Abstract
Objectives
To analyse the effect of first and second premolar extractions on eruption space for upper and lower third molars and on third molar position and angulation during orthodontic treatment.
Methods
The sample consisted of 296 patients of which 218 patients were orthodontically treated without extraction and 78 patients with extraction of first or second premolars. The eruption space for third molars was measured on pre– and posttreatment lateral cephalograms, whereas the angulation, vertical position, the relation with the mandibular canal and the mineralization status of third molars were evaluated using pre– and posttreatment panoramic radiographs. All data were statistically analyzed.
Results
The increase in eruption space and the change in vertical position of upper and lower third molars significantly differed between patients treated with and without premolar extractions, whereas the change in angulation, relationship with the mandibular canal and mineralization status of the third molars did not significantly differ between patients treated with and without premolar extractions.
Conclusions
The retromolar space and the position of third molars significantly change during orthodontic treatment in growing patients. Premolar extractions have a positive influence on the eruption space and vertical position of third molars, whereas they do not influence the angular changes of third molars. Due to the retrospective character of the study, these conclusions should be carefully considered. Further prospective research is necessary for better insights into this complex topic.
Clinical significance
This study stresses the importance of considering the possible effects of orthodontic treatment on third molars during treatment planning.
1
I ntroduction
Accounting for 98% of all impactions, third molars are the most frequently impacted teeth . A recent meta-analysis of 49 studies, involving 83 484 individuals reported a worldwide third molar impaction rate of 24.40% . Different factors such as morphology, mesiodistal width, unfavorable uprighting and path of eruption, have been associated with third molar impaction . However, the main reason for third molar impaction is assumed to be a lack of retromolar space , which was reported by Björk et al. as limited in 90% of third molar impaction cases, . Retromolar space depends in the upper jaw on the growth of the maxillary tuberosity along with alveolar growth and the mesial drift of the upper first molars . In the lower jaw, it depends on the resorption at the anterior border of the mandibular ramus and the direction in which the teeth erupt during the functional phase of eruption . Furthermore, Björk identified several factors linked with the impaction of lower third molars : a vertical direction of condylar growth, a reduced mandibular length, a backward-directed eruption of the mandibular dentition and a retarded maturation of the third molars . The more anteriorly the posterior teeth erupt, the more the retromolar space will increase . Condylar growth in a predominantly vertical direction is associated with reduced resorption at the anterior aspect of the mandibular ramus and forward growth rotation of the mandible, whereas more backward-directed growth at the condyles is associated with increased resorption at the anterior border of the mandibular ramus and a posterior growth rotation .
Besides natural growth, the retromolar space is also influenced by orthodontic treatment . Distalization of the upper first molars has a negative influence on the space available for the eruption of upper third molars , whereas orthodontic treatment carried out with extraction therapy is often found to improve the chance of successful third molar eruption. Several authors reported that most lower and upper third molars erupted successfully after the extraction of second molars . Richardson and Richardson as well as De-la Rosa-Gay et al. also found that the less developed the third molar is at the time of second molar extraction, the higher the chances are for its eruption . Bayram et al., Livas et al. and Halicioglu et al. investigated the effect of first molar extractions on third molar eruption . They concluded that the extraction of first permanent molars considerably reduces the frequency of third molar impaction. Consistent with these findings, several studies have shown that orthodontic treatment involving premolar extractions has a positive influence on the development and position of third molars by increasing the eruption space for the third molar due to mesial movement of the first and second molars during space closure.
However, as previously mentioned, third molar impaction has been associated with other factors, such as an unfavorable inclination of the third molar . During development, third molars permanently change their inclination and undergo important pre-eruptive rotational movements , preventing impaction of the third molar. Several authors reported that orthodontic treatment involving premolar extraction significantly improved third molar angulation due to an increase in retromolar space , whereas other authors did not find significant differences .
Although several studies on the effect of premolar extractions on third molars are published, the sample sizes were often small, a lot of studies did not distinguish between first and second premolar extraction, only considered the effect of first premolar extractions or only investigated lower third molars. Therefore, this retrospective study aimed at investigating the effect of both first and second premolar extraction during orthodontic treatment on the space available for both upper and lower third molars. Furthermore, we investigated the possible change in angulation and vertical position of third molars in patients treated with and without premolar extractions. Additionally, we evaluated the relation between the lower third molars and the alveolar nerve before and after treatment.
