Fluid cognition scores may be affected by higher prenatal exposure to fluoride in public drinking water, with inverse associations observed at concentrations below the World Health Organization guideline and near the US Public Health Service recommended fluoridation concentration.
The observational study included 2,514 children born from 2006 to 2019 across 23 states. Investigators estimated prenatal exposure to fluoridated drinking water by linking residential addresses during pregnancy to census tract–level estimates from routine compliance monitoring records. Prenatal fluoride concentrations ranged from less than 1 to 1,940 μg/L, with a mean of 397 μg/L, and 17% of the children had estimated concentrations of at least 700 μg/L.
The investigators assessed fluid and crystallized cognition, measured with age-corrected, standardized tests from the National Institutes of Health Toolbox Cognition Battery. Fluid cognition incorporated cognitive flexibility, inhibitory control and attention, and memory; whereas crystallized cognition evaluated picture vocabulary. In adjusted nonlinear models, higher prenatal fluoride exposure was associated with lower fluid cognition, with the inverse association becoming statistically significant above 1,107 μg/L. A complementary change-point analysis identified 675 μg/L as the best-fitting change point, above which each additional 100 μg/L was associated with a 0.67-point lower fluid cognition score.
The association was not consistent across cognitive domains. Crystallized cognition did not have a statistically significant inverse association with fluoride in the nonlinear analysis. Above the 275-μg/L change point selected for crystallized cognition, each additional 100 μg/L was associated with a 0.21-point lower score, but the association was not statistically significant.
Higher fluoride concentrations were nonlinearly associated with lower total cognition above 1,135 μg/L. In the change-point analysis, each 100-μg/L increase above the selected 250-μg/L change point was associated with a 0.22-point lower total cognition score. However, the association likely reflected the fluid cognition findings rather than generalized effects across cognitive domains.
Associations with fluid cognition also differed by age. Using the 675-μg/L change point selected in the full sample, each additional 100 μg/L increase was associated with a decrease of 2.70 points in fluid reasoning among children aged younger than 7 years compared with a 0.45 points among those aged 7 years or older. The investigators suggested that the effects of prenatal fluoride exposure may appear larger when cognition is assessed at younger ages because early childhood is a period of rapid neurodevelopment. They also noted that cumulative postnatal experiences, including schooling, may partially buffer earlier effects when cognition is assessed later. Additional research is needed to characterize this pattern.
The results were generally consistent with alternative model adjustments and when individual cohort sites were sequentially excluded. However, inverse probability–weighted analyses evaluating potential selection bias attenuated associations for fluid and total cognition toward. Associations with crystallized cognition remained null across sensitivity analyses.
The study had several limitations. Fluoride exposure was assigned using public water concentrations and residential location rather than each participant’s actual fluoride intake. Sufficient information on tap water sources, bottled or filtered water use, variation in water intake, postnatal exposure, and other fluoride sources was lacking. Exposure measurement error may also have differed among cohort sites because some states had poorer data on public water system boundaries. In addition, inverse probability–weighted analyses suggested potential selection bias. The analytic sample was predominantly White, non-Hispanic, and college-educated. The investigators said the findings warrant replication in samples that are more representative of the US population, include more highly exposed groups, and assess postnatal fluoride levels.
The observational findings did not establish causality. The investigators called for additional studies to identify susceptible exposure periods across prenatal, postnatal, and early childhood development and to examine potential neural pathways underlying the associations.
“These results highlight the need to reevaluate the current [maximum contaminant level] for fluoride in public water systems (4,000 µg/L), which may not adequately protect neurodevelopment,” wrote lead study author Katrina R. Simon, of the Department of Environmental Health Sciences at the Columbia University Mailman School of Public Health, and colleagues.
The study authors reported no conflicts of interest.
Source: American Journal of Epidemiology