Impact of fluorosis on the oral health-related quality of life: a systematic review and meta-analysis.

Impact of fluorosis on the oral health-related quality of life: a systematic review and meta-analysis. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of fluorosis on the oral health-related quality of life: a systematic review and meta-analysis. Paula Lanza Montanher, Sofia Maito Velasco, Renan Canale Peres Montanher, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3745254/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Oct, 2024 Read the published version in Clinical Oral Investigations → Version 1 posted 9 You are reading this latest preprint version Abstract Objective. The aim of this systematic review is to investigate the literature to assess the effect of fluorosis on the Oral Health-Related Quality of Life (OHRQoL). Materials and methods. Included studies were epidemiological investigations, clinical trials, or human studies that directly compared the impact on OHRQoL between individuals with fluorosis and those without, utilizing valid OHRQoL assessment tools. The searches were conducted up to September 2023 in databases, including PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and the Virtual Health Library. Additionally, gray literature sources such as Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest were searched. Reference lists were also manually reviewed for potential eligible studies. The risk of bias in cohort studies was assessed using the Newcastle–Ottawa Scale (NOS), while its modified version was employed for cross-sectional studies. A meta-analysis was performed using the random-effects model in R Statistical Software with a significance level of p<0.05. Results. Out of the 16 included studies, four were suitable for meta-analysis. In total, 16,314 participants, aged 8 to 18, were assessed across the studies. The analysis of the CPQ 8-10 instrument indicated no significant impact (p-value = 0.14). For the CPQ 11-14 the quantitative analysis suggested no significant impact on OHRQoL (p-value = 0.51). Limitations in the included studies primarily pertained to cross-sectional designs, with significant issues such as the absence of sample size calculations, lack of non-response rate reporting, limited consideration of confounding factors, and substantial heterogeneity stemming from diverse diagnostic methods and assessment tools. Conclusion. The overall findings indicated that mild dental fluorosis did not adversely affect the OHRQoL of the studied populations. Clinical relevance. Dental caries preventive fluoridated measures might be indicated even if there would be a risk for mild dental fluorosis as the fluoridated public water. Trial registration. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under number: CRD42020186552. Dental fluorosis Quality of life Cross-Sectional Studies Figures Figure 1 Figure 2 INTRODUCTION According to the World Health Organization (WHO) [ 1 ], fluorosis is characterized by bilateral symmetrical lesions and horizontal streaks on the surface of the dental enamel. Milder grades present with fine lines, opaque and white, which at the most severe levels may evolve into brown spots or depressions with brown spots and corrosion [ 1 ]. It is caused by excessive and prolonged ingestion of fluoride during the tooth formation phase [ 1 – 3 ], mainly from combined sources such as public water supply and toothpaste [ 2 , 4 – 6 ]. Fluorides has been used for dental caries control by public and individual strategies achieving considerable success verified from the dental caries decline in developed [ 7 ] and developing countries [ 8 ], even though this disease remain as a huge public health problem worldwide [ 9 , 10 ]. Public fluoridated water supply initiated in the USA in 1945 [ 11 ], in Brazil in 1953 [ 12 ], and more than 20 nations use it concurrently [ 11 ]. This public policy induces dental caries prevalence and severity reduction in deciduous and permanent teeth for children [ 11 ], and adults [ 13 , 14 ], with low costs [ 15 ], nevertheless associated to dental fluorosis [ 11 ], especially the mild ones. The toothpastes containing at least 1000 ppm fluoride toothpaste used daily is associated to dental caries control and for this reason widely used, however also associated to the prevalence of dental fluorosis [ 16 ]. The effectiveness of dental caries control, maintenance, and prevention of dental fluorosis induced by using low-fluoridated toothpaste remains uncertain without an established lower cut point for fluoride content of 1000 ppm [ 16 ]. Dental fluorosis is asymptomatic and its negative effect on the oral health-related quality of life (OHRQoL) has been investigated in recent years through the aesthetic perception of individuals about this condition [ 3 , 17 – 19 ]. Feelings of anguish, worry, and difficulty in smiling expressed by children with dental fluorosis have been mentioned, especially at more severe levels [ 13 ]. In 2009, a critical review of the literature [ 2 ] revealed that mild fluorosis was not a concern and that it could be positively associated with the OHRQoL because adolescents considered the presence of white spots as more attractive [ 5 , 14 ]. In Colombia [ 15 ], only 25% of those examined with mild fluorosis recognized their teeth as “ugly”. In Brazil, only 40.1% of children aged 12 years, with mild and very mild fluorosis, noticed stains on their teeth [ 20 ]. Nevertheless, the greater the severity of fluorosis, the greater seems to be the degree of individuals dissatisfaction [ 21 – 23 ]. Studies about the effect of fluorosis and OHRQoL have presented distinct results, although no systematic review has studied children and adolescent’s dental fluorosis association with OHRQoL which might be used as evidence to guide public policies in the balance of dental caries and fluorosis control. Thus, this study systematically reviewed the literature to assess the impact of fluorosis on the quality of life, comparing the group with fluorosis and without fluorosis. METHODS Protocol registration The systematic review was conducted through qualitative and quantitative syntheses and was performed according to PRISMA guidelines [ 24 ]. The protocol has been registered at the PROSPERO database (CRD42020186552). PECO question A question structured based on the PECO strategy was formulated. P: people in general; E: exposure to fluorosis; C: non-fluorosis; and O: impact outcomes of fluorosis on OHRQoL. The PECO question was structured as follows: "does fluorosis have an impact on the quality of life of children and adolescents?". Search strategy The searches were developed from Medical Subject Headings (MeSH) descriptors, Boolean logical operators (AND, OR, and NOT), and predefined keywords. The search strategy included the following MeSH terms: (Fluorosis, Dental or Dental Fluorosis or Dental Fluorosis or Mottled Enamel or Enamel, Mottled or Enamels, Mottled or Mottled Enamels) AND (Life Quality or Health-Related Quality Of Life or Health-Related Quality Of Life or OHRQoL) and DeCS: (Fluorosis, Dental or Dental Fluorosis or Dental Fluorosis or Fluorosis, Dental or Mottled Enamel) AND (Quality of Life or OHRQoL or Health-Related Quality Of Life or Health-Related Quality Of Life or Life Quality) entrees Embase. There were no language restrictions and publication year. The search strategies were adapted for each database. Searches were performed until September 2023 in databases: PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and Virtual Health Library, in addition to gray literature: Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest. A manual search was also performed by reading the reference list of the included articles to search for potentially eligible studies. Inclusion and exclusion criteria Databases were searched without limitation of date or language of publication. Epidemiological studies, such as cross-sectional, case–control, cohort, and clinical trials; studies with humans; studies that compared, in the same study the impact on the OHRQoL of individuals with fluorosis (fluorosis group) and individuals without fluorosis (control group); and studies that used any valid instrument to assess the OHRQoL of the participants were included. Case reports and case series studies, letters to the editor, systematic reviews, integrative reviews, scope reviews, narratives, qualitative studies, and studies with human beings in situ were excluded. Study selection Two examiners (P.L.M. and S.R.M.V.) met and discussed the eligibility criteria before starting the search. To remove duplicates, Endnote Web software was used ( http://www.myendnoteweb.com ), followed by manual deletion. Then, in the first stage, the titles and abstracts of articles that met the inclusion criteria were independently read by the reviewers. Potentially eligible articles moved to the second stage of reading the full text. In the presence of disagreements, a third examiner was consulted (M.P.M.) in any of the steps. The following data were extracted by two examiners independently (P.L.M. and S.R.M.V.) and tabulated in Excel 2016 spreadsheets: authors, publication year, country, study type, sample size, gender, age assessed, fluoride concentration in water, investigated outcomes, index used for diagnosis and fluorosis classification, most prevalent fluorosis severity score, fluorosis prevalence, QoL instruments, examiner calibration, statistical analysis, and QoL results (values ​​in the fluorosis group and control group). Risk of bias in individual studies The quality of the articles was also independently assessed by the researchers (P.L.M. and S.R.M.V.) with discussion in cases of divergence. The Newcastle–Ottawa Scale (NOS) was used to assess cohort studies and its modified version for cross-sectional studies. The scale for cohort studies is divided into three dimensions: selection, comparability, and outcome assessment. For case-control studies, the scale is organized into selection of cases and controls, comparability of cases and controls, and determination of exposure. The results of the NOS tool are interpreted as follows: total score ≥ 6 = consistent studies; total score < 6 = inconsistent studies. For the modified NOS tool, the following scores were considered: 0–4 points = unsatisfactory studies; 5–6 points = satisfactory studies, 7–8 points = good studies, and 9 points = very good studies 25 . The NOS assigns a higher score to cohort studies with representation of the exposed cohort community. In case-control studies the NOS yields a higher score when population-based controls are used compared to controls from hospitals. It also assigns a higher score to studies that had a blinded assessment of exposure. Additionally, the NOS assigns a higher score to case-control studies with a comparable non-response rate between cases and controls, as opposed to case-control studies with different response proportions. Statistical analysis A meta-analysis was conducted utilizing the random-effects model through the employment of R Statistical Software (v4.1.2; R Core Team 2021), a free and open-source software for data analysis and performing statistical tests. A significance level was set at p-value < 0.05. Effect measures The results were presented according to the standardized mean difference of the instruments used to measure the QoL and the sample size of each study. RESULTS Literature search The study selection process is summarized in Figure 1. The search strategy resulted in 380 studies. After removing the duplicates, 141 were potentially eligible studies based on the title and abstract reading. Following the analysis, 42 articles were selected for full-text reading. The complete verification of the content allowed the exclusion with the justification of 26 articles. [17,19,20,23,26-47] The remaining 16 studies moved to qualitative synthesis [18,48-59,61-63]. Four studies [18,49,51,58] were included in the meta-analysis. The inter-examiner kappa agreement index was 1. Figure 1. Flowchart of the search strategy and results according to the PRISMA statement. The reasons for the exclusion of the studies were: The studies did not present the control group; the studies only validated the instrument by comparing responses from parents and children; the studies only applied a self-perception questionnaire to participants without QOL scores in the control group; the studies grouped individuals without fluorosis and with mild levels of fluorosis; the studies did not present the result of the application of the QL instrument with fluorosis; the studies applied a questionnaire only on aesthetic satisfaction and did not present data from the analysis of QOL and fluorosis, only the p-value. Description of the studies Table 1 shows the characteristics of the included studies. To classify the severity of fluorosis, seven studies used the Thylstrup Fejerskov Index (TFI) [18,49,51,53,55,62,63], eight studies the Dean index [48,52,54-57,61], and one study the modified Dean index [59]. All studies were subjected to examiner calibration, and the minimum inter-examiner Kappa value for fluorosis was 0.79 (Table 1). Table 1. Main characteristics of included studies. The samples in the included studies ranged from 60 [49] to 7,686 [56] participants, including the groups with and without fluorosis. Considering all the studies, a total of 16,314 participants, 6,422 with fluorosis and 9,892 without fluorosis were evaluated, distributed in Brazil [49,50,53-57], India [58,59], Mexico [51], Australia [18], USA [56], China [52], Líbia [61]Ecuador[63], and Sri Lanka[63]with ages ranging from 8 to 18 years. Several