Long-term follow-up of mandibular dental arch changes in patients with complete non-syndromic unilateral cleft lip, alveolus, and palate

Subjects and treatment protocol

This is a retrospective longitudinal study in patients with a non-syndromic CUCLAP. Inclusion criteria were: non-syndromic as ascertained by the clinical geneticist, Caucasian, born between 1 January 1983 –31 December 1992, Simonart’s band allowed, consecutively treated from birth on with the same treatment protocol in the Cleft Lip and Palate Craniofacial Center, Radboud University Medical Center, Nijmegen, The Netherlands. Exclusion criteria were: additional craniofacial anomaly present, incomplete cleft, incomplete or submucous cleft lip at the other side, not Caucasian, primary operations performed elsewhere, treatment not yet finished.

All surgical procedures were performed by two experienced cleft surgeons and all patients were treated according to a standardized treatment protocol. The treatment protocol consisted of infant orthopedics followed by lip repair (Millard) at 4–8 months, soft palate repair (modified von Langenbeck) at 12–14 months, superiorly based pharyngeal flap at 4–5 years (if needed), maxillary protraction and expansion at 5–6 years for 12–18 months (if needed) followed by minor lip/ala nose correction (if needed), alignment of maxillary incisors and/or maxillary expansion at 9–11 years with a quad-helix or removable appliance followed by secondary bone grafting with a chin or rib graft together with hard palate closure (Boyne & Sands). The orthodontic treatment in the permanent dentition was performed with fixed appliances around the age of 12–15 years followed by fixed retention at the maxillary and mandibular anterior teeth and/or a Hawley retainer in the maxilla. Lastly, in case of severe dysgnathia, combined orthodontic-surgical treatment followed by lip/nose correction was performed, if indicated.

All patient data were anonymized prior to analysis. The use of anonymous data collected during routine patient care is in accordance with Dutch law. Written consent of participants was obtained. This study has been carried out in accordance with the applicable Dutch legislation such as Medical Research involving Human Subjects Act and Medical Treatment Contracts Act concerning reviewal by an accredited research ethics committee. This has been confirmed by the Medical Ethical Committee of the Radboudumc Nijmegen, The Netherlands (File number: 2021-13046).

Materials

Plaster models of 75 consecutive patients directly after (T0), 2 years after (T2) and five years after treatment (T5) were available. The study started (T0) after orthodontic treatment had finished, either after orthodontic treatment alone or after combined orthodontic surgical treatment in case of severe dysgnathia. All plaster casts were scanned with a 3Shape R500 3D Dental Laser scanner (3ShapeR©, Copenhagen, Denmark) using the high-resolution setting, producing a spatial resolution of 0.01 mm as specified by the manufacturer. The occlusal relationship of all models was checked against the intra-oral pictures taken at the same date.

Methods

The mandibular transverse dental arch dimensions were measured by one observer on the digital models at T0, T2 and T5 using the open-source software MeshLab 2016 (Visual Computing Lab ISTI - CNR, Pisa, Italy) (Cignoni et al., 2008). The mandibular inter-canine width was measured between the left and right cusp tips, the inter first and second premolar width between the left and right buccal cusp tips, and the inter-first and second molar width between the mesio-buccal cusp tips (Fig. 1). To determine the error of the method 20 randomly selected digital dental casts were remeasured by the same observer after a one-week interval.

The transverse occlusal relationship was determined by applying the MHB-index (Modified Huddart-Bodenham index) to evaluate arch constriction for each tooth pair. This was done on plaster casts set out on tables in a quiet room by one observer. This index was first developed in 1972 (Huddart & Bodenham, 1972) then modified in 1997 (Heidbuchel & Kuijpers-Jagtman, 1997). For the scoring the dentition is divided into a labial segment, and a buccal cleft and non-cleft segment (Fig. 2). In the labial segment the lateral incisors are not scored as they are often missing or misplaced. In the buccal segments, canines, premolars, and first molars are scored. Each tooth pair can receive a score from −3 to +1 (Fig. 3). The total MHB score for a given model is calculated as the sum of the scored teeth, with a range of the score from −30 to +10 (Noverraz et al., 2015). To determine the intra- and interobserver reliability 50 randomly selected casts were scored twice with an interval of one week by two observers.

