0380/2024 - Community Water Fluoridation and intelligence quotient: Systematic review and meta-analysis of observational studies
Fluoretação da água comunitária e quociente de inteligência: revisão sistemática e meta-análise de estudos observacionais
Autor:
• Ravena Brito Marques - Marques, R.B - <ravenamarques09@gmail.com>ORCID: https://orcid.org/0000-0002-2479-4795
Coautor(es):
• Lucelen Fontoura Bastos - Bastos, L.F - <lucelen@gmail.com>ORCID: https://orcid.org/0000-0002-1617-9602
• Elma Izze da Silva Magalhães - MAGALHÃES, E.I.S. - <elma_izze@hotmail.com>
ORCID: https://orcid.org/0000-0001-9909-9861
• Cecília Cláudia Costa Ribeiro - Ribeiro, C.C.C - <cecilia.ribeiro@ufma.br>
ORCID: https://orcid.org/0000-0003-0041-7618
• Fernando Neves Hugo - Hugo, Fernando Neves - <fernando.hugo@ufgs.br>
ORCID: https://orcid.org/0000-0003-2222-7719
Resumo:
Objective: The study aimed to assess the current level of evidence of the association between community water fluoridation and intelligence. The method used for the study was a systematic review and meta-analysis of observational studies, to evaluate evidence of an association between exposure to community water fluoridation and intelligence using intelligence quotient tests. Indexed databases PubMed/Medline, Embase, Scopus, Web of Science and reference lists of included articles were used. A meta-analysis with random effects models was performed and beta coefficients and pooled standardized mean differences (SMDs) and 95% confidence intervals (95%CI) of IQ scores were estimated in relation to water fluoridation. Results: Of the 941 studies identified by the database search, three studies (N = 1,947 children) were included in the meta-analysis that used adjusted beta linear regression coefficients. There is no meta-analysis for adults because there is only one study for them. In the joint analysis, there was no association between exposure to fluoride in the water supply and IQ, for a linear regression coefficient (called ?) of 1.01 (95% CI: = -0.80 to 2.82). Heterogeneity between studies was low (P = 0.66, I² = 0%). Conclusion and Relevance: This meta-analysis underlines the safety of community water fluoridation concerning IQ\'s intelligence assessment.Palavras-chave:
Fluorides, meta-analysis, systematic review, drinking water, intelligence testsAbstract:
Objetivo: Realizar uma revisão sistemática e meta-análise para avaliar evidências de associação entre exposição à fluoretação da água comunitária e inteligência em populações, sem restrições de idade. Método: Foram incluídos estudos observacionais que avaliaram a associação entre fluoretação da água e inteligência avaliada por testes de quociente de inteligência (QI). A busca na literatura foi realizada no período de maio/2022 a junho/2022 sem restrições de tempo ou idioma. Foram utilizadas bases de dados indexadas PubMed/Medline, Embase, Scopus, Web of Science e listas de referências dos artigos incluídos. A qualidade metodológica dos estudos selecionados foi avaliada pela lista de verificação de avaliação crítica do Joanna Briggs Institute (JBI). Uma meta-análise com modelos de efeitos aleatórios foi realizada para sintetizar os dados quantitativos, e coeficientes beta e diferenças médias padronizadas (SMDs) agrupadas e intervalos de confiança de 95% (IC95%) dos escores de QI foram estimados em relação à fluoretação da água comunitária ( alfa=5%). Resultados: Dos 941 estudos identificados pela busca nas bases de dados, nove estudos observacionais foram incluídos na revisão. Não há meta-análise para adultos, porque há apenas um estudo para eles. Três estudos (N = 1.947 crianças) foram incluídos na meta-análise que utilizou coeficientes de regressão linear beta ajustados. Na análise conjunta, não houve associação entre a exposição ao flúor na água de abastecimento e o QI, para um coeficiente de regressão linear (denominado β) de 1,01 (IC 95%: = -0,80 a 2,82). A heterogeneidade entre os estudos foi baixa (P = 0,66, I² = 0%). Duas metanálises (uma apenas com estudos transversais e outra apenas com estudos de coorte) de diferenças médias padronizadas (SMDs) agrupadas das medidas brutas também foram realizadas para agregar um número maior de estudos. As crianças expostas à fluoretação da água comunitária não apresentaram diferenças nas pontuações médias de QI quando comparadas às crianças não expostas a ela (SMD agrupado: -0,25; IC 95%: -0,64 a 0,14) em uma meta-análise com quatro estudos transversais (N = 889 crianças) e numa segunda meta-análise com três estudos de coorte (SMDs = -0,05; IC 95% = -0,18 a 0,07) (N= 1750 crianças). Conclusão e Relevância: Esta meta-análise confirma a segurança da fluoretação da água comunitária no que diz respeito à avaliação de inteligência do IQ.PALAVRAS-CHAVE: Fluoretos, metanálise, revisão sistemática, água potável, testes de inteligência.
