Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis

Abstract

Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment.Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

Fluoretação da água de abastecimento público: abordagem bioética, legal e política

“…The conclusions of this study warned of the possibility of an adverse effect of high exposure to fluoride in children's neurodevelopment 44 . However, this research presented some methodological biases pointed out by other authors: lack of information at the individual level and high probability of confusion, since covariables were not adjusted.…”

Physicochemical properties and the concentration of anions, major and trace elements in groundwater, treated drinking water and bottled drinking water in Najran area, KSA

“…In particular, studies carried out by Akpata et al (1997) and Albdulaaly et al (2013) in the Hail region of the KSA reported incidences of dental fluorosis among children, and well water fluoride concentrations ranging between 0.3 and 4.0 mg/L. Another series of (more than 20) papers concluded that children exposed to high levels of fluoride in drinking water had lower IQs (Choi et al 2012). NO 3 -in drinking water come from environmental (geogenic) and anthropogenic sources, and include runoff from fertilizer, municipal sewage treatment systems, leaching from septic tanks, erosion of natural deposits and animal wastes (Ricker et al 2001;EPA 2009).…”

Water fluoridation: It really is this simple

“…These studies, which were almost all of very low validity (no adjustment for confounding variables, population level data), were reviewed and meta-analysed by Choi et al, [172] who concluded that the results supported a possibility of adverse neurodevelopmental effects of high fluoride intake. The definition of 'high' fluoride varied considerably in these studies, but most levels were higher than those considered acceptable in the US, and much higher than any level found in New Zealand.…”

“…The authors themselves note that this difference is so small that it "may be within the measurement error of IQ testing". [172] The studies considered only fluoride exposure from drinking water at the population level, although it is likely that other significant environmental sources of fluoride exposure may have been overlooked. In China, for example, grains and other foods are often contaminated with fluoride from coal fires.…”

“…[174] The 2011 SCHER report also concluded that human studies do not support the conclusion that fluoride in drinking water impairs children's development at levels permitted in the EU. [34] In including fluoride in a list of chemicals possibly causing human developmental toxicity, Grandjean and Landrigan [175] cite only the Choi et al [172] review, of which Grandjean is a coauthor, as evidence. While no plausible biological mechanism explains the alleged association of fluoride with IQ, overall there is some evidence of possible, slight adverse effect on the developing brain at high fluoride concentrations.…”