Fluoride Exposure and Children's IQ Scores: A Systematic Review and Meta-Analysis.

IMPORTANCE

Previous meta-analyses suggest that fluoride exposure is adversely associated with children's IQ scores. An individual's total fluoride exposure comes primarily from fluoride in drinking water, food, and beverages.

OBJECTIVE

To perform a systematic review and meta-analysis of epidemiological studies investigating children's IQ scores and prenatal or postnatal fluoride exposure.

DATA SOURCES

BIOSIS, Embase, PsycInfo, PubMed, Scopus, Web of Science, CNKI, and Wanfang, searched through October 2023.

STUDY SELECTION

Studies reporting children's IQ scores, fluoride exposure, and effect sizes.

DATA EXTRACTION AND SYNTHESIS

Data were extracted into the Health Assessment Workplace Collaborative system. Study quality was evaluated using the OHAT risk-of-bias tool. Pooled standardized mean differences (SMDs) and regression coefficients were estimated with random-effects models.

MAIN OUTCOMES AND MEASURES

Children's IQ scores.

RESULTS

Of 74 studies included (64 cross-sectional and 10 cohort studies), most were conducted in China (n = 45); other locations included Canada (n = 3), Denmark (n = 1), India (n = 12), Iran (n = 4), Mexico (n = 4), New Zealand (n = 1), Pakistan (n = 2), Spain (n = 1), and Taiwan (n = 1). Fifty-two studies were rated high risk of bias and 22 were rated low risk of bias. Sixty-four studies reported inverse associations between fluoride exposure measures and children's IQ. Analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure (47 high risk of bias, 12 low risk of bias; n = 20 932 children) showed an inverse association between fluoride exposure and IQ (pooled SMD, -0.45; 95% CI, -0.57 to -0.33; P < .001). In 31 studies reporting fluoride measured in drinking water, a dose-response association was found between exposed and reference groups (SMD, -0.15; 95% CI, -0.20 to -0.11; P < .001), and associations remained inverse when exposed groups were restricted to less than 4 mg/L and less than 2 mg/L; however, the association was null at less than 1.5 mg/L. In analyses restricted to low risk-of-bias studies, the association remained inverse when exposure was restricted to less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in drinking water. In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, -0.15; 95% CI, -0.23 to -0.07; P < .001). Associations remained inverse when exposed groups were restricted to less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine; the associations held in analyses restricted to the low risk-of-bias studies. Analysis of 13 studies with individual-level measures found an IQ score decrease of 1.63 points (95% CI, -2.33 to -0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among low risk-of-bias studies, there was an IQ score decrease of 1.14 points (95% CI, -1.68 to -0.61; P < .001). Associations remained inverse when stratified by risk of bias, sex, age, outcome assessment type, country, exposure timing, and exposure matrix.

CONCLUSIONS AND RELEVANCE

This systematic review and meta-analysis found inverse associations and a dose-response association between fluoride measurements in urine and drinking water and children's IQ across the large multicountry epidemiological literature. There were limited data and uncertainty in the dose-response association between fluoride exposure and children's IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L. These findings may inform future comprehensive public health risk-benefit assessments of fluoride exposures.