Keywords:
Fluoretos, metanálise, revisão sistemática, água potável, testes de inteligência.Conteúdo:
INTRODUCTION
Health authorities and managers have historically recognized the importance of fluoridation in caries control in children and adults based on the scientific evidence that has been accumulated and the results of this public policy, even after the increased use of fluoridated dentifrice1,1715. Fluoride in water supplies is an important public health measure, decreasing demineralization and activating remineralization of mineralized dental tissues3. Since water fluoridation implementation to prevent caries in the 1950s, the only proven adverse effect was mild dental fluorosis caused by fluoride ingestion during the period of tooth enamel mineralization in children up to 8 years old4,5.
Some studies have posed the possibility that fluoride exposure in the early years of life could lead to changes in the central nervous system, contributing to cognitive deficits75. Fetal exposure has also been investigated due to the ability of fluoride to cross the placenta and penetrate the fetal blood-brain barrier, becoming deposited in brain tissues86. But most studies have been done in areas with naturally occurring fluoride in the water, at concentrations far above the limits required to control caries, with ecological design, without adjustment for confounding variables, or in areas with water containing other neurotoxicants such as arsenic and iodine97. The epidemiological evidence is heterogeneous, and therefore it does not make sense to extrapolate the findings to show that community water fluoridation negatively influences IQ10,11,12,8,9,10. The current evidence does not allow stating that community water fluoridation is associated with IQ impairment, indicating the need for new epidemiological studies that can provide more evidence regarding this purported association13,11.
Other longitudinal studies on the subject have recently been performed in areas with community water fluoridation (fluoridation in the range of 0.7-1.0 mg/L), taking into account possible confounding factors and improving study design8,14,6,12. Thus, systematic review and meta-analysis synthesizing evidence from multiple, more recent studies can provide more robust evidence on this subject. The current limits of evidence and the need to critically evaluate it underscore the importance of conducting a systematic review on the topic15,13. In their systematic review, Veneri et al. 2023 found lower IQ scores for fluoride concentrations in water ranging from 0.13 to 5.55 mg/L16,14, meaning that people exposed to fluoride far above the recommended levels for caries prevention were analyzed. In the study, it is proposed to overcome this limitation by conducting a systematic review including only studies with fluoride concentrations in water supplies in the range recommended to prevent caries (0.4 to 1.5 mg/l F). The rationale for selection was based on the established value of up to 1.5 mg/l of fluoride in water described in the “Guideline for drinking water quality” of the World Health Organization (WHO)17,15 and in the Canadian Agency for Drugs and Technologies in Health (CADTH) 12,10. In addition, there is a systematic review with by the National Health and Medical Research Council (2017) of Australia that also used the same range11,9, that is, the inclusion of studies that were within a range that is considered safe was considered.
This systematic review with meta-analysis aimed to evaluate the combined effect of observational studies measuring the association between exposure to community water fluoridation and intelligence in populations with no age restrictions. Intelligence was assessed using IQ tests, considering only studies with fluoride concentrations within the range recommended for caries prevention (between 0.4 mg/l and 1.5 mg/l fluoride). The hypothesis is that exposure to community water fluoridation at levels recommended for the prevention of dental caries is not associated with worse performance on IQ tests.
METHODS
Protocol and Registration
This systematic review followed COSMOS-E guidelines18,16 on systematic reviews and meta-analyses of observational studies of etiology. The detailed protocol of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO - www.crd.york.ac.uk/PROSPERO) under number CRD42021253748.
Context
This research was carried out to answer the question: 1) Is exposure to community water fluoridation associated with intelligence as assessed by IQ tests in populations with no age restrictions?
Outcome and Exposure Measurement
The intelligence levels were measured by scores on intelligence quotient (IQ) tests. Exposure to community water fluoridation was measured based on historical records, self-reported or ecologically by means or range of exposure to community water fluoridation by location (area where the person lived) or not, such as fluoridated area versus non-fluoridated area. The community water fluoridation variable was categorized into fluoride levels ‘non-fluoridated’ and ‘fluoridated groups’. One study assessed fluoride concentration as a continuous variable, such as a reduction in IQ scores by an increase of 1mg/l of fluoride, was not included in this review.