Statistical analysis

Descriptive statistics were performed for all parameters to show the distribution of data, such as means, standard deviations, minimum –maximum values, mean increments between T0 and T2, T2 and T5, and T0 and T5. The intra-observer performance for the transverse mandibular distances (continuous variables) was analyzed using three statistics. The reliability was tested with the Pearson correlation coefficient. Paired sample t-tests were applied to identify systematic differences between the first and second measurement. The duplicate measurement error (DME) was calculated as the SD of the difference between two observations divided by $\sqrt{2}$. Additionally, Bland-Altman plots were made for each variable. The duplo measurements for the intra- and interobserver reliability of the individual teeth scores of the MHB Index score were analyzed by weighted Kappa. Data was analyzed using paired t-tests and ANOVA. Linear regression was applied to test for the effect of age at the end of treatment, sex, opening or closing space of the maxillary lateral incisor at the cleft side, mandibular premolar extraction, maxillary expansion before bone grafting, and treatment outcome (GOSLON Yardstick score) at the end of treatment. The level of significance was set at P < 0.05.

Sample

The total number of patients that met the inclusion criteria was n = 82. Data of 7 patients were missing because 3 moved elsewhere, for 3 patients all treatment records were missing, and 1 patient had no follow-up for unknown reasons. In total 75 consecutive patients were available for the study. The mean age at the end of treatment (T0) was 16.5 years (SD 2.3; range 12.9–22.5), two years after treatment (T2) 18.4 years (SD 2.2; range 14.6–22.7), and five years after treatment (T5) 20.9 years (SD 2.4; range 17.0–26.4). 27 patients were female (36%) and 48 patients were male (64%). 54 patients (72%) had the cleft on the left side and 21 patients (28%) on the right side. Maxillary expansion before bone grafting was done in 20 patients out of 75 (26.7%). In 54 patients (72%) the space for the missing maxillary lateral incisor at the cleft side was closed orthodontically, in 6 patients (8%) the maxillary lateral incisor was present at the cleft side and in 15 patients (20%) the space was opened. Absence of mandibular premolars was found in 19 patients (25.3%). The GOSLON score at the end of treatment was in 36 (48%) patients score 1, in 19 (25.3%) patients score 2, in 14 (18.7%) patients score 3, and score 4 was found in 4 (5.3%) patients. There were no patients with a score of 5 in this sample. Data for the GOSLON were missing of two patients.

Intra- and interobserver performance

The Pearson’s correlation coefficients for the intra-observer reliability of the transverse arch measurements were high, ranging from 0.932 to 0.996 (Table S1). The duplicate measurement error for the measurements varied from 0.19 to 0.54 mm. The mean differences between first and second measurements were very small and showed no significant differences (paired sample t-test). This indicated that intra-observer performance was high. This was also supported by the Bland Altman plots showing a high level of agreement between the first and second measurements (Figs. S1A–S1C).

For the MHB score the intra-observer performance was almost perfect shown by the weighted kappa of 0.93. The inter-observer reliability was also strong with a weighted kappa value of 0.84. This was also supported by the Bland Altman plots showing a high level of agreement between measurements (Figs. S2A–S2B).

Mandibular transverse dimensions

Table 1 shows means and SD of the five mandibular transverse dimensions at the three different time points and Table 2 shows the changes over the five-year study period. The mandibular intercanine distance did not change significantly over time. The interpremolar distances diminished significantly over the 5-year study period. The first premolar distance diminished 0.71 ± 1.38 mm (p = 0.001, 95% CI [0.29–1.12]), while the second premolar distance decreased 0.95 ± 1.74 mm (p < 0.001, 95% CI [0.47–1.43]). The inter first molar distance increased slighty over the 5-year follow-up period but this change was not statistically significant, while the inter second molar distance showed an increase of 0.73 ± 1.49 mm (p = 0.001, 95% CI [−1.13–−0.33]).