validated instruments were used by the included studies to assess the impact of fluorosis on Oral Health-Related Quality of Life (OHRQoL) [18,49-53,56-59, 61-63]. All the included studies are cross-sectional, except one that is a cohort [57]. The fluorosis index used by the studies was Thylstrup-Fejerskov index (TFI) [18,49,51,53,58,62-63], Dean [48,50,52,54-57,61] and modified Dean index [59]. Two studies did not provide the coefficient of calibration for the assessors [56,62] and one presented a kappa < 0.80 [52]. Detailed findings and analyses are presented in Table 1. Tables 2 and 3 present the details of the risk of bias assessment of the studies included after applying the NOS and modified NOS tools. The main deficiencies of the 15 cross-sectional studies were related to the lack of sample calculation [48,49,51,54,55,62], representation [48,49,51,54,56], adjustment of the confounding factor [18,48-56,58,59,61-63], and non-response rate [48,53,54,58, 59,62-63]. Table 2. Quality assessment of the cohort study (Newcastle–Ottawa Scale - NOS) Table 3. Quality assessment of cross-sectional studies (modified Newcastle–Ottawa Scale- modified NOS) Regarding the risk of bias, the included studies followed the following classification after the application of the Newcastle-Ottawa (NOS) tool modified for cross-sectional studies: 3 studies [48,49,54] were considered unsatisfactory (total score of 4 points) 8 studies were considered satisfactory [51,53,55,56,58,59,62,63] (total score between 5-6 points) and 4 studies were considered good (total score of 7 points) [18,50,52,61]. The cohort study [57] was classified as good after the application of the Newcastle Ottawa tool (final total score of 8). Findings between the severity of fluorosis and effect on OHRQoL In a US study [56], very mild to mild fluorosis was the most prevalent, with 12.1%, based on the Dean index. The same occurred in another study, with a prevalence of 7.8% [61]. In a study conducted in Mexico [51], the prevalence of fluorosis was 24%, and 22.9% of the cases were mild based on the TFI for children and adolescents. A significant difference was found in the effect on OHRQoL only among participants aged 11–14 years after the application of the CPQ 11–14. In Australia [18], mild fluorosis was the most prevalent, based on the TFI for children aged 8–10 years (27.7%) and 11–14 years (30.2%). Analyzing the self-perception of oral health in children aged 11 to 14, when the TFI score was equal to 1, pre-adolescents were more likely to notice fluorosis stains and considered their teeth more attractive due to the presence of white spots. In a Chinese study [52], the overall prevalence of fluorosis was 29.7%. The most affected domains were emotional well-being and social well-being, and a significant difference was noted in the perception of children and parents after administering the CPQ and PPQ instruments according to family income, oral health status, frequency of tooth brushing, and visit to the dentist. In the studies from Libya[61] and Ecuador[62], very mild and mild fluorosis were the most prevalent, 7.8% and 28.9%, respectively, and they had no impact on QoL. A similar outcome was observed in a study from Sri Lanka, where moderate fluorosis was the most prevalent, 33%, and they also did not affect QoL. In studies conducted in India [58,59], fluorosis negatively affected the OHRQoL of the individuals. The two studies were conducted in an endemic region with water concentrations of 5.35 ppm F [53] and 0.23–4.3 ppm F [58], with fluorosis prevalence of 31.36% and 93.2%, respectively. These studies concluded that the mean CPQ 11–14 scores increased in all domains with increasing severity of fluorosis. In Brazil, studies revealed a mild effect of fluorosis on the OHRQoL of individuals, with the following specific prevalence and QoL instruments: 19.1% of children and 30.1% of pre-adolescents [50] had very mild to mild fluorosis according to the Dean index, with a significant effect only on the group of Brazilian children administered with the CPQ; 80.3% had mild and 19.7% had most severe fluorosis according to the TFI [53], an effect was noted on the domain of functional limitation among pre-adolescents who were assessed using CPQ and 18.3% had light fluorosis based on of the TFI [49], and an effect was found on the emotional well-being domain using the COQHLQ. Finally, one study in Brazil [57] with a fluorosis prevalence of 14.9% showed a negative association of fluorosis with OHRQoL after the application of the OIDP tool. The main results are summarized in Table 4. Table 4. Descriptive information of the main results of the included studies regarding the effect of fluorosis on OHRQoL Synthesis of the characteristics of the studies in relation to the impact of fluorosis on OHRQoL In the evaluation of OHRQoL among children aged 8 to 10 years using the CPQ 8-10 instrument, a comprehensive analysis of various studies revealed varying outcomes regarding the impact of fluorosis. García-Pérez et al. [51]observed a subtle reduction in OHRQoL among children with fluorosis, while Do LG (2007) [18] indicated a more pronounced influence in this group. Onoriobe et al. (2014) [56] reported a substantial disparity in OHRQoL between children with and without fluorosis. Notably, the standard deviations highlighted the considerable variability in perceptions within each group. These findings collectively suggest that the presence of fluorosis can indeed exert an influence on OHRQoL in this specific age group. In a distinct age bracket, specifically among children aged 11 to 14 years, the impact of fluorosis on OHRQoL was assessed using the CPQ 11-14 instrument across five studies [18,51,56,58,59]. García-Pérez et al. (2017) [51] indicated a slight influence of fluorosis on OHRQoL, with a higher mean CPQ score observed in the fluorosis group. Shyam et al. (2020) [58] reported a moderate impact, as evidenced by increased scores among children with fluorosis. Singh et al. (2018) [59] also noted an effect of fluorosis, although variations in sample sizes and standard deviations were evident. Do LG (2007) [18] found a substantial discrepancy in CPQ scores, with children without fluorosis presenting a higher mean. Notably, Onoriobe et al. (2014) [56] provided valuable insights, demonstrating marked differences in means between the two groups, underscoring the nuanced relationship between fluorosis and OHRQoL in this age group and emphasizing the importance of considering variations in sample characteristics during the interpretation of the impact of fluorosis on OHRQoL. Moreover, this comprehensive analysis extended its scope to various age groups, employing a range of instruments to assess the influence of fluorosis on OHRQoL. Do LG (2007) [18] employed the Parental Perception Questionnaire (PPQ) and identified a significant reduction in OHRQoL among children with fluorosis, characterized by decreased mean scores. Onoriobe et al. (2014) [56] utilized both the Early Childhood Oral Health Impact Scale (ECOHIS) and the Fluorosis Impact Scale (FIS), unveiling distinct impacts of fluorosis on OHRQoL. The ECOHIS indicated a moderate effect, while the FIS revealed a more subtle impact. In contrast, Oliveira et al (2015) [55] adopted the Oral Health Impact Profile (OHIP-14) and disclosed relatively similar mean scores between groups with and without fluorosis. Conversely, Abanto et al. (2014) employed the Child Oral Health Quality of Life Questionnaire (COHQOL) and Impact on Family Scale (IFS), illustrating the discernible impact of fluorosis on OHRQoL and family experiences. These findings collectively underscore the multifaceted relationship between fluorosis and OHRQoL, with variations in sample characteristics, means, and standard deviations accentuating the intricate nature of this relationship across different age groups. The outcome of a negative impact on the participants' quality of life was observed in six studies [49-51,57-59]. In two studies, the effect of fluorosis on quality of life (QoL) was evident in at least one domain of the QoL instruments. Specifically, Abanto et al. [49] and Li et al. [52]reported such effects in the domains of emotional well-being, and Lima et al. [53] identified an impact on functional limitation. Meta-analysis Figure 2 presents the two meta-analysis. The meta-analysis were conducted with studies grouped by OHRQoL instruments CPQ 8-10 [18,49,51] and CPQ 11-14 [18,51,58], more frequent among the primary articles, which allowed the conduction of the meta-analysis and comparison of the groups with and without fluorosis. Figure 2. Forest plots of the first and second meta-analysis of the included studies that used CPQ 8–10 (1) and CPQ 11–14 (2) as a quality-of-life instrument. A meta-analysis was conducted to assess the impact of fluorosis on OHRQoL in children aged 8 to 10 years, incorporating three relevant studies [18,49,51] that employed the CPQ 8-10 instrument (p-value = 0.14; 95% confidence interval, -0.91, 6.63). Furthermore, they did not show significant heterogeneity (Tau²=0.1421; p-value = 0.36; Q value = ; I2 = 1%). A quantitative analysis of three studies [18,51,58] employing the CPQ 11-14 instrument concluded that fluorosis does not have a significant impact on OHRQoL (p-value = 0.51; 95% confidence interval, −0.18, 0.36; heterogeneity: Tau² = 0.03; p-value = 0.08; Q value ; I2 = 61 %). DISCUSSION This systematic review was conducted with the aim of assessing the impact of dental fluorosis on OHRQoL. To achieve this, both qualitative and quantitative analyses were applied to the findings derived from 16 studies included in this review [ 18 , 48 – 59 , 61 – 63 ]. Among these studies, 15 [ 18 , 48 – 56 , 58 , 59 , 61 – 63 ] were of cross-sectional design. It's worth noting that longitudinal studies are generally better suited for examining potential causal relationships, particularly concerning prevalence and conditions 9 . In the analysis of studies utilizing the CPQ 11–14 instrument, it was determined that fluorosis does not have a statistically significant impact on OHRQoL. Results indicated substantial heterogeneity among the studies, what is expected in observational studies. Similarly, to the other meta-analysis involving the CPQ 8–10 instrument, the results do not indicate a statistically significant impact of fluorosis on OHRQoL, reinforcing the credibility of this outcome. Fluorosis, characterized by changes in tooth enamel, is primarily a subjective condition without associated pain or discomfort [ 2 ]. As a result, its impact is assessed through individuals' perception [ 1 , 3 ]. Multiple studies have endeavored to assess its impact on the QoL of various populations [ 2 , 5 , 7 , 9 , 15 , 19 , 20 ]. However, the findings of these studies have not yet provided a definitive conclusion regarding its impact on OHRQoL. This further highlights the ongoing uncertainty surrounding the consideration of fluorosis as a significant public health concern, given the inconclusive nature of the findings regarding its impact on quality of life. Chankanka et al. [ 2 ] demonstrated that pre-adolescents tend to perceive themselves as more attractive due to the presence of white spots on their teeth. A similar observation was made in an Australian study [ 18 ] where, apart from this particular age group, participants' parents also expressed a more positive perception of their children's QoL, suggesting that at mild levels, fluorosis can have a favorable impact on QoL. In contrast, a study conducted in Mexico [ 51 ] and another in Australia [ 14 ] reported that pre-adolescents were more likely to notice the presence of white spots compared to younger children. However, in Brazil [ 50 ], the opposite pattern of perception emerged within the same age groups. These variations could be attributed to the influence of cultural norms on the aesthetic perception of individuals with fluorosis [ 2 ]. The prevalence of very mild fluorosis suggests that regions adhering to recommended water fluoridation standards 65 tend to experience this milder form. On the other hand, areas with high fluoride intake from natural sources may exhibit a higher prevalence of severe conditions [ 5 , 60 ]. Mild fluorosis was consistently observed in numerous studies conducted in Brazil [ 49 , 50 , 53 , 54 ], a pattern partly attributed to the country's longstanding regulations for water fluoridation dating back to 1975, under the Ministry of Health's supervision [ 65 ]. However, it's worth noting that the prevalence of this condition in regions with standardized fluoride levels in water can also be influenced by excess fluoride intake from other sources, such as toothpaste [ 5 , 64 ]. While the prevalence of severe fluorosis and its associated aesthetic concerns is generally low, it is more frequently observed in endemic regions [ 55 ] and has been shown to impact the OHRQoL of individuals [ 2 , 5 , 49 , 50 ]. Primary studies conducted in Mexico [ 51 ] and India [ 52 , 53 ] have demonstrated a negative association between fluorosis and OHRQoL. In Mexico [ 51 ], a significant difference in OHRQoL was identified among individuals aged 11–14 years with severe fluorosis when assessed using the CPQ instrument. These findings were consistent with earlier studies conducted in endemic regions, such as San Luís Potosí, Mexico [ 35 ]. Studies conducted by Shyam et al. [ 58 ] and Singh et al. [ 59 ] in endemic regions with varying fluoride concentrations (0.23–4.3 and 5.35 ppm of F, respectively) further supported the impact of fluorosis on OHRQoL. Shyam et al. [ 58 ] revealed a substantial presence of fluorosis (26.1% grade 4 according to the TFI) and reported that 20% of participants aged 11–14 years perceived their oral health as significantly affected, rating it 1.7 times worse than those without fluorosis. Similarly, in the study by Singh et al.