Search Strategy
The databases searched were MEDLINE via PubMed, EMBASE via OVID, Scopus, and Web of Science. The PECO strategy was used for the search, as follows: Population, consisting of children and adults; Exposure, consisting of exposure to water supply fluoridation in levels recommended for caries prevention; Control/comparison, consisting of not being exposed to community water fluoridation; and Outcome, consisting of intelligence, as measured by IQ tests. In these sources, all articles with the combination of terms related to water fluoridation and intelligence were searched. No filters or restrictions regarding age, gender, ethnicity, language, year of publication or country were used. Regular alerts were set up to update the searches until the final report was published. No new articles appeared after the search period that met the inclusion criteria. The search strategy used controlled vocabulary, such as MeSH (Medical Subject Headings) from the National Library of Medicine, and free terms for each database searched. The search strings were generated by combining keywords and synonyms using Boolean operators OR and AND, following the syntax rules of each library database. Other relevant studies in the reference lists of the included studies were searched. A search was carried out in the LILACS database, but no additional articles were found. The first 100 results of a Google Scholar search were searched and no additional articles were found either. The search period for the articles ran from 1 to June 30, 2024. The search strategies used in each database are listed in Appendix 1.
Eligibility Criteria
Studies that assessed intelligence quantitatively using IQ tests in populations receiving artificially fluoridated water or whose water supply had natural fluoride levels compatible with those recommended for dental caries prevention (fluoride levels between 0.4 mg/l and 1.5 mg/l) were included 12,17,19,10,15,17. For the control group, populations not exposed to water fluoridation or with low fluoride levels in the water supply (?0.4mg/l) were included.
Observational studies were considered eligible, including cohort, case-control, cross-sectional. No community experimental studies and randomized clinical trials were identified in the search. Studies were excluded based on these criteria: 1) study design (ecological studies, qualitative studies, systematic reviews and meta-analyses, case series, animal studies, in vitro studies); 2) population (studies that did not make comparisons between fluoride-exposed and non-exposed populations); or 3) publication type (letter to the editor, literature reviews, scoping reviews, and conference and congress abstracts). The goal was to review existing studies that grouped participants by exposure or non-exposure to community water fluoridation in order to produce a perspective on water fluoridation as a public health measure, regardless of access to other sources of fluoride. Studies that evaluated only urinary fluoride concentrations were also excluded because the aim of this review was to examine fluoride present (or not) in community water supplies. Studies using urinary fluoride were not included because they imply measuring exposure to other sources (e.g., toothpaste, tea, coffee, bone turnonver).
Study Selection
The Endnote software, version X8.0.1, was used to organize the articles identified in all databases. Duplicate articles were identified and removed before the screening of titles and abstracts was done. After that, they were exported to the Rayyan app. Two independent reviewers screened in duplicate the titles and abstracts identified during the electronic and manual searches for eligibility. For all studies selected by reading the title and abstract, and also for studies that were potentially eligible but did not provide sufficient information in the title and abstract, the full text was read and assessed by the two reviewers according to the eligibility criteria. In case of disagreement regarding eligibility, this was settled by consensus with the participation of a third reviewer that acted as a reference.
Data Extraction
A data extraction form made in Microsoft Excel® 2016 (Microsoft Corporation, Washington, USA) was used to collect, tabulate and code relevant data from the included articles. Information extracted included: study identification (authors, country of origin, year of publication), study design, sample size, age range, area (urban or rural), assessment of fluoride exposure (level or duration of fluoride exposure), the test used to diagnose the outcome, confounding factors considered (sex, age, diet, exposure to other sources of fluoride, socioeconomic status), the statistical method used, estimated effect measure, outcome evaluation, reported outcomes, and quality of studies. Effect measures were estimated in the quality of mean differences in IQ scores comparing those exposed and unexposed to fluoridated water. For the studies that considered effect measures in terms of percentiles of fluoride exposure, the percentile with < 0.4 mg/l fluoride was considered unexposed, and the percentiles in the range of 0.4 to 1.5 mg/l were considered exposed. In the age-stratified results, the effect measures for each stratum were reflected in the meta-analysis. For studies with estimates adjusted for different arrangements of confounding variables, the effect measure adjusted for the largest number of variables was extracted and used in the analyses.
