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. 2023 Aug 10;18(8):e0289802. doi: 10.1371/journal.pone.0289802

Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional study

Zeinab Mahboobi 1,2,*, Ataollah Jalili asl 2, Nasrin Sharififard 2, Elnaz Faramarzi 1, Younes Ghavamlaleh 3
Editor: Hadi Ghasemi4
PMCID: PMC10414603  PMID: 37561699

Abstract

Background

Considering the high prevalence of dental caries in adults, it is necessary to study its risk factors to prevent the disease. Gastroesophageal reflux disease (GERD) is a common chronic disease with an increasing incidence that may affect the quality and quantity of saliva.

Objectives

This study aimed to determine the association of gastroesophageal reflux disease (GERD) with dental caries according to the DMFT index in the Azar cohort population.

Materials and methods

This cross-sectional study was performed on data obtained from the enrollment phase of the Azar Cohort Study (ACS), conducted on 15,000 adults aged 35 to 70. Data of 905 subjects with gastroesophageal reflux disease in the ACS—without full denture—together with a control group of 1894 subjects, who were matched in terms of gender and age, were included in this study. Dental caries data and data on GERD, demographic and socioeconomic characteristics, individual and nutritional habits, BMI, and toothbrushing frequency were elicited from the databank of the ACS center. A Generalized Linear Models assuming negative binomial distribution with a log-link function was used for analytical statistics to examine the effect of possible confounding variables.

Results

The DMFT index in the group with GERD was 15.09±6.18, and for the control group was 15.00±6.07. No statistical association was seen between GERD and dental caries. Among the variables included in the regression analysis, being younger and toothbrushing one or more times per day were associated with a lower DMFT index score.

Conclusion

According to the results, having GERD did not increase the risk of dental caries. However, due to the cross-sectional design of the study, the results should be interpreted cautiously. The results showed that oral hygiene is one of the most influential factors in reducing dental caries prevalence.

Introduction

Although dental caries is usually preventable, many people worldwide still suffer from its pain and discomfort, and it imposes high medical costs on individuals and societies [1]. According to previous reports, oral disorders are still a public health challenge [2], and dental caries remains one of the leading health problems in most countries, affecting most adults [3]. A study in 2007 [4] showed that the DMFT index in Iranian adults aged 34‒44 was 11±6.4, which was in the range reported for this age group by the World Health Organization (WHO) in 2004. Approximately 33% of Iranian adults [4] and 35% of the world’s population had untreated caries in permanent teeth, so it has remained the most common public health problem in the last three decades [5]. Differences in oral health status in different societies indicate that behavioral aspects and various socioeconomic and environmental factors prevail in countries and within populations [3].

Dental caries is a complex and multifactorial disease with several proximal and distal determinants. The main risk factors for dental caries are diet, a susceptible host, and microorganisms which act in a complex context of socioeconomic, behavioral, environmental, and demographic factors. In fact, individual behaviors such as oral hygiene habits or dietary patterns are determined by socioeconomic status in which people are born, grow up, work, and age. These conditions provide the opportunities for and limit individual behaviors [6].

It is indicated that some systemic diseases are related to dental caries development. Gastroesophageal reflux disease (GERD) is a condition that may potentially cause tooth decay due to the changes it creates in the oral cavity, such as the oral pH drop, decreased salivation, and disruption of its buffering capacity [7]. Gastroesophageal reflux is a physiological process of effortless backward movement of the contents of the stomach to the esophagus; in contrast, gastroesophageal reflux disease (GERD) occurs when the rate of gastroesophageal reflux is higher than expected and is recognized by both classic and atypical symptoms [8]. Regurgitation and heartburn are usual symptoms of GERD [9]. GERD risk factors are divided into two categories: non-modifiable risk factors, including age, sex, ethnicity, and modifiable risk factors, including lifestyle, dietary habits, and body weight [10]. Gastroesophageal reflux disease is a highly prevalent disease with an estimated prevalence of 43.07% in the Iranian population [11]. The overall approximate daily prevalence of GERD has been reported to be 10‒20% in Europe and the USA and less than 5% in Asia [12], with 5.64% (95% CI: 3.77–8.35) in the Iranian population [11]. A review showed that the incidence of GERD is increasing mainly in North America and East Asia [13], and it is expected to continue to increase due to new dietary habits and lifestyles [7].

The minerals of the tooth surface are in a dynamic equilibrium with the oral fluids, and the enamel of teeth demineralizes and remineralizes several times a day [6]. Caries develop when the balance between these phases is disturbed, and demineralization overcomes remineralization. Saliva is one of the efficient factors in neutralizing the acids produced by bacteria and helps the remineralization phase [6]. Some studies have shown that the quality and quantity of saliva [14, 15] change in patients with GERD. Studies have reported conflicting results regarding the association of GERD with caries. Some studies have reported more caries in individuals with GERD, attributing it to several factors, including changes in the composition and volume of saliva or immunological changes [14, 16, 17]. Some other studies have shown that Streptococcus mutans counts decrease due to a significant drop in salivary pH in patients with GERD, leading to the conclusion that this factor can reduce the incidence of caries in this group [1820]. On the other hand, some studies have shown no association between the disease and an increase in dental caries rate [2123]. Considering the high prevalence of dental caries and GERD and contradictions in the relationship between dental caries and GERD in previous studies, the present study aimed to determine the association of gastroesophageal reflux disease (GERD) and dental caries in the Azar cohort population. This study hypothesizes that there is no association between having GERD and dental caries development, considering potential confounders.

Methods

Design and setting

All the data used in the present analytical cross-sectional study were obtained from the enrollment phase of the Azar Cohort Study (ACS). The ACS was framed in three phases: (1) the pilot phase; (2) the enrolment of participants phase; and (3) three follow-up phases for 15 years. It is a large epidemiological study with a sample size of 15,000 subjects aged 35‒70 in the northwest of Iran in Shabestar, a city in East Azerbaijan Province. The ACS is part of a large prospective longitudinal project called the Persian Cohort (Prospective Epidemiological Research Studies in Iran), which aims to collect data about the relevant risk factors of prevalent non-communicable diseases (NCDs) in Iran [24, 25]. Four valid and reliable questionnaires consisting of 482 items were used to collect data in the Persian cohort, and face-to-face interviews and clinical examinations were used to complete these questionnaires, and the information was registered online in the cohort study database [25, 26].