[ 59 ], pre-adolescents exhibited increased mean scores in all domains of the CPQ instrument in accordance with the severity of fluorosis. These results from India are consistent with earlier Indian studies by Bhagyajyothi et al. [ 21 ] and Jodali et al. [ 22 ], both conducted in endemic regions, and align with findings from the literature review by Chankanka [ 2 ] and a recent study in Iran [ 35 ] (1.2–1.4 ppm of F in water) where the prevalence of severe fluorosis influenced individuals' appearance. Nevertheless, it is imperative to approach the findings of these studies with a degree of caution, recognizing that several methodological limitations were observed in the primary investigations, as depicted in Tables 2 and 3 . Notably, these limitations were predominantly prevalent in cross-sectional studies, particularly following the application of the modified NOS assessment tool. Primarily, a significant shortcoming was the absence of sample size calculations in some studies [ 46 , 49 , 51 , 53 ], a fundamental component for the rigorous planning, accurate interpretation, and overall validity of research results [ 62 ]. Additionally, the studies generally omitted the reporting of non-response rates among participants. Confounding factors were rarely addressed in the included studies; such factors are instrumental in establishing whether variables such as gender and age significantly influence the impact of fluorosis on OHRQoL [ 18 , 48 , 49 , 56 , 58 , 59 ]. Lastly, the primary studies exhibited considerable heterogeneity in their data, primarily stemming from the diverse diagnostic indexes used for fluorosis classification and varying instruments employed for OHRQoL assessments, rendering the comparison of research outcomes and the establishment of standardized statistical data with OHRQoL a complex endeavor. The qualitative analysis of the primary studies assumed significance in elucidating that a considerable majority of the included investigations primarily reported the prevalence of fluorosis within the very mild to mild categories according to Dean's index and TFI. In these cases, the observed consensus suggested a lack of discernible impact on OHRQoL. Conversely, a noteworthy inference from this qualitative evaluation implied that the severity of fluorosis, specifically in moderate categories, could potentially manifest as an influential factor affecting individuals' overall quality of life. It is, however, important to underscore that the amalgamation of data from both groups, i.e., those with and without fluorosis, in many of the selected studies precluded the extraction of separate datasets. This intertwining of data sources introduces the possibility of dilution, which might elucidate the absence of discernible fluorosis-related impact on OHRQoL, thus unveiling an inherent limitation in the scope of this systematic review. This systematic review provides a comprehensive perspective on the relationship between fluorosis and OHRQoL, shedding light on the intricate interplay between fluorosis severity and age groups. These findings prompt further research to explore the multifaceted dimensions of this relationship and the factors that might contribute to these divergent outcomes, ultimately advancing our understanding of the complex interplay between fluorosis and OHRQoL. The authors report that there is no conflict of interest for the study and that this research did not have any funding. CONCLUSION The findings from this systematic review indicate that fluorosis does not exert a significant impact on OHRQoL in children aged 8-14. These results underscore the notion that fluorosis might not severely impact OHRQoL. Further investigations are needed to delve into the intricate aspects of this relationship and identify the factors contributing to varying outcomes. Declarations A. Author Contributions RSB, HMH and JRMB proposed the research idea, and PLM, SMV, TMS, and MPM wrote the main manuscript text and RCPM prepared the figures. All authors reviewed the manuscript. B. Ethics Approval and Consent to Participate. Not applicable. C. Funding No funding was obtained for this study. D. Conflict of interests The authors declare no conflict of interest related to this research paper. References Petersen, Poul Erik, Baez, Ramon J & World Health Organization. (‎2013)‎. Oral health surveys: basic methods, 5th ed. World Health Organization. https://iris.who.int/handle/10665/97035 Chankanka O, Levy SM, Warren JJ, Chalmers JM (2010) A literature review of aesthetic perceptions of dental fluorosis and relationships with psychosocial aspects/oral health-related quality of life. Community Dentistry and Oral Epidemiology. 38: 97-109. https://doi.org/10.1111/j.1600-0528.2009.00507.x Dean HT (1934) Classification of Mottled Enamel Diagnosis. The Journal of the American Dental Association 21:1421-1426. https://doi.org/10.14219/jada.archive.1934.0220 Cangussu MCT, Narvai PC, Fernandez RC, Djehizian V (2002) Dental fluorosis in Brazil: a critical review. Reports in Public Health 18: 7-15. https://doi.org/10.1590/S0102-311X2002000100002 Buzalaf MAR, Delbem ACB, Pessan JP (2021) Rational use of fluoride to control caries lesions. In Magalhães AC, Rios D, Wang L, Buzalaf MAR (Eds.), Cariology: from basic to clinical (1 st ed., pp. 134-153). Manole. Rigo L, Caldas Junior AF, Souza EA, Abegg C, Lodi L (2010) Study on the dental fluorosis in a Southern city of Brazil. Ciência & Saúde Coletiva 15: 1439-48. https://doi.org/10.1590/S1413-81232010000700055 Steiner M, Menghini G, Marthaler TM, Imfeld T (2010) Changes in dental caries in Zurich school-children over a period of 45 years. Schweiz Monatsschr Zahnmed 1084-104. Lauris JRP, Bastos RD, Bastos JRD (2012) Decline in dental caries among 12-year-old children in Brazil, 1980-2005. International Dental Journal 62: 308-14. Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W (2015) Global burden of untreated caries: a systematic review and metaregression. J Dent Res 94: 650-8. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T, et al (2017) Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res 96: 380-7. Iheozor-Ejiofor Z, Worthington HV, Walsh T, O'Malley L, Clarkson JE, Macey R, et al (2015) Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev 6: CD010856. Bastos RD, Olympio KPK, Bijella VT, Buzalaf MAR, Bastos JRD (2005) Trends in dental caries prevalence in 12-year-old schoolchildren between 1976 and 2001 in Bauru, Brazil. Public Health 119: 269-75. Do L, Ha D, Peres MA, Skinner J, Byun R, Spencer AJ (2017) Effectiveness of water fluoridation in the prevention of dental caries across adult age groups. Community Dent Oral Epidemiol 45: 225-32. Peres MA, Peres KG, Barbato PR, Höfelmann DA (2016) Access to Fluoridated Water and Adult Dental Caries: A Natural Experiment. J Dent Res 95: 868-74. Moore D, Poynton M, Broadbent JM, Thomson WM (2017) The costs and benefits of water fluoridation in NZ. BMC Oral Health 17: 134. Walsh T, Worthington HV, Glenny AM, Marinho VC, Jeroncic A (2019) Fluoride toothpastes of different concentrations for preventing dental caries. Cochrane Database Syst Rev 3: CD007868. van Palenstein Helderman WH, Mkasabuni E (1993) Impact of dental fluorosis on the perception of well-being in an endemic fluorosis area in Tanzania. Community Dental Oral Epidemiology 21: 243-4. https://doi.org/10.1111/j.1600-0528.1993.tb00765.x Do LG, Spencer A. Oral health-related quality of life of children by dental caries and fluorosis experience (2017) Journal Public Health Dent 67: 132-9. https://doi.org/10.1111/j.1752-7325.2007.00036.x Tellez M, Santamaria RM, Gomez J, Martignon S (2012) Dental fluorosis, dental caries, and quality of life factors among schoolchildren in a Colombian fluorotic area. Community Dental Health 29: 95-9. https://europepmc.org/article/med/22482258 Moimaz SA, Saliba O, Marques LB, Garbin CA, Saliba NA (2015) Dental fluorosis and its influence on children's life. Brazilian Oral Research 29: 806-83. https://doi.org/10.1590/1807-3107BOR-2015.vol29.0014 Bhagyajyothi CS, Pushpanjali K (2009) Perceptions and concerns about dental fluorosis as assessed by tooth surface index of fluorosis among high school children in an area of endemic fluorosis-Kaiwara. Oral Health & Preventive Dentistry 7: 33-8. https://europepmc.org/article/med/19408813 Jodalli PS, Ankola AV, Hebbal M, Vikneshan M (2013) Aesthetic perceptions regarding fluorosis by children from an area of endemic fluorosis in India. Community Dental Health 30: 249-53. Aguilar-Díaz FC, Irigoyen-Camacho ME, Borges-Yáñez SA (2011) Oral-health-related quality of life in schoolchildren in an endemic fluorosis area of Mexico. Quality of Life Research 20: 1699–1706. https://doi.org/10.1007/s11136-011-9897-4 Moher D, Liberati A, Tetzlaff J, Altman DG (2009) The PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6: e1000097. https://doi.org/10.1371/journal.pmed.1000097 GA Wells, GA Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P (2021) Ottawa Hospital Research Institute. OHRI. Retrieved April 20, 2021, from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp Aimée NR, van Wijk AJ, Maltz M, Varjão MM, Mestrinho HD, Carvalho JC (2017) Dental caries, fluorosis, oral health determinants, and quality of life in adolescents. Clin Oral Investig 21:1811-1820. Doi: 10.1007/s00784-016-1964-3 Aznar FDC. Análise da relação entre as condições de saúde bucal e a qualidade de vida em adolescentes com sobrepeso/obesidade e eutróficos em Bauru - SP [dissertation]. Bauru:Faculdade de Odontologia de Bauru, Universidade de São Paulo; 2015.128 p. Bastos RS. Impacto das condições de saúde bucal em relação à qualidade de vida de adolescentes escolares de 15 a 19 anos, numa dicotomia socioeconômica, no município de Bauru, São Paulo, em 2009 [dissertation]. Bauru: Faculdade de Odontologia de Bauru, Universidade de São Paulo; 2009. 180 p. Michel-Crosato E. Autopercepção de saúde e avaliação das condições bucais dos escolares, de 6 a 15 anos de idade, do município de Pinheiro Preto – SC, 2002 [dissertation]. Araçatuba: Faculdade de Odontologia de Araçatuba, Universidade Estadual Paulista; 2003. 171 p. Do LG, Há DH, Spencer AJ (2016) Natural history and long-term impact of dental fluorosis: a prospective cohort study. Med J Aust 204: 25. https://doi.org/10.5694/mja15.00703 Furtado GE, Sousa ML, Barbosa TS, Wada RS, Martínez-Mier EA, Almeida ME (2012) Percepção da fluorose dentária e avaliação da concordância entre pais e filhos: validação de um instrumento. Cad Saude Pública 28: 1493-505. https://doi.org/10.1590/S0102-311X2012000800008 Marques LB. Prevalência e autopercepção da fluorose dentária em crianças de 12 anos de idade do município de Birigüi-SP [master’s thesis]. Araraquara: Faculdade de Odontologia de Araraquara, Universidade Estadual Paulista; 2008. 66 p. Michel-Crosato E, Barbieri DB, Biazevic MGH, Correia LD (2007) Condição de saúde bucal e autopercepção de fluorose dental: um estudo de base populacional no Sul do Brasil, 2003. Rev Pós Grad 13: 353-7. Duta M, Jipa IT, Amariei C (2014) Oral health status and quality of life in the Danube Delta Reserve Biosphere – child and parent perspectives. Social Science and Arts 2: 587-594 doi:10.5593/SGEMSOCIAL2014/B12/S2.075 Nilchian F, Asgary I, Mastan F (2018) The Effect of Dental Fluorosis on the Quality of Life of Female High School and Precollege Students of High Fluoride-Concentrated Area. J Int Soc Prev Community Dent 8: 314-319. doi: 10.4103/jispcd.JISPCD_94_18 Pavithran VK, Murali R, Krishna M, Shamala A, Yalamalli M, Kumar AV, Raina R (2020) Impact of oral diseases on daily activities among 12- to 15-year-old institutionalized orphan and non-orphan children in Bengaluru city: A cross-sectional analytical study. Indian J Dent Res 31: 396-402. doi: 10.4103/ijdr.IJDR_260_18. Peres KG, Latorre MR, Peres MA, Traebert J, Panizzi M (2003) Impacto da cárie e da fluorose dentária na satisfação com a aparência e com a mastigação de crianças de 12 anos de idade. Cad Saude Pública 19: 323-30. https://doi.org/10.1590/S0102-311X2003000100037 Robinson PG, Nalweyiso N, Busingye J, Whitworth J (2005) Subjective impacts of dental caries and fluorosis in rural Ugandan children. Community Dent Health 22: 231-6. https://www.researchgate.net/publication/7392500_Subject_impacts_of_dental_caries_and_fluorosis_in_rural_Ugandan_children Su H, Peng Q, Jiang Y (2017) Analytical study of signs and symptoms of TMD, fluorosis and caries in different age groups to validate and to find reliability of oral health-related quality of life. Biomedical Research 28: 7923-7929. Ditterich RG. Prevalência e autopercepção de fluorose dentária em escolares de 12 anos residentes no município de Ponta Grossa-PR [master’s thesis]. Ponta Grossa: Universidade Estadual de Ponta Grossa; 2006. 160 p. Menezes LMB. Autopercepção da fluorose dental, bem-estar dos portadores e responsabilidade legal [dissertation]. Piracicaba: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas; 2001. 