Outcomes of pulpectomy in the primary dentition and age-related morphological changes in the root canal of primary molars: A retrospective study

Objectives To investigate the factors inuencing primary tooth survival after pulpectomy and to elucidate age-related morphological changes in the root canal of primary molars. Materials and Methods This retrospective study included 592 primary anterior teeth and 583 primary molars after pulpectomy. Survival analysis was performed to determine the predictors of pulpectomy failure. Cone-beam computed tomography (CBCT) data of the maxillary rst primary teeth from 63 children aged 3–8 years were collected, and Spearman’s correlation and binary logistic regression were performed to assess age-related changes in canal morphology. Results Periapical periodontitis, Vitapex ® lling, and non-general anesthesia treatment increased the failure risk of anterior primary teeth pulpectomy. Older age at treatment increased the primary molar pulpectomy failure risk. On CBCT analysis, the ratio of canal length to root length for the mesiobuccal (MB), distobuccal (DB), and palatal (P) roots negatively correlated with age (P<0.05). The ratio between the root canal wall area with inner diameter lesser than 0.15 mm and the whole root canal wall area (R .15 ) at plane D of the MB canals positively correlated with age (P<0.05). The number of discontinuous canals (N dis ) for the MB and DB roots increased with age and the canal area at plane D for MB and P canals negatively correlated with age (P<0.05). Conclusions Older age at treatment for primary molar pulpectomy and periapical lesions, non-general anesthesia treatment, and Vitapex ® lling for anterior primary teeth pulpectomy may predict a higher failure risk. Age-related morphological changes in the primary molar root canal were evident and could be a reason for treatment failure.


Background
Dental caries is a prevalent chronic disease in children, especially in developing countries. In China, the fourth national oral epidemiological investigation showed that the prevalence of dental caries in children aged 5 years was 71.9% and that the mean decayed-missing-lled teeth (dmft) index was 4.24 [1], both of which were considerably higher than those 10 years earlier (66.0%, dmft=3.5) [2]. Dental caries in the primary dentition progresses rapidly, often affecting the pulp within a short duration. In China, the incidence of periapical periodontitis is high in primary teeth [3]. The American Association of Pediatric Dentistry (AAPD) recommends pulpectomy as an elective treatment for periapical periodontitis in primary teeth and regards pulpectomy as a nal treatment to retain primary teeth with diffuse irreversible pulpitis or pulp necrosis [4].
Previously, research has largely focused on primary tooth pulpectomy, mainly on lling materials [5][6][7], irrigant [8], and instrumentation methods [9,10], reporting success rates between 56% and 97%. However, a short follow-up period or the small sample size of these studies have led to varying success rates, as Page 3/18 mentioned above. A large number of primary teeth treated with pulpectomy were evaluated in this study, with a follow-up of more than two years for most teeth.
It is imperative for operators to be familiar with the canal morphology of primary teeth to perform a successful pulpectomy. Research indicates that the canal morphology of permanent teeth is signi cantly different at different ages [11,12]. Primary teeth exist in the mouth for a much shorter time than permanent teeth. Whether the canal system of primary teeth changes with age, and whether these changes in uence the success of pulpectomy is still unknown. Owing to physiological absorption, it is impossible to obtain complete primary teeth of different ages for micro-CT or other in vitro analysis. The application and development of cone-beam computed tomography (CBCT) in stomatology provides a new method for studying the canal morphological characteristics of primary teeth. Through CBCT, it is possible to unravel the complete morphology of the canal in vivo. This technique has already been applied in the morphological analysis of permanent teeth [13,14]. In this study, CBCT was used to observe and measure the canal system of primary molars.
The aims of this study are as follows: 1) To study the long-term survival rate of pulpectomy in primary teeth and to analyse the potential factors in uencing its success.
2) To study the age-related changes in the root canal system of primary molars using CBCT.

Materials And Methods
This retrospective study was approved by the Ethics Committee of Peking University School and Hospital of Stomatology (approval number: PKUSSIRB-201949122).

