applied to analyze and quantify the risk of bias in the studies included. Summary measures
Individual means and standard deviations (SD) were collected from the lateral cephalometric measurements. Synthesis of results
The cephalometric measurements were pooled through several meta-analyses applying a random effects model. This modelling was used because of the expected heterogeneity of the samples included. Comprehensive Meta-Analysis
Results Study selection
Initially, 4995 articles were screened. Only 14 of them appeared to have fulfilled the inclusion criteria based on the information provided in the abstracts. Full copies of the articles were retrieved. After reading the full texts, eight articles were excluded because they did not match the primary inclusion criteria, i.e. a direct comparison of patients with UCLP undergoing surgery to the lip and palate with patients undergoing only lip repairs.11–18 Six papers were included in the qualitative synthesis,2,4,5–8 however only four were included in the meta-analysis4,5,7,8 (Fig. 1). The studies by Mars and Houston2 and Liao and Mars6 were excluded from the statistical analysis due to methodological issues. The first study did not record the mean age at lip repair of the sample; in the second study, the mean age at lip surgery was 7 years for patients who had undergone lip repair only and 1 year for patients who had undergone lip and palate repair. The studies included in the meta-analysis reported the following mean age at lip repair for the patients who had undergone a lip operation only (OL): 9.5 months,4 44 months,5 9 months,7 and before 24 months.8 The patients who had undergone lip and palate surgery (OLP) had lip surgery at a mean age of 5.5 months,4 27 months,5 9 months,7 and before 24 months.8 For this group, palate surgery was performed at 20 months,4 54 months,5 38 months,7 and before 36 months.8 Study characteristics
Sample sizes ranged from 10 subjects5 to 47 subjects.8 All patients included in the samples had UCLP. A group of patients who had undergone operations on both the lip and palate (OLP) was compared to another in which patients had undergone operations on the lip only (OL). The authors used different surgery techniques. For lip repair, the Millard technique,5,6,8 Tennison technique,6 or rotation-advancement7 was used. However, patients had sometimes presented to the treatment facility with a lip repair and no clear indication of the surgery technique
52
Bichara et al.
Fig. 1. Flow chart showing the results of the search process.
that had been applied. In other cases, multiple techniques were used.4,6 Palate repair was done using the Oxford method,5 a vomerine mucoperiosteal flap and palatal mucoperiosteal flap,6 by mucoperiosteal pushback,7 or by two-flap technique.8 One article only informed that multiple techniques were used,2 and another4 provided no description of the technique used. Five studies4–8 stated that the patients in the samples had not undergone bone grafting surgery and one2 had no information on whether bone grafting surgery had been done or not. All articles evaluated lateral cephalometric measurements to assess maxillary and mandibular size and/or relative positioning. The lateral cephalograms analyzed were obtained at the age of 13.78 years,7 19.75 years,4 20.1 years,2,8 23 years,6 and 26.5 years5 for the OL group, and 14.64 years,7 16.4 years,2 18.58 years,4 19 years,6 20.8 years,5 and 20.41 years8 for the OLP group. The mean age at lip repair for the patients who had undergone surgery to the lip only (OL) in the selected studies was 9 months,7 9.5 months,4 44 months,5 and before 24 months.8 The patients who had undergone lip and palate surgery (OLP) had lip surgery
at a mean age of 5.5 months,4 9 months,7 27 months,5 and before 24 months.8 For this group, palate surgery was performed at 20 months, 38 months, 54 months, and before 36 months, respectively.
in any study. In three of the six studies evaluated in the systematic review, the intermaxillary relationship (A point– nasion–B point; ANB) was found to be significantly different between the OL and OLP groups.6–8
Risk of bias within studies
The methodology checklist (Table 1)19 showed an overall moderate risk of bias; some studies presented a higher risk of bias2,6 than others.4,5,7,8 Results of individual studies
Regarding the maxillary position (sella– nasion–A point (SNA) angle), Mars and Houston,2 Capelozza Filho et al.,4 Kupucu et al.,5 Li et al.,7 and Chen et al.8 showed no statistical difference between patients with UCLP who had undergone a lip repair only and those who had undergone both lip and palate surgery. Only Liao and Mars6 showed significant differences in maxillary position between these tested groups (P = 0.002). Mandibular position (sella– nasion–B point (SNB) angle) was not different between the OL and OLP groups
Risk of bias across studies
Despite the small number of articles included in the review, publication bias was tested. Article distribution in the funnel plot did not show asymmetry, and therefore no publication bias was found for SNA, SNB, or ANB angles (Fig. 2). Synthesis of results
Ultimately only four studies could be included in the meta-analysis. The necessary data for SNA, SNB, and ANB angles were extracted (Table 2) and pooled (Table 3). On meta-analysis, no significant differences were found for SNA and SNB angles between patients with UCLP who had lip and palate surgery (OLP) and those who had lip surgery only (OL), as demonstrated by the forest plots (Fig. 3). Pooled
Table 1. Methodology checklist for the articles selected for the systematic review (adopted from the National Institute for Health and Care Excellence). Articles
Quality criteria
Mars and Kupucu et al., Capelozza Liao and Li et al., Chen et al., Houston, 19902 19955 Filho et al., 19964 Mars, 20056 20067 20128 1. The study sample represents the population of interest with regard to key characteristics, sufficient to limit potential bias to the results a. Are the source population or the population of interest adequately described with Yes Yes Yes Yes respect to key characteristics? b. Are the sampling frame and recruitment adequately described, possibly including No Yes Yes Yes methods to identify the sample, period of recruitment, and place of recruitment? c. Are inclusion and exclusion criteria adequately described? Yes Yes Yes Yes d. Is participation in the study by eligible individuals adequate? Yes Yes Yes Yes e. Is the baseline study sample adequately described with respect to key characteristics? No Yes Yes Yes 2. The prognostic factor of interest is adequately measured in study participants, sufficient to limit potential bias a. Is a clear definition or description of the prognostic factor(s) measured provided? Yes Yes b. Are continuous variables reported, or appropriate cut-off points (that is, not dataNo Yes dependent) used? c. Are the prognostic factor measured and the method of measurement valid and Yes Yes reliable enough to limit misclassification bias? d. Are complete data for prognostic factors available for an adequate proportion of the No Yes study sample? e. Are the method and setting of measurement the same for all study participants? Yes Yes f. Are appropriate methods employed if imputation is used for missing data on No Unclear prognostic factors?
