Prevalence and Characteristics of Congenitally Missing Permanent Teeth among Orthodontic Patients in Southern Croatia.

BACKGROUND: Congenitally missing permanent teeth (CMPT) was recognized as a clinical and public health problem in pediatric dentistry. AIM: To determine the prevalence of CMPT among orthodontic patients in Southern Croatia.
MATERIALS AND METHODS: In a retrospective study, we analyzed CMPT in patients from three different regions in Southern Croatia (SC). Two orthodontic practices from each region were selected and a total of 4649 records of patients aged 6 - 15 years, who were clinically examined for orthodontic treatment between 2008 and 2015, were evaluated. We excluded 219 patients and 4430 patients remained for further analysis.
RESULTS: There was no difference in prevalence of CMPT among regions in Southern Croatia, and the whole sample was evaluated. CMPT was found in 345(7.8%) patients. The highest proportion of CMPT was with one or two missing teeth 122 (81.9%) and 158 (80.6%), followed by those with three to five missing teeth or moderate hypodontia, 25(16.8%) and 35(17.9%), in males, and females respectively. Bilateral hypodontia of the lower second premolars and upper second incisors was more common than unilateral hypodontia.
CONCLUSIONS: The obtained results of high prevalence of CMPT in Southern Croatia reinforce the need for a timely diagnostics and treatment of moderate and severe cases.

Introduction

Hypodontia or congenitally missing permanent teeth (CMPT) is recognized as a clinical and public health problem in dental medicine (). CMPT is commonly associated with specific syndromes and conditions such as Down’s syndrome, ectodermal dysplasia and cleft lip and palate (-). The etiology of non-syndromic and familial CMPT is unidentified and multifactorial, including mutations of candidate genes, AXIN2, MSX1, PAX9, WNT10A (-). Patients with hypodontia may suffer from inappropriate articulation, infra-occlusion, reduced chewing capacity and poor esthetic appearance which can affect their self-esteem and professional performance (, , ). The timing of development of permanent teeth can occur up to 15 years of age. However, it is vital to recognize CMPT in early childhood, if possible at the age of 7 - 9 years, to properly treat it, even before the child recognizes the differences compared to his/her peers (, ). Duration and cost of the CMPT treatment depend on the severity and position of the missing teeth (). Also, therapy may be a severe financial burden for orthodontic patients and their families ().

Systematic reviews and meta-analyses extensively studied the prevalence of CMPT in different populations (-). The most recent meta-analyses showed the prevalence of CMPT in Europe of 7.0% (95% confidence interval 6.0% to 8.0%), based on studies published from 2002 to 2012 (). The reported population differences in the prevalence of CMPT were almost 38 fold, i.e., Israeli 0.3% vs. Slovenian or Irish 13.6% (). Few national population studies showed significant differences in the prevalence of CMPT in different regions. Legovic et al. () compared two areas in Croatia, Aktan et al. () examined six regions in Turkey, while Behr et al. () studied different regions around Regensburg in Germany. Previous studies on the prevalence of CMPT in Croatia were performed twenty years ago (-). Hence, the present study aimed to examine the prevalence of CMPT among orthodontic patients in different regions of Southern Croatia (i.e., Town of Split, littoral region, and continental region) with the population of 455, 000 according to 2011 census ().

We hypothesized that there is no difference among different regions of Southern Croatia and that the frequency of CMPT corresponds to the frequency interval for Europeans, which was published in the contemporary literature (, ).

Materials and Methods

This retrospective cross-sectional study included all orthodontic patients aged 6- 15 years recorded and clinically examined in six orthodontic practices (OP) in Southern Croatia, during the period between 2008 and mid-2015. Two practices were located in the capital town of Southern Croatia, the city of Split; other two were placed in regional urban cities in the littoral region, and the last two in the dominantly continental region. Databases in each OP, which integrated dental and orthodontic treatment history, related medical and panoramic radiographs (OPT), casts, and additional treatment records, were used to evaluate patients. The data for analysis included the date of birth and OPT, gender, permanent residential address, the specific type and the total number of missing permanent teeth in each participant with CMPT. Third molars, including their absence, were not evaluated. Among 4649 orthodontic patients, those who permanently lived outside Southern Croatia, with the incomplete dental record, without OPT or low-quality OTP in the database, were excluded from the study. Additional exclusion criteria were cleft lip and palate, congenital syndromes and conditions related to CMPT (Figure 1). All OPTs were recorded in JPG format for further analysis. Two authors performed observation of OTPs and detection of CMPT, JB and IG, and Kappa coefficients were calculated.

