Higher fluoride exposure was associated with lower IQ scores in children across multiple countries, according to a comprehensive systematic review and meta-analysis published in JAMA Pediatrics.

The review analyzed 74 studies, including 64 cross-sectional and 10 prospective cohort studies, from 10 countries. Most studies were conducted in China (n=45), followed by India (n=12), Iran (n=4), Mexico (n=4), Canada (n=3), Pakistan (n=2), and one each from Denmark, New Zealand, Spain, and Taiwan.

Individual-level data analysis showed an IQ score decrease of 1.63 points per 1-mg/L increase in urinary fluoride. Among low risk-of-bias studies, the decrease was 1.14 points.

Of the 74 studies, 52 were rated as having high risk of bias, while 22 were rated as low risk. Among the low risk studies, 13 were rated low risk across all seven domains, and nine were rated low risk in six domains with probably high risk in no more than one domain.

The analysis revealed consistent inverse associations across different subgroups. By sex, the standardized mean difference (SMD) was -0.45 for females and -0.53 for males. Age-based analysis showed an SMD of -0.38 for children under 10 years and -0.52 for those 10 and older.

For studies measuring urinary fluoride, inverse associations remained significant at concentrations below 4 mg/L (14 studies, n=8019 children), below 2 mg/L (6 studies, n=4692 children), and below 1.5 mg/L (5 studies, n=4219 children).

The study found evidence of publication bias. However, trim-and-fill analysis supported the significant inverse association after imputation of additional studies.

In the US, where no studies were conducted, the CDC estimated that water and processed beverages provide approximately 75% of a person's fluoride intake. The Environmental Protection Agency estimated that 40% to 70% of fluoride intake comes from fluoridated drinking water.

The US Geological Survey estimated that 172,000 US residents are served by domestic wells exceeding the EPA's enforceable standard of 4.0 mg/L fluoride in drinking water, and 522,000 are served by wells exceeding the nonenforceable standard of 2.0 mg/L. The US Centers for Disease Control and Prevention recommends 0.7 mg/L as the concentration that maximizes fluoride's oral health benefits while minimizing potential harms

The researchers noted that while their analysis was not designed to address the broader public health implications of water fluoridation in the US, the results may inform future comprehensive public health risk-benefit assessments of fluoride exposures.

The study's strengths included its large literature base, predefined systematic search and screening process, risk-of-bias assessment of individual studies, prespecified subgroup analyses, and use of both group-level and individual-level exposure data. Limitations included the high number of studies classified as high-risk of bias and the predominance of cross-sectional study designs.

The authors declared having no competing interests.