Yes
Yes
Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes
Yes Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes Unclear
Yes No
Yes Unclear
Yes Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes Yes
No Yes Unclear Yes
Yes Yes
Unclear
Unclear Unclear
Unclear
Unclear Unclear
No No
Unclear Unclear
Unclear Unclear
the presentation of invalid results Yes Yes Yes Yes Yes Yes
No Yes
Yes Yes
Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
4. Important potential confounders are appropriately accounted for, limiting potential bias with respect to the prognostic a. Are all important confounders, including treatments, measured? Are clear definitions No Yes of the important confounders measured provided? b. Is measurement of all important confounders valid and reliable? No Yes c. Are the method and setting of measurement of confounders the same for all study Unclear Yes participants? d. Are appropriate methods employed if imputation is used for missing data on Unclear Unclear confounders? e. Are important potential confounders accounted for in the study design? No Unclear f. Are important potential confounders accounted for in the analysis (that is, appropriNo Unclear ate adjustment)?
Yes Yes Yes
factor of interest Yes No
Yes Yes Yes
53
Yes No
Primary palatoplasty in cleft lip and palate
Yes Yes
3. The outcome of interest is adequately measured in study participants, sufficient to limit potential bias a. Is a clear definition of the outcome of interest provided, including duration of followYes Yes up? b. Are the outcome that was measured and the method of measurement valid and Yes Yes reliable enough to limit misclassification bias? c. Are the method and setting of measurement the same for all study participants? Yes Yes
5. The statistical analysis is appropriate for the design of the study, limiting potential for a. Is the presentation of data sufficient to assess the adequacy of the analysis? b. Where several prognostic factors are investigated, is the strategy for model building appropriate and based on a conceptual framework or model? c. Is the selected model adequate for the design of the study? d. Is there any selective reporting of results? e. Are only pre-specified hypotheses investigated in the analyses?
Yes
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Bichara et al.
Fig. 2. Funnel plots showing no publication bias for SNA, SNB, or ANB.
Table 2. Sample size, mean values, and standard deviations for SNA, SNB, and ANB of the UCLP groups who had only lip surgery (OL) and lip and palate surgery (OLP). OLP
OL
Study
SNB
SNA Kupucu et al., 19955 Capelozza Filho et al., 19964 Li et al., 20067 Chen et al., 20128
ANB
SNA
SNB
ANB
n
Mean
SD
Mean
SD
Mean
SD
n
Mean
SD
Mean
SD
Mean
SD
10 23 35 15
74.7 77.2 73.64 79.25
3 3.8 4.5 4.9
74.7 77.2 77.34 78.98
3.1 3.9 4.9 3.2
0 0 3.7 0.2
2.2 3.2 4.0 4.3
30 35 47 16
76.3 76 73.3 75.4
3.5 5.6 5.5 6.5
76.9 76.8 75.1 79.6
4.7 3.8 4.6 6.4
0.5 0.8 1.81 4.17
3.8 4.6 3.1 5.1
SD, standard deviation; SNA, sella–nasion–A point; SNB, sella–nasion–B point; ANB, A point–nasion–B point; UCLP, unilateral cleft lip and palate. Table 3. SNA, SNB, and ANB: differences between means, the P-value for each comparison, the weight of every study, and the pooled P-value.
Std diff mean Kupucu et al., 19955 Capelozza Filho et al., 19964 Li et al., 20067 Chen et al., 20128
SNB
SNA
Study
P-value
Weight %
0.47 0.24
0.201 0.37
18.83 28.14
0.05 0.64
0.813 0.080
34.18 18.85
Pooled P-value
0.532
Std diff mean
P-value
Weight %
0.503 0.104
0.173 0.698
19.33 27.95
0.45 0.135
0.046 0.709
32.72 20.01
ANB Pooled P-value
0.795
Std diff mean
P-value
Weight %
0.14 0.19
0.695 0.469
15.58 28.76
0.40 0.92
0.104 0.015
41.09 14.56
Pooled P-value
0.012
SNA, sella–nasion–A point; SNB, sella–nasion–B point; ANB, A point–nasion–B point; Std Diff Mean, standard mean difference.
Fig. 3. Forest plots representing results for ANB, SNA and SNB angle of all studies included in this meta-analysis and the pooled result.
