Treatment outcome in patients with bilateral cleft lip and palate. An intercentre study on dentofacial morphology until 12 years of age.
A scientific essay in Medical Sciences
DOCTORAL THESIS defended in public on 29th of June 2011
Chapter 1 introduces the topic of complete bilateral cleft lip and palate (CBCLP). The etiologic factors (genetic, epigenetic and environmental) related to the condition are discussed. Incidence of cleft lip and palate and the associated anomalies is shortly presented. Patients with CBCLP require an interdisciplinary approach of treatment, which is outlined in this chapter. Each cleft centre follows its own treatment protocol. In this chapter, the treatment protocol of the centre, where this study was performed, is shortly discussed. Facial growth disturbances are frequently observed in these patients, which might be attributed to intrinsic and functional factors, but this also might have iatrogenic causes. Therefore craniofacial morphology and dental arch development are described in operated and non-operated BCLP patients. At the end of this chapter, the objectives of the thesis are outlined.
In chapter 2 the results of a retrospective longitudinal intercentre outcome study on dental arch relationships in three European CLP centres are presented. Dental casts of 204 consecutive patients with complete bilateral cleft lip and palate (CBCLP) were compared and evaluated longitudinally. The age of the patients was ranging between 4.5 to 13.5 years of age. The evaluation was performed with the BCLPyardstick, which rates dental arch relationships, at 6, 9, and 12 years of age. Increments for each interval (from 6 to 9 years, 6 to 12 years, and 9 to 12 years) were analyzed by logistic and linear regression models. There were no significant differences in outcome measures between the centres at age 9 or at age 12. At age 6, centre B showed significantly better results (p=0.027), but this difference diminished as the yardstick score for this group increased over time (linear regression analysis), the difference with the reference category (centre C, boys) for the intervals 6 to 12 and 9 to 12 years being 10.4% (p=0.041) and 12.9% (p=0.009), respectively. Despite different treatment protocols, dental arch relationships in the three centres were comparable in final scores at age 9 and 12 years. Delaying hard palate closure and employing infant orthopedics did not appear to be advantageous in the long run. Premaxillary osteotomy employed in centre B appeared to be associated with less favorable development of the dental arch relationship between 9 and 12 years.
In chapter 3, two scoring systems: the Huddart/Bodenham system (HB-system) and the Bauru-BCLP yardstick (BCLP-yardstick) were compared. The purpose of this study was to classify treatment outcome in terms of dental arch relationships in patients with CBCLP and to evaluate the predictive value of these scoring systems for treatment outcome. Dental arch relationships of 43 CBCLP patients were evaluated longitudinally at 6, 9, and 12 years. For each age group the HB-scores were correlated with the BCLP-yardstick scores using Spearman's correlation coefficient. The predictive value of the two scoring systems was evaluated by backward regression analysis. Intra-observer Kappa values for the BCLP-yardstick scoring for the two observers were 0.506 and 0.627, respectively, and the interobserver reliability was ranging between 0.427 and 0.581. The intra-observer reliability for the HBsystem was ranging from 0.92 to 0.97 and the interobserver reliability from 0.88 to 0.96. The BCLP-yardstick scores of 6 and 9 years together were predictors for the outcome at 12 years (explained variance 41.3%). Adding the incisor and lateral HB-scores in the regression model increased the explained variance to 67%. The BCLP-yardstick and the HB-system are reliable scoring systems for evaluation of dental arch relationships of CBCLP patients. The HB-system categorizes treatment outcome into similar categories as the BCLP-yardstick. In case a more sensitive measure of treatment outcome is needed, selectively both scoring systems should be used.
In chapter 4 the prevalence of tooth agenesis and patterns of hypodontia are evaluated in a large sample of patients with complete bilateral cleft lip and palate (BCLP). Serial panoramic radiographs (the first radiograph was taken at 10.5-13.5 yr of age) of 240 patients with BCLP (172 male patients, 68 female patients) were examined. Third molars were not included in the evaluation. Agenesis of at least one tooth was present in 59.8% of patients. Upper laterals and upper and lower second premolars were missing most frequently. Using the tooth agenesis code (TAC), 52 different agenesis patterns were identified, of which simultaneous agenesis of 12, 22, 15, 25, 35, and 45 was the most frequent pattern. Nine of the 240 patients showed combined BCLP and oligodontia.
In chapter 5 the craniofacial morphology and soft tissue profile in patients with complete bilateral cleft lip and palate (CBCLP) is compared at 9 years of age. The patients were treated in two European cleft centres, which both had a delayed hard palate closure but different treatment protocols. Cephalometric data of 83 consecutively treated CBCLP patients were compared (Gothenburg, nA=44; Nijmegen, nB=39). In total, 18 hard tissue and 10 soft tissue landmarks were digitized by one operator. To determine the intra-observer reliability, 20 cephalograms were digitized twice with a monthly interval. Paired t-test, Pearson correlation coefficients and multiple regression models were applied for statistical analysis. Hard and soft tissue data was superimposed by the generalized Procrustes analysis. In Nijmegen, the maxilla was protrusive for hard (SNA) and soft tissue (Snss) values (p=0.001, p=0.030respectively) and the maxillary incisors were retroclined (p <0.001), influencing the nasolabial angle (as-ss-Is), which was increased in comparison to Gothenburg (p=0.004). In conclusion, both centres showed a favorable craniofacial form at 9 to 10 years of age, although there were significant differences in the maxillary prominence, the incisor inclination and soft tissue cephalometric values. Follow-up of these patients until facial growth has ceased, may elucidate components for outcome improvement.
In chapter 6 the results of a longitudinal study into craniofacial morphology and soft tissue profile changes of patients with complete bilateral cleft lip and palate (CBCLP) from 6 to 12 years of age are presented. Lateral cephalograms from 148 patients with CBCLP treated consecutively at three European cleft centres, Gothenburg (nA =37), Nijmegen (nB=26), and Oslo (nC=85), with different treatment protocols were evaluated. A total of 18 hard tissue and 10 soft tissue landmarks were digitized by one operator. To determine intra-observer reliability, 20 cephalograms per age group were digitized twice at a one-month interval. Paired t-test, Pearson correlation coefficients, and multiple regression models were applied for statistical analysis. ANOVA and Tukey-B, as a post-hoc test, were used to evaluate the increments and compare centre. Hard and soft tissue data were superimposed using the generalized Procrustes analysis. For Nijmegen, the increments (between 6 and 12 years) of the variables SNA, ANB, NS-NL, NL-ML, Snss, and Snpg were significantly different from the two other centres (p=0.018 to <0.001). SNPg increments were significantly different between Nijmegen and Oslo (p=0.002). The three cleft centres followed different treatment protocols, but the main differences in craniofacial morphology until 12 years of age were the growth pattern and the maxillary and upper incisor variables. Follow up of these patients until facial growth has ceased, may elucidate components for improving outcome.
In chapter 7 the goals and objectives of the study as a whole are presented. The strengths and weakness of the study are discussed as well as the different methodological considerations that have been encountered. The main objective was to improve our knowledge on treatment outcome in CBCLP patients. In this chapter, it is evaluated to what extent we reached the goal of our investigation and furthermore suggestions for future research are done.