2
Materials and methods
2.1
Materials
The sample consisted of pre- and posttreatment panoramic radiographs and lateral cephalograms of growing patients, orthodontically treated with or without premolar extractions and with radiographic evidence of at least one third molar. Patients with craniofacial disorders, agenesis or missing teeth before the start of treatment were not included. All of the included patients were treated in the Department of Orthodontics of the University Hospitals Leuven, Leuven, Belgium and finished their treatment between January 2008 and December 2014. The cephalometric radiographs as well as the panoramic radiographs were generated by a Veraview, Morita (Kyoto, Japan) or a Cranex Tome, Soredex (Tuusula, Finland). All radiographs were stored as DICOM files. Patients with insufficient radiographic image quality were excluded (n = 6). Because of overlap of the left and right side on a cephalometric radiograph, patients with asymmetrical premolar extractions were excluded (n = 18). It has been reported that the space available for upper third molars might be influenced by orthodontic distalization appliances . Therefore, we also excluded 188 patients in the non-extraction group and 29 patients in the extraction group who were treated with fixed appliances together with a distalization appliance, such as headgear. The final sample consisted of 296 patients, of which 116 patients were treated with functional and fixed appliances and 24 patients had expansion of the upper jaw before treatment with fixed appliances. Of the 296 patients, 218 patients (103 males, 115 females) were treated without extractions of premolars and 78 patients (37 males, 41 females) were treated with extractions of first or second premolars. Of the 78 patients treated with extractions, 23 patients only had extractions in the upper jaw, 7 patients only had extractions in the lower jaw and 48 patients had extractions in both jaws. In the upper jaw, the first premolar was extracted in 54 patients, whereas the second premolar was extracted in 17 patients. In the lower jaw, the first premolar was extracted in 25 patients and the second premolar in 30 patients.
2.2
Methods
On the lateral cephalograms, the mandibular plane angle and the space available for the upper and lower third molar was measured ( Fig. 1 ). According to the mandibular plane angle, defined by Steiner as the SN-GoGn angle , the sample was divided into three groups: normal growth cases (27° < SN-GoGn < 37°), open growth cases (SN-GoGn > 37°) and closed growth cases (SN-GoGn < 27°). The eruption space in the upper jaw was defined as the distance from the pterygoid vertical (PTV) to the distal surface of the upper first molar (M1) along the occlusal plane (PTV-M1). The eruption space in the lower jaw was defined as the distance from Ricketts’ Xi-point to the distal surface of the lower second molar crown along the occlusal plane (Xi-M2). Both measurements rely on the cephalometric analysis of Ricketts . Additionally, the eruption space in the lower jaw was also scored on panoramic radiographs using the classification suggested by Pell & Gregory (horizontal classification; stages 1, 2 and 3) ( Fig. 2 ). The angulation of the third molars was scored on the panoramic radiographs, the upper third molar using the Archer’s classification ( Fig. 3 ) and the lower based on Winter’s classification ( Fig. 4 ). Additionally, the angle between the long axis of the second and third molar (M2^M3) was measured. In case the third molar had a distoangular inclination, the angle was taken as a positive value in the upper jaw and as a negative value in the lower jaw, whereas a mesioangular inclination was classified as a negative angle in the upper jaw and a positive angle in the lower jaw. The vertical position of the third molars compared to the adjacent second molar was also scored on the panoramic radiographs, in the upper jaw using Archer’s classification ( Fig. 5 ) and in the lower jaw using the classification suggested by Pell & Gregory (vertical classification; stages 1, 2 and 3) ( Fig. 2 ). Furthermore, the relation between lower third molars and the mandibular canal was evaluated by the classification suggested by Whaites . A close relationship between the roots of the lower third molar and the mandibular canal was assumed when one of the following landmarks were seen on the panoramic radiograph: loss of tramlines, narrowing of the tramlines, alteration of direction of the inferior canal at root apex, and a radiolucent band across the roots ( Fig. 6 ). Finally, Demirjian’s classifications was used to examine the mineralization status of the third molars ( Fig. 7 ).
2.3
Statistical analysis
All measurements were performed in a scoring program written in MATLAB™ which randomized the order of DICOM images and saved the results as comma separated value files . This approach minimized bias, reduced the possibility of man made errors and meanwhile facilitated efficient data handling and statistical analyses.
