Oral and dental manifestations of celiac disease in children: a case–control study

This is a case–control study based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [16] guidelines for reporting case–control studies. Data were collected between September 2017 and February 2020.

The sample size was calculated based on a previous study [13] using the outcome variable type I DEDs. Based on the study, the odds ratio of developing DED among CD subjects was estimated to be 3.21 compared to controls and was used for determining the total sample size, using power 80% and alpha risk 5%, which was found to be 200 participants (100 patients and 100 healthy controls).

The inclusion criteria were the following for the patient group: children aged 6–14 years with biopsy-proven clinical diagnosis of CD based on the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria [1]. For the control group the inclusion criteria were as follows: healthy children with no chronic illnesses. The exclusion criteria involved children with CD that were treated with corticosteroids, had mental or physical disabilities, or congenital or chromosomal abnormalities. Participants with excessive intake of fluoride or tetracycline or with clinically manifest dental fluorosis were also excluded, as were children undergoing orthodontic treatment.

Patients were recruited in the pediatric gastroenterology clinic at King Abdulaziz University Hospital (KAUH). One hundred forty-nine contact numbers from the list of CD patients provided by the GI department were contacted; 104 subjects responded and agreed to participate (response rate was 69.8%). In order to select a control group, each CD subject was given two invitation letters of enrolment to distribute randomly to two classmates. A total of 208 invitation letters were provided for the CD children (the response rate was 50%). If parents approved their child’s participation, a phone contact was carried out to make sure that the participants were healthy. Parents were asked to bring their child to the Pediatric Dentistry Clinics in King Abdulaziz University Dental Hospital (KAUDH). The child and parents were taken to the dental clinic, where parents were asked to complete a validated parent questionnaire. This step was followed by a clinical examination of the child. The dental exam concerned RAS and DEDs using Aine's classification system [17]. Caries experience using the decayed, missed, and filled teeth index (dmft index for primary teeth and DMFT index for permanent teeth) was carried out according to WHO criteria [18]. Oral consequences related to advanced stages of untreated caries were measured using the pulp, ulceration, fistula, or abscess index (PUFA for permenant teeth/pufa for primary teeth) [19]. Malocclusion was assessed using the Dental Aesthetic Index (DAI) [20]. The clinical examinations were performed by a single trained calibrated examiner (kappa values for intra examiner reliabilities of DMFT = 0.87, dmft = 0.85, PUFA = 0.93, pufa = 0.92, DED = 0.82, and DAI = 0.93). The parent questionnaire was formulated to assess the general health status of each child. It was written in Arabic and divided into two parts. The first part comprised information regarding the child's sociodemographic data, general medical history, medications, and specific questions concerning the diagnosis and symptoms of CD. The second part concerned knowledge of the child's dental history, dietary habits, brushing habits, and specific questions related to water sources.

The parent questionnaire was validated following its development. The validity was tested using content validity. It was given to a group of five medical and dental experts for the assessment of each item, based on specific criteria. Each item was given a score, and then a total average score was determined by dividing each count by the total number of experts. The content validity index for items (I-CVI) was calculated; any item with a score < 0.78 was modified in terms of structure or language. Following this, the content validity index for the whole scale (S-CVI) was calculated [21]. The mean I-CVI score was 0.96. The following content validity indices for S-CVI were obtained: relevance = 0.96, clarity = 0.97, simplicity = 0.98, and ambiguity = 0.98.

In order to test the reliability of the parent questionnaire, 20 parents of children attending KAUH not included in the study were interviewed (in the Arabic language). The interview was repeated two weeks later for test–retest reliability; the test illustrated high reliability, with an intraclass correlation (ICC) of 0.82.

Ethical considerations were followed according to the Declaration of Helsinki. Approval to execute the study was obtained from the Research Ethics Committee at King Abdulaziz University (KAU) (number 078–09-17). Also, parents had to sign a parental consent form for the participation of their child.

