Large US ECHO Cohort Study Finds No Overall Link Between Prenatal Water Fluoride and Children's Behavior

Prenatal exposure to fluoride (搜索)搜索该药品 in public drinking water was not associated with children's emotional or behavioral problems overall, according to a cohort study published in JAMA Network Open (搜索)搜索该词条. The analysis, drawn from the Environmental Influences on Child Health Outcomes (ECHO) Cohort, tracked fluoride concentrations at the census-tract level across 34 US states, making it one of the largest US investigations of the question to date.

The findings contrast with some earlier reports linking prenatal fluoride (搜索)搜索该药品 to poorer socioemotional outcomes, a discrepancy the authors attribute in part to methodological differences in how exposure was measured.

Study Design and Population

The study used data from ECHO Cohort cycle 1, which comprises 69 ongoing pregnancy and pediatric cohort sites across the US and Puerto Rico. The current sample included 5,520 children from 20 cohort sites, with a mean age of 5.8 years, comprising 2,849 boys and 2,671 girls.

Most participants were White (60.5%), 24.8% were Hispanic, 15.2% were Black, and 11.5% reported multiple races or ethnicities. Race and Hispanic ethnicity were reported separately, so these categories were not mutually exclusive. Families lived in 2,604 census tracts spanning 34 states.

Fluoride (搜索)搜索该药品 levels in public drinking water sources were assigned at the census tract level from public water compliance records and linked to each month of pregnancy using residential address histories. Census tract estimates were averaged over three-year monitoring periods, allowing time-weighted prenatal exposure estimates that accounted for residential moves. Children's emotional and behavioral problems were measured with the Child Behavior Checklist (CBCL), a parent-report assessment of internalizing and externalizing problems.

Analyses were adjusted for child sex, season of conception, age at CBCL assessment, maternal education and age at delivery, smoking in pregnancy, and parity, as well as socioeconomic vulnerability and census-tract population density. The authors chose not to adjust for race or ethnicity because doing so could obscure existing disparities in exposure or outcomes.

Exposure Levels Relative to Federal Guidance

Prenatal fluoride (搜索)搜索该药品 exposures via drinking water ranged from less than 1.4 mcg/L to 3,272.5 mcg/L. Overall, 1,522 participants (27.6% of the total) were exposed to drinking water fluoride above the US Public Health Service (搜索)搜索该词条 (USPHS) optimal fluoridation concentration of 700 mcg/L. The USPHS recommendation aims to balance dental benefits against potential harms at higher exposure levels; previous ecological studies have associated fluoride above 4,000 mcg/L in drinking water with skeletal fluorosis (搜索)搜索该疾病, kidney and thyroid dysfunction, and negative effects on the central nervous system.

Primary Analysis Shows No Association

After adjustment, the analysis found no associations between fluoride (搜索)搜索该药品 exposure and children's behavioral or emotional problems in either continuous or categorical analyses. There was also no difference between exposure above the USPHS guideline and exposure at or below it. Sensitivity analyses produced results consistent with the main model.

Exploratory Change-Point Findings at Higher Exposure

Exploratory linear change-point sensitivity models showed that the slope of the association between fluoride (搜索)搜索该药品 exposure and externalizing problem scores changed at a fluoride level of 625 mcg/L. The authors emphasized that this was a model-derived inflection point rather than an established biological or safety threshold. Above this point, the adjusted mean difference in scores was 1.59 points per 500 mcg/L increase in fluoride exposure, indicating a positive association at higher exposure levels.

For internalizing problems, the change point was at 1,825 mcg/L. With fewer than ten children above that level, the researchers did not interpret the association above this point.

In subgroup analyses, internalizing problems were negatively associated with fluoride (搜索)搜索该药品 levels in the multiracial subgroup, with an adjusted mean difference of −1.34 points per 500 mcg/L increase in fluoride. Conversely, externalizing problems were positively associated with fluoride exposure in the subgroup aged six years or above. Neither interaction was statistically significant for race/ethnicity or age, respectively.

According to the authors, the post-inflection increase in externalizing problem scores suggests that such associations may emerge at higher levels of exposure and warrant further study.

Accounting for Divergent Prior Results

Prior studies reporting associations used biospecimens such as urine samples or state-level measures of public water fluoride (搜索)搜索该药品 exposure. The authors noted that methodological differences may contribute to the contrasting findings. Biomarkers integrate fluoride exposure from all sources, making it harder to isolate the contribution from drinking water and to develop targeted interventions and appropriate regulatory mechanisms. The current study used census-tract-level water estimates rather than state-level measures or biospecimens.

Limitations

The study could not adjust for postnatal fluoride (搜索)搜索该药品 exposures or other sources of fluoride exposure. It assessed only one exposure source, and water fluoride measurements may not accurately reflect individual-level intake or total exposure; exposure misclassification could reduce the ability to detect an association. Detailed water-drinking behavior was not captured, and non-residential sources of drinking water were not accounted for. Finally, the sample was predominantly White and non-Hispanic, and most mothers were college-educated, limiting generalizability.

Conclusions

This cohort study did not demonstrate associations between prenatal fluoride (搜索)搜索该药品 exposure via public drinking water and behavioral or emotional problems in children, and the authors reported no association at the current USPHS-recommended concentration. The change-point analysis found a positive association with externalizing problems above the model-derived inflection point, while exploratory subgroup analyses separately identified a negative association with internalizing problems in the multiracial subgroup and a positive association with externalizing problems among children aged six years or older — neither of which was statistically significant on interaction testing. The authors concluded that future studies should further examine these associations while assessing other sources of fluoride exposure that might affect children's psychological and developmental health.