data from all articles for the ANB angle showed statistically significant differences between the OL and OLP groups (Fig. 3). Discussion
A very common characteristic of patients with UCLP who have undergone primary reconstructive surgery is a significant maxillary retrusion. The surgical protocol for patients with UCLP usually advocates primary palatal surgery after lip repair. This approach is based on the hypothesis
that palatal surgery is the main aetiological factor in maxillary retrusion, therefore palatal repair is postponed. As well as the obvious immediate impact of lip repair on facial aesthetics, palate repair performed at a younger age is crucial for feeding,20 speech,21,22 and breathing23 functions. The treatment of subjects with UCLP is complex, multidisciplinary, and can be lengthy.24 The reported consequences of lip and palate repair on the craniofacial development of patients with cleft remain
controversial. Problems such as sampling, availability of a control group of patients who have not undergone primary surgery, the lack of standardized surgical procedures (including age at surgery), the different methods of assessment, and ethical issues have hindered the possibility of drawing sound scientifically-based conclusions. After a systematic search to identify related articles published since 1960, only six papers were selected for this systematic review/meta-analysis. Of these, only four4–8 were included in the
Primary palatoplasty in cleft lip and palate meta-analysis. Heterogeneity was assumed as they presented different population origins, age ranges, and surgical techniques. Mars and Houston2 and Liao and Mars6 had the same sample origin but very different mean ages from one group to another. Lateral cephalometric radiographs were utilized in all studies; however different cephalometric analyses were employed. Therefore, only one variable measuring maxillary sagittal positioning (SNA angle), one concerning mandibular positioning (SNB angle), and one describing the maxillomandibular relationship (ANB angle) were common to every study. All studies in the meta-analysis were nonrandomized retrospective clinical trials. Despite the lack of scientific conclusions regarding the best timing for palatal surgery in patients with UCLP, it is strongly believed that a child’s quality of life is improved by palatal repair at a younger age.13–15 Therefore it is considered unethical to leave a child without this treatment option. Small sample sizes further hindered the power of the meta-analysis. Although having similar stated results, the conclusions reported in the selected studies were controversial. Since there was no difference between non-cleft individuals and subjects with UCLP with only lip repair (OL), Mars and Houston2 concluded that lip surgery would not be detrimental to maxillary growth. This was despite their findings of no statistical differences between OL and OLP patients. Liao and Mars6 found statistical differences for SNA in a comparison of Sri Lankan patients with UCLP who had undergone lip and palate surgery and patients who had undergone lip surgery only, supporting the previous conclusions. However, the first study did not record the age at lip repair and in the second study the mean age at lip surgery was 7 years for patients operated only on the lip (OL) and 1 year for patients operated on the lip and palate (OLP). Therefore, neither study was considered for the meta-analysis since this difference in surgery timing could have caused a significant bias. The pooled result for the SNA angle of the four studies included in the meta-analysis4–8 showed no statistical difference between OLP patients and OL patients. Individually, none of these studies reported a significant difference between OL and OLP patients. These findings indicate that lip surgery may be the most important factor in the impairment of maxillary growth in UCLP. The A point, measured in all studies as representing the anterior maxilla
projection, should be considered with caution due to malformations in the anterior region of the maxilla brought about by the cleft, which make it very difficult to locate properly. The pooled data for the SNB angle from the articles in the meta-analysis showed no significant differences for mandibular position, meaning no detrimental effects for OLP patients. As stated for the SNA angle, no report of a significant difference between OL and OLP patients was found for the SNB angle. Overall, a significant difference in ANB angle was found between the groups. Despite the fact that no statistical differences were found in three of the primary studies included,4,5,7 Chen et al.8 showed a statistical difference between patients with UCLP who had undergone a lip and palate operation compared to those who were operated only on the lip. However, the standard mean difference here was only 0.368, probably a false-positive finding or a difference without clinical significance. This meta-analysis sheds some light on the main cause of impaired maxillary growth in patients with UCLP operated on the lip and palate. However, the cephalometric variables examined do not include all skeletal facial features of the operated patients with UCLP. The size of the maxilla and mandible, vertical dimensions, and soft tissue profile could not be analyzed due to a lack of available data. Limitations
Cephalometric evaluation of patients with craniofacial deformities is not always accurate. Some features are very hard to access, such as the cephalometric A point in patients with UCLP, where the maxillary anterior region is damaged by the cleft. The use of cone beam computed tomography (CBCT) images would probably be helpful in identifying and adapting better landmarks for patients with UCLP.25 Moreover, the data presented in the studies enrolled in the meta-analysis were collected retrospectively. There is no precise information on the timing of primary surgeries, the surgical technique employed, the skill and experience of the surgeon, and any secondary surgeries, such as primary alveolar reconstruction. There are ethical reasons for some of these methodological limitations, since this type of study is usually conducted in developing countries where some patients are not treated in specialized hospitals. In order to improve the strength of evidence provided in this article, further studies are necessary to evaluate the
55
impact of primary surgeries on facial growth. It appears imperative to standardize the variables in order to evaluate the outcomes with greater precision. Funding
A student grant from CAPES (Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior) was provided to Lı´via Monteiro Bichara. Competing interests
We do not have any competing interests to declare. Ethical approval
This research did not involve human subjects. Patient consent
Not required. References 1. Silva Filho OG, Normando AD, Capelozza Filho L. Mandibular morphology and spatial position in patients with clefts: intrinsic or iatrogenic? Cleft Palate Craniofac J 1992;29:369–75. 2. Mars M, Houston WJ. A preliminary study of facial growth and morphology in unoperated male unilateral cleft lip and palate subjects over 13 years of age. Cleft Palate J 1990;27:7–10. 3. Normando D, Silva Filho OG, Capelozza Filho L. Influence of surgery on maxillary growth in cleft lip and/or palate patients. J Craniomaxillofac Surg 1992;20:111–8. 4. Capelozza Filho L, Normando AD, Silva Filho OG. Isolated influences of lip and palate surgery on facial growth: comparison of operated and unoperated male adults with UCLP. Cleft Palate Craniofac J 1996;33:51– 6. 5. Kupucu MR, Gu¨rsu KG, Enacar A, Aras S. The effect of cleft lip repair on maxillary morphology in patients with unilateral complete cleft lip and palate. Plast Reconstr Surg 1995;97:1371–5. 6. 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. 7. Li Y, Shi B, Song QG, Zuo H, Zheng Q. Effects of lip repair on maxillary growth and facial soft tissue development in patients with a complete unilateral cleft of lip, alveolus and palate. J Craniomaxillofac Surg 2006;34:355–61. 8. Chen ZQ, Wu J, Chen RJ. Sagittal maxillary growth pattern in unilateral cleft lip and
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9.