120 p. Calderón ZM de, Abanto J, Sá Oliveira G, Haddad AE, Bönecker M (2021) Does fluorosis have an impact on peruvian children’s oral health related quality of life? Rev Gaúch Odontol 69: e2021002. available from: https://doi.org/10.1590/1981-8637202100023412 García-Pérez A, González-Aragón Pineda AE, Villanueva Gutiérrez T, Pérez Pérez NG, Gómez-Clavel JF (2022) Impact of diseases of the hard tissues of teeth on oral health-related quality of life of schoolchildren in area with a high concentration of fluoride in drinking water. Community Dent Health 394: 240-246. doi:10.1922/CDH_00078Garcia-Perez07 Idon PI, Udoye C, Sotunde O, Idon MI, Janada Y, PY (2018) Psychological impact, quality of life and treatment needs among adult patients with dental fluorosis in an endemic region of Northern Nigeria. Tropical Dental Journal 41: 42-52. Kumar V, Gaunkar R, Thakker J, Ankola AV, Iranna Hebbal M, Khot AJP, Goyal V, Ali A, Eldwakhly E (2023) Pediatric Dental Fluorosis and Its Correlation with Dental Caries and Oral-Health-Related Quality of Life: A Descriptive Cross-Sectional Study among Preschool Children Living in Belagavi. Children (Basel)10: 286. doi: 10.3390/children10020286. PMID: 36832415 Ghada T, Nancy K, Mohamed A. El-Yazeed, Ehab M. Radwan, Marwa Saber Abd El Salam (2022) Impact of dental Fluorosis on quality of life of a group of Children in a Rural area in Nubia Region. IJPHRD 13: 127-33. https://medicopublication.com/index.php/ijphrd/article/view/18183 Varshney S, Menon I, Gupta R, Arora V, Sharma A, Rohatgi L (2022) Effect of Dental Fluorosis on Oral Health-Related Quality of Life and Daily Performances Among 12- and 15-year-old School-going Children Residing in High- and Low-Fluoridated Areas of Meerut District. Asian Journal of Pharmaceutical Research and Health Care 14: 94-101. DOI: 10.4103/ajprhc.ajprhc_34_22 Biazevic MG, Rissotto RR, Michel-Crosato E, Mendes LA, Mendes MO (2008) Relationship between oral health and its impact on quality of life among adolescentes. Brazilian Oral Research 22: 36-42. https://doi.org/10.1590/S1806-83242008000100007 Abanto J, Ortega AO, Raggio DP, Bönecker M, Mendes FM, Ciamponi AL (2014) Impact of oral diseases and disorders on oral-health-related quality of life of children with cerebral palsy. Special Care in Dentistry 34: 56-63. https://doi.org/10.1111/scd.12028 Barbosa TS, Gavião MB, Castelo PM, Leme MS (2016) Factors Associated with Oral Health-related Quality of Life in Children and Preadolescents: A Cross-sectional Study. Oral Health & Preventive Dentistry 14: 137-48. DOI 10.3290/j.ohpd.a35301 García-Pérez A, Irigoyen-Camacho ME, Borges-Yáñez SA, Zepeda-Zepeda MA, Bolona-Gallardo I, Maupomé G (2017) Impact of caries and dental fluorosis on oral health-related quality of life: a cross-sectional study in schoolchildren receiving water naturally fluoridated at above-optimal levels. Clinical Oral Investigations 21: 2771-2780 https://doi.org/10.1007/s00784-017-2079-1 Li YJ, Gao YH, Zhang Y (2014) The impact of oral health status on the oral health-related quality of life (OHRQoL) of 12-year-olds from children's and parents' PERSPECTIVES. Community Dental Health 31: 240-4. DOI 10.1922/CDH_3346Zhang05 Lima LMS, Dantas-Neta NB, Moura WS, Moura MS, Mantesso A, Moura LFAD, Lima MDM (2014) Impact of dental fluorosis on the quality of life of children and adolescents. Rev Odontol UNESP 43: 326-332. https://doi.org/10.1590/rou.2014.052 Michel-Crosato E, Biazevic MG, Crosato E (2005) Relationship between dental fluorosis and quality of life: a population based study. Brazilian Oral Research 19: 150-5. https://doi.org/10.1590/S1806-83242005000200014 Oliveira DC, Ferreira FM, Morosini IA, Torres-Pereira CC, Martins SP, Fraiz FC (2015) Impact of Oral Health Status on the Oral Health-Related Quality of Life of Brazilian Male Incarcerated Adolescents. Oral Health & Preventive Dentistry 13: 417-25. DOI 10.3290/j.ohpd.a33922 Onoriobe U, Rozier RG, Cantrell J, King RS (2014) Effects of enamel fluorosis and dental caries on quality of life. Journal Dental of Research 93: 972-9. https://doi.org/10.1177/0022034514548705 Peres KG, Peres MA, Araujo CL, Menezes AM, Hallal PC (2009) Social and dental status along the life course and oral health impacts in adolescents: a population-based birth cohort. Health Quality of Life Outcomes 22: 95. https://doi.org/10.1186/1477-7525-7-95 Shyam R, Bhadravathi CM, Kumar A, Pahwa M, Rani G, Phogat R (2020) Impact of dental fluorosis on the oral health related quality of life among 11- to 14-year-old school children in endemic fluoride areas of Haryana (India). International Dental Journal 70: 340-346. DOI 10.1111/idj.12567 Singh S, Saha S, Singh S, Shukla N, Reddy V (2018) Oral health-related quality of life among 12-15-year children suffering from dental fluorosis residing at endemic fluoride belt of Uttar Pradesh, India. Quality of Life Research 16: 54-57. DOI 10.4103/jiaphd.jiaphd_139_16 Jokovic A, Locker D, Guyatt G (2006) Short forms of the Child Perceptions Questionnaire for 11–14-year-old children (CPQ11–14): Development and initial evaluation. Health Qual Life Outcomes 4: 4. Arheiam A, Aloshiby A, Gaber A, Fakron S (2022) Dental Fluorosis and Its Associated Factors Amongst Libyan Schoolchildren. Int Dent J 72: 853-858. doi: 10.1016/j.identj.2022.04.010 Constante CAP, Pérez RER, Rodríguez VJP, Cabrera AMA, Armas VA del Carmen (2020). Impact of dental fluorosis over the quality of life of ecuadorian teenagers between 11 and 14 years. Odontología Vital 32: 21-28. Thilakarathne BKG, Ekanayake L, Schensul JJ, Reisine S (2023) Impact of dental fluorosis on the oral health related quality of life of adolescents in an endemic area. J Oral Biol Craniofac Res 13: 448-452. doi: 10.1016/j.jobcr.2023.03.015. Barbosa TS, Steiner-Oliveira C, Gavião MBD (2010) Tradução e adaptação brasileira do Parental-Caregiver Perceptions Questionnaire (P-CPQ). Saúde e Sociedade 19: 698-708. Godinho GNF. Oral Impacts on Daily Performances- OIDP: estudo transversal de validação para população portuguesa, 2015 [master 's thesis]. Lisboa: Faculdade de Medicina Dentária, Universidade de Lisboa; 2015. 49p. Tables Tables 1-4 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files SupplementoryInfo.docx Tables.docx Cite Share Download PDF Status: Published Journal Publication published 17 Oct, 2024 Read the published version in Clinical Oral Investigations → Version 1 posted Editorial decision: Revision requested 14 Feb, 2024 Reviews received at journal 06 Feb, 2024 Reviews received at journal 01 Feb, 2024 Reviewers agreed at journal 07 Jan, 2024 Reviewers agreed at journal 07 Jan, 2024 Reviewers invited by journal 05 Jan, 2024 Editor assigned by journal 26 Dec, 2023 Submission checks completed at journal 26 Dec, 2023 First submitted to journal 12 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3745254","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":263990033,"identity":"edf478a0-c4a7-4feb-9f1b-6d1c37db8a5b","order_by":0,"name":"Paula Lanza Montanher","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Paula","middleName":"Lanza","lastName":"Montanher","suffix":""},{"id":263990034,"identity":"999f30fc-a7f5-4409-b43b-817598cd94c4","order_by":1,"name":"Sofia Maito Velasco","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"Maito","lastName":"Velasco","suffix":""},{"id":263990035,"identity":"4b90f08b-aed7-4767-81c5-6408e5b0d433","order_by":2,"name":"Renan Canale Peres Montanher","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Renan","middleName":"Canale Peres","lastName":"Montanher","suffix":""},{"id":263990036,"identity":"37bdcba0-6d0b-4ada-b843-d1da321b3e39","order_by":3,"name":"Thais Moraes Souza","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Thais","middleName":"Moraes","lastName":"Souza","suffix":""},{"id":263990037,"identity":"6d4b31d2-84df-457f-9daa-5d9aebd9b7b2","order_by":4,"name":"Mariela Peralta-Mamani","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Mariela","middleName":"","lastName":"Peralta-Mamani","suffix":""},{"id":263990038,"identity":"30fa0930-8809-4efd-a363-949aba1297ce","order_by":5,"name":"José Roberto Magalhães Bastos","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"Roberto Magalhães","lastName":"Bastos","suffix":""},{"id":263990039,"identity":"647f7848-ab9a-455c-95d6-213840380608","order_by":6,"name":"Heitor Marques Honório","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Heitor","middleName":"Marques","lastName":"Honório","suffix":""},{"id":263990040,"identity":"c3ec8024-d5e0-4fb1-86eb-3a59f6d383c6","order_by":7,"name":"Roosevelt Silva Bastos","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYFACHgjFDyIYG4jRwQbSksDAINlAshaDA8RqMZ/fe/Djzx829sY30p89YNxxj7AWmWN8ydI8CWmJ227kmBswnikmrEWCjcdAmiHhcILZjRw2Cca2BKK0GP/8kXDY3nhG+jOitZhJ8CQcZtwgkWBGrJa8NGuetLTEGWfemBskniFGC/PZwzd/2NjY87cDQ+zjDiK0IAM2BhI1gLSMglEwCkbBKMAGAOeiM/ZI17M1AAAAAElFTkSuQmCC","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":true,"prefix":"","firstName":"Roosevelt","middleName":"Silva","lastName":"Bastos","suffix":""}],"badges":[],"createdAt":"2023-12-12 18:59:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3745254/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3745254/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00784-024-05991-x","type":"published","date":"2024-10-17T15:57:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49081423,"identity":"19c42c1b-af03-44a7-a6f4-26ce4aa0823f","added_by":"auto","created_at":"2024-01-02 20:01:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":294692,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the search strategy and results according to the PRISMA statement.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3745254/v1/b66c365f07a2bc7dc13c0ebc.png"},{"id":49080033,"identity":"f4a7191f-4967-404b-aa96-1352a5278d5b","added_by":"auto","created_at":"2024-01-02 19:53:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":178067,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of the first and second meta-analysis of the included studies that used CPQ 8–10 (1) and CPQ 11–14 (2) as a quality-of-life instrument.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3745254/v1/880fedfe791ce4b11b7f51eb.png"},{"id":67149705,"identity":"643fa439-5e4a-47f6-b8d5-5dc05be0e59c","added_by":"auto","created_at":"2024-10-21 16:13:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":922595,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3745254/v1/3a6b6e0e-ca8b-42ed-b44b-dd050ff37793.pdf"},{"id":49080032,"identity":"fe5b7e89-a084-412e-84c6-a7b3e8db5278","added_by":"auto","created_at":"2024-01-02 19:53:38","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19875,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementoryInfo.docx","url":"https://assets-eu.researchsquare.com/files/rs-3745254/v1/a157eb7c228e7bff0683e1ed.docx"},{"id":49080035,"identity":"0e7d78f5-e0e0-4964-8db0-45806102846a","added_by":"auto","created_at":"2024-01-02 19:53:38","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":39126,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-3745254/v1/aaa6063bc508ab1b529c31f6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of fluorosis on the oral health-related quality of life: a systematic review and meta-analysis.","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAccording to the World Health Organization (WHO) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], fluorosis is characterized by bilateral symmetrical lesions and horizontal streaks on the surface of the dental enamel. Milder grades present with fine lines, opaque and white, which at the most severe levels may evolve into brown spots or depressions with brown spots and corrosion [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is caused by excessive and prolonged ingestion of fluoride during the tooth formation phase [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], mainly from combined sources such as public water supply and toothpaste [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFluorides has been used for dental caries control by public and individual strategies achieving considerable success verified from the dental caries decline in developed [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and developing countries [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], even though this disease remain as a huge public health problem worldwide [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Public fluoridated water supply initiated in the USA in 1945 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], in Brazil in 1953 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and more than 20 nations use it concurrently [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This public policy induces dental caries prevalence and severity reduction in deciduous and permanent teeth for children [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and adults [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with low costs [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], nevertheless associated to dental fluorosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], especially the mild ones. The toothpastes containing at least 1000 ppm fluoride toothpaste used daily is associated to dental caries control and for this reason widely used, however also associated to the prevalence of dental fluorosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The effectiveness of dental caries control, maintenance, and prevention of dental fluorosis induced by using low-fluoridated toothpaste remains uncertain without an established lower cut point for fluoride content of 1000 ppm [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDental fluorosis is asymptomatic and its negative effect on the oral health-related quality of life (OHRQoL) has been investigated in recent years through the aesthetic perception of individuals about this condition [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Feelings of anguish, worry, and difficulty in smiling expressed by children with dental fluorosis have been mentioned, especially at more severe levels [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In 2009, a critical review of the literature [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] revealed that mild fluorosis was not a concern and that it could be positively associated with the OHRQoL because adolescents considered the presence of white spots as more attractive [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In Colombia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], only 25% of those examined with mild fluorosis recognized their teeth as \u0026ldquo;ugly\u0026rdquo;. In Brazil, only 40.1% of children aged 12 years, with mild and very mild fluorosis, noticed stains on their teeth [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Nevertheless, the greater the severity of fluorosis, the greater seems to be the degree of individuals dissatisfaction [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies about the effect of fluorosis and OHRQoL have presented distinct results, although no systematic review has studied children and adolescent\u0026rsquo;s dental fluorosis association with OHRQoL which might be used as evidence to guide public policies in the balance of dental caries and fluorosis control. Thus, this study systematically reviewed the literature to assess the impact of fluorosis on the quality of life, comparing the group with fluorosis and without fluorosis.