The recruitment phase of the ACS started in October 2014 and continued until 2015. The profile of the ACS and research methods have been described previously [26]. The ACS was approved by the Ethical Committee of Tabriz University of Medical Sciences (record number: tbmed.rec.1393.205). Ethical approval of the present study was received from the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1401.080) on April 2022, and after that, the Azar Cohort Center provided access to data needed in this study [2426].

Participants and sample size

In the present study, data from subjects with a history of GERD in the ACS were recruited. The GERD group consisted of patients who provided positive answers to these questions from the medical questionnaire of the ACS: “Have you ever been diagnosed with gastroesophageal reflux disease?” and “Have you had reflux of food from the stomach to the esophagus in the past year?”. A total of 2010 patients with GERD were identified in the Azar cohort population. Subjects with full dentures were excluded from this study, and data of 905 subjects without full dentures qualified for the GERD group. Also, a comparison group, including subjects without GERD, who had no full dentures and were matched in terms of gender and age, was selected randomly from the ACS databank. Considering 1894 subjects in the control group, data from 2799 participants were included in this study. Fig 1 presents the selection process of the study subjects.

Fig 1. Flow diagram of the number of study subjects.

Fig 1

Variables and data measurement

All the data for this study were obtained from the databank of the ACS. One general, two medical, and one nutrition questionnaire were used to collect information in the Azar cohort study [25, 26]. Among the variables of the Azar cohort study used in the present study, dental caries and body mass index (BMI) were measured based on clinical examinations by trained examiners. Dental caries was recorded as the number of decayed, missing, and filled teeth (DMFT index) according to WHO criteria [27], and the examiner was uninformed of the systemic conditions of the participants. GERD history and the frequency of regurgitation in the ACS were collected using a medical questionnaire by face-to-face interview method and based on the participants’ self-report. Information on demographic characteristics (age and gender) and socioeconomic conditions (educational level and wealth score index) was gathered by the general questionnaire. According to the Persian Cohort Study, to measure economic status, the wealth score index was recorded based on long-lasting belongings and housing characteristics. Information related to behavioral habits (toothbrushing frequency, tobacco use, alcohol drinking, and consumption of free sugars) was extracted from the medical questionnaire and the food frequency questionnaire [26].

In the present study, the frequency of regurgitation was divided into three groups based on the data distribution in the samples, including once or more/week, 2–3 times/month, and no regurgitation [28]. The educational level was classified into two groups: (1) illiterate, elementary school, and middle school (0–8 years of schooling) and (2) high school, high school graduate, and higher education, including associate degree, bachelor’s degree, master’s degree, and doctorate (≥9 years of schooling). The wealth score index was classified into five groups from the poorest to the richest (very poor ≤ -.7966159, poor = -.7966160 to -.3232089, moderate = -.3232090 to .2767860, good = .2767861 to .8069400, and very good = .8069401+). The measurement of food consumption in the food frequency questionnaire of the ACS was based on the amount and frequency of daily, weekly, monthly, and yearly consumption. Categorizing the free sugars consumption (gr/day) was based on the data distribution in the sample (Sweet foods: ≤10.34, 10.35–23.90, and >23.91; sweet drinks: ≤18.93, 18.94–62.08, and ≥62.09; natural fruit juice: ≤0.000, 0.001–7.56 and ≥7.57). The body mass index was categorized into three groups: overweight (≥25), normal (18.5‒24.9), and underweight (<18.5).

Statistical analysis

Data analysis was conducted by IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, N.Y., USA) at a significance level of <0.05. In the present study, the DMFT index was used as the outcome variable. Independent sample t-test and one-way ANOVA were used to compare the mean DMFT scores between subgroups.

Considering the DMFT index as a count data and according to its distribution, the negative binomial with log-link function in Generalized Linear Models (GLM) analysis was used to analyze the relationship between dental caries and the independent variables. According to the aim of this study, the main independent variables that might be affecting dental health were GERD and the frequency of food regurgitation. The variables potentially affecting this relationship, considering confounding effects, include demographic factors (age and gender), socioeconomic status (wealth score index and educational level), behavioral habits (tobacco use, alcohol consumption, frequency of toothbrushing, consumption of sweet foods and beverages containing free sugars), and BMI. The variables whose p-value was <0.2 in the univariate analysis were considered for being included in the multiple regression analysis. The variable selection process for the multiple regression was based on the backward-stepwise method.

Results

Description of the sample

In the study population of the Azar cohort, 905 subjects with GERD did not have full dentures and entered as GERD group. In the present study, more than 60% of the participants were women. About half were in the age range of 35–45 years. Half of the participants had less than 9 years of education, and this was 63% in people with GERD. Most participants belonged to the middle or higher groups regarding the wealth score index. Considering individual habits, around 12% of subjects used tobacco, 2% used to have alcoholic drinks, and 60% brushed their teeth once or more per day. In the group with GERD, about half of the participants brushed their teeth once or more per day. Two-thirds of participants did not report regurgitation symptoms, and nearly 80% were overweight or obese. The DMFT index score varied between 0 and 32 for the participants. The mean DMFT (SD) in the groups with GERD and the control group were 15.09 (6.18) and 15.00 (6.07), respectively. Table 1 shows the frequency distributions of the evaluated variables in the subjects with GERD and control groups.

Table 1. Characteristics of the participants in the GERD and control groups.

