Prenatal Fluoride Exposure Linked to Hyperactivity Risk in Preschoolers, Study Finds

A new analysis of hundreds of mother-child pairs in rural New England has found that higher fluoride exposure during pregnancy, measured in an unusual but increasingly valued biological archive—maternal toenails—is associated with increased odds that children will score in the at-risk range for externalizing behaviour problems, particularly hyperactivity, at age five. The study, conducted within the New Hampshire Birth Cohort Study and published in the journal Environmental Advances, also uncovered a sex-specific signal: girls whose mothers carried higher toenail fluoride concentrations in early pregnancy showed elevated odds of at-risk depressive symptoms, an association not seen in boys. Notably, fluoride concentrations measured in household tap water did not show statistically significant associations with any of the behavioural outcomes examined.

The findings arrive amid a widening scientific debate over fluoride, a substance added to community water supplies at 0.7 milligrams per litre to prevent tooth decay, yet one that occurs naturally in groundwater at levels that can vary dramatically with local geology. In rural New Hampshire, where many families rely on private, unregulated wells drilled into fluoride-bearing rock, concentrations can be far higher than in fluoridated municipal systems; roughly thirteen percent of wells in regions underlain by felsic igneous rock exceed the U.S. Environmental Protection Agency’s secondary maximum contaminant level of 2.0 milligrams per litre. Against this backdrop, the research team set out to test whether prenatal fluoride exposure is linked not to intelligence, which has dominated the literature, but to the social-emotional and behavioural dimensions of child development that have received far less scrutiny.

Methodologically, the study distinguishes itself through its choice of exposure biomarker. Most previous prospective studies relied on maternal urinary fluoride, which reflects intake over only about six hours—a snapshot that can fluctuate with tea drinking, meal composition, and water consumption on a given day. Toenails, by contrast, grow slowly and integrate fluoride exposure over approximately three to six months, capturing cumulative intake from all sources: drinking water, beverages prepared with fluoridated water, seafood, tea, and the inadvertent swallowing of fluoridated dental products. Because fluoride readily crosses the placenta and penetrates the blood-brain barrier, the developing fetal brain is directly exposed, making the timing and magnitude of maternal exposure biologically consequential.

The researchers analyzed toenail clippings collected from women at roughly 28 weeks of gestation and again about five weeks after delivery, yielding estimates of fluoride exposure during early pregnancy and mid-to-late pregnancy respectively. Samples were analyzed at the Indiana University School of Dentistry using a hexamethyldisiloxane microdiffusion procedure coupled with fluoride ion-selective electrode detection, and specimens weighing less than 2.5 milligrams were excluded after validation work showed that smaller samples produce unreliable results. Household tap water collected at enrollment was analyzed with a fluoride ion-selective electrode as well. The final analytic samples comprised 358 mother-child pairs with toenail fluoride data and 381 pairs with water fluoride data, drawn from a cohort recruited between 2009 and 2013 from prenatal clinics serving women using private water systems.

Children’s behaviour was assessed at age five with the Behavior Assessment System for Children, Second Edition, Parent Rating Scale for preschoolers, a validated instrument that generates age-standardized T-scores across clinical scales such as hyperactivity, aggression, attention problems, anxiety, depression, and withdrawal, along with composite indices of externalizing problems, internalizing problems, and overall behavioural symptoms. Scores of 60 or above fall into the at-risk range. In this sample, most children scored near the normative mean, with between six and twenty-eight percent in the at-risk range depending on the scale. The analysis was preregistered, and the modeling strategy used generalized estimating equations to estimate the odds of at-risk outcomes per one microgram per gram increase in toenail fluoride, with interaction terms testing for differences by child sex and exposure window.

The headline result was statistically robust: each one microgram per gram increase in toenail fluoride reflecting early pregnancy was associated with thirty-nine percent higher odds of scoring in the at-risk range for externalizing problems, with a confidence interval running from fifteen to sixty-seven percent above baseline. The late-pregnancy estimate was similar in magnitude, at thirty percent higher odds, though its confidence interval narrowly included the null. On the individual clinical scales, early-pregnancy fluoride was linked to twenty percent higher odds of at-risk hyperactivity, and the late-pregnancy estimate of twenty-four percent approached significance. The pattern suggests that no single trimester stands out as uniquely vulnerable; rather, fluoride exposure across pregnancy appears relevant to externalizing behaviour.