Bias Risk Assessment
The individual methodological quality of the studies included in this review was assessed by two independent reviewers based on the Joanna Briggs Institute (JBI) critical appraisal checklist20,18. The JBI is tool that has been developed to critically assess the risk of bias of quantitative analytical studies. As the JBI has tools that were developed specifically for observational studies, we understood that using it was adequate for the purpose of evaluating the quality of the studies included in this review.
The checklist contains eight questions for cross-sectional studies and eleven questions for cohort studies, with four possible answers: ‘yes’, ‘no’, ‘unclear’, or ‘not applicable’. The number of positive responses is summed, and in this systematic review, a percentage <50% to indicate low quality, 50 to 70% to indicate intermediate quality, and >75% to indicate high quality was taken into account21moola2023. Disagreements were resolved by reaching a consensus, with the participation of a third reviewer as a referee.
Statistical Analysis
Stata 14.0 software (StataCorp, College Station, Texas, USA) and Cochrane Review Manager (RevMan) were used for the meta-analysis. Heterogeneity between studies was assessed using Q-statistic and I² measures, considering a significance level of 0.1022,20. Data from individual studies were pooled using a random effects model23,21, and the adjusted estimates of the studies were combined to perform the meta-analysis. A sensitivity analysis was performed, including the only article with adult participants. Forest plots were used to display the results.
The relationship between exposure to community water fluoridation and IQ scores was assessed based on the effect estimate (beta coefficient) and respective 95% CIs published in each study. A meta-analysis of pooled standardized mean differences (SMDs) of crude measures was also performed to aggregate a larger number of studies, as most did not have an adjustment for confounding variables. The meta-analysis included studies with IQ scores and an unexposed/low fluoride group (reference group), and a group exposed to fluoride at the recommended range to prevent caries. In a meta-regression analysis, the coefficients associated with variables such as age, sex, parental education, family income and others were estimated and weighted according to the study standard error and respective 95% confidence intervals (95% CI). The outcome was measured from the mean IQ test scores. Considering that each intelligence test used is designed to measure general intelligence, data from all eligible studies were used to estimate the effects of exposure to community water fluoridation on intelligence.
RESULTS
Study Description
Three studies were included in the beta regression coefficient meta-analysis, and seven were included in the pooled standardized mean differences (SMDs) meta-analysis. The results of the screening and selection of the included articles are illustrated in the flow diagram (Figure 1).
Figure 1. Flowchart of study search and selection
Health authorities and managers have historically recognized the importance of fluoridation in caries control in children and adults based on the scientific evidence that has been accumulated and the results of this public policy, even after the increased use of fluoridated dentifrice1,1715. Fluoride in water supplies is an important public health measure, decreasing demineralization and activating remineralization of mineralized dental tissues3. Since water fluoridation implementation to prevent caries in the 1950s, the only proven adverse effect was mild dental fluorosis caused by fluoride ingestion during the period of tooth enamel mineralization in children up to 8 years old4,5.
Some studies have posed the possibility that fluoride exposure in the early years of life could lead to changes in the central nervous system, contributing to cognitive deficits75. Fetal exposure has also been investigated due to the ability of fluoride to cross the placenta and penetrate the fetal blood-brain barrier, becoming deposited in brain tissues86. But most studies have been done in areas with naturally occurring fluoride in the water, at concentrations far above the limits required to control caries, with ecological design, without adjustment for confounding variables, or in areas with water containing other neurotoxicants such as arsenic and iodine97. The epidemiological evidence is heterogeneous, and therefore it does not make sense to extrapolate the findings to show that community water fluoridation negatively influences IQ10,11,12,8,9,10. The current evidence does not allow stating that community water fluoridation is associated with IQ impairment, indicating the need for new epidemiological studies that can provide more evidence regarding this purported association13,11.