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Bichara et al. palate patients with unrepaired cleft palate. J Craniofac Surg 2012;23:491–3. Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. 2009. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Introduction to meta-analysis. 1st ed. Chichester: John Wiley & Sons; 2009. De May A, Franck D, Cuylits N, Swennen G, Malevez C, Lejour M. Early one-stage repair of complete unilateral cleft lip and palate. J Craniofac Surg 2009;20:1723–8. Fudalef P, Obloj B, Miller Drabikowska D, Samarcew-Krawczak A, Dudkiewicz Z. Midfacial growth in a consecutive series of preadolescent children with complete unilateral cleft lip and palate following a one stage simultaneous repair. Cleft Palate Craniofac J 2008;45:667–73. Oberpi S, Chigurupati R, Vargervik K. Morphologic and management characteristics of individuals with unilateral cleft lip and palate who required maxillary advancement. Cleft Palate Craniofac J 2008;45:42–9. Nollet PJ, Katsaros C, Huyskens RW, Borstlap WA, Bronkhorst EM, Kuijpers-Jagtman AM. Cephalometric evaluation of long-term craniofacial development in unilateral cleft lip and palate patients treated with delayed hard palate closure. Int J Oral Maxillofac Surg 2008;37:123–30.
15. Diah E, Lo LJ, Huang CS, Sudjatmiko G, Susanto I, Chen YR. Maxillary growth of adult patients with unoperated cleft: answers to the debates. Plast Reconstr Aesthet Surg 2007;60:407–13. 16. Liao YF, Mars M. Long-term effects of lip repair on dentofacial morphology in patients with unilateral cleft lip and palate. Cleft Palate Craniofac J 2005;42:526–32. 17. Nandlal Utreja A, Tewari A, Chari PS. Effects of variation in the timing of palatal repair on sagittal craniofacial morphology in complete cleft lip and palate children. J Indian Soc Pedod Prev Dent 2000;18:153–60. 18. Smahel Z, Mu¨llerova Z, Nejedly A, Horak I. Changes in craniofacial development due to modifications of the treatment of unilateral cleft lip and palate. Cleft Palate Craniofac J 1998;35:240–7. 19. National Institute for Health and Care Excellence. The guidelines manual. London: NICE; 2009. 20. Masarei AG, Sell D, Habel A, Mars M, Sommerlad BC, Wade A, et al. The nature of feeding in infants with unrepaired cleft lip and/or palate compared with healthy noncleft infants. Cleft Palate Craniofac J 2007;44:321–8. 21. Lohmander A, Persson C. A longitudinal study of speech production in Swedish children with unilateral cleft lip and palate and two-stage palatal repair. Cleft Palate Craniofac J 2008;45:32–4.
22. Chapman KL, Hardin-Jones MA, Goldstein JA, Halter KA, Havlik RJ, Schulte J. Timing of palatal surgery and speech outcome. Cleft Palate Craniofac J 2008;45:297–308. 23. Holland S, Gabbay JS, Heller JB, O’Hara C, Hurwitz D, Ford MD, et al. Delayed closure of the hard palate leads to speech problems and deleterious maxillary growth. Plast Reconstr Surg 2007;119:1302–10. 24. Voshol IE, van Adrichem LN, van der Wal KG, Koudstaal MJ. Influence of pharyngeal flap surgery on maxillary outgrowth in cleft patients. Int J Oral Maxillofac Surg 2013;42:192–7. 25. Wong RW, Chau AC, Ha¨gg U. 3D CBCT McNamara’s cephalometric analysis in an adult southern Chinese population. Int J Oral Maxillofac Surg 2011;40:920–5.
Address: David Normando Department of Orthodontics Federal University of Para´ Boaventura da Silva St 567-1201 Bele´m Para´ 66 055-090 Brazil Tel.: +55 91 91446316 E-mails: [email protected], [email protected]
Systematic Review Cleft Lip and Palate
Impact of primary palatoplasty on the maxillomandibular sagittal relationship in patients with unilateral cleft lip and palate: a systematic review and meta-analysis
L. M. Bichara1, R. C. Arau´jo1, C. Flores-Mir2, D. Normando1 1 Orthodontics Department, Federal University of the State of Para´, Bele´m, Para´, Brazil; 2 School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
L. M. Bichara, R. C. Arau´jo, C. Flores-Mir, D. Normando:Impact of primary palatoplasty on the maxillomandibular sagittal relationship in patients with unilateral cleft lip and palate: a systematic review and meta-analysis. Int. J. Oral Maxillofac. Surg. 2015; 44: 50–56. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. The study objective was to evaluate, through a meta-analysis, the impact of primary palatoplasty on the sagittal maxillary and mandibular relationship among patients with complete unilateral cleft lip and palate (UCLP). Electronic database and hand searches were performed. Controlled clinical trials involving non-syndromic UCLP patients were included. Selected papers had to include a group of patients undergoing lip and palate repair and a group undergoing lip repair only. Data heterogeneity was demonstrated and individual means, standard deviations, and sample sizes were collected and summarized using a random effects model meta-analysis. Although six articles were selected for the systematic review, only four were included in the meta-analysis due to large discrepancies in the standard surgical protocol. Only one variable assessing the intermaxillary relationship (A point–nasion–B point; ANB), maxillary position (sella–nasion–A point; SNA), and mandibular position (sella– nasion–B point; SNB) was common among the selected studies. No significant differences in SNA and SNB were indentified between patients undergoing lip surgery alone and those undergoing lip and palate surgery. Evaluation of ANB showed a small statistical standard mean difference of 0.368. Impaired maxillary sagittal growth, observed in patients with UCLP, appears to be a basic consequence of lip surgical repair. Additional changes to the maxilla and mandible produced by palatal repair are minor. Methodologically rigorous controlled studies are needed to provide a stronger evidencebased basis for the surgical management of patients with UCLP.