Variables Categories GERD group (N %) N = 905 Control group (N %) N = 1894 Total (N %) N = 2799
Gender
Female 560 (61.88) 1158 (61.14) 1718 (61.38)
Male 345 (38.12) 736 (38.86) 1081 (38.62)
Age at interview
35–45 482 (53.26) 992 (52.37) 1474 (52.66)
46–55 323(35.69) 662 (34.95) 985 (35.19)
56–65 90 (9.94) 214 (11.30) 304 (10.86)
≥66 10 (1.11) 26 (1.38) 36 (1.29)
Wealth score index
Very poor 146 (16.13) 230 (12.14) 376 (13.42)
Poor 117 (12.93) 178 (9.40) 295 (10.54)
Moderate 201 (22.21) 343 (18.11) 544 (19.44)
Good 224 (24.15) 491 (25.92) 715 (25.54)
Very good 217 (23.98) 652 (34.42) 869 (31.05)
Years of education
0–8 569 (62.87) 852 (44.98) 1421 (50.77)
≥9 336 (37.12) 1042 (55.02) 1378 (49.23)
Tobacco use
Yes 106 (11.71) 234 (12.35) 340 (12.15)
No 799 (88.29) 1660 (87.65) 2459 (87.85)
Alcohol drinking
Yes 17 (1.88) 40 (2.11) 57 (2.04)
No 888 (98.12) 1854 (99.89) 2742 (97.96)
Toothbrushing
<1/day 455 (50.28) 668 (35.27) 1123 (40.12)
≥1/day 450 (49.72) 1226 (64.73) 1676 (59.88)
Sweet foods (gr/day)
(Free sugars: gr/day) >23.91 268 (29.61) 654 (34.55) 922 (32.95)
10.35–23.90 320 (35.36) 601 (31.75) 921 (32.92)
≤10.34 317 (35.03) 638 (33.70) 955 (34.13)
Sweet beverages
(Free sugars: gr/day) ≥62.09 243 (26.85) 644 (34.02) 887 (31.70)
18.94–62.08 280 (30.94) 606 (32.01) 886 (31.67)
≤18.93 382 (42.21) 643 (33.97) 1025 (36.63)
Natural fruit juice
(Free sugars: gr/day) ≥7.563 260 (28.73) 638 (33.70) 898 (32.09)
.001–7.562 235 (25.97) 442 (23.35) 677 (24.20)
≤0.000 410 (45.30) 813 (42.95) 1223 (43.71)
Body Mass Index (kg/m 2 )
<18.5 2 (0.22) 11 (0.58) 13 (0.46)
18.5–24.9 167 (18.45) 425 (22.44) 592 (21.15)
≥ 25 736 (81.33) 1458 (76.98) 2194 (78.39)
Frequency of regurgitation
Once or more/week 60 (6.63) 45 (2.38) 105 (3.75)
2–3 times/month 154 (17.02) 249 (13.14) 403 (14.40)
No 691 (76.35) 1600 (84.48) 2291 (81.85)
DMFT (Mean ± SD) 15.09 ± 6.18 15.00 ± 6.07 15.03 ± 6.10

Analytical results

Although the DMFT index was higher in the group suffering from GERD than in the control group, both compare mean analysis and univariate regression analysis indicated no statistical association between GERD and dental caries. Table 2 presents the mean ± SD for DMFT in different subgroups of independent variables separately for the group suffering from GERD and the control group.

Table 2. The mean ± SD of DMFT in independent variables in the GERD and control groups.

Variables Categories GERD group Mean ± SD p-value Control group Mean ± SD p-value
Gastroesophageal reflux disease 0.73
Yes 15.09 ± 6.18 ------
No ------ 15.00 ± 6.07
Frequency of regurgitation 0.87*
Once or more/week 14.74 ± 5.32 14.70 ± 5.33 0.57*
2–3 times/month 14.91 ± 5.80 15.36 ± 6.08
No 15.15 ± 6.31 14.94 ± 6.07
Gender
Female 14.54 ± 5.60 ≤0.001 14.91 ± 5.60 0.42
Male 15.97 ± 6.93 15.15 ± 6.74
Age at interview
35–45 13.51 ± 5.73 ≤0.001* 13.75 ± 5.57 ≤0.001*
46–55 16.15 ± 5.75 15.87 ± 6.13
56–65 19.28 ± 6.72 17.73 ± 6.46
≥66 18.90 ± 9.40 18.04 ± 7.27
Wealth score index
Very poor 15.84 ± 6.62 0.02* 16.05 ± 6.51 0.08*
Poor 16.19 ± 6.06 15.17 ± 6.44
Moderate 15.15 ± 6.12 14.87 ± 6.15
Good 14.13 ± 6.24 14.74 ± 5.99
Very good 14.91 ± 5.81 14.85 ± 5.78
Years of education
0–8 15.72 ± 6.33 ≤0.001 15.70 ± 6.34 ≤0.001
≥9 14.01 ± 5.77 14.43 ± 5.77
Tobacco use
Yes 17.19 ± 7.04 ≤0.001 16.29 ± 7.27 ≤0.001
No 14.81 ± 6.00 14.82 ± 5.84
Alcohol drinking
Yes 15.12 ± 7.92 0.22 16.55 ± 7.91 0.98
No 15.09 ± 6.15 14.97 ± 6.02
Toothbrushing
<1/day 15.96 ± 6.61 ≤0.001 16.03 ± 6.75 ≤0.001
≥1/day 14.21 ± 5.58 14.44 ± 5.58
Sweet foods (gr/day)
(Free sugars: gr/day) >23.91 14.68 ± 6.09 0.08* 15.12 ± 5.94 0.82*
10.35–23.90 14.81 ± 5.91 14.95 ± 6.09
≤10.34 15.71 ± 6.48 14.93 ± 6.18
Sweet beverages
(Free sugars: gr/day) ≥62.09 15.18±6.15 0.69* 15.24 ± 6.16 0.46*
18.94–62.08 14.83±5.93 14.89 ± 5.95
≤18.93 15.22±6.38 14.87 ± 6.12
Natural fruit juice
(Free sugars: gr/day) ≥7.563 14.91 ± 6.49 0.69* 14.80 ± 6.13 0.56*
0.001–7.562 14.94 ± 6.38 15.15 ± 6.52
≤0.000 15.28 ± 5.86 15.09 ± 5.75
Body Mass Index (kg/m 2 )
<18.5 18.00 ± 2.83 0.33* 16.55 ± 6.99 0.69*
18.5–24.9 15.65 ± 6.34 14.94 ± 6.23
≥25 14.95 ± 6.14 15.01 ± 6.01

*One-way ANOVA

Independent sample t-test

In the univariate analysis, a significant relationship was observed between the DMFT index and the variables of educational level (p = 0.02) and frequency of toothbrushing (p≤0.001). The variables whose p-value was < 0.2 and included in the multiple regression analysis were age at the interview, years of education, tobacco use, and toothbrushing frequency.

The results of the multiple regression analysis showed a significant association between the outcome variable and toothbrushing frequency so that lack of daily toothbrushing was associated with an increase in dental caries prevalence of approximately 4-fold [IRR = 4.43 (95% CI: 2.85–6.90), p≤0.001]. Also, in this study, there was significantly less dental caries in younger age groups of 35–45 years and 46–55 years [IRR = 0.01 (95% CI: 0.00–0.09) p≤0.001 & IRR = 0.12 (95% CI: 0.02–0.82) p = 0.03, respectively]. Table 3 presents the results of univariate and multiple regression analysis using negative binomial regression to determine the effect of independent variables on the DMFT index.