Figure 1

Flowchart showing the number and distribution of participants with congenitally missing permanent teeth (CMPT) through the study

In the final sample of 4430 orthodontic patients aged 6-15 years, OPTs were divided into groups according to the severity of CMPT. Mild hypodontia was defined if one or two teeth were missing, moderate hypodontia if there were three to five missing teeth, and cases of six or more missing teeth were described as severe hypodontia or oligodontia ().

MS Excel 2010 (Microsoft Office 2010, Microsoft, Redmond, WA) and SPSS Statistics 17.0 for Windows (SPSS Inc., Chicago, IL) were used for data management and statistical analysis. Chi-square test was used to evaluate the prevalence differences among different urban zones. The differences between sexes, sides of the jaw and opposing jaws were calculated using 2-by-2 tables and presented by odds ratios (ORs) including 95% confidence intervals (95% CI) (). Statistical significance was set to 0.05.

Results

The intra-observer and interobserver agreements for the first and second observer in detecting OPTs with CMPT were completed (Cohen Kappa = 1.0). The final sample for evaluation consisted of 4430 participants aged 6 - 15 years. 4085 participants were with no CMPT (92.2%), while 345 (7.8%) participants were with CMPT (Figure 1). The mean age of the patients was 10.6±2.1 years. Table 1 shows age and sex distribution of the study sample.

Table 1

Distribution of participants with congenitally missing permanent teeth (CMPT) and evaluated sample across different age groups

Age group (years)		Males				Females				Total
		NCMT	N	%		NCMT	N	%		NCMT	N	%
6.0 - 6.9		4	46	8.7		3	54	5.6		7	100	7.0
7.0 - 7.9		13	168	7.7		18	72	25.0		31	240	12.9
8.0 - 8.9		27	150	18.0		26	149	17.4		53	299	17.7
9.0 – 9.9		15	315	4.8		32	167	19.2		47	482	9.8
10.0 – 10.9		21	390	5.4		35	328	10.7		56	718	7.8
11.0 – 11.9		26	286	9.1		33	408	8.1		59	694	8.5
12.0 – 12.0		21	200	10.5		22	400	5.5		43	600	7.2
13.0 – 13.9		12	588	2.0		16	268	6.0		28	856	3.3
14.0 – 14.0		8	117	6.8		7	216	3.2		15	333	4.5
15.0 – 15.9		2	40	5.0		4	68	5.9		6	108	5.6
Total		149	2300	6.5		196	2130	9.2		345	4430	7.8

NCMPT = number of participants with CMPT; N = total number of participants.

In males, 62 of 722 (8.6%), 50 of 781 (6.4%) and 37 of 648 (5.7%), and in females 70 of 712 (9.8%), 58 of 690 (8.4%) and 68 of 532 (12.8%) patients with CMPT were found in the city of Split, littoral and continental regions, respectively. There was no statistically significant difference in prevalence of CMPT among different regions in males, χ2 (2, 2300) =4.25, (p =0.119), and in females, χ2 (2, 2130) =5.20, (p =0.074). Therefore, we evaluated the whole study sample for further analysis, separately for males and females.

In total, the prevalence of CMPT in tested sample was higher in females (9.2%) when compared to males (6.5%), OR = 1.42 (95% CI, 1.14 to 1.77), (p=0.002). Mild, moderate and severe CMPT were similarly distributed between males and females, without statistically significant difference. The prevalence of 1 missing permanent tooth was 66 (44.3%) in males and 83 (42.3%) in females, while of 2 teeth was 56 (37.6%) in males and 75 (38.3%) in females. Bilateral hypodontia of lower second premolars and upper second incisors was more common than unilateral hypodontia. Additionally, moderate CMPT, or subjects with 3, 4 or 5 missing permanent teeth, were 11 (7.4%), 10 (6.7%) and 4 (2.7%) in males and 15 (7.7%), 16 (8.2%) and 4 (2.0%) respectively. Severe CMPT or oligodontia was distributed as follows: 6 missing teeth were found in 2 females, eight missing teeth in 2 males, and finally, 11 missing teeth in single male (Table 2).