0901-5027/01050 + 07
Keywords: cleft lip; cleft palate; craniofacial abnormalities; surgery; oral. Accepted for publication 12 August 2014 Available online 10 September 2014
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Primary palatoplasty in cleft lip and palate While primary repair of cleft lip and palate has not been shown to have a significant influence on mandibular morphology,1 maxillary growth deficiencies are very common in patients with unilateral cleft lip and palate (UCLP) who have undergone an early surgical intervention.2–4 The most frequently adopted surgical protocol in the treatment of cleft considers primary palatoplasty to be the major reason for maxillary growth impairment in subjects with UCLP. This is corroborated by several studies that have compared individuals with operated UCLP vs. unoperated patients.2–8 However, some studies4,5 have shown that the cumulative maxillary growth disturbance attributable to lip and palate repair is not significantly worse than that determined by lip repair alone. This suggests that lip repair may be the most important factor in maxillary growth disturbance in patients with UCLP. This comprehensive review was undertaken to review the available evidence regarding which of these surgical procedures has a greater effect on maxillary and mandibular growth. The answer to this clinically relevant question should help us to develop better treatment strategies for patients with cleft lip and palate thereby improving both functional and wellbeing outcomes. Methods
The PRISMA checklist9 was utilized as a reporting guide. This meta-analysis was registered at PROSPERO (the international prospective register of systematic reviews) under registration code CRD 42012003360. For eligibility, all articles had to have compared patients with complete UCLP who had undergone lip repair followed by palate repair to patients who had undergone lip surgery and no palate repair. Information sources
The databases used were PubMed, Cochrane Library, ScienceDirect, SciELO, and BIREME. A partial grey literature search was undertaken using Google Scholar. A hand search of the references of selected articles was also carried out to identify any article that could have been missed in the electronic database searches. Key words ‘cleft lip palate’ were searched in combination with ‘growth’, ‘surgery’, and ‘repair’. All references were managed using reference manager software (RefWorks) and duplicate hits were removed. Search limits were the following: controlled clinical trial, prospective or
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retrospective, systematic review, metaanalysis, with human samples, no language restriction, from 1960 to the end of the search on 4 September 2013.
software10 was used to perform the statistical analysis. All forest plots and funnel plots, as part of the meta-analysis, were also produced by the software.
Study selection
Risk of bias across studies
The search was performed independently by two researchers (LMB and RCA). If the title and/or abstract appeared to fulfil the inclusion criteria, the article was selected for full retrieval. All abstracts had to mention patients with UCLP and a group of patients undergoing lip surgery only and a group of patients undergoing both lip and palate surgery. Additionally, all studies had to have used a lateral cephalometric analysis. Once full articles were obtained, a second selection stage was executed in which the same set of criteria was applied. Confirmation of inclusion was sought in cases where the title/abstract was misleading due to the limited description contained within them.
A funnel plot was generated using the same software to verify publication bias.
Data collection process
Both researchers retrieved the required information separately. The information selected was then checked jointly and any disagreements resolved. If necessary a third author (DN) was involved in the final decision. The information retrieved from the final selection of articles included the following: author(s), year of publication, recruitment process (random, consecutive, convenience), sample size, inclusion criteria, country of origin, age at the time of surgery, error of method, sample matching (age, gender, origin, type of cleft), surgical technique, confounding factors, analysis, and the pertinent data. Risk of bias in individual studies
A methodology checklist was applied to analyze and quantify the risk of bias in the studies included. Summary measures
Individual means and standard deviations (SD) were collected from the lateral cephalometric measurements. Synthesis of results
The cephalometric measurements were pooled through several meta-analyses applying a random effects model. This modelling was used because of the expected heterogeneity of the samples included. Comprehensive Meta-Analysis
Results Study selection
Initially, 4995 articles were screened. Only 14 of them appeared to have fulfilled the inclusion criteria based on the information provided in the abstracts. Full copies of the articles were retrieved. After reading the full texts, eight articles were excluded because they did not match the primary inclusion criteria, i.e. a direct comparison of patients with UCLP undergoing surgery to the lip and palate with patients undergoing only lip repairs.11–18 Six papers were included in the qualitative synthesis,2,4,5–8 however only four were included in the meta-analysis4,5,7,8 (Fig. 1). The studies by Mars and Houston2 and Liao and Mars6 were excluded from the statistical analysis due to methodological issues. The first study did not record the mean age at lip repair of the sample; in the second study, the mean age at lip surgery was 7 years for patients who had undergone lip repair only and 1 year for patients who had undergone lip and palate repair. The studies included in the meta-analysis reported the following mean age at lip repair for the patients who had undergone a lip operation only (OL): 9.5 months,4 44 months,5 9 months,7 and before 24 months.8 The patients who had undergone lip and palate surgery (OLP) had lip surgery at a mean age of 5.5 months,4 27 months,5 9 months,7 and before 24 months.8 For this group, palate surgery was performed at 20 months,4 54 months,5 38 months,7 and before 36 months.8 Study characteristics
Sample sizes ranged from 10 subjects5 to 47 subjects.8 All patients included in the samples had UCLP. A group of patients who had undergone operations on both the lip and palate (OLP) was compared to another in which patients had undergone operations on the lip only (OL). The authors used different surgery techniques. For lip repair, the Millard technique,5,6,8 Tennison technique,6 or rotation-advancement7 was used. However, patients had sometimes presented to the treatment facility with a lip repair and no clear indication of the surgery technique
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Bichara et al.
Fig. 1. Flow chart showing the results of the search process.
that had been applied. In other cases, multiple techniques were used.4,6 Palate repair was done using the Oxford method,5 a vomerine mucoperiosteal flap and palatal mucoperiosteal flap,6 by mucoperiosteal pushback,7 or by two-flap technique.8 One article only informed that multiple techniques were used,2 and another4 provided no description of the technique used. Five studies4–8 stated that the patients in the samples had not undergone bone grafting surgery and one2 had no information on whether bone grafting surgery had been done or not. All articles evaluated lateral cephalometric measurements to assess maxillary and mandibular size and/or relative positioning. The lateral cephalograms analyzed were obtained at the age of 13.78 years,7 19.75 years,4 20.1 years,2,8 23 years,6 and 26.5 years5 for the OL group, and 14.64 years,7 16.4 years,2 18.58 years,4 19 years,6 20.8 years,5 and 20.41 years8 for the OLP group. The mean age at lip repair for the patients who had undergone surgery to the lip only (OL) in the selected studies was 9 months,7 9.5 months,4 44 months,5 and before 24 months.8 The patients who had undergone lip and palate surgery (OLP) had lip surgery
at a mean age of 5.5 months,4 9 months,7 27 months,5 and before 24 months.8 For this group, palate surgery was performed at 20 months, 38 months, 54 months, and before 36 months, respectively.