Table 3. Univariate and multiple regression analysis of the association between DMFT index and independent variables using the negative binomial with log-link function in Generalized Linear Models (n = 2799).

Variables Categories IRR * p-value IRR * p-value
Gastroesophageal reflux disease
Yes 1.01 (0.93–1.09) 0.89
No 1
Frequency of regurgitation
Once or more/week 1.04 (0.85–1.28) 0.68
2–3 times/month 1.00 (0.90–1.12) 0.98
No 1
Gender
Female 0.96 (0.89–1.04) 0.30
Male 1
Age at interview
35–45 0.74 (0.53–1.05) 0.09 0.01 (0.00–0.09) ≤0.001
46–55 0.87 (0.62–1.23) 0.44 0.12 (0.02–0.82) 0.03
56–65 0.99 (0.70–1.42) 0.98 1.06 (0.14–7.97) 0.96
≥66 1 1
Wealth score index
Very poor 1.07 (0.95–1.22) 0.26
Poor 1.05 (0.91–1.20) 0.51
Moderate 1.01 (0.90–1.13) 0.90
Good 0.98 (0.88–1.08) 0.68
Very good 1
Years of education
0–8 1.10 (1.02–1.18) 0.02
≥9 1
Tobacco use
Yes 1.12 (0.99–1.26) 0.06
No 1
Alcohol drinking
Yes 1.07 (0.82–1.41) 0.60
No 1
Toothbrushing
<1/day 5.04 (3.19–7.97) ≤0.001 4.43 (2.85–6.90) ≤0.001
≥1/day 1 1
Sweet foods
(Free sugars: gr/day) >23.91 0.82 (0.47–1.43) 0.49
10.35–23.90 0.75 (0.43–1.31) 0.31
≤10.34 1
Sweet beverages
(Free sugars: gr/day) ≥62.09 1.26 (0.73–2.17) 0.41
18.94–62.08 0.88 (0.51–1.53) 0.65
≤18.93 1
Natural fruit juice
(Free sugars: gr/day) ≥7.563 0.73 (0.43–1.23) 0.23
0.001–7.562 0.93 (0.52–1.65) 0.80
≤0.000 1
Body Mass Index (kg/m 2 )
≥25 0.99 (0.90–1.09) 0.83
<18.5 1.11 (0.63–1.95) 0.72
18.5–24.9 1

*Incidence Rate Ratio

Entered in the multiple regression analysis

Discussion

The most common dental complication reported in patients with gastroesophageal reflux disease (GERD) is tooth erosion [29, 30]; however, few studies have investigated the relationship between this medical condition and dental caries [1923]. The present study aimed to determine the association between GERD and dental caries based on the DMFT index, considering potential confounding variables through regression analysis. There was no significant association between GERD and a higher rate of dental caries compared with healthy subjects. The results showed no significant association between DMFT index score and the frequency of regurgitation, gender, socioeconomic status, BMI, use of tobacco and alcohol, and consumption of sweet foods, sweet drinks, and natural fruit juice. However, a significant relationship was observed between lower DMFT and being younger and daily toothbrushing frequency.

Our study did not show any significant relationship between GERD and a higher rate of dental caries, which was in line with the results of studies by Watanabe, Sîmpălean, and Munoz [2123]. However, some studies revealed a possibility of increased dental caries in patients with GERD due to decreased salivary flow, swallowing dysfunction and low salivary buffering capacity [14, 16]. It has been reported that some other factors like parafunctional habits, such as bruxism, or the individual’s lifestyle, such as improper oral hygiene, play a role in increasing caries in patients with GERD [31, 32]. A study by Borysenko et al. indicated that the prevalence and intensity of dental caries were high in patients with GERD compared with healthy controls and concluded that it could be attributed to immunological changes in GERD patients [17]. On the other hand, some studies showed lower dental caries rates in patients with GERD compared with healthy subjects as a result of dramatic oral pH drops due to acid reflux. These studies indicated that pH drop leads to a reduction in the population of the bacteria, including Streptococcus mutans colonies, as the main microbial aetiological factor in the development of tooth decay. Filipi explained that although S. mutans can survive in pH values <4.2, the pH decline in the oral cavity of GERD might be so remarkable that it can stop the metabolic activity of S. mutans [1820]. It might be concluded that in patients suffering from GERD, despite the decrease in the quantity and quality, and buffering capacity of saliva, which can lead to a higher risk of caries, the decline in the population of cariogenic bacteria in the oral cavity leads to a lower risk of caries. The combination of these two factors possibly leads to the absence of a significant relationship between GERD and dental caries.

The present study showed a significant relationship between the participants’ age and the DMFT index score, with less dental caries in the younger age groups, consistent with other studies. This finding might be attributed to the fact that the effects of risk factors in caries development are cumulative and increase with age [6, 23, 33, 34]. In addition to age, a statistically significant relationship was observed between brushing teeth once a day or more and lower DMFT index scores. Toothbrushing is a well-established method to regularly clean the teeth from microbial plaque, as one of the main aetiological factors of caries development [35].

Lukacs believed that gender differences affect dental caries prevalence through both biological (genetics, hormones, and reproductive history) and anthropological (behavioral) factors, with women exhibiting more dental caries [36]; however, in the present study, no relationship was detected between gender and dental caries, consistent with a study by Abbass [37]. Also, there was no significant relationship between the DMFT index score and socioeconomic status. A systematic review by Costa et al. in 2012 indicated that the educational level, occupation, and subject’s income are related to tooth decay [38]. On the other hand, a systematic review by Reisine and Psoter in 2001 showed a weaker association between socioeconomic conditions and dental caries in adults due to fewer studies and methodological limits [39]. Schwendicke reported a stronger relationship between socioeconomic status and dental caries in developed countries [40]. Developed and developing countries were defined according to the 2008 World Bank classification. It is commonly used to categorize the world into “low and middle-income” (developing) and “high-income” countries (developed) [41]. Therefore, one justification for the non-significant relationship in our study may be that Iran is a developing country. Also, due to the nature of the study, in which data were collected with questionnaires and based on the self-report, the answers to the questions related to socioeconomic conditions may not be completely reliable.

The present study showed no association between BMI and DMFT scores. A systematic review by Silva et al. in 2013 showed insufficient evidence to prove the relationship between obesity and caries [42]. Most systematic studies concluded that there is no consensus regarding the relationship between BMI and dental caries and suggested the need for properly designed studies in this field [4345].