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol registration\u003c/h2\u003e \u003cp\u003eThe systematic review was conducted through qualitative and quantitative syntheses and was performed according to PRISMA guidelines [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The protocol has been registered at the PROSPERO database (CRD42020186552).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePECO question\u003c/h2\u003e \u003cp\u003eA question structured based on the PECO strategy was formulated. P: people in general; E: exposure to fluorosis; C: non-fluorosis; and O: impact outcomes of fluorosis on OHRQoL. The PECO question was structured as follows: \"does fluorosis have an impact on the quality of life of children and adolescents?\".\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy\u003c/h2\u003e \u003cp\u003eThe searches were developed from Medical Subject Headings (MeSH) descriptors, Boolean logical operators (AND, OR, and NOT), and predefined keywords. The search strategy included the following MeSH terms: (Fluorosis, Dental or Dental Fluorosis or Dental Fluorosis or Mottled Enamel or Enamel, Mottled or Enamels, Mottled or Mottled Enamels) AND (Life Quality or Health-Related Quality Of Life or Health-Related Quality Of Life or OHRQoL) and DeCS: (Fluorosis, Dental or Dental Fluorosis or Dental Fluorosis or Fluorosis, Dental or Mottled Enamel) AND (Quality of Life or OHRQoL or Health-Related Quality Of Life or Health-Related Quality Of Life or Life Quality) entrees Embase. There were no language restrictions and publication year. The search strategies were adapted for each database.\u003c/p\u003e \u003cp\u003eSearches were performed until September 2023 in databases: PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and Virtual Health Library, in addition to gray literature: Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest. A manual search was also performed by reading the reference list of the included articles to search for potentially eligible studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eDatabases were searched without limitation of date or language of publication. Epidemiological studies, such as cross-sectional, case\u0026ndash;control, cohort, and clinical trials; studies with humans; studies that compared, in the same study the impact on the OHRQoL of individuals with fluorosis (fluorosis group) and individuals without fluorosis (control group); and studies that used any valid instrument to assess the OHRQoL of the participants were included.\u003c/p\u003e \u003cp\u003eCase reports and case series studies, letters to the editor, systematic reviews, integrative reviews, scope reviews, narratives, qualitative studies, and studies with human beings in situ were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eTwo examiners (P.L.M. and S.R.M.V.) met and discussed the eligibility criteria before starting the search. To remove duplicates, Endnote Web software was used (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.myendnoteweb.com\u003c/span\u003e\u003cspan address=\"http://www.myendnoteweb.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), followed by manual deletion. Then, in the first stage, the titles and abstracts of articles that met the inclusion criteria were independently read by the reviewers. Potentially eligible articles moved to the second stage of reading the full text. In the presence of disagreements, a third examiner was consulted (M.P.M.) in any of the steps.\u003c/p\u003e \u003cp\u003eThe following data were extracted by two examiners independently (P.L.M. and S.R.M.V.) and tabulated in Excel 2016 spreadsheets: authors, publication year, country, study type, sample size, gender, age assessed, fluoride concentration in water, investigated outcomes, index used for diagnosis and fluorosis classification, most prevalent fluorosis severity score, fluorosis prevalence, QoL instruments, examiner calibration, statistical analysis, and QoL results (values ​​in the fluorosis group and control group).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias in individual studies\u003c/h2\u003e \u003cp\u003eThe quality of the articles was also independently assessed by the researchers (P.L.M. and S.R.M.V.) with discussion in cases of divergence. The Newcastle\u0026ndash;Ottawa Scale (NOS) was used to assess cohort studies and its modified version for cross-sectional studies. The scale for cohort studies is divided into three dimensions: selection, comparability, and outcome assessment. For case-control studies, the scale is organized into selection of cases and controls, comparability of cases and controls, and determination of exposure. The results of the NOS tool are interpreted as follows: total score\u0026thinsp;\u0026ge;\u0026thinsp;6\u0026thinsp;=\u0026thinsp;consistent studies; total score\u0026thinsp;\u0026lt;\u0026thinsp;6\u0026thinsp;=\u0026thinsp;inconsistent studies. For the modified NOS tool, the following scores were considered: 0\u0026ndash;4 points\u0026thinsp;=\u0026thinsp;unsatisfactory studies; 5\u0026ndash;6 points\u0026thinsp;=\u0026thinsp;satisfactory studies, 7\u0026ndash;8 points\u0026thinsp;=\u0026thinsp;good studies, and 9 points\u0026thinsp;=\u0026thinsp;very good studies \u003csup\u003e25\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe NOS assigns a higher score to cohort studies with representation of the exposed cohort community. In case-control studies the NOS yields a higher score when population-based controls are used compared to controls from hospitals. It also assigns a higher score to studies that had a blinded assessment of exposure. Additionally, the NOS assigns a higher score to case-control studies with a comparable non-response rate between cases and controls, as opposed to case-control studies with different response proportions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eA meta-analysis was conducted utilizing the random-effects model through the employment of R Statistical Software (v4.1.2; R Core Team 2021), a free and open-source software for data analysis and performing statistical tests. A significance level was set at p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eEffect measures\u003c/h2\u003e \u003cp\u003eThe results were presented according to the standardized mean difference of the instruments used to measure the QoL and the sample size of each study.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eLiterature search\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study selection process is summarized in Figure 1. The search strategy resulted in 380 studies. After removing the duplicates, 141 were potentially eligible studies based on the title and abstract reading. Following the analysis, 42 articles were selected for full-text reading. The complete verification of the content allowed the exclusion with the justification of 26 articles. [17,19,20,23,26-47]\u003c/p\u003e\n\u003cp\u003eThe remaining 16 studies moved to qualitative synthesis [18,48-59,61-63]. Four studies [18,49,51,58] were included in the meta-analysis. \u0026nbsp;The inter-examiner kappa agreement index was 1.\u003c/p\u003e\n\u003cp\u003eFigure 1. Flowchart of the search strategy and results according to the PRISMA statement.\u003c/p\u003e\n\u003cp\u003eThe reasons for the exclusion of the studies were: The studies did not present the control group; the studies only validated the instrument by comparing responses from parents and children; the studies only applied a self-perception questionnaire to participants without QOL scores in the control group; the studies grouped individuals without fluorosis and with mild levels of fluorosis; the studies did not present the result of the application of the QL instrument with fluorosis; the studies applied a questionnaire only on aesthetic satisfaction and did not present data from the analysis of QOL and fluorosis, only the p-value.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDescription of the studies\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 shows the characteristics of the included studies. To classify the severity of fluorosis, seven studies used the Thylstrup Fejerskov Index (TFI) [18,49,51,53,55,62,63], eight studies the Dean index [48,52,54-57,61], and one study the modified Dean index [59]. All studies were subjected to examiner calibration, and the minimum inter-examiner Kappa value for fluorosis was 0.79 (Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1. Main characteristics of included studies.\u003c/p\u003e\n\u003cp\u003eThe samples in the included studies ranged from 60 [49] to 7,686 [56] participants, including the groups with and without fluorosis. Considering all the studies, a total of 16,314 participants, 6,422 with fluorosis and 9,892 without fluorosis were evaluated, distributed in Brazil [49,50,53-57], India [58,59], Mexico [51], Australia [18], USA [56], China [52], Líbia [61]Ecuador[63], and Sri Lanka[63]with ages ranging from 8 to 18 years.\u003c/p\u003e\n\u003cp\u003eSeveral validated instruments were used by the included studies to assess the impact of fluorosis on Oral Health-Related Quality of Life (OHRQoL) [18,49-53,56-59, 61-63]. All the included studies are cross-sectional, except one that is a cohort [57]. The fluorosis index used by the studies was Thylstrup-Fejerskov index (TFI) [18,49,51,53,58,62-63], Dean [48,50,52,54-57,61] and modified Dean index [59]. Two studies did not provide the coefficient of calibration for the assessors [56,62] and one presented a kappa \u0026lt; 0.80 [52]. Detailed findings and analyses are presented in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTables 2 and 3 present the details of the risk of bias assessment of the studies included after applying the NOS and modified NOS tools. The main deficiencies of the 15 cross-sectional studies were related to the lack of sample calculation [48,49,51,54,55,62], representation [48,49,51,54,56], adjustment of the confounding factor [18,48-56,58,59,61-63], and non-response rate [48,53,54,58, 59,62-63].\u003c/p\u003e\n\u003cp\u003eTable 2. Quality assessment of the cohort study (Newcastle–Ottawa Scale - NOS)\u003c/p\u003e\n\u003cp\u003eTable 3. Quality assessment of cross-sectional studies (modified Newcastle–Ottawa Scale- modified NOS)\u003c/p\u003e\n\u003cp\u003eRegarding the risk of bias, the included studies followed the following classification after the application of the Newcastle-Ottawa (NOS) tool modified for cross-sectional studies: 3 studies [48,49,54] were considered unsatisfactory (total score of 4 points) 8 studies were considered satisfactory [51,53,55,56,58,59,62,63] (total score between 5-6 points) and 4 studies were considered good (total score of 7 points) [18,50,52,61]. The cohort study [57] was classified as good after the application of the Newcastle Ottawa tool (final total score of 8).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings between the severity of fluorosis and effect on OHRQoL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn a US study [56], very mild to mild fluorosis was the most prevalent, with 12.1%, based on the Dean index. The same occurred in another study, with a prevalence of 7.8% [61].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn a study conducted in Mexico [51], the prevalence of fluorosis was 24%, and 22.9% of the cases were mild based on the TFI for children and adolescents. A significant difference was found in the effect on OHRQoL only among participants aged 11–14 years after the application of the CPQ 11–14.\u003c/p\u003e\n\u003cp\u003eIn Australia [18], mild fluorosis was the most prevalent, based on the TFI for children aged 8–10 years (27.7%) and 11–14 years (30.2%). Analyzing the self-perception of oral health in children aged 11 to 14, when the TFI score was equal to 1, pre-adolescents were more likely to notice fluorosis stains and considered their teeth more attractive due to the presence of white spots.\u003c/p\u003e\n\u003cp\u003eIn a Chinese study [52], the overall prevalence of fluorosis was 29.7%. The most affected domains were emotional well-being and social well-being, and a significant difference was noted in the perception of children and parents after administering the CPQ and PPQ instruments according to family income, oral health status, frequency of tooth brushing, and visit to the dentist.