in any study. In three of the six studies evaluated in the systematic review, the intermaxillary relationship (A point– nasion–B point; ANB) was found to be significantly different between the OL and OLP groups.6–8
Risk of bias within studies
The methodology checklist (Table 1)19 showed an overall moderate risk of bias; some studies presented a higher risk of bias2,6 than others.4,5,7,8 Results of individual studies
Regarding the maxillary position (sella– nasion–A point (SNA) angle), Mars and Houston,2 Capelozza Filho et al.,4 Kupucu et al.,5 Li et al.,7 and Chen et al.8 showed no statistical difference between patients with UCLP who had undergone a lip repair only and those who had undergone both lip and palate surgery. Only Liao and Mars6 showed significant differences in maxillary position between these tested groups (P = 0.002). Mandibular position (sella– nasion–B point (SNB) angle) was not different between the OL and OLP groups
Risk of bias across studies
Despite the small number of articles included in the review, publication bias was tested. Article distribution in the funnel plot did not show asymmetry, and therefore no publication bias was found for SNA, SNB, or ANB angles (Fig. 2). Synthesis of results
Ultimately only four studies could be included in the meta-analysis. The necessary data for SNA, SNB, and ANB angles were extracted (Table 2) and pooled (Table 3). On meta-analysis, no significant differences were found for SNA and SNB angles between patients with UCLP who had lip and palate surgery (OLP) and those who had lip surgery only (OL), as demonstrated by the forest plots (Fig. 3). Pooled
Table 1. Methodology checklist for the articles selected for the systematic review (adopted from the National Institute for Health and Care Excellence). Articles
Quality criteria
Mars and Kupucu et al., Capelozza Liao and Li et al., Chen et al., Houston, 19902 19955 Filho et al., 19964 Mars, 20056 20067 20128 1. The study sample represents the population of interest with regard to key characteristics, sufficient to limit potential bias to the results a. Are the source population or the population of interest adequately described with Yes Yes Yes Yes respect to key characteristics? b. Are the sampling frame and recruitment adequately described, possibly including No Yes Yes Yes methods to identify the sample, period of recruitment, and place of recruitment? c. Are inclusion and exclusion criteria adequately described? Yes Yes Yes Yes d. Is participation in the study by eligible individuals adequate? Yes Yes Yes Yes e. Is the baseline study sample adequately described with respect to key characteristics? No Yes Yes Yes 2. The prognostic factor of interest is adequately measured in study participants, sufficient to limit potential bias a. Is a clear definition or description of the prognostic factor(s) measured provided? Yes Yes b. Are continuous variables reported, or appropriate cut-off points (that is, not dataNo Yes dependent) used? c. Are the prognostic factor measured and the method of measurement valid and Yes Yes reliable enough to limit misclassification bias? d. Are complete data for prognostic factors available for an adequate proportion of the No Yes study sample? e. Are the method and setting of measurement the same for all study participants? Yes Yes f. Are appropriate methods employed if imputation is used for missing data on No Unclear prognostic factors?
Yes
Yes
Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes
Yes Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes Unclear
Yes No
Yes Unclear
Yes Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes Yes
No Yes Unclear Yes
Yes Yes
Unclear
Unclear Unclear
Unclear
Unclear Unclear
No No
Unclear Unclear
Unclear Unclear
the presentation of invalid results Yes Yes Yes Yes Yes Yes
No Yes
Yes Yes
Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
4. Important potential confounders are appropriately accounted for, limiting potential bias with respect to the prognostic a. Are all important confounders, including treatments, measured? Are clear definitions No Yes of the important confounders measured provided? b. Is measurement of all important confounders valid and reliable? No Yes c. Are the method and setting of measurement of confounders the same for all study Unclear Yes participants? d. Are appropriate methods employed if imputation is used for missing data on Unclear Unclear confounders? e. Are important potential confounders accounted for in the study design? No Unclear f. Are important potential confounders accounted for in the analysis (that is, appropriNo Unclear ate adjustment)?
Yes Yes Yes
factor of interest Yes No
Yes Yes Yes
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Yes No
Primary palatoplasty in cleft lip and palate
Yes Yes
3. The outcome of interest is adequately measured in study participants, sufficient to limit potential bias a. Is a clear definition of the outcome of interest provided, including duration of followYes Yes up? b. Are the outcome that was measured and the method of measurement valid and Yes Yes reliable enough to limit misclassification bias? c. Are the method and setting of measurement the same for all study participants? Yes Yes
5. The statistical analysis is appropriate for the design of the study, limiting potential for a. Is the presentation of data sufficient to assess the adequacy of the analysis? b. Where several prognostic factors are investigated, is the strategy for model building appropriate and based on a conceptual framework or model? c. Is the selected model adequate for the design of the study? d. Is there any selective reporting of results? e. Are only pre-specified hypotheses investigated in the analyses?
Yes
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Bichara et al.
Fig. 2. Funnel plots showing no publication bias for SNA, SNB, or ANB.
Table 2. Sample size, mean values, and standard deviations for SNA, SNB, and ANB of the UCLP groups who had only lip surgery (OL) and lip and palate surgery (OLP). OLP
OL
Study
SNB
SNA Kupucu et al., 19955 Capelozza Filho et al., 19964 Li et al., 20067 Chen et al., 20128
ANB
SNA
SNB
ANB
n
Mean
SD
Mean
SD
Mean
SD
n
Mean
SD
Mean
SD
Mean
SD
10 23 35 15
74.7 77.2 73.64 79.25
3 3.8 4.5 4.9
74.7 77.2 77.34 78.98
3.1 3.9 4.9 3.2
0 0 3.7 0.2
2.2 3.2 4.0 4.3
30 35 47 16
76.3 76 73.3 75.4
3.5 5.6 5.5 6.5
76.9 76.8 75.1 79.6
4.7 3.8 4.6 6.4
0.5 0.8 1.81 4.17
3.8 4.6 3.1 5.1
SD, standard deviation; SNA, sella–nasion–A point; SNB, sella–nasion–B point; ANB, A point–nasion–B point; UCLP, unilateral cleft lip and palate. Table 3. SNA, SNB, and ANB: differences between means, the P-value for each comparison, the weight of every study, and the pooled P-value.