Our study showed no significant relationship between the behavioral risk factors mentioned in this study (sweet foods, sweet drinks, natural fruit juices, and tobacco and alcohol use) and DMFT scores. Few studies that measure the relationship between intake of sugary substances and dental caries have been conducted in the adult age group [46]. Although most of these studies showed a significant relationship between sugar consumption and tooth decay [46, 47], some reported no association [4850], consistent with the present study. This heterogeneity in the results of the studies may be due to confounding factors, such as concurrent consumption of caries-protective foods at meals or differences in fluoride exposure [6]. A Study by Voelker showed that smoking can affect dental health through its influence on the buffering capacity of saliva and levels of secretory IgA [51]; however, the present study showed no significant association between DMFT and smoking. Despite the positive relationship between tobacco use and dental caries in some systematic reviews, they mentioned that this relationship might not be valid due to the poor quality of the studies [52, 53]. Few studies have examined the relationship between alcohol consumption and tooth decay. In contrast with our results, some studies showed a significant increase in the DMFT index and alcohol use [5456]. On the other hand, according to some studies, the high fluoride content in alcoholic beverages is a barrier to new caries development [57, 58].

This research was based on a population-based study with a large sample size and can be representative of the society. However, our study had some limitations. Because this study is cross-sectional, it only shows the relationship/lack of the relationship between desired variables, and the findings are not sufficient to establish a cause-and-effect association. Information about GERD was collected through a questionnaire and based on the participants’ self-report. Also, the duration of gastroesophageal reflux disease was not investigated in the ACS; therefore, the results should be interpreted cautiously.

In conclusion, our study did not show a significant association between GERD and dental caries based on the DMFT index score. As discussed, the results of other studies in this area were not consistent. The high variability between the results of different studies can be related to several factors, including the frequency of regurgitation, the duration of GERD, swallowing disorders, the buffering capacity of saliva, and the design of studies. Prospective longitudinal studies with a sufficient sample size are necessary to reach a better conclusion. There is serious concern about dental caries in Iran, mainly due to the lack of coherent preventive programs. Emphasis on oral and dental hygiene, including regular toothbrushing once a day or more, can be among the most influential factors in reducing dental caries.

Supporting information

S1 Dataset

(XLS)

Acknowledgments

The authors are grateful for the support of Tabriz University of Medical Sciences and the Liver and Gastrointestinal Diseases Research Center. The authors also are deeply indebted to all the subjects participated in this study. We appreciate the contribution of the investigators and the staff of the Azar cohort study. We thank the close collaboration of the Shabestar health center. In addition, we would like to thank the Persian cohort study staff for their technical support.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Hadi Ghasemi

21 May 2023

PONE-D-23-10589Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional studyPLOS ONE

Dear Dr. Mahboobi,

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Data used in the present study was obtained from the database of the Azar Cohort study. The Azar cohort study was supported by the liver and gastrointestinal diseases research center (Grant number 700/108 on 14 March 2016) at Tabriz University of Medical Sciences. The Iranian Ministry of Health and Medical Education has contributed to the funding used in the PERSIAN cohort through Grant no.700/534. The funders had no role in the study design, data analysis, interpretation, and writing the manuscript in this study.“

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Reviewer #1: No

Reviewer #2: Partly

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Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Thank you for asking me to review the manuscript titled “Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population. A cross-sectional study”

The article is relevant to the field of Internal medicine and Dentistry. However, there are flaws in the write -up;

Introduction

A major drawback of this manuscript is that the authors failed to review literature on GERD and dental caries. In addition, they didn’t identify any gap/s in literature that their study would want to address.

Generally, the paragraphs don’t flow into each other – the previous paragraph doesn’t flow to the next.

Methods

In addition to other confounding variables, the authors should have considered the oral hygiene status of the participants.

Similarly, there is no information on the fluoride exposure of the participants in the study.

Although information on free sugar consumption was obtained, the frequency of free sugar consumption between meals will be more appropriate in relation to caries formation.

Classification of GERD frequency of regurgitation should be referenced

Results

It would have been better to compare the mean DMFT scores of both groups based on the different variables (socio-demographic, oral health practices and BMI) before the regression analysis.

Discussion

This is inadequate- the authors didn’t discuss the reasons behind their findings

Reviewer #2: Title: It is limited, as there are many other factors that have been checked other than GERD. So you need to modify your title accordingly.

Abstract:

- Objectives: There are many other objectives that were not mentioned.

- Materials and methods: very confusing, as I don’t understand if all your data obtained from dataset

previously recorded, Or the clinical examination and the interviews were conducted as part of this

study. This same comment is applied to methodology section that needs to be re-written.

Introduction:

Line 53: move word ‘still’ after ‘are’.

Line 60: consistency in writing word ‘socioeconomic’.

Next to first paragraph, additional paragraph should be added to briefly preset the socioeconomic and environmental factors that is related or may affect dental caries.

Line 78: Add reference.

Add null hypothesis to the last paragraph

Methods:

-Very confusing as mentioned previously, which data that have been obtained from previous records and which data were obtained by clinical examination and questionnaires in this study??

-And if questionnaires were used, you have to specify is it online , face to face interview, paper based?

-What was the response rate in each questionnaire, number of items in each questionnaire, how these items were validated, any piloting for the questionnaire was done?

-Why 905 were selected from 2010 patients with GERD, and how these patients were selected.

-GERD patients only were diagnosed based on the two questions that have been mentioned.

- What do you mean by oral examiner, this is not acceptable description.

- Variables and data measurement section is not clear and more details should be added.

- Line 134-136: What are the categories?

Tables:

-Wealth index: what are the ranges of poor, moderate ….by numbers?

- Footnotes should be added to your tables

-

Discussion:

Line 202: Add few studies as you have mentioned in the text.

Line 208, 209: rephrase the sentence using DMFT term.

Line 223: Add reference

Line 231: Reference 33, 34 are irrelevant

Line 242: Discuss further regarding developing country and provide reference.

Line 253: Few studies… (however one reference was mentioned)

Line 258: Add reference

Line 258-260: The discussion is weak regarding the tobacco consumption

Discussion section needs improvement and more details and justifications for your findings should be presentd.

General comments:

English language needs to be checked.

It is nice to see at least one figure.

References need to be checked as many sentences need referencing, and some references are not really relevant to the text.

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Attachment

Submitted filename: review.docx

PLoS One. 2023 Aug 10;18(8):e0289802. doi: 10.1371/journal.pone.0289802.r003

Author response to Decision Letter 0


16 Jun 2023

Response to Reviewers:

Reviewer 1:

Introduction

• A major drawback of this manuscript is that the authors failed to review literature on GERD and dental caries. In addition, they didn’t identify any gap/s in literature that their study would want to address.