Socio-demographic data revealed a mean age of 10.67 ± 2.39 years for the children with CD and 10.69 ± 2.36 years for the healthy controls (P = 0.971). In both the CD and control groups, 50% of participants were girls. Comparing the CD patients and control groups, there were no statistically significant differences between the two groups in terms of gender (P = 1.00), age categories (P = 0.980), family income (P = 0.874), mother education (P = 0.052), and father education (P = 0.781).

The oral hygiene and dietary habits of the participants are shown in Table 1. The proportion of children with CD that habitually took part in daily tooth brushing was significantly higher than the proportion of the control group (60.6% vs. 46.2%; P = 0.037). There were no statistically significant differences between CD patients and the controls in terms of frequency of tooth brushing (P = 0.535), getting help with brushing (P = 0.889), swallowing toothpaste (P = 0.42), water source (P = 0.249), use of Zamzam holy water (P = 0.507), consumption of sweets (P = 0.323), intake of carbohydrates (P = 0.308), and daily intake of soft drinks (P = 0.369).

In this study, RAS was found in 42.3% of CD children and 15.4% of the controls (P < 0.001) (Fig. 1). Having CD significantly increased the odds of having RAS by 4.03 times the rate of the healthy controls (95%, CI = 2.09–7.81). Similarly, children with CD had more frequent DEDs than controls (70.2% vs. 34.6%, P < 0.001), and CD children were 4.45 times more likely to have DEDs than healthy controls (95%, CI = 2.48–7.97). Figure 2a–f represents the different forms of DEDs that were recognized in the study. Furthermore, children with CD were less likely to have DEDs Grade 0 (OR = 0.27) but more likely to have DEDs Grade I (OR = 3.39) than controls. Dental caries was evaluated as caries prevalence, using the combined caries experience for both primary and permanent teeth combined (DMFT/dmft), as a dichotomous variable (DMFT/dmft > 0 or DMFT/dmft = 0). When there is no caries experience in primary or permanent teeth, the score is equal to zero; caries severity is evaluated using the continuous variable of decayed, missed, and filled index for permanent and primary teeth (DMFT/dmft). There was no statistically significant difference found between CD cases and controls in the frequency of malocclusion of various severities (Table 2).

Dental caries experience among the study participants are shown in Table 3. Children with CD were less likely to have experienced dental caries than healthy controls. In terms of the dmft of the primary dentition, the mean dmft in children with CD (5.01 ± 4.0) was significantly lower than healthy controls (6.56 ± 4.20) (P = 0.019). Also, the mean number of decayed teeth in children with CD was significantly lower (3.70 ± 3.65) than healthy controls (5.13 ± 3.86) (P = 0.018). When considering the dental caries in the permanent dentition, DMFT showed no significant difference between the two groups (P = 0.200), but the mean number of decayed permanent teeth in children with CD (2.81 ± 3.21) was significantly higher than healthy controls (1.90 ± 2.18) (P = 0.021). Furthermore, when the dental caries consequences were analyzed as a continuous variable, the mean pufa in primary teeth was statistically lower in the CD group (1.44 ± 2.14) compared to the control group (2.66 ± 3.10) (P = 0.004). When the dental caries consequences were analyzed as a continuous variable, the pulpal consequences were significantly lower in children with CD (1.59 ± 2.05) than healthy controls (2.84 ± 3.19) (P = 0.005). Also, the pulpal consequences were significantly lower in children with CD (1.33 ± 1.93) than healthy controls (2.67 ± 3.11) (P = 0.001). The mean PUFA in permanent teeth was not statistically different between the two groups (P = 0.096) but the pulpal consequences were significantly higher in children with CD (0.46 ± 1.02) than healthy controls (0.22 ± 0.53) (P = 0.044).

Three multiple logistic regressions were used to evaluate the effects of CD on RAS, DED, and dental caries, controlling for teeth brushing. Children with CD had 3.79 times more likely of having RAS (95%, CI 1.96–7.35) compared to children without CD (P < 0.001). Also, the CD group were 4.39 times more likely to have DEDs (95% CI, 2.44–7.89) than controls. CD was not shown to be a significant predictor of dental caries (P = 0.235) in this model (Table 4).