Table 2

Distribution by the position in the mouth and frequency of specific congenitally permanent missing teeth (CMPT) according to the World Dental Federation (FDI) notation in mild, moderate and severe hypodontia in evaluated sample

No. (FDI)	Males	Females	Total		No.(FDI)	Males	Females	Total
Mild hypodontia, 1 or 2 teeth					15, 25, 45	-	2	2
12	6	4	10		15, 34, 45	-	1	1
15	4	4	8		15, 35, 45	1	-	1
22	4	7	11		22, 34, 44	-	1	1
25	1	2	3		22, 35, 45	1	1	2
31	2	1	3		25, 35, 47	1	-	1
35	23	34	57		25, 35, 45	-	3	3
37	1	2	3		32, 35, 42	-	1	1
41	1	0	1		32, 37, 42	-	1	1
42	1	2	3		34, 35, 45	2	-	2
44	1	0	1		35, 44, 45	2	-	2
45	17	28	45		44, 45, 46	1	-	1
47	5	-	5		12, 22, 32, 42	-	1	1
12, 22	11	12	23		12, 22, 25, 45	-	1	1
12, 45	1	1	2		12, 22, 35, 45	2	3	5
15, 25	1	6	7		15, 25, 32, 42	-	1	1
15, 37	-	1	1		15, 25, 35, 45	6	7	13
15, 45	1	2	3		12, 15, 25, 45	1	-	1
22, 25	1	-	1		12, 15, 22, 25	-	2	2
25,35	1	4	5		27, 31, 41, 47	-	1	1
25, 45	1	-	1		27, 31, 37, 47	1	-	1
31, 35	1	-	1		12, 22, 15, 35, 45	-	1	1
31, 41	1	-	1		12, 22, 25, 35, 45	1	-	1
32, 42	1	2	3		12, 22, 35, 37, 47	1	-	1
33, 43	-	2	2		13, 17, 27, 37, 47	-	1	1
35, 42	1	-	1		14, 15, 25, 35, 45	1	-	1
35, 45	35	38	73		15, 24, 25, 35, 45	1	-	1
35, 47	-	1	1		17, 27, 35, 45, 47	-	1	1
37, 47	-	4	4		27, 31, 37, 41, 47	-	1	1
37, 45	-	1	1
					Severe hypodontia, 6 and more teeth
Moderate hypodontia 3 to 5 teeth					14, 15, 24, 25, 35, 45	-	1	1
12, 22, 24	-	1	1		15, 23, 25, 35, 44, 45	-	1	1
12, 22, 35	1	1	2		13, 14, 15, 24, 25, 35, 44, 45	1	-	1
12,22, 45	2	-	2		14, 15, 17, 24, 25, 27, 37, 47	1	-	1
15, 25, 35	-	3	3		31, 34, 35, 22, 25, 12, 15, 41, 44, 45, 47	-	1	1
Total						149	196	345

In total, 287 and 384 missing teeth were found in 149 males and 196 females, respectively, indicating similar affection between sexes, OR = 0.98 (95% CI, 0.76 to 1.28). The mandibular teeth were significantly more affected than maxillary, 191 (66.6%) vs. 96 (33.4%), OR = 1.99 (95% CI, 1.48 to 2.67) and 246 (64.1%) vs. 138 (35.9%), OR = 1.78 (95%CI, 1.39 to 2.29) in males and females respectively, without significant difference between genders. Amongst 287 missing teeth in males, the most commonly missing were teeth No. 35 (28.5%), followed by No. 45 (26.7%), No.12 (9.0%), No. 22 (8.3%), No. 15 and No. 25 (6.3%). Eight different teeth were not missing. Amongst 384 missing teeth in females, the most frequently missing tooth was No. 35 (26.3%), followed by No. 45 (24.0%), No. 25 (8.9%), No. 15 (8.6%), No. 22 (8.3%) and No. 12 (7.3%). Six different teeth were not missing (Table 3).

Table 3

Frequency and percentage (%) of specific congenitally missing permanent teeth (CMPT) in an evaluated sample by the position in the mouth according to the World Dental Federation (FDI) notation to a specific tooth.