Response: The text was edited as suggested by the reviewer.

Page 3, Lines 64¬¬¬¬–70; Page 5, Lines 92¬¬¬¬–100.

• Generally, the paragraphs don’t flow into each other – the previous paragraph doesn’t flow to the next.

Response: The text editing has been performed as suggested by the reviewer.

Methods

• In addition to other confounding variables, the authors should have considered the oral hygiene status of the participants.

• Similarly, there is no information on the fluoride exposure of the participants in the study.

Response: The present study is a subsample of the data of an epidemiological study with a sample size of 15,000 people (Azar Cohort Study). Due to the large sample size, some variables, such as oral hygiene status and fluoride intake, were not investigated.

Also, due to the inclusion criteria of the Azar Cohort Study— permanent residence in the Shabestar district—it can be concluded that they were exposed to fluoride in the same conditions.

• Although information on free sugar consumption was obtained, the frequency of free sugar consumption between meals will be more appropriate in relation to caries formation.

Response: Based on studies by Sheiham (2001) and Moynihan (2014), both the frequency of consumption and the total amount of free sugars are important in the etiology of caries. Considering the common risk factor approach, in the present study, the amount of free sugars intake was used instead of the frequency of consumption.

A. Sheiham. Dietary effects on dental diseases. Public Health Nutrition. 2001.4(2B),569-591.

P.J. Moynihan and S.A.M. Kelly, Effect on Caries of Restricting Sugars Intake: Systematic Review to Inform WHO Guidelines. Journal of Dental Research. 2014. 93(1):8-18.

• Classification of GERD frequency of regurgitation should be referenced.

Response: It was added on page 8, line 164.

According to the classification of Wenzl 2020 (Never, Less than weekly, Weekly, Daily) and considering the data distribution in the sample, it was classified into three groups.

E.M. Wenzl, R. Ried, A. Borenich, W. Petritsch, H.H. Wenzl. Low prevalence of gastroesophageal reflux symptoms in vegetarians. Indian Journal of Gastroenterology.

GERD comprises a broad spectrum of disorders. The typical symptoms of GERD in adult patients are retrosternal or sub-sternal burning, regurgitation, epigastric pain, and dysphagia. Symptoms related to the reflux of gastric contents into the esophagus – principally heartburn and regurgitation – are widespread in the general population. Regurgitation, the perception of gastric contents moving from the stomach into the esophagus, experienced by 40–50% of patients with reflux disease, is also a typical symptom.

R. JONES & J. P. GALMICHE. Review: What do we mean by GERD? Definition and diagnosis. Alimentary pharmacology & therapeutics. 2005; 22 (Suppl. 1): 2–10.

Results

• It would have been better to compare the mean DMFT scores of both groups based on the different variables (socio-demographic, oral health practices and BMI) before the regression analysis.

Response: Table 2 was added according to the reviewer's suggestion.

Page 12, Line 235.

Discussion

• This is inadequate- the authors didn’t discuss the reasons behind their findings.

Response: The discussion section was expanded, and more details and justifications were discussed.

Page 15, Lines 267–272; Page 15, Lines 281–283; Pages 15 & 16, Lines 291–294; Page 16, Lines 311–313.

Reviewer 2:

Title

• It is limited, as there are many other factors that have been checked other than GERD. So you need to modify your title accordingly.

Response: According to the primary objective of this study, the main independent variable that might affect dental health was GERD. The variables potentially affecting this relationship, considering confounding effects, include demographic factors (age and gender), socioeconomic status (wealth score index and educational level), behavioral habits (tobacco use, alcohol consumption, frequency of toothbrushing, and consumption of sweet foods and beverages containing free sugars), and BMI.

Abstract

• Objectives: There are many other objectives that were not mentioned.

Response: According to the primary objective of this study, the main independent variable that might affect dental health was GERD. The other variables potentially affecting this relationship, considering confounding effects, include: demographic factors (age and gender), socioeconomic status (wealth score index and educational level), behavioral habits (tobacco use, alcohol consumption, frequency of toothbrushing, and consumption of sweet foods and beverages containing free sugars), and BMI.

• Materials and methods: very confusing, as I don’t understand if all your data obtained from dataset previously recorded, Or the clinical examination and the interviews were conducted as part of this study. This same comment is applied to methodology section that needs to be re-written.

Response: The “Methods” section was rewritten for more clarity. All data used in the present study was obtained from the dataset of ACS and had been recorded previously.

Introduction

• Line 53: move word ‘still’ after ‘are’.

Response: The text was edited as suggested by the reviewer.

Page 3, Line 55.

• Line 60: consistency in writing word ‘socioeconomic’.

Response: The text was edited as suggested by the reviewer.

Page 3, Line 62.

• Next to first paragraph, additional paragraph should be added to briefly preset the socioeconomic and environmental factors that is related or may affect dental caries.

Response: The text was edited as suggested by the reviewer.

Page 3 & 4, Lines 62–70.

• Line 78: Add reference.

Response: It was added.

Page 4, Line 88.

• Add null hypothesis to the last paragraph.

Response: It was added.

Page 5, lines 103–104.

Methods

• Very confusing as mentioned previously, which data that have been obtained from previous records and which data were obtained by clinical examination and questionnaires in this study? (This same comment is applied to methodology section that needs to be re-written).

Response: The “Methods” section was rewritten for more clarity. All the data used in this analytical cross-sectional study were obtained from the enrollment phase of the ACS and had been recorded previously.

• And if questionnaires were used, you have to specify is it online, face to face interview, paper based?

Response: It was addressed on page 6, Line 115.

Four questionnaires (one general, two medical, and one nutrition) consisting of 482 items were used to collect information in the Azar Cohort Study; and face-to-face interviews and clinical examinations were used to complete these questionnaires. Data are recorded online and stored in a centralized database and in 3 other locations, being backed up every 30 minutes.

• What was the response rate in each questionnaire, number of items in each questionnaire, how these items were validated, any piloting for the questionnaire was done?

Response: Since face-to-face interviews and clinical examinations were used to complete these questionnaires and the information was registered online in the cohort study databank, the response rate was 100%. All questionnaires are checked for completeness by field supervisors. It was addressed on page 6, Lines 115–118.