Other longitudinal studies on the subject have recently been performed in areas with community water fluoridation (fluoridation in the range of 0.7-1.0 mg/L), taking into account possible confounding factors and improving study design8,14,6,12. Thus, systematic review and meta-analysis synthesizing evidence from multiple, more recent studies can provide more robust evidence on this subject. The current limits of evidence and the need to critically evaluate it underscore the importance of conducting a systematic review on the topic15,13. In their systematic review, Veneri et al. 2023 found lower IQ scores for fluoride concentrations in water ranging from 0.13 to 5.55 mg/L16,14, meaning that people exposed to fluoride far above the recommended levels for caries prevention were analyzed. In the study, it is proposed to overcome this limitation by conducting a systematic review including only studies with fluoride concentrations in water supplies in the range recommended to prevent caries (0.4 to 1.5 mg/l F). The rationale for selection was based on the established value of up to 1.5 mg/l of fluoride in water described in the “Guideline for drinking water quality” of the World Health Organization (WHO)17,15 and in the Canadian Agency for Drugs and Technologies in Health (CADTH) 12,10. In addition, there is a systematic review with by the National Health and Medical Research Council (2017) of Australia that also used the same range11,9, that is, the inclusion of studies that were within a range that is considered safe was considered.
This systematic review with meta-analysis aimed to evaluate the combined effect of observational studies measuring the association between exposure to community water fluoridation and intelligence in populations with no age restrictions. Intelligence was assessed using IQ tests, considering only studies with fluoride concentrations within the range recommended for caries prevention (between 0.4 mg/l and 1.5 mg/l fluoride). The hypothesis is that exposure to community water fluoridation at levels recommended for the prevention of dental caries is not associated with worse performance on IQ tests.
METHODS
Protocol and Registration
This systematic review followed COSMOS-E guidelines18,16 on systematic reviews and meta-analyses of observational studies of etiology. The detailed protocol of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO - www.crd.york.ac.uk/PROSPERO) under number CRD42021253748.
Context
This research was carried out to answer the question: 1) Is exposure to community water fluoridation associated with intelligence as assessed by IQ tests in populations with no age restrictions?
Outcome and Exposure Measurement
The intelligence levels were measured by scores on intelligence quotient (IQ) tests. Exposure to community water fluoridation was measured based on historical records, self-reported or ecologically by means or range of exposure to community water fluoridation by location (area where the person lived) or not, such as fluoridated area versus non-fluoridated area. The community water fluoridation variable was categorized into fluoride levels ‘non-fluoridated’ and ‘fluoridated groups’. One study assessed fluoride concentration as a continuous variable, such as a reduction in IQ scores by an increase of 1mg/l of fluoride, was not included in this review.
Search Strategy
The databases searched were MEDLINE via PubMed, EMBASE via OVID, Scopus, and Web of Science. The PECO strategy was used for the search, as follows: Population, consisting of children and adults; Exposure, consisting of exposure to water supply fluoridation in levels recommended for caries prevention; Control/comparison, consisting of not being exposed to community water fluoridation; and Outcome, consisting of intelligence, as measured by IQ tests. In these sources, all articles with the combination of terms related to water fluoridation and intelligence were searched. No filters or restrictions regarding age, gender, ethnicity, language, year of publication or country were used. Regular alerts were set up to update the searches until the final report was published. No new articles appeared after the search period that met the inclusion criteria. The search strategy used controlled vocabulary, such as MeSH (Medical Subject Headings) from the National Library of Medicine, and free terms for each database searched. The search strings were generated by combining keywords and synonyms using Boolean operators OR and AND, following the syntax rules of each library database. Other relevant studies in the reference lists of the included studies were searched. A search was carried out in the LILACS database, but no additional articles were found. The first 100 results of a Google Scholar search were searched and no additional articles were found either. The search period for the articles ran from 1 to June 30, 2024. The search strategies used in each database are listed in Appendix 1.
Eligibility Criteria
Studies that assessed intelligence quantitatively using IQ tests in populations receiving artificially fluoridated water or whose water supply had natural fluoride levels compatible with those recommended for dental caries prevention (fluoride levels between 0.4 mg/l and 1.5 mg/l) were included 12,17,19,10,15,17. For the control group, populations not exposed to water fluoridation or with low fluoride levels in the water supply (?0.4mg/l) were included.
Observational studies were considered eligible, including cohort, case-control, cross-sectional. No community experimental studies and randomized clinical trials were identified in the search. Studies were excluded based on these criteria: 1) study design (ecological studies, qualitative studies, systematic reviews and meta-analyses, case series, animal studies, in vitro studies); 2) population (studies that did not make comparisons between fluoride-exposed and non-exposed populations); or 3) publication type (letter to the editor, literature reviews, scoping reviews, and conference and congress abstracts). The goal was to review existing studies that grouped participants by exposure or non-exposure to community water fluoridation in order to produce a perspective on water fluoridation as a public health measure, regardless of access to other sources of fluoride. Studies that evaluated only urinary fluoride concentrations were also excluded because the aim of this review was to examine fluoride present (or not) in community water supplies. Studies using urinary fluoride were not included because they imply measuring exposure to other sources (e.g., toothpaste, tea, coffee, bone turnonver).