A second observer randomly reassessed 20% of the radiographs for all mentioned classifications to determine the inter-observer variability, whereas the main observer also randomly reassessed 20% of the radiographs to determine intra-observer variability. Intra-class correlation (ICC) and the standard error of measurement (SEM) were calculated for the continuous measurements (PTV-M1, Xi-M2, M2^M3). Weighted kappa was used for the ordinal measurements and a simple kappa was calculated for the nominal measurements.
For the comparison of nominal, ordinal and continuous variables between patients treated with and without premolar extractions, Fisher’s exact tests and Mann-Whitney U tests were used. Associations between ordinal and/or continuous variables were evaluated with Spearman correlations. To evaluate the changes over time for the continuous measurement, a linear model for longitudinal measurements with an unstructured covariance matrix was used. Age and gender were added as confounders. The growth pattern was added as a time-varying factor in the analysis of Xi-M2. A similar approach is followed for the ordinal data and the nominal scores, but the linear model is replaced with a logistic regression model using generalized estimating equations (GEE) to handle the correlation between both time points and teeth. P-values smaller than 0.05 are considered statistically significant. All analyses have been performed using SAS software, version 9.4 of the SAS System for Windows. Copyright © 2016 SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA.
This study was registered and approved by the medical ethics committee of the University Hospitals Leuven (registration number S56447).
2
Materials and methods
2.1
Materials
The sample consisted of pre- and posttreatment panoramic radiographs and lateral cephalograms of growing patients, orthodontically treated with or without premolar extractions and with radiographic evidence of at least one third molar. Patients with craniofacial disorders, agenesis or missing teeth before the start of treatment were not included. All of the included patients were treated in the Department of Orthodontics of the University Hospitals Leuven, Leuven, Belgium and finished their treatment between January 2008 and December 2014. The cephalometric radiographs as well as the panoramic radiographs were generated by a Veraview, Morita (Kyoto, Japan) or a Cranex Tome, Soredex (Tuusula, Finland). All radiographs were stored as DICOM files. Patients with insufficient radiographic image quality were excluded (n = 6). Because of overlap of the left and right side on a cephalometric radiograph, patients with asymmetrical premolar extractions were excluded (n = 18). It has been reported that the space available for upper third molars might be influenced by orthodontic distalization appliances . Therefore, we also excluded 188 patients in the non-extraction group and 29 patients in the extraction group who were treated with fixed appliances together with a distalization appliance, such as headgear. The final sample consisted of 296 patients, of which 116 patients were treated with functional and fixed appliances and 24 patients had expansion of the upper jaw before treatment with fixed appliances. Of the 296 patients, 218 patients (103 males, 115 females) were treated without extractions of premolars and 78 patients (37 males, 41 females) were treated with extractions of first or second premolars. Of the 78 patients treated with extractions, 23 patients only had extractions in the upper jaw, 7 patients only had extractions in the lower jaw and 48 patients had extractions in both jaws. In the upper jaw, the first premolar was extracted in 54 patients, whereas the second premolar was extracted in 17 patients. In the lower jaw, the first premolar was extracted in 25 patients and the second premolar in 30 patients.