The Azar Cohort Study was set up in three phases: (i) pilot study; (ii) enrolment of participants; and (iii) regular follow-up of subjects for 15 years (Farhang 2019). The aim of the pilot phase was to appraise the feasibility of the study and reveal any unmet needs for undertaking the full-scale AZAR cohort study. Specifically, the pilot phase aimed to implement valid and reproducible methods and test the structured questionnaires. Also, the items in the questionnaires were categorized and presented in their own subgroups and were not numbered.

Poustchi H, Eghtesad S, Kamangar F, Etemadi A, Keshtkar AA, Hekmatdoost A, et al. Prospective Epidemiological Research Studies in Iran (the PERSIAN Cohort Study): Rationale, Objectives, and Design. Am J Epidemiol. 2018;187(4):647-655.

Farhang S, Faramarzi E, Amini Sani N, Poustchi H, Ostadrahimi A, Alizadeh BZ, Somi MH. Cohort Profile: The AZAR cohort, a health-oriented research model in areas of major environmental change in Central Asia. Int J Epidemiol. 2019; 48(2):382-382h.

• Why 905 were selected from 2010 patients with GERD, and how these patients were selected.

Response: According to the exclusion criteria, subjects with full dentures were excluded from the present study.

It was addressed on page 6, Line 133.

A total of 2010 patients with GERD were identified in the Azar cohort population, and 905 subjects without full dentures qualified for the case group. Fig 1 presents the selection process of the study subjects.

• GERD patients only were diagnosed based on the two questions that have been mentioned.

Response: The present study is a subsample of the data of a large epidemiological study with a sample size of 15,000 people (Azar Cohort Study). Due to the large sample size, data were collected by questionnaires.

GERD comprises a broad spectrum of disorders. The typical symptoms of GERD in adult patients are retrosternal or sub-sternal burning, regurgitation, epigastric pain, and dysphagia. Regurgitation, the perception of gastric contents moving from the stomach into the esophagus, experienced by 40–50% of patients with reflux disease, is also a typical symptom (Jones 2005).

R. JONES & J. P. GALMICHE. Review: What do we mean by GERD? Definition and diagnosis. Alimentary pharmacology & therapeutics. 2005; 22 (Suppl. 1): 2–10.

• What do you mean by oral examiner? This is not acceptable description.

Response: The text was edited as suggested by the reviewer.

Page 7, Line 152.

• Variables and data measurement section is not clear and more details should be added.

Response: The “Variables and data measurement” section was rewritten, and some details were added for more clarity.

Page 7 & 8, Lines 149–177.

• Line 134-136: What are the categories?

Response: It was addressed in the text.

Page 8, Lines 174–175.

Tables

• Wealth index: what are the ranges of poor, moderate ….by numbers?

Response: It has been addressed in the text.

Page 8, Lines 169–171.

• Footnotes should be added to your tables

Response: The tables were revised as suggested by the reviewer.

Pages 10, 12 & 13.

Discussion

• Line 202: Add few studies as you have mentioned in the text.

Response: It was added.

Page 14, Line 245.

• Line 208, 209: rephrase the sentence using DMFT term.

Response: The text was edited as suggested by the reviewer.

Page 14, Line 252.

• Line 223: Add reference

Response: It was added.

Page 15, Line 267.

• Line 231: Reference 33, 34 are irrelevant.

Response: The references were revised as suggested by the reviewer.

Page 15, Line 280.

• Line 242: Discuss further regarding developing country and provide reference.

Response: It was addressed on page 15 & 16, Lines 291–294.

• Line 253: Few studies… (However one reference was mentioned)

Response: The reference provided for this section is a systematic review study to Inform WHO Guidelines and was published in 2014. It is mentioned in this article that “The majority of studies identified were conducted on children, while only four studies were on adults".

Moynihan PJ, Kelly SA. Effect on caries of restricting sugars intake: systematic review to inform WHO guidelines. J Dent Res. 2014;93(1):8-18.

• Line 258: Add reference

Response: It was added on page 16, line 311.

According to the Fejerskov and Manji model for caries causation, at the individual level and in the presence of adequate saliva, optimum fluoride exposure and nutritional pattern are important determining factors for the development of caries.

• Line 258-260: The discussion is weak regarding the tobacco consumption.

Response: The text was revised as suggested by the reviewer.

Page 16, Lines 311–312

• Discussion section needs improvement and more details and justifications for your findings should be presented.

Response: The discussion section was expanded, and the reasons behind the findings were discussed.

General comments

• English language needs to be checked.

Response: The English text was edited professionally.

• It is nice to see at least one figure.

Response: It was added on page 7, Line 140.

• References need to be checked as many sentences need referencing, and some references are not really relevant to the text.

Response: References were revised and irrelevant references were deleted.

Attachment

Submitted filename: Response to Reviewers-Mahboobi.doc

Decision Letter 1

Hadi Ghasemi

10 Jul 2023

PONE-D-23-10589R1Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional studyPLOS ONE

Dear Dr. Mahboobi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Hadi Ghasemi

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

**********

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

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Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: No

**********

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Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for addressing all comments, few comments were added to the revised manuscript itself. Thank you

Reviewer #3: All comments by previous reviewer have been addressed adequately. The methods have been addressed comprehensively, the discussion has been improved upon. Also the English has been adequately corrected. This new reviewed article makes a better read.

Reviewer #4: General Comments:

The paper "Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional study" presents a study that looked at the relationship between GERD and dental caries using the DMFT index. The study investigates potential confounding variables and gives a thorough analysis of the findings. Overall, the work is well-written and structured, and it contributes significantly to the subject of dentistry. While some small edits and clarifications are needed, the manuscript gives a compelling research study with relevant findings.

Specific Comments:

Introduction:

The introduction gives a clear context and rationale for the research. Given that tooth erosion is a prevalent issue in GERD patients, it effectively emphasizes the necessity of knowing the relationship between GERD and dental caries. The introduction also discusses the existing literature gap about the relationship between GERD and dental caries. However, at the end of the introductory section, a more clear and focused statement of the study's aims would be beneficial with clear hypothesis.

Methods:

The methods section discusses the study's design, participant selection, and data collection procedures in detail. Given its widespread usage in dentistry research, the use of the DMFT index as a measure of dental caries is justified. However, some small clarifications are required. For example, more information on how GERD was assessed, such as the questions or criteria utilized in the questionnaire, would be beneficial. The limitations of self-reported data, as well as their potential impact on the study's conclusions, should also be addressed.