Tooth (FDI)	Males	Females	Total
11	- (0.0)	- (0.0)	- (0.0)
12	26 (9.4)	28 (7.3)	56 (8.2)
13	1 (0.3)	1 (0.3)	2 (0.3)
14	3 (1.0)	1 (0.3)	4 (0.6)
15	18 (6.3)	33 (8.6)	51 (7.6)
16	- (0.0)	- (0.0)	- (0.0)
17	1 (0.3)	2 (0.5)	3 (0.4)
21	0 (0.0)	1 (0.3)	1 (0.1)
22	24 (8.3)	31 (8.1)	55 (8.2)
23	0 (0.0)	1 (0.3)	1 (0.1)
24	3 (1.0)	2 (0.5)	5 (0.7)
25	18 (6.3)	34 (8.9)	52 (7.7)
26	- (0.0)	- (0.0)	- (0.0)
27	2 (0.7)	4 (1.0)	6 (0.9)
31	5 (1.7)	4 (1.0)	9 (1.3)
32	1 (0.3)	6 (1.6)	7 (1.0)
33	0 (0.0)	2 (0.5)	2 (0.3)
34	2 (0.7)	3 (0.8)	5 (0.8)
35	82 (28.5)	101 (26.3)	183 (27.2)
36	- (0.0)	- (0.0)	- (0.0)
37	4 (1.4)	11 (2.9)	15 (2.2)
41	2 (0.7)	3 (0.8)	5 (0.7)
42	3 (1.0)	8 (2.1)	11 (1.6)
43	0 (0.0)	2 (0.5)	2 (0.3)
44	5 (1.7)	3 (0.8)	8 (1.2)
45	77 (26.7)	93 (24.2)	170 (25.3)
46	1 (0.3)	0 (0.0)	1 (0.1)
47	9 (3.1)	10 (2.6)	19 (2.8)
Total	288 (100.0)	384 (100.0)	672 (100.0)

Discussion

Our findings of the prevalence of CMPT, 6.5% and 9.2% in males and females, respectively, or 7.8% for both genders, showed one of the highest prevalences in Europe. Our results are closest to those reported by Rølling () for Danish school children (7.8%) and study by Magnusson () from Iceland (7.9%). Khalaf et al. in their meta-analysis of 40 studies () reported 95% CI prevalence of 6.0 - 8.0%. Higher prevalence of congenitally missing permanent teeth in females and the highest affection of the lower second premolars following upper lateral incisors and upper second premolars followed the pattern of distribution of specific teeth in CMPT from other studies (-).

Our results are also within range of prevalence of CMPT reported in previous studies from Croatia, range from 2.32% in the study by Miličić and Čanak () up to 7.99% in the study by Miličić et al. () originating from the 20th century. Bioarchaeological investigations of orthodontic anomalies from Croatia reported up to 41.02% and 30.61% of CMPT prevalence in Late Antiquity and Early Medieval periods, respectively (, ). Reports of CMPT from Croatia vary in sample size and age cohorts. Miličić and Čanak () in their study on orthodontic patients age 7-21 years from the University of Zagreb in 1975, also found that second mandibular premolars were the most affected teeth, followed by the upper lateral incisors and upper second premolars, with higher prevalence in females. They found similar affection in both jaws () which was not the case in our study. Visković et al. () in their research from the city of Zadar in Northern Dalmatia, found a CMPT prevalence of 5.52% in the sample of orthodontic patients 8 - 20 years of age. They also found a slightly higher prevalence of CMPT in females than in males, with higher prevalence in the maxilla. The most affected teeth were upper lateral incisors followed by the mandibular second premolars, while in our study the most affected teeth were mandibular second premolars. The most affected were tooth No. 22 (17.12%), followed by tooth No. 35. Another retrospective study, which was conducted in 1994 at the University of Zagreb, included orthodontic patients aged 6-18 years during previous ten years, reported CMPT prevalence of 7.99% (). Miličić et al. () found higher affection of upper lateral incisors (41.5%) followed by lower (34.12%) and higher (18.69%) second premolars. Investigation of the prevalence of CMPT on 6 - 18-year-old orthodontic patients in two other Croatian regions, Slavonia and Istria, by Legović et al. (), showed significantly higher CMPT in Istria (6.25%) than in Slavonia (2.34%). CMPT in the mandible prevailed among the children from Istria, while that in the maxilla among the children in Slavonia (). Two-thirds of the missing teeth in our study were located in the maxilla, while recent meta-analyses by Khalaf et al. () reported similar distribution between jaws.