2.2
Methods
On the lateral cephalograms, the mandibular plane angle and the space available for the upper and lower third molar was measured ( Fig. 1 ). According to the mandibular plane angle, defined by Steiner as the SN-GoGn angle , the sample was divided into three groups: normal growth cases (27° < SN-GoGn < 37°), open growth cases (SN-GoGn > 37°) and closed growth cases (SN-GoGn < 27°). The eruption space in the upper jaw was defined as the distance from the pterygoid vertical (PTV) to the distal surface of the upper first molar (M1) along the occlusal plane (PTV-M1). The eruption space in the lower jaw was defined as the distance from Ricketts’ Xi-point to the distal surface of the lower second molar crown along the occlusal plane (Xi-M2). Both measurements rely on the cephalometric analysis of Ricketts . Additionally, the eruption space in the lower jaw was also scored on panoramic radiographs using the classification suggested by Pell & Gregory (horizontal classification; stages 1, 2 and 3) ( Fig. 2 ). The angulation of the third molars was scored on the panoramic radiographs, the upper third molar using the Archer’s classification ( Fig. 3 ) and the lower based on Winter’s classification ( Fig. 4 ). Additionally, the angle between the long axis of the second and third molar (M2^M3) was measured. In case the third molar had a distoangular inclination, the angle was taken as a positive value in the upper jaw and as a negative value in the lower jaw, whereas a mesioangular inclination was classified as a negative angle in the upper jaw and a positive angle in the lower jaw. The vertical position of the third molars compared to the adjacent second molar was also scored on the panoramic radiographs, in the upper jaw using Archer’s classification ( Fig. 5 ) and in the lower jaw using the classification suggested by Pell & Gregory (vertical classification; stages 1, 2 and 3) ( Fig. 2 ). Furthermore, the relation between lower third molars and the mandibular canal was evaluated by the classification suggested by Whaites . A close relationship between the roots of the lower third molar and the mandibular canal was assumed when one of the following landmarks were seen on the panoramic radiograph: loss of tramlines, narrowing of the tramlines, alteration of direction of the inferior canal at root apex, and a radiolucent band across the roots ( Fig. 6 ). Finally, Demirjian’s classifications was used to examine the mineralization status of the third molars ( Fig. 7 ).
2.3
Statistical analysis
All measurements were performed in a scoring program written in MATLAB™ which randomized the order of DICOM images and saved the results as comma separated value files . This approach minimized bias, reduced the possibility of man made errors and meanwhile facilitated efficient data handling and statistical analyses.
A second observer randomly reassessed 20% of the radiographs for all mentioned classifications to determine the inter-observer variability, whereas the main observer also randomly reassessed 20% of the radiographs to determine intra-observer variability. Intra-class correlation (ICC) and the standard error of measurement (SEM) were calculated for the continuous measurements (PTV-M1, Xi-M2, M2^M3). Weighted kappa was used for the ordinal measurements and a simple kappa was calculated for the nominal measurements.
For the comparison of nominal, ordinal and continuous variables between patients treated with and without premolar extractions, Fisher’s exact tests and Mann-Whitney U tests were used. Associations between ordinal and/or continuous variables were evaluated with Spearman correlations. To evaluate the changes over time for the continuous measurement, a linear model for longitudinal measurements with an unstructured covariance matrix was used. Age and gender were added as confounders. The growth pattern was added as a time-varying factor in the analysis of Xi-M2. A similar approach is followed for the ordinal data and the nominal scores, but the linear model is replaced with a logistic regression model using generalized estimating equations (GEE) to handle the correlation between both time points and teeth. P-values smaller than 0.05 are considered statistically significant. All analyses have been performed using SAS software, version 9.4 of the SAS System for Windows. Copyright © 2016 SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA.
This study was registered and approved by the medical ethics committee of the University Hospitals Leuven (registration number S56447).
3
Results
The descriptive data are summarized in Table 1 . The orthodontic treatment took significantly more time for patients treated with extractions of premolars compared to patients treated without extractions (p = 0.011). The age at start and end of treatment was not significantly different between both groups (p = 0.791 and p = 0.143, respectively). General outcome information and pairwise comparisons for all mentioned classifications are summarized in Table 2 .