Results:

The results section is well-organized and presents the study's findings clearly. The statistical analysis, including regression analysis, strengthens the study. However, for significant findings, it would be beneficial to provide the effect sizes to provide a better understanding of the magnitude of the associations observed.

Discussion:

The discussion section explores the study's findings in depth in relation to previous studies, noting both consistent and contradictory findings. The discussion is enriched by the inclusion of numerous aspects that may contribute to the association between GERD and dental caries, such as salivary flow, swallowing difficulty, and oral hygiene behaviors. However, a more extensive examination of the potential processes behind the observed relationships, particularly those related to the decline in cariogenic bacteria despite lower saliva quality and quantity, would be beneficial. Furthermore, the study's limitations, such as its cross-sectional design and dependence on self-reporting, are noted correctly. The conclusion emphasizes the need for additional research, which is appropriate.

Language and Structure:

The manuscript is generally well-written with clear and concise language.

Figures and Tables:

The figures and tables provided in the manuscript are relevant and contribute to the understanding of the results.

Overall, the manuscript makes an important contribution to the field of dentistry by exploring the relationship between GERD and dental caries. The study is well-designed, and the results are effectively presented and analyzed.

**********

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Reviewer #2: No

Reviewer #3: Yes: ADEBAYO PETER Adewuyi

Reviewer #4: Yes: Furqan Ahmed

**********

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Attachment

Submitted filename: Revised Manuscript with Trachchanges-Mahboobi NS.doc

PLoS One. 2023 Aug 10;18(8):e0289802. doi: 10.1371/journal.pone.0289802.r005

Author response to Decision Letter 1


24 Jul 2023

Response to Reviewers:

Reviewer 2:

1. What do you mean by proximal and distal determinants?

Response: “The chain of events leading to an adverse health outcome can be both proximal and distal; proximal factors act directly or almost directly to cause diseases, while distal factors are further back in the causal chain and act via a number of intermediary causes.”

Petersen PE. Sociobehavioural risk factors in dental caries – international perspectives. Community Dent Oral Epidemiol 2005; 33: 274–9.

2. Add reference (page 4, line 65).

Response: The content of this paragraph is from chapter 4 of the book "Dental Caries: the disease and its clinical management" which is about the epidemiology of dental caries. The book has been referenced at the end of the paragraph.

3. Re-phrase, it is not clear.

Response: It was re-phrased (page 4, line 67)

These conditions provide the opportunities for and limit individual behaviors.

4. What are these numbers, which currency? (Line 169)

Response: It’s not a currency. The Wealth Score Index (WSI) in the Azar Cohort Study was based on assets such as dishwashers, vehicles, and flat-screen TVs as well as house conditions (e.g. the number of rooms, and type of ownership). This index was determined via Multiple Correspondence Analysis (MCA) and grouped into five quintiles, the first being the lowest and the fifth being the highest score.

Reviewer 4:

1. Introduction:

The introduction gives a clear context and rationale for the research. Given that tooth erosion is a prevalent issue in GERD patients, it effectively emphasizes the necessity of knowing the relationship between GERD and dental caries. The introduction also discusses the existing literature gap about the relationship between GERD and dental caries. However, at the end of the introductory section, a more clear and focused statement of the study's aims would be beneficial with clear hypothesis.

Response: It was addressed on page 5, line 101:

This study hypothesizes that there is no association between having GERD and dental caries development considering potential confounders.

2. Methods:

The methods section discusses the study's design, participant selection, and data collection procedures in detail. Given its widespread usage in dentistry research, the use of the DMFT index as a measure of dental caries is justified. However, some small clarifications are required. For example, more information on how GERD was assessed, such as the questions or criteria utilized in the questionnaire, would be beneficial. The limitations of self-reported data, as well as their potential impact on the study's conclusions, should also be addressed.

Response: It was done; page 7, lines 148-150.

- Among the variables of the Azar cohort study used in the present study, dental caries and body mass index (BMI) were measured based on clinical examinations by trained examiners. Dental caries was recorded as the number of decayed, missing, and filled teeth (DMFT index) according to WHO criteria [27], and the examiner was uninformed of the systemic conditions of the participants.

Other variables of the present study, including having GERD, were determined using a questionnaire and based on the participants' self-report (It has been addressed on pages 7 & 8; lines 152-161). The criterion for having GERD was the answer to these two questions: “Have you ever been diagnosed with gastroesophageal reflux disease?” and “Have you had reflux of food from the stomach to the esophagus in the past year?” (It has been addressed on page 6; lines 126-129).

The limitations of the study design and self-reported data have been considered in Discussion section (page 17, lines 324-329).

3. Results:

The results section is well-organized and presents the study's findings clearly. The statistical analysis, including regression analysis, strengthens the study. However, for significant findings, it would be beneficial to provide the effect sizes to provide a better understanding of the magnitude of the associations observed.

Response: It was addressed on page 11; line 223.

4. Discussion:

The discussion section explores the study's findings in depth in relation to previous studies, noting both consistent and contradictory findings. The discussion is enriched by the inclusion of numerous aspects that may contribute to the association between GERD and dental caries, such as salivary flow, swallowing difficulty, and oral hygiene behaviors. However, a more extensive examination of the potential processes behind the observed relationships, particularly those related to the decline in cariogenic bacteria despite lower saliva quality and quantity, would be beneficial. Furthermore, the study's limitations, such as its cross-sectional design and dependence on self-reporting, are noted correctly. The conclusion emphasizes the need for additional research, which is appropriate.

Response: It was done; page 15, lines 265-267.

Filipi explained that although S. mutans can survive in pH values <4.2, the pH decline in the oral cavity of GERD might be so remarkable that it can stop the metabolic activity of S. mutans.

With best regards and thanks for the careful review and valuable comments of the reviewers.

Attachment

Submitted filename: Response to Reviewers-Mahboobi.doc

Decision Letter 2

Hadi Ghasemi

26 Jul 2023

Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional study

PONE-D-23-10589R2

Dear Dr. Zeinab Mahboobi,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Hadi Ghasemi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Hadi Ghasemi

31 Jul 2023

PONE-D-23-10589R2

Association between gastroesophageal reflux disease and dental caries among adults in the Azar cohort population: A cross-sectional study

Dear Dr. Mahboobi:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Hadi Ghasemi

Academic Editor

PLOS ONE

Associated Data

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    Supplementary Materials

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    Submitted filename: Revised Manuscript with Trachchanges-Mahboobi NS.doc

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    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


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