Community water, salt, milk, and dental products have been fluoridated in varying degrees for more than 60 y to prevent dental caries, while fluoride supplementation has been recommended to prevent bone fractures (Jones et al. 2005). In addition, people may be exposed to fluoride through the consumption of naturally contaminated drinking water, dietary sources, dental products, and other sources (Doull et al. 2006). Whereas fluoride is added to drinking water [in the United States at levels of 0.7–1.2 mg/L (Doull et al. 2006)] to promote health, populations with exceptionally high exposures, often from naturally contaminated drinking water, are at risk of adverse health effects, including fluorosis.
In the United States, the U.S. Environmental Protection Agency (EPA) is responsible for establishing maximum permissible concentrations of contaminants, including fluoride, in public drinking-water systems. These standards are guidelines for restricting the amount of fluoride contamination in drinking water, not standards for intentional drinking-water fluoridation. In 2006 the U.S. EPA asked the U.S. National Research Council (NRC) to reevaluate the existing U.S. EPA standards for fluoride contamination, including the maximum contaminant level goal (MCLG, a concentration at which no adverse health effects are expected) of 4 mg/L, to determine if the standards were adequate to protect public health (Doull et al. 2006). The committee concluded that the MCLG of 4 mg/L should be lowered because it puts children at risk of developing severe enamel fluorosis, and may be too high to prevent bone fractures caused by fluorosis (Doull et al. 2006). The Committee also noted some experimental and epidemiologic evidence suggesting that fluoride may be neurotoxic (Doull et al. 2006).
The National Toxicology Program (NTP) recently reviewed animal studies on the effects of fluoride on neurobehavioral outcomes and concluded that there was a moderate level of evidence for adverse effects of exposures during adulthood, a low level of evidence for effects of developmental exposures on learning and memory, and a need for additional research, particularly on the developmental effects of exposures consistent with those resulting from water fluoridation in the United States (Doull et al. 2006; NTP 2016). Human studies have shown a direct relationship between the serum fluoride concentrations of maternal venous blood and cord blood, indicating that the placenta is not a barrier to the passage of fluoride to the fetus (Shen and Taves, 1974). Fluoride was shown to accumulate in rat brain tissues after chronic exposures to high levels, and investigators have speculated that accumulation in the hippocampus might explain effects on learning and memory (Mullenix et al. 1995). An experimental study on mice has shown that fluoride exposure may have adverse effects on neurodevelopment, manifesting as both cognitive and behavioral abnormalities later in life (Liu et al. 2014).
Most epidemiologic studies demonstrating associations between fluoride exposure and lower neuropsychological indicators have been conducted in populations living in regions with endemic fluorosis that are exposed to high levels of fluoride in contaminated drinking water. The epidemiologic evidence is limited, however, with most studies using an ecologic design to estimate childhood exposures based on neighborhood measurements of fluoride (e.g., drinking water levels) rather than personal exposure measures. Moreover, almost all existing studies of childhood outcomes are cross-sectional in nature, rendering them weak contributors towards causal inference.
The main objective of this study was to assess the potential impact of prenatal exposures to fluoride on cognitive function and test hypotheses related to impacts on overall cognitive function. We hypothesized that fluoride concentrations in maternal urine samples collected during pregnancy, a proxy measure of prenatal fluoride exposure, would be inversely associated with cognitive performance in the offspring children. Overall, to our knowledge, this is one of the first and largest longitudinal epidemiologic studies to exist that either address the association of early life exposure to fluoride to childhood intelligence or study the association of fluoride and cognition using individual biomarker of fluoride exposure.