Participants
The study participants were selected among healthy children below the age of 9 years, who received pulpectomy of the primary teeth in the Department of Pediatric Dentistry at Peking University Hospital of Stomatology. The inclusion criteria were as follows: 1) Teeth treated because of irreversible pulpitis or pulp necrosis, with or without periodontitis, for which radiographic examination showed no involvement of the permanent successor and minimal or no root resorption.
2) Teeth that had not undergone trauma.
3) Teeth that underwent regular postoperative examination with follow-up time ≥1.5 years. 4) Teeth for which complete records were available.
All pulpectomies were completed in compliance with the AAPD guidelines [4]. A six-month visit interval was recommended.

Data collection
The following information from an electronic medical record system (Beijing Jiahe Meikang Information Technology, Beijing, China) of Peking University Hospital of Stomatology was collected: 1. Demographic characteristics.
2. Information obtained from the rst visit, including the date, rank of attending doctor (intern or expert), tooth position (anterior or posterior), treatment method (under general anesthesia (GA) or not [GA or non-GA]), periapical lesion (yes or no), clinical and radiographic manifestations, root lling material (iodoform zinc oxide paste [15]  3. Information obtained during follow-up, including following visit dates, chief complaints, and clinical and radiographic examination. If the tooth was already missing, the date of loss and the associated symptoms were recorded.

Clinical and radiological evaluation
The pulpectomy was considered clinically successful in the absence of pain, abnormal mobility, gingival pathology, and severe crown restoration defects necessitating root canal retreatment or extraction, in relation to the tooth. If not, it was labelled as clinical failure.
If the radiographic examination revealed a decrease in size or disappearance of the initial periapical lesions within 6 months [4], with no new appearances of periapical lesions and/or pathological root resorption, the treatment was classi ed as a radiological success; otherwise it was classi ed as a radiological failure.
The interventional outcome was de ned as a success only if the treatment exhibited both clinical and radiological success. In addition, premature loss and delayed root resorption of primary teeth after treatment were classi ed as failure [4]. The primary teeth were evaluated for premature loss or delayed root resorption by comparison with the contralateral teeth and/or other adjacent teeth without pulp treatment. If there were no contralateral teeth and adjacent teeth without pulp treatment, it was estimated based on the development stage of the permanent successor.
All periapical lms involved in this study were re-examined. Radiographic examinations were independently performed by two pediatric dentists. Cohen's kappa statistic showed excellent reproducibility between the two investigators, with a measurement agreement of 0.85 and intra-examiner reliability (over two weeks) of 0.87. CBCT images were acquired using the 3D Accuitomo type F17 (Morita, Kyoto, Japan) at 80-90 kV and 5 mA. The voxel and slice thicknesses were both 0.125 mm. All CBCT exposures were performed by a licenced radiologist strictly in accordance with the manufacturer's recommended protocol.

Measurements
The CBCT scan data were saved in DICOM format and transferred to Mimics 17.0 (Materialise Technologies, Leuven, Belgium). Several points and values were de ned as below, to aid with the measurement of each root and canal (Fig. 1a). L R : length of the root measured from points A to B along the tooth axis. L C : length of the canal measured from points A to C along the tooth axis.
Plane D: canal cross-section, 1/3*L R away from point A along the tooth axis.
If the root canal cavity reappeared after disappearing toward the root tip, it was recorded as a discontinuous canal, as shown in Fig. 1a. The L C and L R were measured.
The canal cross-section at plane D was reconstructed. First, an appropriate threshold for accurate segmentation of the canal cavity was selected for each canal. The threshold value was determined as follows. We rst measured the grey value range of the lip in the CBCT at three different positions and calculated the difference between the minimum and maximum grey values for each position. Then, the mean of the three differences was calculated and recorded as "d". The minimum grey value of the canal image was recorded as "c", and d plus c was "p", which was recorded as the reference threshold value of canal. Following this, the reference grey value "p" was slightly adjusted for improved accuracy according to the operator's judgement.
After determination of a proper canal threshold, a three-dimensional (3D) model of the canal section at plane D was generated and measured, as shown in Fig. 1b. The detailed procedure is listed in Fig. 2. STL (stereo lithography) is a 3D graphics le format for rapid prototyping manufacturing.
The following outcome variables were calculated and recorded: 1) L C /L R : Ratio of the canal length and root length.
2) N dis : The number of discontinuous root canals.
3) R . 15 : The ratio of the root canal wall area with an inner diameter lesser than 0.15 mm and the total root canal wall area at plane D. 4) Area of canal at plane D, measured using Image J (National Institutes of Health, Bethesda, USA) Before starting the study, 69 canal cross-section samples not included in this study were used to assess the consistency of image segmentation with the index of mean intersection over union (MIoU). The MIoU was 0.81.