The sample for this study was recruited from patients who attended six different orthodontics practices during a specific period, in three different urban zones in Southern Croatia, to represent target population of orthodontic patients more appropriately and to detect a different pattern among regions. Preventive and restorative dental and interceptive orthodontic treatments are available and free of charge to all Croatian residents under the age of 18 years (). More severe conditions, syndromes, and cases that require more advanced, multidisciplinary and long-term treatment, are commonly referred to oral and maxillofacial national reference hospital (University Hospital Dubrava, Zagreb, Croatia), or to reference centers for specific conditions or syndromes in the European Union. For that reason, the target sample included only participants without hereditary conditions or syndromes correlated with CMPT. The number of mild cases involving one or two missing teeth may be even higher because of general dentists’ decisions and agreement with the patient and their parents not to treat CMPT or refer their patient to orthodontic evaluation and sophisticated treatment (). Previous systematic review and meta-analysis from 2014 by Khalaf et al. () was set as a reference to compare prevalence from this study. Our main finding of CMPT prevalence is among highest reported for studies in Europe (). Older meta-analysis of prevalence of CMPT from 2004 by Polder et al. (), which excluded orthodontic patients, reported considerable variation in prevalence of CMPT, from 0.3% in the Israeli population of grade school children in Jerusalem, reported by Rosenzweig and Gabarski (), to 36.5% in the Dariusleut Hutterites of Western Canada, reported by Mahaney et al. (). It is difficult to compare the studies because of different methods of sampling and observation, age range, sex, including hereditary or environmental factors (). Khalaf et al. () showed that recent studies reported a higher prevalence of hypodontia if compared to the previous meta-analysis by Polder et al. (), which may be attributed to better diagnostics and inclusion of more prevalence studies. Polder et al. () in their meta-analysis excluded studies with orthodontic patients which are more interested in orthodontic evaluation and possible treatment with a chance to be recognized and recorded. Khalaf et al. () also found no statistically significant differences in the prevalence of CMPT between orthodontic patients and other population types. We found a significantly higher prevalence of CMPT in females than in males which are in general agreement with meta-analyses by Polder et al. () and Khalaf et al. (), while Mattheeuws et al. () found no differences between genders.

In our study, the prevalence of CMPT in the mandible was almost two-fold higher than in the maxilla, while previous meta-analyses reported similar affection of both jaws (, ). Also, we found that the lower second premolars were most affected teeth in both genders, followed by the upper second incisors in males and upper second premolars in females. Upper central incisors and almost all first molars were not affected. Our findings are in agreement with previous meta-analyses of prevalence and distribution of specific teeth of CMPT by Polder et al. () and Khalaf et al. (). Specific geographic regions, including littoral and continental, did not affect the prevalence of CMPT in both genders, which indicates similar affection in the whole region. Behr et al. () reported significantly different prevalence in the city of Regensburg and regions outside Regensburg, Germany. Another geographically oriented study by Aktan et al. () showed significant difference among six areas in Turkey.

The appropriate timing for the optimal orthodontic treatment approach depends on the localization and number of congenitally missing teeth, age, skeletal and dental characteristics of the patient as well as available finances and patient motivation (, ). Clinical problems faced in treating CMPT patients embrace amount of space, aligning teeth, deep overbite and the final retention (). The joint microdontia of adjacent teeth, retaining deciduous teeth, and the abnormal eruptive paths and drifting of the successional teeth influence the amount of space (). The clinical decision whether the plan includes space closure with eventual teeth reshaping or space opening with subsequent placement of dental implants or other restorative treatment needs evidence-based treatment planning (). The interdisciplinary approach and interaction between the orthodontist and other specialists such as prosthodontists, periodontists, endodontists, restorative dentists and oral surgeons are essential for an optimal therapeutic outcome.

Conclusion

Our findings showed a similar prevalence of CMPT in different urban zones in Southern Croatia. The most commonly missing permanent teeth were mandibular second premolars followed by the maxillary upper second premolars in females and upper second incisors in males. The occurrence of bilateral hypodontia of lower second premolars and upper second incisors are more common than unilateral hypodontia. The quantity of missing teeth and severity of hypodontia was within the range reported in previous studies across Croatia and Europe. Further national and regional epidemiological studies may attribute to understand better possible geographic variations in the prevalence of CMPT which may improve the therapeutic approach.

The high prevalence of CMPT in Southern Croatia reinforces the need for a timely diagnostics. In view of the high prevalence of CMPT in Southern Croatia, it is suggested that treatment of moderate and severe cases needs to be initiated.