Abstract
Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to “Humans”; “Central nervous system”; “Fluorides”; and “Neurologic manifestations” were searched in a systematic way on PubMed, Scopus, Web of Science, Lilacs, Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.
Highlights
Following the parameters of GRADE, the level of evidence was considered as very low even for individuals exposed to high doses of F, due to imprecision problems (Table 3)
Despite the large numbers of participants in the analysis, detected problems of inaccuracy can be elucidated by possible methodological disparities in the studies that might interfere in the intelligence quotient (IQ) analysis and neurological manifestations
Another important limitation to be considered is the predominance of cross-sectional studies in this systematic review
Summary
Data regarding the year of publication, study design, participant characteristics (origin and sample size), mean age, F concentration measurement parameters, diagnostic criteria for assessment of cognitive performance, results and statistical analysis were extracted and tabulated. To assess the methodological quality and risk of bias, the checklist of Fowkes and F ulton[12] was applied This checklist has domains that relate to study and sample design; control group characteristics; quality of measures and results; and distorted integrity and influences. A sensitivity analyses was used to explore the influence of each study in the pooled meta-analysis or publication bias results. This analysis was adopted in case of substantial or considerable (50 to 100%) heterogeneity, or significant publication bias (p < 0.05).
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