Statistical analysis
Statistical analyses were conducted using SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). The survival rate of teeth after pulpectomy was determined using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression analysis. Variables with P<0.1 in the univariate analysis were included in the multivariate analysis to be explored as possible risk factors. Factors previously reported to in uence success were also included. The variables included in the Cox analysis were age, rank of attending doctor, treatment method, presence of periapical lesion, root canal lling material, and the crown restoration material. The Wald test (Backward: Wald) method was used, and the signi cance level of the selected and excluded variables was 0.05.
The normality of data from CBCT was tested using the Kolmogorov-Smirnov one-sample test. The Spearman correlation coe cients between R .15 , L C /L R , area of canal at plane D, and age were calculated, and the linear regression coe cient between N dis and age was calculated by binary logistic regression.
The signi cance level was set at P<0.05. All included pulpectomies were divided into two groups: primary anterior teeth interventions and primary molar interventions. By the end of February 2019, 246 (41.6%) primary anterior teeth interventions and 363 (62.3%) primary posterior teeth interventions met the criteria for failure. Kaplan-Meier analysis showed that the median survival time for primary anterior teeth was 990 days and that for primary posterior teeth was 772 days. The cumulative survival rates of primary anterior teeth at 24 months and 30 months were 72.3% and 58.2% and that of primary molars were 57.1% and 37%, respectively. Anterior teeth suffered less treatment failure than posterior teeth (P<0.001).

Results
The results of the multivariate Cox proportional hazards regression analysis are shown in Table 2. For primary anterior teeth, the failure risk of pulpectomy with GA was signi cantly lower than that of pulpectomy with no-GA. Treatment for teeth with periapical lesions and Vitapex ® lling were more likely to fail (P<0.05). For posterior primary teeth, age and the crown restoration material had a statistically signi cant impact on the failure risk of pulpectomy ( Table 2). The failure risk of pulpectomies increased with age, and the hazard ratio (HR) was 1.185 (95% CI, 1.082-1.297) (P<0.001). Interventions with GIC restorations were more likely to fail (P<0.05).
We found a positive correlation between R .15 of MB roots and age (r s =0.326, P<0.001), indicating that the canal diameter decreased with age. However, a similar result was not obtained for DB and P roots. L C /L R for MB, DB, and P roots were negatively correlated with age (Fig. 3), suggesting a decrease in the canal length. The area of canal at plane D for MB and P roots diminished with age (P<0.05) ( Table 3). Binary logistic regression analysis revealed that the occurrence of discontinuous canals for MB and DB roots increased signi cantly with age (Table 4).