\u003c/p\u003e\n\u003cp\u003eIn the studies from Libya[61] and Ecuador[62], very mild and mild fluorosis were the most prevalent, 7.8% and 28.9%, respectively, and they had no impact on QoL. A similar outcome was observed in a study from Sri Lanka, where moderate fluorosis was the most prevalent, 33%, and they also did not affect QoL.\u003c/p\u003e\n\u003cp\u003eIn studies conducted in India [58,59], fluorosis negatively affected the OHRQoL of the individuals. The two studies were conducted in an endemic region with water concentrations of 5.35 ppm F [53] and 0.23–4.3 ppm F [58], with fluorosis prevalence of 31.36% and 93.2%,\u0026nbsp;respectively. These studies concluded that the mean CPQ 11–14 scores increased in all domains with increasing severity of fluorosis.\u003c/p\u003e\n\u003cp\u003eIn Brazil, studies revealed a mild effect of fluorosis on the OHRQoL of individuals, with the following specific prevalence and QoL instruments: 19.1% of children and 30.1% of pre-adolescents [50] had very mild to mild fluorosis according to the Dean index, with a significant effect only on the group of Brazilian children administered with the CPQ; 80.3% had mild and 19.7% had most severe fluorosis according to the TFI [53], an effect was noted on the domain of functional limitation among pre-adolescents who were assessed using CPQ and 18.3% had light fluorosis based on of the TFI [49], and an effect was found on the emotional well-being domain using the COQHLQ.\u003c/p\u003e\n\u003cp\u003eFinally, one study in Brazil [57] with a fluorosis prevalence of 14.9% showed a negative association of fluorosis with OHRQoL after the application of the OIDP tool. The main results are summarized in Table 4.\u003c/p\u003e\n\u003cp\u003eTable 4. Descriptive information of the main results of the included studies regarding the effect of fluorosis on OHRQoL\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSynthesis of the characteristics of the studies in relation to the impact of fluorosis on OHRQoL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the evaluation of OHRQoL among children aged 8 to 10 years using the CPQ 8-10 instrument, a comprehensive analysis of various studies revealed varying outcomes regarding the impact of fluorosis. García-Pérez et al. [51]observed a subtle reduction in OHRQoL among children with fluorosis, while Do LG (2007) [18] indicated a more pronounced influence in this group. Onoriobe et al. (2014) [56] reported a substantial disparity in OHRQoL between children with and without fluorosis. Notably, the standard deviations highlighted the considerable variability in perceptions within each group. These findings collectively suggest that the presence of fluorosis can indeed exert an influence on OHRQoL in this specific age group.\u003c/p\u003e\n\u003cp\u003eIn a distinct age bracket, specifically among children aged 11 to 14 years, the impact of fluorosis on OHRQoL was assessed using the CPQ 11-14 instrument across five studies [18,51,56,58,59]. García-Pérez et al. (2017) [51] indicated a slight influence of fluorosis on OHRQoL, with a higher mean CPQ score observed in the fluorosis group. Shyam et al. (2020) [58] reported a moderate impact, as evidenced by increased scores among children with fluorosis. Singh et al. (2018) [59] also noted an effect of fluorosis, although variations in sample sizes and standard deviations were evident. Do LG (2007) [18] found a substantial discrepancy in CPQ scores, with children without fluorosis presenting a higher mean. Notably, Onoriobe et al. (2014) [56] provided valuable insights, demonstrating marked differences in means between the two groups, underscoring the nuanced relationship between fluorosis and OHRQoL in this age group and emphasizing the importance of considering variations in sample characteristics during the interpretation of the impact of fluorosis on OHRQoL.\u003c/p\u003e\n\u003cp\u003eMoreover, this comprehensive analysis extended its scope to various age groups, employing a range of instruments to assess the influence of fluorosis on OHRQoL. Do LG (2007) [18] employed the Parental Perception Questionnaire (PPQ) and identified a significant reduction in OHRQoL among children with fluorosis, characterized by decreased mean scores. Onoriobe et al. (2014) [56] utilized both the Early Childhood Oral Health Impact Scale (ECOHIS) and the Fluorosis Impact Scale (FIS), unveiling distinct impacts of fluorosis on OHRQoL. The ECOHIS indicated a moderate effect, while the FIS revealed a more subtle impact. In contrast, Oliveira et al (2015) [55] adopted the Oral Health Impact Profile (OHIP-14) and disclosed relatively similar mean scores between groups with and without fluorosis. Conversely, Abanto et al. (2014) employed the Child Oral Health Quality of Life Questionnaire (COHQOL) and Impact on Family Scale (IFS), illustrating the discernible impact of fluorosis on OHRQoL and family experiences. These findings collectively underscore the multifaceted relationship between fluorosis and OHRQoL, with variations in sample characteristics, means, and standard deviations accentuating the intricate nature of this relationship across different age groups.\u003c/p\u003e\n\u003cp\u003eThe outcome of a negative impact on the participants' quality of life was observed in six studies [49-51,57-59]. In two studies, the effect of fluorosis on quality of life (QoL) was evident in at least one domain of the QoL instruments. Specifically, Abanto et al. [49] and Li et al. [52]reported such effects in the domains of emotional well-being, and Lima et al. [53] identified an impact on functional limitation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeta-analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 2 presents the two meta-analysis. The meta-analysis were conducted with studies grouped by OHRQoL instruments CPQ 8-10 [18,49,51] and CPQ 11-14 [18,51,58], more frequent among the primary articles, which allowed the conduction of the meta-analysis\u0026nbsp;and comparison of the groups with and without fluorosis.\u003c/p\u003e\n\u003cp\u003eFigure 2. Forest plots of the first and second meta-analysis of the included studies that used CPQ 8–10 (1) and CPQ 11–14 (2) as a quality-of-life instrument.\u003c/p\u003e\n\u003cp\u003eA meta-analysis was conducted to assess the impact of fluorosis on OHRQoL in children aged 8 to 10 years, incorporating three relevant studies [18,49,51] that employed the CPQ 8-10 instrument (p-value = 0.14; 95% confidence interval, -0.91, 6.63). Furthermore, they did not show significant heterogeneity (Tau²=0.1421; p-value = 0.36; Q value = \u0026nbsp; \u0026nbsp;; I2 = 1%). A quantitative analysis of three studies [18,51,58] employing the CPQ 11-14 instrument concluded that fluorosis does not have a significant impact on OHRQoL (p-value = 0.51; 95% confidence interval, −0.18, 0.36; heterogeneity: Tau² = 0.03; p-value = 0.08; Q value ; I2 = 61 %).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis systematic review was conducted with the aim of assessing the impact of dental fluorosis on OHRQoL. To achieve this, both qualitative and quantitative analyses were applied to the findings derived from 16 studies included in this review [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR49 CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57 CR58\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan additionalcitationids=\"CR62\" citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. Among these studies, 15 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR49 CR50 CR51 CR52 CR53 CR54 CR55\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan additionalcitationids=\"CR62\" citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e] were of cross-sectional design. It's worth noting that longitudinal studies are generally better suited for examining potential causal relationships, particularly concerning prevalence and conditions \u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the analysis of studies utilizing the CPQ 11\u0026ndash;14 instrument, it was determined that fluorosis does not have a statistically significant impact on OHRQoL. Results indicated substantial heterogeneity among the studies, what is expected in observational studies. Similarly, to the other meta-analysis involving the CPQ 8\u0026ndash;10 instrument, the results do not indicate a statistically significant impact of fluorosis on OHRQoL, reinforcing the credibility of this outcome.\u003c/p\u003e \u003cp\u003eFluorosis, characterized by changes in tooth enamel, is primarily a subjective condition without associated pain or discomfort [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. As a result, its impact is assessed through individuals' perception [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Multiple studies have endeavored to assess its impact on the QoL of various populations [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, the findings of these studies have not yet provided a definitive conclusion regarding its impact on OHRQoL. This further highlights the ongoing uncertainty surrounding the consideration of fluorosis as a significant public health concern, given the inconclusive nature of the findings regarding its impact on quality of life.\u003c/p\u003e \u003cp\u003eChankanka et al. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] demonstrated that pre-adolescents tend to perceive themselves as more attractive due to the presence of white spots on their teeth. A similar observation was made in an Australian study [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] where, apart from this particular age group, participants' parents also expressed a more positive perception of their children's QoL, suggesting that at mild levels, fluorosis can have a favorable impact on QoL. In contrast, a study conducted in Mexico [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e] and another in Australia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] reported that pre-adolescents were more likely to notice the presence of white spots compared to younger children. However, in Brazil [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], the opposite pattern of perception emerged within the same age groups. These variations could be attributed to the influence of cultural norms on the aesthetic perception of individuals with fluorosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prevalence of very mild fluorosis suggests that regions adhering to recommended water fluoridation standards \u003csup\u003e65\u003c/sup\u003e tend to experience this milder form. On the other hand, areas with high fluoride intake from natural sources may exhibit a higher prevalence of severe conditions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Mild fluorosis was consistently observed in numerous studies conducted in Brazil [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], a pattern partly attributed to the country's longstanding regulations for water fluoridation dating back to 1975, under the Ministry of Health's supervision [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. However, it's worth noting that the prevalence of this condition in regions with standardized fluoride levels in water can also be influenced by excess fluoride intake from other sources, such as toothpaste [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile the prevalence of severe fluorosis and its associated aesthetic concerns is generally low, it is more frequently observed in endemic regions [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e] and has been shown to impact the OHRQoL of individuals [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Primary studies conducted in Mexico [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e] and India [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e] have demonstrated a negative association between fluorosis and OHRQoL. In Mexico [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], a significant difference in OHRQoL was identified among individuals aged 11\u0026ndash;14 years with severe fluorosis when assessed using the CPQ instrument. These findings were consistent with earlier studies conducted in endemic regions, such as San Lu\u0026iacute;s Potos\u0026iacute;, Mexico [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Studies conducted by Shyam et al. [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e] and Singh et al. [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e] in endemic regions with varying fluoride concentrations (0.23\u0026ndash;4.3 and 5.35 ppm of F, respectively) further supported the impact of fluorosis on OHRQoL. Shyam et al. [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e] revealed a substantial presence of fluorosis (26.1% grade 4 according to the TFI) and reported that 20% of participants aged 11\u0026ndash;14 years perceived their oral health as significantly affected, rating it 1.7 times worse than those without fluorosis. Similarly, in the study by Singh et al.[\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e], pre-adolescents exhibited increased mean scores in all domains of the CPQ instrument in accordance with the severity of fluorosis. These results from India are consistent with earlier Indian studies by Bhagyajyothi et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and Jodali et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], both conducted in endemic regions, and align with findings from the literature review by Chankanka [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and a recent study in Iran [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] (1.2\u0026ndash;1.4 ppm of F in water) where the prevalence of severe fluorosis influenced individuals' appearance.