| Non extraction (N = 218) | Extraction (N = 78; PM1 = 79, PM2 = 47) | p-value | ||
|---|---|---|---|---|
| Gender (n/N (%)) | Male | 103/218 (47.2) | 37/78 (47.4) | 0.977 |
| Female | 115/218 (52.8) | 41/78 (52.6) | ||
| Age pretreatment (years) | Mean | 12.9 | 13.1 | 0.791 |
| Range | 7.9–18.2 | 7.3–19.3 | ||
| Age post-treatment (years) | Mean | 15.5 | 16.0 | 0.143 |
| Range | 12.2–20.3 | 12.5–21.3 | ||
| Treatment (years) | Mean | 2.6 | 2.9 | 0.011 * |
| Angle classification (n/N (%)) | Class I | 92/218 (42.2) | 29/78 (37.2) | 0.657 |
| Class II | 116/218 (53.2) | 44/78 (56.4) | ||
| Class III | 10/218 (4.6) | 5/78 (6.4) |
| Variable | Measurement | NE | PM1 | PM2 | Pairwise comparisons | ||
|---|---|---|---|---|---|---|---|
| p-value | p-value | p-value | |||||
| NE vs PM1 | NE vs PM2 | PM1 vs PM2 | |||||
| PTV-M1 | start of treatment | ||||||
| mean (mm) | 16.7 | 17 | 17.4 | ||||
| median (mm) | 16.3 | 17 | 17.6 | ||||
| IQR (mm) | (14.6;19.1) | (15.0;19.2) | (16.8;18.8) | ||||
| >18 mm (%) | 30.6 | 38.8 | 31.3 | 1 0.310 | 1 1.000 | 1 0.767 | |
| end of treatment | |||||||
| mean (mm) | 18.8 | 22 | 22.5 | ||||
| median (mm) | 18.9 | 21.8 | 22.9 | ||||
| IQR (mm) | (16.4;21.0) | (19.3;24.2) | (21.2;23.9) | ||||
| >18 mm (%) | 58.9 | 83.7 | 100 | 1 <0.001 * | 1 <0.001 * | 1 0.184 | |
| change | 2 <0.001 * | 2 <0.001 * | 2 0.889 | ||||
| mean (mm) | 2.1 | 4.9 | 5.6 | ||||
| median (mm) | 1.7 | 4.5 | 5.1 | ||||
| IQR (mm) | (−0.9;4.6) | (1.6;8.7) | (2.9;8.2) | ||||
| PTV-M1 at end >18 mm when at start <18 mm (%) | 58.6 | 83.3 | 100 | 1 0.012 * | 1 0.007 * | 1 0.300 | |
| Xi-M2 | start of treatment | ||||||
| mean (mm) | 17.8 | 16.4 | 17.2 | ||||
| median (mm) | 17.4 | 15.1 | 16.8 | ||||
| IQR (mm) | (15.6;19.8) | (13.5;18.8) | (14.6;19.2) | ||||
| >25 mm (%) | 2.6 | 0 | 0 | 1 1.000 | 1 1.000 | 1 1.000 | |
| end of treatment | |||||||
| mean (mm) | 22.6 | 24.6 | 25.4 | ||||
| median (mm) | 22.7 | 24.1 | 25.1 | ||||
| IQR (mm) | (20.0;24.6) | (21.8;26.6) | (22.5;27.9) | ||||
| >25 mm (%) | 21.3 | 48 | 55.2 | 1 0.006 * | 1 <0.001 * | 1 0.785 | |
| change | 2 <0.0001 * | 2 <0.0001 * | 2 0.869 | ||||
| mean (mm) | 5 | 7.9 | 6.9 | ||||
| median (mm) | 5.1 | 7.3 | 6.3 | ||||
| IQR (mm) | (1.7;7.9) | (5.6;9.9) | (4.2;9.1) | ||||
| PTV-M1 at end >25 mm when at start <25 mm (%) | 20.5 | 45.8 | 55.2 | 1 0.009 * | 1 0.001 * | 1 0.586 | |
| PGH | start of treatment | ||||||
| PGH-1 (%) | 2 | 6 | 3 | ||||
| PGH-2 (%) | 28 | 27 | 23 | ||||
| PGH-3 (%) | 70 | 67 | 74 | ||||
| end of treatment | |||||||
| PGH-1 (%) | 23 | 47 | 77 | ||||
| PGH-2 (%) | 66 | 49 | 23 | ||||
| PGH-3 (%) | 11 | 4 | 0 | ||||
| change | 3 0.011 * | 3 <0.0001 * | 3 0.001 * | ||||
| Archer (inclination) | start of treatment | ||||||
| stage 1 (%) | 8 | 9 | 16 | ||||
| stage 2 (%) | 16 | 8 | 7 | ||||
| stage 3 (%) | 75 | 83 | 74 | ||||
| stage 4,5,6 and 7 (%) | 1 | 0 | 3 | ||||