Std diff mean Kupucu et al., 19955 Capelozza Filho et al., 19964 Li et al., 20067 Chen et al., 20128
SNB
SNA
Study
P-value
Weight %
0.47 0.24
0.201 0.37
18.83 28.14
0.05 0.64
0.813 0.080
34.18 18.85
Pooled P-value
0.532
Std diff mean
P-value
Weight %
0.503 0.104
0.173 0.698
19.33 27.95
0.45 0.135
0.046 0.709
32.72 20.01
ANB Pooled P-value
0.795
Std diff mean
P-value
Weight %
0.14 0.19
0.695 0.469
15.58 28.76
0.40 0.92
0.104 0.015
41.09 14.56
Pooled P-value
0.012
SNA, sella–nasion–A point; SNB, sella–nasion–B point; ANB, A point–nasion–B point; Std Diff Mean, standard mean difference.
Fig. 3. Forest plots representing results for ANB, SNA and SNB angle of all studies included in this meta-analysis and the pooled result.
data from all articles for the ANB angle showed statistically significant differences between the OL and OLP groups (Fig. 3). Discussion
A very common characteristic of patients with UCLP who have undergone primary reconstructive surgery is a significant maxillary retrusion. The surgical protocol for patients with UCLP usually advocates primary palatal surgery after lip repair. This approach is based on the hypothesis
that palatal surgery is the main aetiological factor in maxillary retrusion, therefore palatal repair is postponed. As well as the obvious immediate impact of lip repair on facial aesthetics, palate repair performed at a younger age is crucial for feeding,20 speech,21,22 and breathing23 functions. The treatment of subjects with UCLP is complex, multidisciplinary, and can be lengthy.24 The reported consequences of lip and palate repair on the craniofacial development of patients with cleft remain
controversial. Problems such as sampling, availability of a control group of patients who have not undergone primary surgery, the lack of standardized surgical procedures (including age at surgery), the different methods of assessment, and ethical issues have hindered the possibility of drawing sound scientifically-based conclusions. After a systematic search to identify related articles published since 1960, only six papers were selected for this systematic review/meta-analysis. Of these, only four4–8 were included in the
Primary palatoplasty in cleft lip and palate meta-analysis. Heterogeneity was assumed as they presented different population origins, age ranges, and surgical techniques. Mars and Houston2 and Liao and Mars6 had the same sample origin but very different mean ages from one group to another. Lateral cephalometric radiographs were utilized in all studies; however different cephalometric analyses were employed. Therefore, only one variable measuring maxillary sagittal positioning (SNA angle), one concerning mandibular positioning (SNB angle), and one describing the maxillomandibular relationship (ANB angle) were common to every study. All studies in the meta-analysis were nonrandomized retrospective clinical trials. Despite the lack of scientific conclusions regarding the best timing for palatal surgery in patients with UCLP, it is strongly believed that a child’s quality of life is improved by palatal repair at a younger age.13–15 Therefore it is considered unethical to leave a child without this treatment option. Small sample sizes further hindered the power of the meta-analysis. Although having similar stated results, the conclusions reported in the selected studies were controversial. Since there was no difference between non-cleft individuals and subjects with UCLP with only lip repair (OL), Mars and Houston2 concluded that lip surgery would not be detrimental to maxillary growth. This was despite their findings of no statistical differences between OL and OLP patients. Liao and Mars6 found statistical differences for SNA in a comparison of Sri Lankan patients with UCLP who had undergone lip and palate surgery and patients who had undergone lip surgery only, supporting the previous conclusions. However, the first study did not record the age at lip repair and in the second study the mean age at lip surgery was 7 years for patients operated only on the lip (OL) and 1 year for patients operated on the lip and palate (OLP). Therefore, neither study was considered for the meta-analysis since this difference in surgery timing could have caused a significant bias. The pooled result for the SNA angle of the four studies included in the meta-analysis4–8 showed no statistical difference between OLP patients and OL patients. Individually, none of these studies reported a significant difference between OL and OLP patients. These findings indicate that lip surgery may be the most important factor in the impairment of maxillary growth in UCLP. The A point, measured in all studies as representing the anterior maxilla
projection, should be considered with caution due to malformations in the anterior region of the maxilla brought about by the cleft, which make it very difficult to locate properly. The pooled data for the SNB angle from the articles in the meta-analysis showed no significant differences for mandibular position, meaning no detrimental effects for OLP patients. As stated for the SNA angle, no report of a significant difference between OL and OLP patients was found for the SNB angle. Overall, a significant difference in ANB angle was found between the groups. Despite the fact that no statistical differences were found in three of the primary studies included,4,5,7 Chen et al.8 showed a statistical difference between patients with UCLP who had undergone a lip and palate operation compared to those who were operated only on the lip. However, the standard mean difference here was only 0.368, probably a false-positive finding or a difference without clinical significance. This meta-analysis sheds some light on the main cause of impaired maxillary growth in patients with UCLP operated on the lip and palate. However, the cephalometric variables examined do not include all skeletal facial features of the operated patients with UCLP. The size of the maxilla and mandible, vertical dimensions, and soft tissue profile could not be analyzed due to a lack of available data. Limitations
