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INTRODUCTION
The use of fluoride in dental caries management is one of the great milestones in dentistry, and has been recognized as the main factor responsible for the significant decline in caries prevalence around the worldu. Epidemiological data from communities with access to a fluoridated public water supply provided the initial evidence that fluoride promotes oral health 3, 4 .
Caries prevention mechanisms through the action of fluorides are post-eruptive, occurring through their topical cumulative effect, and acting on the dynamics of demineralization/remineralization 5 . However, excessive fluoride intake during the tooth development period can cause dental fluorosis, which is the only proven relevant side effect of fluoride use 2 .
Fluorosis is a worldwide public health problem and, like caries, has also been related to socioeconomic factors. The type of water consumed is one of these factors, and the consumption ofwell water is one ofthe consequences of people’s socioeconomic condition 6 . Many communities still drink groundwater, often with fluoride concentration greater than the 1.5 ppm recommended by the World Health Organization. This increases the risk of fluorosis, thereby constituting a serious public health problem 7 .
The high fluoride concentration in well water may be caused by lithology or by contamination from local industries or agrobusiness operations that increase the risk of heavy metals, pesticides, nitrates, radon and fluoride in the water 8, 9 . Other factors are the amount and duration of precipitation, infiltration rate, level of groundwater exploitation in the area, etc. 10 . The increasing uptake of groundwater resources can also affect the distribution and concentration of fluoride 11 .
Some studies correlate the consumption of groundwater with high prevalence of fluorosis because fluoride and arsenic are the main pollutants in groundwater. Fluoride concentration in the water increases with depth, with wells deeper than 30 m containing the highest amounts. The risk of fluorosis is proportional to the amount of fluoridated water the child is exposed to.
Fluorosis is classified as mild, moderate or severe 6-8, 12 . Plasma and urine fluoride concentration is proportional to the fluoride concentration in the water consumed 10, 11 .
In view of the growing concern about this issue, the aim of this study was to conduct a systematic review to determine whether children’s risk of fluorosis is related to drinking fluoridated groundwater.
MATERIALS AND METHOD
This systematic review was conducted in accordance with the guidelines of the Cochrane handbook for systematic review of Interventions, following the four-phase diagram of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The study protocol was registered at the National Institute of Health Research Database (CRD42021227298).
The research question was adapted from the PECO framework for the systematic review of clinical studies:
Population (P): Patients up to 18 years
Exposure (E): Groundwater
Comparison (C): Exposure to water from supply network or commercial mineral water
Outcome (O): Fluorosis
In terms of research questions, based on the PECO model, the review aimed to assess the current knowledge and literature for the effect of patient exposure to groundwater on the outcome of fluorosis. The criteria followed in this study are described in Table 1.
2.1 Literature search strategy
A comprehensive search was conducted to identify potentially relevant studies by exploring a range of electronic databases (Medline via PubMed, Scopus, Cochrane Library, Science Direct, Web of Science Core Collection, Medline via Ovid, Lilacs, and Embase). Additionally, a Google scholar and reference search on grey literature was undertaken to identify any other relevant published work. The search was conducted without applying any date limits or language restrictions.
The search strategy included the terms: “Children”, “child” and “Fluoride”, “Fluorine”, “Water Well*”, and “Water Ground*”; and “Fluoridated water”, “water fluoridation” and “Enamel defect*”, “Fluorosis”.
Trade names of various classes of sealers were also used as a part of the search strategy. Boolean operators (“OR” and “AND”) were used to join search terms related to the search question (Table 2). Table 3 shows the literature searches and results found in Pubmed, Scopus, Cochrane, Web of Science Core Collection, Medline via Ovid, BVS, and Embase.
Table 2 Search terms.
| Search 1 | 'Children', 'child' |
| Search 2 | 'Fluoride', 'Fluorine', 'Water Well*', 'Water Ground*' |
| Search 3 | 'Fluoridated water', 'water fluoridation', 'drinking water' |
| Search 4 | 'Enamel defect*', 'Fluorosis' |
Table 3 Literature searches and number of articles found.