Transverse dental arch relationships

Table 3 shows means and SD for the MHB scores at the three different time points and Table 4 shows the changes after treatment over the five-year study period. For all arch segments –labial and cleft and non-cleft buccal segment—the MHB scores deteriorated significantly over the 5-year follow-up period and during each post-treatment period. The decrease for the labial segment was small (0.56 ± 1.45 MHB point, p = 0.006, 95% CI [0.17–0.96]) during the 5-year period, while the change for the buccal cleft segment was the largest (2.07 ± 2.67 MHB point, p < 0001, 95% CI [1.35–2.79]).

Factors that influence changes of mandibular transverse distances

Table 5 shows the results of the linear regression analysis for factors affecting the changes of the mandibular transverse distances for all time intervals. The deterioration of the intercanine distance two years after treatment (T0-T2) was affected by sex and GOSLON score at the end of treatment, showing that deterioration was less for girls and more when a higher GOSLON score was present at the end of treatment (R² = 0.21). The deterioration of the inter first-premolar distance was larger when the space was closed for a missing maxillary lateral (R² = 0.15).

Between two and five years after treatment (T2-T5), the decrease of the mandibular inter first molar width was affected by the GOSLON score at T0 showing that the decrease was less when the GOSLON at T0 was smaller (R² = 0.14).

For the whole 5-year period (T0-T5) only maxillary expansion had a significant effect, i.e., the intercanine distance decreased more when maxillary expansion was performed during treatment, but the explained variance was low (R² = 0.13).

Yet overall, no clear picture was emerging when looking at the effect of the different factors on the changes of the distances.

Factors that influence changes in the MHB Scores

Table 6 shows the results of the linear regression analysis for contributing factors for changes of the MHB-scores. The influencing factors had the greatest effect the first two years after treatment. From T0-T2 deterioration of the labial segment was affected by mandibular premolar absence showing that the deterioration was less if the mandibular premolar was absent (R² = 0.17). On the buccal cleft segment, the deterioration was higher if the patient was younger at the end of treatment, space closure of a missing maxillary lateral incisor was conducted, and the GOSLON score at the end of treatment was higher (R² = 0.31). On the buccal non-cleft segment, the deterioration was affected by patient’s age at the end of treatment and space closure for a missing maxillary lateral, showing that less deterioration happened if the patient was older at the end of treatment and no space closure was conducted for a missing maxillary lateral (R² = 0.21). The deterioration of the total arch constriction score was smaller when the patient was older at the end of treatment, no space closure was conducted for a missing maxillary lateral and the GOSLON score was smaller at the end of treatment (R² = 0.29).

Between two and five years after treatment (T2-T5), the deterioration on the buccal non-cleft segment was larger if the mandibular premolar was absent (R² = 0.15) and the total score was more deteriorated if maxillary expansion was conducted (R² = 0.20). For the total post-treatment period (T0-T5), age had an effect on the scores of the buccal cleft segment and the total arch constriction. The scores deteriorated less if the patients were older at the end of treatment (R² = 0.30 and R² = 0.26, respectively).

Overall, the effect of different factors on the deterioration of interarch relationships remained unclear because all of the explained variances were low.

Strengths and weaknesses of the study

This study is performed in a large sample of consecutive patients observed for 5 years after treatment. There are hardly any studies about stability after treatment focusing on the mandibular arch. The loss to follow up was low (only 7 out of 82 patients—less than 10%). The patients were treated from birth on in one center with the same protocols by two experienced surgeons which is important to notice as it has been proven that the skills of the surgeon play an important role in the final result (Shaw & Semb, 2017). However, the present study is a retrospective study and performed in one center which means the results are valid for Caucasians and for the treatment protocol which is employed in the center.