Cephalometric evaluation of patients with craniofacial deformities is not always accurate. Some features are very hard to access, such as the cephalometric A point in patients with UCLP, where the maxillary anterior region is damaged by the cleft. The use of cone beam computed tomography (CBCT) images would probably be helpful in identifying and adapting better landmarks for patients with UCLP.25 Moreover, the data presented in the studies enrolled in the meta-analysis were collected retrospectively. There is no precise information on the timing of primary surgeries, the surgical technique employed, the skill and experience of the surgeon, and any secondary surgeries, such as primary alveolar reconstruction. There are ethical reasons for some of these methodological limitations, since this type of study is usually conducted in developing countries where some patients are not treated in specialized hospitals. In order to improve the strength of evidence provided in this article, further studies are necessary to evaluate the
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impact of primary surgeries on facial growth. It appears imperative to standardize the variables in order to evaluate the outcomes with greater precision. Funding
A student grant from CAPES (Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior) was provided to Lı´via Monteiro Bichara. Competing interests
We do not have any competing interests to declare. Ethical approval
This research did not involve human subjects. Patient consent
Not required. References 1. Silva Filho OG, Normando AD, Capelozza Filho L. Mandibular morphology and spatial position in patients with clefts: intrinsic or iatrogenic? Cleft Palate Craniofac J 1992;29:369–75. 2. Mars M, Houston WJ. A preliminary study of facial growth and morphology in unoperated male unilateral cleft lip and palate subjects over 13 years of age. Cleft Palate J 1990;27:7–10. 3. Normando D, Silva Filho OG, Capelozza Filho L. Influence of surgery on maxillary growth in cleft lip and/or palate patients. J Craniomaxillofac Surg 1992;20:111–8. 4. Capelozza Filho L, Normando AD, Silva Filho OG. Isolated influences of lip and palate surgery on facial growth: comparison of operated and unoperated male adults with UCLP. Cleft Palate Craniofac J 1996;33:51– 6. 5. Kupucu MR, Gu¨rsu KG, Enacar A, Aras S. The effect of cleft lip repair on maxillary morphology in patients with unilateral complete cleft lip and palate. Plast Reconstr Surg 1995;97:1371–5. 6. 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. 7. Li Y, Shi B, Song QG, Zuo H, Zheng Q. Effects of lip repair on maxillary growth and facial soft tissue development in patients with a complete unilateral cleft of lip, alveolus and palate. J Craniomaxillofac Surg 2006;34:355–61. 8. Chen ZQ, Wu J, Chen RJ. Sagittal maxillary growth pattern in unilateral cleft lip and
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Bichara et al. palate patients with unrepaired cleft palate. J Craniofac Surg 2012;23:491–3. Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. 2009. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Introduction to meta-analysis. 1st ed. Chichester: John Wiley & Sons; 2009. De May A, Franck D, Cuylits N, Swennen G, Malevez C, Lejour M. Early one-stage repair of complete unilateral cleft lip and palate. J Craniofac Surg 2009;20:1723–8. Fudalef P, Obloj B, Miller Drabikowska D, Samarcew-Krawczak A, Dudkiewicz Z. Midfacial growth in a consecutive series of preadolescent children with complete unilateral cleft lip and palate following a one stage simultaneous repair. Cleft Palate Craniofac J 2008;45:667–73. Oberpi S, Chigurupati R, Vargervik K. Morphologic and management characteristics of individuals with unilateral cleft lip and palate who required maxillary advancement. Cleft Palate Craniofac J 2008;45:42–9. Nollet PJ, Katsaros C, Huyskens RW, Borstlap WA, Bronkhorst EM, Kuijpers-Jagtman AM. Cephalometric evaluation of long-term craniofacial development in unilateral cleft lip and palate patients treated with delayed hard palate closure. Int J Oral Maxillofac Surg 2008;37:123–30.
15. Diah E, Lo LJ, Huang CS, Sudjatmiko G, Susanto I, Chen YR. Maxillary growth of adult patients with unoperated cleft: answers to the debates. Plast Reconstr Aesthet Surg 2007;60:407–13. 16. Liao YF, Mars M. Long-term effects of lip repair on dentofacial morphology in patients with unilateral cleft lip and palate. Cleft Palate Craniofac J 2005;42:526–32. 17. Nandlal Utreja A, Tewari A, Chari PS. Effects of variation in the timing of palatal repair on sagittal craniofacial morphology in complete cleft lip and palate children. J Indian Soc Pedod Prev Dent 2000;18:153–60. 18. Smahel Z, Mu¨llerova Z, Nejedly A, Horak I. Changes in craniofacial development due to modifications of the treatment of unilateral cleft lip and palate. Cleft Palate Craniofac J 1998;35:240–7. 19. National Institute for Health and Care Excellence. The guidelines manual. London: NICE; 2009. 20. Masarei AG, Sell D, Habel A, Mars M, Sommerlad BC, Wade A, et al. The nature of feeding in infants with unrepaired cleft lip and/or palate compared with healthy noncleft infants. Cleft Palate Craniofac J 2007;44:321–8. 21. Lohmander A, Persson C. A longitudinal study of speech production in Swedish children with unilateral cleft lip and palate and two-stage palatal repair. Cleft Palate Craniofac J 2008;45:32–4.
22. Chapman KL, Hardin-Jones MA, Goldstein JA, Halter KA, Havlik RJ, Schulte J. Timing of palatal surgery and speech outcome. Cleft Palate Craniofac J 2008;45:297–308. 23. Holland S, Gabbay JS, Heller JB, O’Hara C, Hurwitz D, Ford MD, et al. Delayed closure of the hard palate leads to speech problems and deleterious maxillary growth. Plast Reconstr Surg 2007;119:1302–10. 24. Voshol IE, van Adrichem LN, van der Wal KG, Koudstaal MJ. Influence of pharyngeal flap surgery on maxillary outgrowth in cleft patients. Int J Oral Maxillofac Surg 2013;42:192–7. 25. Wong RW, Chau AC, Ha¨gg U. 3D CBCT McNamara’s cephalometric analysis in an adult southern Chinese population. Int J Oral Maxillofac Surg 2011;40:920–5.
Address: David Normando Department of Orthodontics Federal University of Para´ Boaventura da Silva St 567-1201 Bele´m Para´ 66 055-090 Brazil Tel.: +55 91 91446316 E-mails: [email protected], [email protected]
