Segurança da Fluoretação da água: meta-análises do efeito do flúor no nível recomendado para a prevenção da cárie no quociente de inteligência e hipotireoidismo

Abstract

A fluoride concentration in the water supply is recommended between 0.5 and 1.0 mg/l, in order to maximize its effects in preventing tooth decay. The World Health Organization has a concentration of up to 1.5 mg/l as a reference value. On the other hand, its presence in concentrations above this value leads to an increased risk of dental fluorosis and progressively higher concentrations lead to greater risks of skeletal fluorosis. The safety of fluoride in drinking water continues to be the subject of widespread debate within the academic community and society at large, with a large and heterogeneous scientific literature examining the potential systemic adverse effects of fluoride in drinking water, despite evidence supporting its implementation as public health measure. In this sense, previous studies have examined the association between fluoride and systemic effects, such as hypothyroidism and intelligence. More recent studies have postulated that fluoride, when present in high levels in the water supply or associated with other forms, can affect the proper functioning of the thyroid. Furthermore, some studies have raised the hypothesis that exposure to fluorides in the first years of life would result in changes in the central nervous system, which could lead to cognitive impairment. The hypothesis of this Thesis is that exposure to fluoride in the water supply at levels recommended for caries prevention is not associated with worse performance on IQ tests or with primary or subclinical hypothyroidism. CHAPTER I of this thesis is the original manuscript 1 “Community Water Fluoridation and intelligence quotient: Systematic review and meta analysis of observational studies”, whose objective is to evaluate the evidence of the association between exposure to fluoride in the water supply and intelligence. CHAPTER II of this thesis is the original manuscript 2 “Community water fluoridation and hypothyroidism: systematic review and meta-analysis of observational studies”, which aimed to carry out a systematic review and meta-analysis of observational studies to evaluate the association between exposure to water fluoride and hypothyroidism. For both studies, a systematic review and meta-analysis was carried out, considering only observational studies carried out with fluoride concentrations within a recommended range for caries prevention (between 0.4 and 1.5 mg/l of fluoride). No community experimental studies and randomized clinical trials were found in the search. The literature search was conducted between May/2022 and June/2022 without restrictions on the age of participants, publication time or language. The indexed databases PubMed/Medline, Embase, Scopus, Web of Science and reference lists of included articles were used. The methodological quality of the selected studies was assessed using the Joanna Briggs Institute (JBI) critical checklist. Meta-analysis with random effects models was used to synthesize quantitative data, estimating beta linear regression coefficients and standardized mean differences (SMDs) grouped from IQ scores in relation to public water fluoridation, and Odds Ratios (OR) grouped from exposure to public water fluoridation and primary or subclinical hypothyroidism. As results of manuscript 1, three studies (N = 1947 children) were included in the linear regression coefficient meta-analysis with adjusted betas. In the grouped analysis, there was no association between exposure to fluoride in the water supply and IQ, for a linear regression coefficient β of 1.01 (95% CI: = -0.80 to 2.82). Two meta-analyses of standardized mean differences with raw measurements (one only with cross-sectional studies and the other only with longitudinal studies) were carried out to aggregate a greater number of studies that only had raw mean values and the respective standard deviations of IQ scores. Fluoride exposure showed no difference in mean IQ scores compared with the unexposed group (pooled SMD: -0.25; 95% CI: -0.64 to 0.14) for meta-analysis with four cross-sectional studies (N= 889 children) and for meta-analysis with three longitudinal studies (SMDs = -0.05; 95% CI = -0.18 to 0.07) (N = 1750 children), respectively, reinforcing the safety of using fluoride in public water supply in relation to intelligence measured by IQ . As results of manuscript 2, three cross-sectional observational studies (N=2332 participants) were included in the systematic review and meta-analysis. Heterogeneity between studies was high (P=0.031, I²=71.1%). No significant association was observed between exposure to fluoride in the water supply and hypothyroidism (pooled OR: 1.40; 95% CI: 0.84 to 2.35), showing that existing evidence does not support an association between fluoridation of water and hypothyroidism. In summary, the research results of this thesis showed that exposure to fluoride in water at levels used for cavity prevention (range between 0.4 mg/l and 1.5 mg/l fluoride) was not associated with lower intelligence, as measured by IQ test scores, nor with hypothyroidism, but evidence available is still insufficient, therefore, more quality primary studies are needed to confirm whether fluoridation is associated with hypothyroidism or not. Thus, it is possible to state that, based on the synthesis of evidence, water fluoridation remains a safe measure for preventing tooth decay.