\u003c/p\u003e \u003cp\u003eNevertheless, it is imperative to approach the findings of these studies with a degree of caution, recognizing that several methodological limitations were observed in the primary investigations, as depicted in Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Notably, these limitations were predominantly prevalent in cross-sectional studies, particularly following the application of the modified NOS assessment tool. Primarily, a significant shortcoming was the absence of sample size calculations in some studies [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], a fundamental component for the rigorous planning, accurate interpretation, and overall validity of research results [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. Additionally, the studies generally omitted the reporting of non-response rates among participants. Confounding factors were rarely addressed in the included studies; such factors are instrumental in establishing whether variables such as gender and age significantly influence the impact of fluorosis on OHRQoL [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Lastly, the primary studies exhibited considerable heterogeneity in their data, primarily stemming from the diverse diagnostic indexes used for fluorosis classification and varying instruments employed for OHRQoL assessments, rendering the comparison of research outcomes and the establishment of standardized statistical data with OHRQoL a complex endeavor.\u003c/p\u003e \u003cp\u003eThe qualitative analysis of the primary studies assumed significance in elucidating that a considerable majority of the included investigations primarily reported the prevalence of fluorosis within the very mild to mild categories according to Dean's index and TFI. In these cases, the observed consensus suggested a lack of discernible impact on OHRQoL. Conversely, a noteworthy inference from this qualitative evaluation implied that the severity of fluorosis, specifically in moderate categories, could potentially manifest as an influential factor affecting individuals' overall quality of life. It is, however, important to underscore that the amalgamation of data from both groups, i.e., those with and without fluorosis, in many of the selected studies precluded the extraction of separate datasets. This intertwining of data sources introduces the possibility of dilution, which might elucidate the absence of discernible fluorosis-related impact on OHRQoL, thus unveiling an inherent limitation in the scope of this systematic review.\u003c/p\u003e \u003cp\u003eThis systematic review provides a comprehensive perspective on the relationship between fluorosis and OHRQoL, shedding light on the intricate interplay between fluorosis severity and age groups. These findings prompt further research to explore the multifaceted dimensions of this relationship and the factors that might contribute to these divergent outcomes, ultimately advancing our understanding of the complex interplay between fluorosis and OHRQoL.\u003c/p\u003e \u003cp\u003eThe authors report that there is no conflict of interest for the study and that this research did not have any funding.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe findings from this systematic review indicate that fluorosis does not exert a significant impact on OHRQoL in children aged 8-14. These results underscore the notion that fluorosis might not severely impact OHRQoL. Further investigations are needed to delve into the intricate aspects of this relationship and identify the factors contributing to varying outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eA. Author Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRSB, HMH and JRMB proposed the research idea, and PLM, SMV, TMS, and MPM wrote the main manuscript text and RCPM prepared the figures. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB. Ethics Approval and Consent to Participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC. Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD. Conflict of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest related to this research paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003ePetersen, Poul Erik, Baez, Ramon J \u0026amp; World Health Organization. (\u0026lrm;2013)\u0026lrm;. Oral health surveys: basic methods, 5th ed. World Health Organization. https://iris.who.int/handle/10665/97035\u003c/li\u003e\n \u003cli\u003eChankanka O, Levy SM, Warren JJ, Chalmers JM (2010) A literature review of aesthetic perceptions of dental fluorosis and relationships with psychosocial aspects/oral health-related quality of life. Community Dentistry and Oral Epidemiology. 38: 97-109. https://doi.org/10.1111/j.1600-0528.2009.00507.x\u003c/li\u003e\n \u003cli\u003eDean HT (1934) Classification of Mottled Enamel Diagnosis. The Journal of the American Dental Association 21:1421-1426. https://doi.org/10.14219/jada.archive.1934.0220\u003c/li\u003e\n \u003cli\u003eCangussu MCT, Narvai PC, Fernandez RC, Djehizian V (2002) Dental fluorosis in Brazil: a critical review. Reports in Public Health 18: 7-15. https://doi.org/10.1590/S0102-311X2002000100002\u003c/li\u003e\n \u003cli\u003eBuzalaf MAR, Delbem ACB, Pessan JP (2021) Rational use of fluoride to control caries lesions. In Magalh\u0026atilde;es AC, Rios D, Wang L, Buzalaf MAR (Eds.), Cariology: from basic to clinical (1\u003csup\u003est\u003c/sup\u003e ed., pp. 134-153). Manole.\u003c/li\u003e\n \u003cli\u003eRigo L, Caldas Junior AF, Souza EA, Abegg C, Lodi L (2010) Study on the dental fluorosis in a Southern city of Brazil. Ci\u0026ecirc;ncia \u0026amp; Sa\u0026uacute;de Coletiva 15: 1439-48. https://doi.org/10.1590/S1413-81232010000700055\u003c/li\u003e\n \u003cli\u003eSteiner M, Menghini G, Marthaler TM, Imfeld T (2010) Changes in dental caries in Zurich school-children over a period of 45 years. Schweiz Monatsschr Zahnmed 1084-104.\u003c/li\u003e\n \u003cli\u003eLauris JRP, Bastos RD, Bastos JRD (2012) Decline in dental caries among 12-year-old children in Brazil, 1980-2005. International Dental Journal 62: 308-14.\u003c/li\u003e\n \u003cli\u003eKassebaum NJ, Bernab\u0026eacute; E, Dahiya M, Bhandari B, Murray CJ, Marcenes W (2015) Global burden of untreated caries: a systematic review and metaregression. J Dent Res 94: 650-8.\u003c/li\u003e\n \u003cli\u003eKassebaum NJ, Smith AGC, Bernab\u0026eacute; E, Fleming TD, Reynolds AE, Vos T, et al (2017) Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res 96: 380-7.\u003c/li\u003e\n \u003cli\u003eIheozor-Ejiofor Z, Worthington HV, Walsh T, O\u0026apos;Malley L, Clarkson JE, Macey R, et al (2015) Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev 6: CD010856.\u003c/li\u003e\n \u003cli\u003eBastos RD, Olympio KPK, Bijella VT, Buzalaf MAR, Bastos JRD (2005) Trends in dental caries prevalence in 12-year-old schoolchildren between 1976 and 2001 in Bauru, Brazil. Public Health 119: 269-75.\u003c/li\u003e\n \u003cli\u003eDo L, Ha D, Peres MA, Skinner J, Byun R, Spencer AJ (2017) Effectiveness of water fluoridation in the prevention of dental caries across adult age groups. Community Dent Oral Epidemiol 45: 225-32.\u003c/li\u003e\n \u003cli\u003ePeres MA, Peres KG, Barbato PR, H\u0026ouml;felmann DA (2016) Access to Fluoridated Water and Adult Dental Caries: A Natural Experiment. J Dent Res 95: 868-74.\u003c/li\u003e\n \u003cli\u003eMoore D, Poynton M, Broadbent JM, Thomson WM (2017) The costs and benefits of water fluoridation in NZ. BMC Oral Health 17: 134.\u003c/li\u003e\n \u003cli\u003eWalsh T, Worthington HV, Glenny AM, Marinho VC, Jeroncic A (2019) Fluoride toothpastes of different concentrations for preventing dental caries. Cochrane Database Syst Rev 3: CD007868.\u003c/li\u003e\n \u003cli\u003evan Palenstein Helderman WH, Mkasabuni E (1993) Impact of dental fluorosis on the perception of well-being in an endemic fluorosis area in Tanzania. Community Dental Oral Epidemiology 21: 243-4. https://doi.org/10.1111/j.1600-0528.1993.tb00765.x\u003c/li\u003e\n \u003cli\u003eDo LG, Spencer A. Oral health-related quality of life of children by dental caries and fluorosis experience (2017) Journal Public Health Dent 67: 132-9. https://doi.org/10.1111/j.1752-7325.2007.00036.x\u003c/li\u003e\n \u003cli\u003eTellez M, Santamaria RM, Gomez J, Martignon S (2012) Dental fluorosis, dental caries, and quality of life factors among schoolchildren in a Colombian fluorotic area. Community Dental Health 29: 95-9. https://europepmc.org/article/med/22482258\u003c/li\u003e\n \u003cli\u003eMoimaz SA, Saliba O, Marques LB, Garbin CA, Saliba NA (2015) Dental fluorosis and its influence on children\u0026apos;s life. Brazilian Oral Research 29: 806-83. https://doi.org/10.1590/1807-3107BOR-2015.vol29.0014\u003c/li\u003e\n \u003cli\u003eBhagyajyothi CS, Pushpanjali K (2009) Perceptions and concerns about dental fluorosis as assessed by tooth surface index of fluorosis among high school children in an area of endemic fluorosis-Kaiwara. Oral Health \u0026amp; Preventive Dentistry 7: 33-8. https://europepmc.org/article/med/19408813\u003c/li\u003e\n \u003cli\u003eJodalli PS, Ankola AV, Hebbal M, Vikneshan M (2013) Aesthetic perceptions regarding fluorosis by children from an area of endemic fluorosis in India. Community Dental Health 30: 249-53.\u003c/li\u003e\n \u003cli\u003eAguilar-D\u0026iacute;az FC, Irigoyen-Camacho ME, Borges-Y\u0026aacute;\u0026ntilde;ez SA (2011) Oral-health-related quality of life in schoolchildren in an endemic fluorosis area of Mexico. Quality of Life Research 20: 1699\u0026ndash;1706. https://doi.org/10.1007/s11136-011-9897-4\u003c/li\u003e\n \u003cli\u003eMoher D, Liberati A, Tetzlaff J, Altman DG (2009) The PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6: e1000097. https://doi.org/10.1371/journal.pmed.1000097\u003c/li\u003e\n \u003cli\u003eGA Wells, GA Shea B, O\u0026apos;Connell D, Peterson J, Welch V, Losos M, Tugwell P (2021) Ottawa Hospital Research Institute. OHRI. Retrieved April 20, 2021, from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp\u003c/li\u003e\n \u003cli\u003eAim\u0026eacute;e NR, van Wijk AJ, Maltz M, Varj\u0026atilde;o MM, Mestrinho HD, Carvalho JC (2017) Dental caries, fluorosis, oral health determinants, and quality of life in adolescents. Clin Oral Investig 21:1811-1820. Doi: 10.1007/s00784-016-1964-3\u003c/li\u003e\n \u003cli\u003eAznar FDC. An\u0026aacute;lise da rela\u0026ccedil;\u0026atilde;o entre as condi\u0026ccedil;\u0026otilde;es de sa\u0026uacute;de bucal e a qualidade de vida em adolescentes com sobrepeso/obesidade e eutr\u0026oacute;ficos em Bauru - SP [dissertation]. Bauru:Faculdade de Odontologia de Bauru, Universidade de S\u0026atilde;o Paulo; 2015.128 p.\u003c/li\u003e\n \u003cli\u003eBastos RS. Impacto das condi\u0026ccedil;\u0026otilde;es de sa\u0026uacute;de bucal em rela\u0026ccedil;\u0026atilde;o \u0026agrave; qualidade de vida de adolescentes escolares de 15 a 19 anos, numa dicotomia socioecon\u0026ocirc;mica, no munic\u0026iacute;pio de Bauru, S\u0026atilde;o Paulo, em 2009 [dissertation]. Bauru: Faculdade de Odontologia de Bauru, Universidade de S\u0026atilde;o Paulo; 2009. 180 p.\u003c/li\u003e\n \u003cli\u003eMichel-Crosato E. Autopercep\u0026ccedil;\u0026atilde;o de sa\u0026uacute;de e avalia\u0026ccedil;\u0026atilde;o das condi\u0026ccedil;\u0026otilde;es bucais dos escolares, de 6 a 15 anos de idade, do munic\u0026iacute;pio de Pinheiro Preto \u0026ndash; SC, 2002 [dissertation]. Ara\u0026ccedil;atuba: Faculdade de Odontologia de Ara\u0026ccedil;atuba, Universidade Estadual Paulista; 2003. 171 p.\u003c/li\u003e\n \u003cli\u003eDo LG, H\u0026aacute; DH, Spencer AJ (2016) Natural history and long-term impact of dental fluorosis: a prospective cohort study. Med J Aust 204: 25. https://doi.org/10.5694/mja15.00703\u003c/li\u003e\n \u003cli\u003eFurtado GE, Sousa ML, Barbosa TS, Wada RS, Mart\u0026iacute;nez-Mier EA, Almeida ME (2012) Percep\u0026ccedil;\u0026atilde;o da fluorose dent\u0026aacute;ria e avalia\u0026ccedil;\u0026atilde;o da concord\u0026acirc;ncia entre pais e filhos: valida\u0026ccedil;\u0026atilde;o de um instrumento. Cad Saude P\u0026uacute;blica 28: 1493-505. https://doi.org/10.1590/S0102-311X2012000800008\u003c/li\u003e\n \u003cli\u003eMarques LB. Preval\u0026ecirc;ncia e autopercep\u0026ccedil;\u0026atilde;o da fluorose dent\u0026aacute;ria em crian\u0026ccedil;as de 12 anos de idade do munic\u0026iacute;pio de Birig\u0026uuml;i-SP [master\u0026rsquo;s thesis]. Araraquara: Faculdade de Odontologia de Araraquara, Universidade Estadual Paulista; 2008. 66 p.\u003c/li\u003e\n \u003cli\u003eMichel-Crosato E, Barbieri DB, Biazevic MGH, Correia LD (2007) Condi\u0026ccedil;\u0026atilde;o de sa\u0026uacute;de bucal e autopercep\u0026ccedil;\u0026atilde;o de fluorose dental: um estudo de base populacional no Sul do Brasil, 2003. Rev P\u0026oacute;s Grad 13: 353-7.\u003c/li\u003e\n \u003cli\u003eDuta M, Jipa IT, Amariei C (2014) Oral health status and quality of life in the Danube Delta Reserve Biosphere \u0026ndash; child and parent perspectives. Social Science and Arts 2: 587-594 doi:10.5593/SGEMSOCIAL2014/B12/S2.075\u003c/li\u003e\n \u003cli\u003eNilchian F, Asgary I, Mastan F (2018) The Effect of Dental Fluorosis on the Quality of Life of Female High School and Precollege Students of High Fluoride-Concentrated Area. J Int Soc Prev Community Dent 8: 314-319. doi: 10.4103/jispcd.JISPCD_94_18\u003c/li\u003e\n \u003cli\u003ePavithran VK, Murali R, Krishna M, Shamala A, Yalamalli M, Kumar AV, Raina R (2020) Impact of oral diseases on daily activities among 12- to 15-year-old institutionalized orphan and non-orphan children in Bengaluru city: A cross-sectional analytical study. Indian J Dent Res 31: 396-402. doi: 10.4103/ijdr.IJDR_260_18.