| Searches related to the descriptors | |||||
| 'Children' OR 'child' #1 | 'Fluoride' OR 'Fluorine' OR 'Water Well*' OR 'Water Ground*' #2 | 'Fluoridated water' OR 'water fluoridation' OR 'drinking water' #3 | 'Children' OR 'child' #4 | #1 AND #2 AND #3 AND #4 | |
| Pubmed | 1,313,471 | 60,645 | 51,561 | 4,240 | 388 |
| Scopus | 3,169,927 | 246,326 | 1,185 | 4,935 | --
55 |
| Cochrane | 144,754 | 10,081 | 3,828 | 539 | 15 |
| Web of Science | 2,263,174 | 691,017 | 114,744 | 7,714 | --
665 |
| Medline via Ovid | 2,239,364 | 61,373 | 48,523 | 1,946 | 1 |
| Virtual Health Library (BVS/VHL) | 2,510,968 | 351,664 | 83,293 | 8,888 | 564 |
| Embase | 1,679,224 | 67,398 | 67,435 | 4,438 | 501 |
| Total | 2,189 | ||||
2.2 Study Selection
Literature search results were de-duplicated by using Mendeley software (Thomson Reuters, New York, NY). Articles were initially screened based on the title and abstract according to the scope (i.e., articles that do not report fluorosis and exposure to groundwater) and publication type (i.e., reviews, comments, letters, or abstracts).
2.3 Data Extraction and Quality Assessment
Based on the selection criteria, two examiners (LV, FC) examined the titles and abstracts independently, and any disagreements were resolved according to a predefined strategy, using consensus and arbitration as appropriate. If the disagreement could not be resolved, then a third investigator (AS) agreed to help reach a consensus. Furthermore, a manual search of the reference lists of relevant studies was performed.
The seven domains of ROB-2 instrument were scored to quantify the risk of bias: confounding bias, measurement of exposure bias, selection bias, post-exposure interventions bias, missing data bias, measurement of the outcome bias and selection of the reported result. Subsequently, an overall judgement was made to mark each study as low risk of bias, high risk of bias or some concerns.
RESULTS
The literature search after the identification period found 2189 articles (Table 3), of which 368 were screened according to the selection criteria, and 15 were selected, as shown in Figure 1.
The main data extracted from the selected studies are shown in Table 4. Data came from 4 continents, including Asia with 53.3% of studies, Africa with 20%, and Europe and America with 13.3% each. Participant ages were 14 to 16 years. Regarding the index used for diagnosing dental fluorosis, Dean’s index was the most frequent, being adopted in 60% of the studies, followed by the Thylstrup-Fejerskov Index (TFI) in 20%. Other indices used were WHO, Pendry’s and Horowitz’s, with 6.7%.
Table 4 Summary of the studies selected for this systematic review.
| Study ID | Country | Subjects' age in years | Total number of children | Index used for diagnosing dental fluorosis |
| Akpata et al. 13 | Saudi Arabia | 12-15 | 2355 | Modified Thylstrup-Fejerskov Index (TFI) |
| Alarcon-Herrera et al. 14 | Mexico | 6-12 | 333 | Dean's index |
| Arif et al. 15 | India | 5-13 | 1136 | Dean's index |
| Gautam et al. 16 | India | 4–16 | 90 | Dean's index |
| Ibrahim et al. 17 | Sudan | 7-16 | 113 | Dean's index |
| Indermitte et al. 18 | Estonia | 7-15 | 2,627 | Dean's index |
| Ismail et al. 19 | Canada | 0-7 | 48 | Pendrys' Fluorosis Risk Index (Modified Fluorosis Risk Index) |
| Mandinic et al. 20 | Serbia | 12 | 164 | Dean's index |
| Narwaria et al. 21 | India | 5-12 | 750 | Dean's index |
| Rango et al. 22 | Main Ethiopian Rift Valley | 10-15 | 491 | Thylstrup and Fejerskov index (TFI) |
| Ray et al. 23 | India | 1-5 and 11-15 | 2,159 | WHO |
| Shanthi et al. 24 | India | 9-12 | 1,500 | Dean's index |
| Shomar et al. 25 | Gaza Strip | 5–16 | 353 | Dean's index |
| Tobayiwa et al. 26 | Zimbabwe I | 8-15 | 200 | Thylstrup and Fejerskov index (TFI) |
| Zhu et al. 27 | China | 8–12 | 9,030 | Horowitz's Tooth Surface Index of Fluorosis (modification of Dean's index) |
Table 5 shows the main data on fluoride concentration in the water (0.1 to 18mg/L), and prevalence of fluorosis (4.25 to 100%), which were both highly heterogenous.