Study Selection
The Endnote software, version X8.0.1, was used to organize the articles identified in all databases. Duplicate articles were identified and removed before the screening of titles and abstracts was done. After that, they were exported to the Rayyan app. Two independent reviewers screened in duplicate the titles and abstracts identified during the electronic and manual searches for eligibility. For all studies selected by reading the title and abstract, and also for studies that were potentially eligible but did not provide sufficient information in the title and abstract, the full text was read and assessed by the two reviewers according to the eligibility criteria. In case of disagreement regarding eligibility, this was settled by consensus with the participation of a third reviewer that acted as a reference.
Data Extraction
A data extraction form made in Microsoft Excel® 2016 (Microsoft Corporation, Washington, USA) was used to collect, tabulate and code relevant data from the included articles. Information extracted included: study identification (authors, country of origin, year of publication), study design, sample size, age range, area (urban or rural), assessment of fluoride exposure (level or duration of fluoride exposure), the test used to diagnose the outcome, confounding factors considered (sex, age, diet, exposure to other sources of fluoride, socioeconomic status), the statistical method used, estimated effect measure, outcome evaluation, reported outcomes, and quality of studies. Effect measures were estimated in the quality of mean differences in IQ scores comparing those exposed and unexposed to fluoridated water. For the studies that considered effect measures in terms of percentiles of fluoride exposure, the percentile with < 0.4 mg/l fluoride was considered unexposed, and the percentiles in the range of 0.4 to 1.5 mg/l were considered exposed. In the age-stratified results, the effect measures for each stratum were reflected in the meta-analysis. For studies with estimates adjusted for different arrangements of confounding variables, the effect measure adjusted for the largest number of variables was extracted and used in the analyses.
Bias Risk Assessment
The individual methodological quality of the studies included in this review was assessed by two independent reviewers based on the Joanna Briggs Institute (JBI) critical appraisal checklist20,18. The JBI is tool that has been developed to critically assess the risk of bias of quantitative analytical studies. As the JBI has tools that were developed specifically for observational studies, we understood that using it was adequate for the purpose of evaluating the quality of the studies included in this review.
The checklist contains eight questions for cross-sectional studies and eleven questions for cohort studies, with four possible answers: ‘yes’, ‘no’, ‘unclear’, or ‘not applicable’. The number of positive responses is summed, and in this systematic review, a percentage <50% to indicate low quality, 50 to 70% to indicate intermediate quality, and >75% to indicate high quality was taken into account21moola2023. Disagreements were resolved by reaching a consensus, with the participation of a third reviewer as a referee.
Statistical Analysis
Stata 14.0 software (StataCorp, College Station, Texas, USA) and Cochrane Review Manager (RevMan) were used for the meta-analysis. Heterogeneity between studies was assessed using Q-statistic and I² measures, considering a significance level of 0.1022,20. Data from individual studies were pooled using a random effects model23,21, and the adjusted estimates of the studies were combined to perform the meta-analysis. A sensitivity analysis was performed, including the only article with adult participants. Forest plots were used to display the results.
The relationship between exposure to community water fluoridation and IQ scores was assessed based on the effect estimate (beta coefficient) and respective 95% CIs published in each study. A meta-analysis of pooled standardized mean differences (SMDs) of crude measures was also performed to aggregate a larger number of studies, as most did not have an adjustment for confounding variables. The meta-analysis included studies with IQ scores and an unexposed/low fluoride group (reference group), and a group exposed to fluoride at the recommended range to prevent caries. In a meta-regression analysis, the coefficients associated with variables such as age, sex, parental education, family income and others were estimated and weighted according to the study standard error and respective 95% confidence intervals (95% CI). The outcome was measured from the mean IQ test scores. Considering that each intelligence test used is designed to measure general intelligence, data from all eligible studies were used to estimate the effects of exposure to community water fluoridation on intelligence.
RESULTS
Study Description
Three studies were included in the beta regression coefficient meta-analysis, and seven were included in the pooled standardized mean differences (SMDs) meta-analysis. The results of the screening and selection of the included articles are illustrated in the flow diagram (Figure 1).
Figure 1. Flowchart of study search and selection