The sex-specific findings added a further layer of complexity. Among girls, each one microgram per gram increase in early-pregnancy toenail fluoride was associated with thirty-seven percent higher odds of at-risk depressive symptoms, while no association appeared in boys—a statistically significant interaction. Suggestive but imprecise signals also emerged for anxiety and withdrawal in girls in relation to late-pregnancy exposure. This pattern is intriguing because prior fluoride studies, particularly those examining intelligence outcomes, have often reported stronger effects in boys. The authors note that internalizing and externalizing problems may share transdiagnostic roots, including emotion dysregulation, and that sex-specific biological responses to prenatal exposures could shape which behavioural domain is affected.

Plausible biological mechanisms are beginning to take shape in the literature. Fluoride has been implicated in disruption of the thyroid axis, a concern in pregnancy because the fetus depends entirely on maternal thyroid hormones during the first trimester, and even mild maternal thyroid dysfunction has been linked to both internalizing and externalizing problems in children. Fluoride exposure has also been shown to induce oxidative stress in animal and human studies, a pathway independently associated with behavioural problems in offspring. Low iodine status, which compromises thyroid hormone synthesis, may exacerbate fluoride’s effects, and emerging evidence suggests thyroid regulation and oxidative stress responses differ by fetal sex. None of these mechanisms is confirmed as the driver of the observed associations, but together they offer a coherent framework for future investigation.

Why did water fluoride fail to predict outcomes while toenail fluoride succeeded? The authors argue that toenails capture total intake from all dietary and product sources, whereas a single tap-water measurement reflects only one exposure pathway and ignores individual differences in consumption volume. This mismatch can produce exposure misclassification that biases associations toward the null. Median water fluoride in the sample was about 0.2 milligrams per litre—comparable to other communities with naturally occurring fluoride—but values ranged from 0.02 to 13.8 milligrams per litre, and correlations between water and toenail measures, while positive, were moderate. The authors also caution that some participants may have reduced tap-water consumption after learning their wells exceeded arsenic guidelines during the study.

The study’s limitations temper its implications. The cohort was predominantly white, college-educated, married, and relatively affluent, and relied on unregulated private wells, so the findings cannot be assumed to extend to populations drinking optimally fluoridated municipal water. Postnatal fluoride exposure was not measured, toenail growth rates vary between individuals, and only a small fraction of children scored in the at-risk range, limiting statistical power. Yet extensive sensitivity analyses—adjusting for co-occurring metals, imputing missing data, removing influential observations, and modeling outcomes continuously—left the primary conclusions intact. The authors call for longitudinal follow-up, validation of toenail fluoride reference ranges in pregnant populations, and exposome-wide approaches that jointly model fluoride alongside the many other prenatal environmental exposures that shape the developing brain.

Subject of Research: The association between prenatal fluoride exposure measured in maternal toenails and social-emotional and behavioural outcomes in preschool children.

Article Title: Long-term exposure to prenatal fluoride and social-emotional and behavioural outcomes in children in the New Hampshire Birth Cohort Study

Article References: Goodman, C. V., Karagas, M. R., Peacock, J. L., Korrick, S., Flora, D., Lanphear, B., Martinez-Mier, E. A., Tamayo-Cabeza, G., Lippert, F., & Till, C. (2026). Long-term exposure to prenatal fluoride and social-emotional and behavioural outcomes in children in the New Hampshire Birth Cohort Study. Environmental Advances, 25, Article 100753. https://doi.org/10.1016/j.envadv.2026.100753

Image Credits: AI Generated

DOI: 10.1016/j.envadv.2026.100753

Keywords: fluoride, prenatal exposure, child behaviour, hyperactivity, New Hampshire Birth Cohort Study, toenail biomarker, drinking water, neurodevelopment, thyroid, externalizing problems, internalizing problems, private wells