Table 5 Results of the studies selected for this systematic review.
| Study ID | F- concentration informed by the authors, in ground water analyzed | Daily Water Consumption | Prevalence (total) of fluorosis | Prevalence of dental fluorosis (mild) | Prevalence of fluorosis (moderate) | Prevalence of fluorosis (severe) |
| Akpata et al 13 | 0.543 to 2.848 ppm | - | 90.7% | 14.73% | 31.25% | 44.67% |
| Alarcon-Herrera et al 14 | <1.5 to 16 mg/L | - | 86.4% | 67.88% | 10.8% | 7.8% |
| Arif et al 15 | 0.5 to 8.5 mg/L. | >4 mg/day | 69.3% | 31.9% | 58.6% | 9.4% |
| Gautam et al 16 | 0.64 to 14.62 mg/L | - | 90.8% | - | - | - |
| Ibrahim et al 17 | 0.25 to 2.56 ppm | - | 95.5% | 63.7% | 27.4% | 4.4% |
| Indermitte et al 18 | 0.01 to 7.20 mg/L | - | 17.5% | - | - | - |
| Ismail et al 19 | < 3.8 ppm | - | 66.7 % | - | - | - |
| Mandinic et al 20 | 0.10 to 11 ppm | - | 4.2% | 3.65 | 0 | 0.6 |
| Narwaria et al 21 | 1.5 to 3 ppm | - | 45.4% | 20.8 % | 19.47 % | 5.2 % |
| Rango et al 22 | 1.1–18 mg/L (8.5 ± 4.1 mg/L) | 1.2 ± 0.4 L/d | 100% | 17% | 29% | 45% |
| Ray et al 23 | 0.2 to 2.1 ppm | - | 24.9% | 8.33% | 2.17% | - |
| Shanthi et al 24 | <0.7 to 3.5 ppm | - | 48.3% | 35% | 9.2% | 4.1% |
| Shomar et al 25 | 0.7 to 2.6 ppm | - | 60% | - | - | - |
| Tobayiwa et al 26 | 5-10 ppm | - | 64% | - | - | - |
| Zhu et al 27 | 1.0 to 2.0 mg/L | - | 38.6% | 25.6% | 10.0% | 3.0% |
Figure 2 shows the quality assessment of the studies considered. In general, the domains presented a low risk of bias.
DISCUSSION
This study performed a systematic review of the literature to assess the risk of fluorosis in children exposed to drinking groundwater. The studies evaluated reported high fluoride concentration in the water consumed.
Fluoride intake has beneficial effects, as a complement to prevent and control dental caries, as well as adverse effects, mainly tooth enamel and skeletal fluorosis following prolonged exposure to high concentrations 1-2 . Excessive fluoride intake usually occurs through the consumption of groundwater that is naturally rich in fluoride. The assessment of the distribution of high groundwater fluoride is therefore of great practical significance for drinking water safety 28 . The WHO recommends a fluoride concentration in drinking water in the range of 0.5 to 1.5 mg/L 29 . The current review only included research papers reporting consumption of groundwater with fluoride concentration above 1.5 mg/L.
Fluorides are naturally ubiquitous in the environment (water, soil, air, etc.). The amount of fluoride in water can be georeferenced, and high levels have been reported in certain places, especially in Asia and Africa 20 .
Several studies conducted around the world provide strong evidence of association between fluoride concentration in drinking water and prevalence of fluorosis 13,14,16,18,21, 22 . To facilitate data collection, the current study evaluated the risk in children because most primary studies consider school-age children, who are easily screened.
Increasing fluoride intake with fluoridated water can increase the risk of dental fluorosis in a situation of high exposure in children under 8 years of age. Nevertheless, in adults, such exposure is not a problem, but provides protection against dental
caries 30 .
The only way to prevent dental fluorosis in children is to ensure that the fluoride concentration in the water they consume is within safe limits 18 . It should be noted that water is used in food preparation as well as for drinking. The current review found that in places all over the world where people drink groundwater with high fluoride concentration, there is higher prevalence of dental fluorosis. Even though public health officers are aware of the negative impact of dental fluorosis, a condition affecting much of the population in developing countries, governments do not address the issue 28 . The inability to find alternative water sources is a challenge to the reduction of exposure to high fluoride levels.
Some studies assess the risk and/or prevalence of fluorosis in populations exposed to groundwater, most of which consider water from wells or natural sources. The concentration of fluoride in spring water is lower than in groundwater. Only two systematic reviews addressed this issue, both of which were based on local data 7, 31 . A study with data at global level was therefore considered necessary. The selected studies indicate that the prevalence of dental fluorosis increases with the concentration of fluoride in groundwater. To prevent dental fluorosis, it is suggested that groundwater wells should be routinely analyzed for fluoride concentration, and if necessary, treated appropriately with fluoridation or defluoridation, to ensure an anti-caries effect with minimum risk of fluorosis.
