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Developmental Fluoride Neurotoxicity: Clinical Importance versus Statistical Significance

Siamak Sabour, Zahra Ghorbani

School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran, E-mail:

Environ Health Perspect 121:a70–a70 (2013). [Online 1 March 2013]

The author declares they have no actual or potential competing financial interests.

We were interested to read the article by Choi et al. (2012), who investigated the effects of increased fluoride exposure and delayed neurobehavioral development by reviewing published studies and performing a meta-analysis. Of the 39 studies identified, the authors considered 27 to be eligible. Choi et al. reported a mean difference in IQ (intelligence quotient) score between exposed and reference populations of –0.4 (95% confidence interval: –0.5, –0.3) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas.

Even if we ignore the weaknesses of the study (Choi et al. 2012), including a lack of individual-level information and the high probability of confounding because the authors did not adjust for covariates, a difference of 0.4 in mean IQ is clinically negligible (Jeckel et al. 2007; Rothman et al. 2008; Szklo and Nieto 2007) even though it was statistically significant. In general, clinical importance takes priority over statistical significance. The p-value can easily change from significant to nonsignificant because of sample size or the mean difference and standard deviation of the variable in the study population (Jeckel et al. 2007; Rothman et al. 2008; Szklo and Nieto 2007). As Choi et al. (2012) pointed out in their conclusion, there is a “possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment.” Such a conclusion can be considered an ecological fallacy, which can easily lead to misinterpretation of the results. It is important to know that statistics cannot provide a simple substitute for clinical judgment (Jeckel et al. 2007; Rothman et al. 2008; Szklo and Nieto 2007).

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Choi AL, Sun G, Zhang Y, Grandjean P. 2012. Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 120:1362–1368.

Jeckel JF, Katz DL, Elmore JG, Wild DMG. 2007. Epidemiology, Biostatistics, and Preventive Medicine. 3rd ed. Philadelphia:Saunders/Elsevier.

Rothman JK, Greenland S, Lash TL. 2008. Modern Epidemiology. 3rd ed. Philadelphia:Wolters Kluwer/Lippincott Williams & Wilkins.

Szklo M, Nieto FJ. 2007. Epidemiology; Beyond the Basics. 2nd ed. Sudbury, MA:Jones and Bartlett.

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