| end of treatment | |||||||
| stage 1 (%) | 12 | 5 | 6 | ||||
| stage 2 (%) | 20 | 13 | 13 | ||||
| stage 3 (%) | 66 | 82 | 81 | ||||
| stage 4,5,6 and 7 (%) | 2 | 0 | 0 | ||||
| change | |||||||
| stage 1 | 3 0.094 | 3 0.056 | 3 0.671 | ||||
| stage 2 | 3 0.562 | 3 0.547 | 3 0.835 | ||||
| stage 3 | 3 0.404 | 3 0.262 | 3 0.651 | ||||
| Winter | start of treatment | ||||||
| stage 1 (%) | 20 | 25 | 20 | ||||
| stage 2 (%) | 8 | 20 | 7 | ||||
| stage 4 (%) | 71 | 55 | 73 | ||||
| stage 3,5 and 6 (%) | 1 | 0 | 0 | ||||
| end of treatment | |||||||
| stage 1 (%) | 17 | 29 | 30 | ||||
| stage 2 (%) | 2 | 4 | 2 | ||||
| stage 4 (%) | 81 | 67 | 68 | ||||
| stage 3,5 and 6 (%) | 1 | 0 | 0 | ||||
| change | |||||||
| stage 1 | 3 0.260 | 3 0.102 | 3 0.570 | ||||
| stage 2 | 3 0.889 | 3 0.840 | 3 0.790 | ||||
| stage 4 | 3 0.900 | 3 0.085 | 3 0.228 | ||||
| M2^M3 | UPPER JAW: | ||||||
| start of treatment | |||||||
| mean (°) | 13.7 | 13.2 | 9.4 | ||||
| median (°) | 13.4 | 15.6 | 12.6 | ||||
| IQR (°) | (6.2;22.9) | (2.9;22.2) | (5.5;17.7) | ||||
| end of treatment | |||||||
| mean (°) | 14.3 | 12.9 | 11.3 | ||||
| median (°) | 12.9 | 16.4 | 13.5 | ||||
| IQR (°) | (2.7;23.4) | (4.4;25.3) | (2.4;19.1) | ||||
| change | 2 0.708 | 2 0.715 | 2 0.574 | ||||
| LOWER JAW: | |||||||
| start of treatment | |||||||
| mean (°) | 25.7 | 26.6 | 26.5 | ||||
| median (°) | 24.9 | 24.1 | 25.7 | ||||
| IQR (°) | (16.8;33.9) | (15.5;37.0) | (17.5;33.0) | ||||
| end of treatment | |||||||
| mean (°) | 26.4 | 26.6 | 23.2 | ||||
| median (°) | 26.3 | 27.2 | 25.1 | ||||
| IQR (°) | (19.0;33.3) | (16.6;35.6) | (13.6;31.2) | ||||
| change | 2 0.817 | 2 0.100 | 2 0.319 | ||||
| Archer (vertical) | start of treatment | ||||||
| stage 1,2 and 3 (%) | 5 | 8 | 6 | ||||
| stage 4 and 5 (%) | 95 | 92 | 94 | ||||
| end of treatment | |||||||
| stage 1,2 and 3 (%) | 15 | 43 | 42 | ||||
| stage 4 and 5 (%) | 85 | 57 | 58 | ||||
| change | 3 0.030 * | 3 0.049 * | 3 0.542 | ||||
| PGV | start of treatment | ||||||
| PGV-1 (%) | 0 | 4 | 0 | ||||
| PGV-2 (%) | 1 | 0 | 0 | ||||
| PGV-3 (%) | 99 | 96 | 100 | ||||
| end of treatment | |||||||
| PGV-1 (%) | 2 | 16 | 5 | ||||
| PGV-2 (%) | 10 | 10 | 33 | ||||
| PGV-3 (%) | 88 | 74 | 62 | ||||
| Probability of PGV=3 at end (%) | 89 | 74 | 62 | 3 0.024 * | 3 0.0001 * | 3 0.331 | |
| Whaites | positive relationship at start of treatment (%) | 20 | 24 | 20 | |||
| positive relationship at end of treatment (%) | 40 | 34 | 33 | ||||
| change | 3 0.236 | 3 0.444 | 3 0.726 | ||||
| Demirjian | start of treatment | ||||||
| Stage 1,2,3 and 4 (%) | 86 | 80 | 84 | ||||
| Stage 4,5,6,7 and 8 (%) | 14 | 20 | 16 | ||||
| end of treatment | |||||||
| Stage 1,2,3 and 4 (%) | 30 | 29 | 28 | ||||
| Stage 4,5,6,7 and 8 (%) | 70 | 71 | 72 | ||||
| change | 3 0.319 | 3 0.179 | 3 0.579 | ||||
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