\u003c/li\u003e\n \u003cli\u003ePeres KG, Latorre MR, Peres MA, Traebert J, Panizzi M (2003) Impacto da c\u0026aacute;rie e da fluorose dent\u0026aacute;ria na satisfa\u0026ccedil;\u0026atilde;o com a apar\u0026ecirc;ncia e com a mastiga\u0026ccedil;\u0026atilde;o de crian\u0026ccedil;as de 12 anos de idade. Cad Saude P\u0026uacute;blica 19: 323-30. https://doi.org/10.1590/S0102-311X2003000100037\u003c/li\u003e\n \u003cli\u003eRobinson PG, Nalweyiso N, Busingye J, Whitworth J (2005) Subjective impacts of dental caries and fluorosis in rural Ugandan children. Community Dent Health 22: 231-6. https://www.researchgate.net/publication/7392500_Subject_impacts_of_dental_caries_and_fluorosis_in_rural_Ugandan_children\u003c/li\u003e\n \u003cli\u003eSu H, Peng Q, Jiang Y (2017) Analytical study of signs and symptoms of TMD, fluorosis and caries in different age groups to validate and to find reliability of oral health-related quality of life. Biomedical Research 28: 7923-7929.\u003c/li\u003e\n \u003cli\u003eDitterich RG. Preval\u0026ecirc;ncia e autopercep\u0026ccedil;\u0026atilde;o de fluorose dent\u0026aacute;ria em escolares de 12 anos residentes no munic\u0026iacute;pio de Ponta Grossa-PR [master\u0026rsquo;s thesis]. Ponta Grossa: Universidade Estadual de Ponta Grossa; 2006. 160 p.\u003c/li\u003e\n \u003cli\u003eMenezes LMB. Autopercep\u0026ccedil;\u0026atilde;o da fluorose dental, bem-estar dos portadores e responsabilidade legal [dissertation]. Piracicaba: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas; 2001. 120 p.\u003c/li\u003e\n \u003cli\u003eCalder\u0026oacute;n ZM de, Abanto J, S\u0026aacute; Oliveira G, Haddad AE, B\u0026ouml;necker M (2021) Does fluorosis have an impact on peruvian children\u0026rsquo;s oral health related quality of life? Rev Ga\u0026uacute;ch Odontol 69: e2021002. available from: https://doi.org/10.1590/1981-8637202100023412\u003c/li\u003e\n \u003cli\u003eGarc\u0026iacute;a-P\u0026eacute;rez A, Gonz\u0026aacute;lez-Arag\u0026oacute;n Pineda AE, Villanueva Guti\u0026eacute;rrez T, P\u0026eacute;rez P\u0026eacute;rez NG, G\u0026oacute;mez-Clavel JF (2022) Impact of diseases of the hard tissues of teeth on oral health-related quality of life of schoolchildren in area with a high concentration of fluoride in drinking water. Community Dent Health 394: 240-246. doi:10.1922/CDH_00078Garcia-Perez07\u003c/li\u003e\n \u003cli\u003eIdon PI, Udoye C, Sotunde O, Idon MI, Janada Y, PY (2018) Psychological impact, quality of life and treatment needs among adult patients with dental fluorosis in an endemic region of Northern Nigeria. Tropical Dental Journal 41: 42-52.\u003c/li\u003e\n \u003cli\u003eKumar V, Gaunkar R, Thakker J, Ankola AV, Iranna Hebbal M, Khot AJP, Goyal V, Ali A, Eldwakhly E (2023) Pediatric Dental Fluorosis and Its Correlation with Dental Caries and Oral-Health-Related Quality of Life: A Descriptive Cross-Sectional Study among Preschool Children Living in Belagavi. Children (Basel)10: 286. doi: 10.3390/children10020286. PMID: 36832415\u003c/li\u003e\n \u003cli\u003eGhada T, Nancy K, Mohamed A. El-Yazeed, Ehab M. Radwan, Marwa Saber Abd El Salam (2022) Impact of dental Fluorosis on quality of life of a group of Children in a Rural area in Nubia Region. IJPHRD 13: 127-33. https://medicopublication.com/index.php/ijphrd/article/view/18183\u003c/li\u003e\n \u003cli\u003eVarshney S, Menon I, Gupta R, Arora V, Sharma A, Rohatgi L (2022) Effect of Dental Fluorosis on Oral Health-Related Quality of Life and Daily Performances Among 12- and 15-year-old School-going Children Residing in High- and Low-Fluoridated Areas of Meerut District. Asian Journal of Pharmaceutical Research and Health Care 14: 94-101. DOI: 10.4103/ajprhc.ajprhc_34_22\u003c/li\u003e\n \u003cli\u003eBiazevic MG, Rissotto RR, Michel-Crosato E, Mendes LA, Mendes MO (2008) Relationship between oral health and its impact on quality of life among adolescentes. Brazilian Oral Research 22: 36-42. https://doi.org/10.1590/S1806-83242008000100007\u003c/li\u003e\n \u003cli\u003eAbanto J, Ortega AO, Raggio DP, B\u0026ouml;necker M, Mendes FM, Ciamponi AL (2014) Impact of oral diseases and disorders on oral-health-related quality of life of children with cerebral palsy. Special Care in Dentistry 34: 56-63. https://doi.org/10.1111/scd.12028\u003c/li\u003e\n \u003cli\u003eBarbosa TS, Gavi\u0026atilde;o MB, Castelo PM, Leme MS (2016) Factors Associated with Oral Health-related Quality of Life in Children and Preadolescents: A Cross-sectional Study. Oral Health \u0026amp; Preventive Dentistry 14: 137-48. DOI 10.3290/j.ohpd.a35301\u003c/li\u003e\n \u003cli\u003eGarc\u0026iacute;a-P\u0026eacute;rez A, Irigoyen-Camacho ME, Borges-Y\u0026aacute;\u0026ntilde;ez SA, Zepeda-Zepeda MA, Bolona-Gallardo I, Maupom\u0026eacute; G (2017) Impact of caries and dental fluorosis on oral health-related quality of life: a cross-sectional study in schoolchildren receiving water naturally fluoridated at above-optimal levels. Clinical Oral Investigations 21: 2771-2780 https://doi.org/10.1007/s00784-017-2079-1\u003c/li\u003e\n \u003cli\u003eLi YJ, Gao YH, Zhang Y (2014) The impact of oral health status on the oral health-related quality of life (OHRQoL) of 12-year-olds from children\u0026apos;s and parents\u0026apos; PERSPECTIVES. Community Dental Health 31: 240-4. DOI 10.1922/CDH_3346Zhang05\u003c/li\u003e\n \u003cli\u003eLima LMS, Dantas-Neta NB, Moura WS, Moura MS, Mantesso A, Moura LFAD, Lima MDM (2014) Impact of dental fluorosis on the quality of life of children and adolescents. Rev Odontol UNESP 43: 326-332. https://doi.org/10.1590/rou.2014.052\u003c/li\u003e\n \u003cli\u003eMichel-Crosato E, Biazevic MG, Crosato E (2005) Relationship between dental fluorosis and quality of life: a population based study. Brazilian Oral Research 19: 150-5. https://doi.org/10.1590/S1806-83242005000200014\u003c/li\u003e\n \u003cli\u003eOliveira DC, Ferreira FM, Morosini IA, Torres-Pereira CC, Martins SP, Fraiz FC (2015) Impact of Oral Health Status on the Oral Health-Related Quality of Life of Brazilian Male Incarcerated Adolescents. Oral Health \u0026amp; Preventive Dentistry 13: 417-25. DOI 10.3290/j.ohpd.a33922\u003c/li\u003e\n \u003cli\u003eOnoriobe U, Rozier RG, Cantrell J, King RS (2014) Effects of enamel fluorosis and dental caries on quality of life. Journal Dental of Research 93: 972-9. https://doi.org/10.1177/0022034514548705\u003c/li\u003e\n \u003cli\u003ePeres KG, Peres MA, Araujo CL, Menezes AM, Hallal PC (2009) Social and dental status along the life course and oral health impacts in adolescents: a population-based birth cohort. Health Quality of Life Outcomes 22: 95. https://doi.org/10.1186/1477-7525-7-95\u003c/li\u003e\n \u003cli\u003eShyam R, Bhadravathi CM, Kumar A, Pahwa M, Rani G, Phogat R (2020) Impact of dental fluorosis on the oral health related quality of life among 11- to 14-year-old school children in endemic fluoride areas of Haryana (India). International Dental Journal 70: 340-346. DOI 10.1111/idj.12567\u003c/li\u003e\n \u003cli\u003eSingh S, Saha S, Singh S, Shukla N, Reddy V (2018) Oral health-related quality of life among 12-15-year children suffering from dental fluorosis residing at endemic fluoride belt of Uttar Pradesh, India. Quality of Life Research 16: 54-57. DOI 10.4103/jiaphd.jiaphd_139_16\u003c/li\u003e\n \u003cli\u003eJokovic A, Locker D, Guyatt G (2006) Short forms of the Child Perceptions Questionnaire for 11\u0026ndash;14-year-old children (CPQ11\u0026ndash;14): Development and initial evaluation. Health Qual Life Outcomes 4: 4.\u003c/li\u003e\n \u003cli\u003eArheiam A, Aloshiby A, Gaber A, Fakron S (2022) Dental Fluorosis and Its Associated Factors Amongst Libyan Schoolchildren. Int Dent J 72: 853-858. doi: 10.1016/j.identj.2022.04.010\u003c/li\u003e\n \u003cli\u003eConstante CAP, P\u0026eacute;rez RER, Rodr\u0026iacute;guez VJP, Cabrera AMA, Armas VA del Carmen (2020). Impact of dental fluorosis over the quality of life of ecuadorian teenagers between 11 and 14 years. Odontolog\u0026iacute;a Vital 32: 21-28.\u003c/li\u003e\n \u003cli\u003eThilakarathne BKG, Ekanayake L, Schensul JJ, Reisine S (2023) Impact of dental fluorosis on the oral health related quality of life of adolescents in an endemic area. J Oral Biol Craniofac Res 13: 448-452. doi: 10.1016/j.jobcr.2023.03.015.\u003c/li\u003e\n \u003cli\u003eBarbosa TS, Steiner-Oliveira C, Gavi\u0026atilde;o MBD (2010) Tradu\u0026ccedil;\u0026atilde;o e adapta\u0026ccedil;\u0026atilde;o brasileira do Parental-Caregiver Perceptions Questionnaire (P-CPQ). Sa\u0026uacute;de e Sociedade 19: 698-708.\u003c/li\u003e\n \u003cli\u003eGodinho GNF. Oral Impacts on Daily Performances- OIDP: estudo transversal de valida\u0026ccedil;\u0026atilde;o para popula\u0026ccedil;\u0026atilde;o portuguesa, 2015 [master \u0026apos;s thesis]. Lisboa: Faculdade de Medicina Dent\u0026aacute;ria, Universidade de Lisboa; 2015. 49p.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"Tables 1-4 are available in the Supplementary Files section"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Dental fluorosis, Quality of life, Cross-Sectional Studies","lastPublishedDoi":"10.21203/rs.3.rs-3745254/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3745254/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective.\u003c/strong\u003eThe aim of this systematic review is to investigate the literature to assess the effect of fluorosis on the Oral Health-Related Quality of Life (OHRQoL).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods.\u003c/strong\u003e Included studies were epidemiological investigations, clinical trials, or human studies that directly compared the impact on OHRQoL between individuals with fluorosis and those without, utilizing valid OHRQoL assessment tools. The searches were conducted up to September 2023 in databases, including PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and the Virtual Health Library. Additionally, gray literature sources such as Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest were searched. Reference lists were also manually reviewed for potential eligible studies. The risk of bias in cohort studies was assessed using the Newcastle–Ottawa Scale (NOS), while its modified version was employed for cross-sectional studies. A meta-analysis was performed using the random-effects model in R Statistical Software with a significance level of p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003eOut of the 16 included studies, four were suitable for meta-analysis. In total, 16,314 participants, aged 8 to 18, were assessed across the studies. The analysis of the CPQ 8-10 instrument indicated no significant impact (p-value = 0.14). For the CPQ 11-14 the quantitative analysis suggested no significant impact on OHRQoL (p-value = 0.51). Limitations in the included studies primarily pertained to cross-sectional designs, with significant issues such as the absence of sample size calculations, lack of non-response rate reporting, limited consideration of confounding factors, and substantial heterogeneity stemming from diverse diagnostic methods and assessment tools.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion.\u003c/strong\u003eThe overall findings indicated that mild dental fluorosis did not adversely affect the OHRQoL of the studied populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical relevance. \u003c/strong\u003eDental caries preventive fluoridated measures might be indicated even if there would be a risk for mild dental fluorosis as the fluoridated public water.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration.\u003c/strong\u003e This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under number: CRD42020186552.\u003c/p\u003e","manuscriptTitle":"Impact of fluorosis on the oral health-related quality of life: a systematic review and meta-analysis.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 19:53:33","doi":"10.21203/rs.3.rs-3745254/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-14T12:12:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-06T19:57:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-01T07:37:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"17a21fb6-1819-49e8-a129-8dfae06eb6f1","date":"2024-01-07T22:42:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2c41b3ea-bfab-47ad-8604-b3fa58948465","date":"2024-01-07T13:59:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-05T11:45:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-27T02:40:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-27T02:40:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Oral Investigations","date":"2023-12-12T18:50:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5f94638d-9e0d-4d46-8056-d817c121961a","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-21T16:10:29+00:00","versionOfRecord":{"articleIdentity":"rs-3745254","link":"https://doi.org/10.1007/s00784-024-05991-x","journal":{"identity":"clinical-oral-investigations","isVorOnly":false,"title":"Clinical Oral Investigations"},"publishedOn":"2024-10-17 15:57:39","publishedOnDateReadable":"October 17th, 2024"},"versionCreatedAt":"2024-01-02 19:53:33","video":"","vorDoi":"10.1007/s00784-024-05991-x","vorDoiUrl":"https://doi.org/10.1007/s00784-024-05991-x","workflowStages":[]},"version":"v1","identity":"rs-3745254","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3745254","identity":"rs-3745254","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}