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Association of lifetime exposure to fluoride and cognitive functions in Chinese children: A pilot study.Abstract
Highlights
- Elevated fluoride concentrations in drinking water may be neurotoxic.
- We carried out a pilot study of 51 first-grade children with stable lifetime fluoride exposures.
- Moderate and severe fluorosis was associated with deficits in digit span total and backward scores.
- The dose-dependence underlying the association needs to be characterized in detail.
Background: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development.
Methods: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-R) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models.
Results: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-R digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of ? 4.28 (95% CI ? 8.22, ? 0.33) and backward score with ? 2.13 (95% CI ? 4.24, ? 0.02).
Conclusions:
This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail.
EXCERPTS:
Introduction
The developing human brain is much more susceptible to injury caused by toxicants than is the mature brain, and the damage incurred is likely to be of a permanent nature as the major windows of developmental vulnerability occur in utero and during infancy and early childhood (Grandjean and Landrigan, 2006, Rice and Barone, 2000). Chemicals can, therefore, cause permanent brain injury at low levels of exposure that would have little or no adverse effect in an adult (Grandjean and Landrigan, 2014).
Fluoride occurs naturally in the environment from the weathering of fluoride-containing rocks and soils, and leaching from soil into groundwater. Fluoride is also released into the environment via coal combustion and other industrial sources, either by direct deposition or by deposition to soil and subsequent runoff into water (NRC (National Research Council), 2006, WHO (World Health Organization), 2002). The major sources of human exposure to fluoride are drinking water, food, dental products, and pesticides (NRC, 2006). Fluoride is a trace element that is necessary for the human body. A proper amount of fluoride not only prevents dental caries, but also promotes the use of calcium and phosphorus and the calcium sediment in the bone, stimulates bone growth and maintains bone health (Dean and Elvove, 1936, WHO (World Health Organization), 1958).
However, the developing human brain may be exposed prenatally to fluoride as fluoride readily crosses the placenta (ATSDR, 2003). In laboratory studies, the central nervous system (CNS) may be vulnerable to fluoride. Fluoride accumulates in brain tissues and may affect the hippocampus, the central processor of memory, in learning and memory functions (Mullenix et al., 1995, Chioca et al., 2008). Potential effects on the neurodevelopment in children have been explored mainly in China where many urban and rural communities are located in endemic fluorosis areas. Thus, a National Research Council report reviewed the effects of fluoride in drinking water on human health, including the cognitive capacities in children (NRC, 2006). Many relevant studies were identified that, collectively, supported the hypothesis that fluoride is a developmental neurotoxicant, but because many of the studies did not provide sufficient information about the neurobehavioral tests used and the testing conditions, the report recommended that additional, more rigorous research be conducted.
In response to this report, the U.S. Department of Health and Human Services (DHHS) is proposing to set the recommended level of fluoride in drinking water at 0.7 mg/L, the lower end of the current range of 0.7 to 1.2 mg/L, and the U.S. Environmental Protection Agency (U.S. EPA) is considering lowering the maximum amount of fluoride allowed in drinking water, which is currently 4 mg/L (U.S. EPA, 2011).
To investigate the effects of increased fluoride exposure on children’s neurobehavioral development, we performed a systematic review and meta-analysis of 27 cross-sectional studies of children exposed to fluoride in drinking water, mainly from China (Choi et al., 2012). Our results showed that the standardized weighted mean difference (SMD) in IQ score between exposed and reference populations across studies that gave the average difference in standard deviations (SDs) was ? 0.45 (95% confidence interval: ? 0.56, ? 0.36). For commonly used IQ scores with a mean of 100 and a SD of 15, 0.45 SDs is equivalent to 6.75 points (rounded to 7 points). The results therefore showed an average IQ decrement of about seven points in children with increased fluoride exposure. The elevated exposure groups had access to drinking water with fluoride concentrations ranging from 0.57 mg/L to 11.5 mg/L. As the average difference in terms of IQ between elevated and background exposure groups corresponded to approximately 7 points, our review highlighted a need to further characterize the dose–response association including improving assessment and control of potential confounders.
The current pilot study was undertaken to assess the feasibility of administering a comprehensive battery of neurodevelopmental tests to a population of school children in China in order to test the hypothesis that increased fluoride exposure is related to impairments in neurobehavioral development. Specifically, we identified a population of children who had been exposed to stable fluoride concentrations in drinking water since conception and assessed the feasibility and validity of exposure assessment and neurobehavioral testing under field conditions in rural China. In this country, a country-wide effort to provide microbiologically safe drinking-water in rural communities secured piped spring water or well-water for each household. Families residing at the same location could therefore be characterized in regard to fluoride exposure based on the concentration of fluoride in a child’s water source.
Section snippets
Study population
We carried out a field study of 51 first-grade children, aged 6–8 years in 2011, who resided in Mianning County in southern Sichuan, China. While there is a wide range of fluoride concentrations in drinking water in this area, the residence-specific water sources have very stable fluoride levels. For families remaining at the same residence, the children have therefore been exposed to a stable fluoride concentration since conception. Children who did not speak Chinese, who were not students at…
Table 1 shows the characteristics of the 51 study children. There were slightly more girls than boys (53% vs. 47%), and the average age was 7.1 years. All subjects had birth weight more than 2500 g. The hemoglobin and hematocrit levels were within normal ranges and did not suggest the presence of iron deficiency. Household income in the past year was less than 3000 yuan (US $462 in 2011) for the majority of families (61%), and most of the caretakers were farmers (96%). The distributions of…
Results of our pilot study showed that moderate and severe dental fluorosis was significantly associated with deficits in WISC-IV digit span. Children with moderate or severe dental fluorosis scored significantly lower in total and backward digit span tests than those with normal or questionable fluorosis. These results suggest a deficit in working memory. Scores on other tests did not show significant relationships with indices of fluoride exposure.
The 2006 National Research Council report…
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ABSTRACT ONLINE AT https://www.sciencedirect.com/science/article/abs/pii/S0892036214001809?via%3Dihub
SEE CORRIGENDUM at http://fluoridealert.org/wp-content/uploads/choi-2015.corrigendum.pdf
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