Discussion
In this study, the survival rate of primary anterior teeth 24 months after pulpectomy was 72.3% and that of primary posterior teeth was 57.1%, which was similar to the ndings of previous studies (63.3%-78.5%) [16][17][18][19][20]. The survival rate of primary anterior teeth was signi cantly higher than that of primary molars. This distinction may be due to a difference in the root canal morphology. Most anterior primary teeth have a single canal and few lateral branches or root tip bifurcations [21], but different forms of the accessory root canal are common in primary molars. Morabito et al. observed 30 primary molars under a scanning electron microscope and found that 21 of them had an accessory root canal at the bottom of the pulp chamber, in which pulp tissue and necrotic tissue were observed [22]. Therefore, primary anterior and posterior teeth were analysed independently in this study.
Among primary anterior teeth, the intervention failure risk of teeth with periapical lesions was signi cantly higher than that of teeth without periapical lesions. It is impossible to remove all pathogenic bacteria in the periapical tissue through root canal preparation, and residual bacteria can increase the postoperative failure risk. Chen et al. also reported worse prognosis of pulpectomy in primary teeth with periapical lesions [23]. However, interventions in primary molars with periapical lesions had a similar survival rate to teeth without periapical lesions. As mentioned before, the canal system of primary molars is more complicated than that of primary anterior teeth, and canal debridement is di cult. It is speculated that there is more residual infection in the primary molar canal system than in the root canals of anterior teeth, which can also cause recurrence of periapical periodontitis. In anterior teeth, non-GA treatment and Vitapex ® pulpectomy has a lower survival rate, which was consistent with ndings of other studies [24,25].
For primary molars, we found that the treatment at older ages was more likely to fail than that at a younger age, and the difference is statistically signi cant. This nding has never been reported previously. According to previous studies [12,26,27], permanent teeth show age-related changes, and secondary dentine deposition may change the root canal diameter or lead to severe canal calci cation, increasing the di culty of root canal preparation. In primary molars, similar age-related changes were also reported by Amano et al., who indicated that the volume ratio between the pulp chamber and the crown is larger in the primary dentition than in the mixed dentition [28]. Ahmed suggested that it is necessary to study the relationship between canal morphology and pulpectomy failure [29]. Therefore, it is hypothesised that age-related changes in primary molars may affect the outcome of pulpectomy.
The variable R .15 was calculated to determine the di culty of the 15 K-le entering the canal. In this study, R .15 increased and the canal area at plane D of the MB canal decreased with age, indicating a decrease in the canal diameter. Similarly, Ge et al. studied the primary molars of children aged 3-8 years and found that the root canal ori ce area in the mesial root decreased with age (P<0.01) [30]. Furthermore, we observed that most MB canal cross-sections were oval or attened in the coronal-third of the root, and the canal diameter decreased rapidly with age (Fig. 4). The presence of an oval canal and a smaller canal diameter are challenging for mechanical and chemical canal instrumentation, resulting in larger areas of the dentine wall being untouched [31]. However, R .15 in DB and P canals were not found to correlate with age in this study. This is because most DB canal diameters were smaller than 0.15 mm or showed a complete calci cation at plane D at a young age in this study. In contrast to DB canals, for P canals, nearly all diameters at plane D were larger than 0.15 mm for all ages, but the canal area at plane D reduced signi cantly with age, re ecting the age-related changes in P canals.
Calci cation in the apical third of the canal is re ected by the variables L C /L R and N dis . The morphological analysis showed that L C /L R decreased and N dis increased signi cantly with age. Acquired dentine formation causes a decrease in the inner canal diameter, even partial or complete locking of the canal, resulting in length shortening and canal interruption. However, canal calci cation in the apical third is usually incomplete, and in some canals, the lumen could still be observed below the calci cation. Compared with the continuous root canal, it is more di cult to clean those discontinuous ones. In the case of primary anterior teeth, owing to the large canal diameter and the simple canal system, age-related acquired dentine formation has minimal impact on canal morphology. This may be the reason why the survival rate in primary anterior teeth did not change with age.
There are some limitations to this study. First, the inconsistency between radiographic and clinical manifestations makes it di cult to detect periapical diseases on time. However, in children, the potential damage caused by multiple radiographic evaluations should be carefully considered to determine if the risk-bene t ratio. Second, this is a retrospective study based on existing case records, in which there may be a recording inaccuracy. In order to avoid false records, we also checked the X-ray lm when the records were examined. Third, the variables used in this study were static-observation CBCT indices, and the evaluation of the di culty of root canal preparation was partly based on the diameter of the root canal, which cannot fully represent the actual situation of mechanical preparation. We hope that new technology can be invented to simulate the mechanical preparation process in the future, so the agerelated changes can be estimated more accurately.

Conclusions
The survival rate of primary anterior teeth was signi cantly higher than that of primary molars. For primary anterior teeth, the absence of periapical lesions, GA, and iodoform zinc oxide paste lling may improve the survival rate; for primary molars, a younger age at treatment may predict more successful treatment results. Root canal changes with age were evident, which may be one of the reasons for the failure of primary molar pulpectomy. These ndings are reminders of the necessity of treating primary anterior teeth and primary molars differently and indicate directions to improve the success of pulpectomy in primary molars.