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Invited Perspective: Prenatal and childhood exposure to fluoride and cognitive development: findings from the longitudinal MINIMat cohort in rural Bangladesh.
| Environmental Health Perspectives (EHP) | By Christine Till, PhD | 133(2).
Bangladesh-IQ IQ Score Review

Abstract

PREPRINT. ISSUE IN PROGRESS.

Community water fluoridation (CWF) is widely endorsed by dental and public health organizations as a cost-effective and equitable way to reduce dental caries.1 Excessive levels of fluoride can have detrimental effects on health, but the evidence remains intensely debated at lower levels.2,3

The National Toxicology Program (NTP) released a long-awaited systematic review4 and meta-analysis5 examining the link between fluoride exposure and cognitive or neurodevelopmental effects in humans. The NTP found “moderate confidence” in the association between higher fluoride levels and lower intelligence in children. This review evaluated 72 studies on fluoride exposure and children’s intelligence quotient (IQ), with 64 studies (89%) showing an inverse relationship. Nineteen of these studies were deemed high-quality by the NTP, 18 of which reported an inverse association between fluoride exposure and IQ in children. Of these 18, fifteen were cross-sectional studies (from thirteen different study populations) and three were prospective birth cohort studies (from two different study populations). The NTP further concluded that “confidence in the associations at lower fluoride levels could be increased by additional prospective cohort studies with individual fluoride exposure measures.”4

Water fluoridation has been in practice for over 75 years, but prospective cohort studies investigating the potential risks of fluoride to cognitive development only emerged in the past decade. These studies, conducted across seven cohorts in five countries – Canada6, Mexico7–9, Spain10, Denmark11, and Sweden12 – included more than 2500 children. A significant inverse association between higher levels of gestational fluoride exposure and lower IQ in children was reported in 4 of the 7 studies.

In this issue of Environmental Health Perspectives, Singh et al. present findings from a new prospective cohort study linking low-level fluoride exposure with reduced cognitive scores in children.13 This research, involving 500 mother-child pairs from the MINIMat cohort from Bangladesh, measured urinary fluoride levels during fetal development and at 5 and 10 years of age. The investigators found significant inverse associations between maternal urinary fluoride and children’s full-scale raw scores at both ages. These associations remained significant even after controlling for confounders. Childhood fluoride exposure, which also showed negative associations with child cognitive scores, seemed less influential than maternal exposure during pregnancy. The multiple exposure measurements used by Singh et al adds further evidence that gestation is a critical window of vulnerability to fluoride.

This study is important for several reasons. First, it is the fifth out of now eight prospective cohort studies6–13 to report a significant inverse association between gestational exposure to fluoride and lower cognitive scores in children. A 1 mg/L increase in maternal urinary fluoride concentration was associated with a full-scale raw score decrease of 0.11 to 0.14 standard deviations. The consistency of this effect at both ages is noteworthy; the findings support the persistence of exposure-related deficits and address previous concerns about the reliability of cognitive testing measurements in young children.

Second, the median urinary fluoride levels in the pregnant women from the MINIMat cohort (0.63 mg/L) are nearly identical to those reported from first-trimester spot samples of 155 women in California (0.64 mg/L).14 Urinary fluoride is a biological measure of total fluoride exposure from all sources, including food, beverages, dental products, and from bone fluoride stores.

Third, household drinking water fluoride concentrations ranged from 0.04 to 0.74 mg/L at the children’s 10-year-old follow-up visit (98% from private wells). These levels are similar to approximately 85% of Americans receiving artificially- or naturally-fluoridated water from community water systems.15

Drinking water was considered an important source of fluoride in the MINIMat cohort given that people drink large amounts of water in hot climates. Water fluoride levels were moderately correlated (r = 0.44) with the children’s urinary fluoride levels; a stronger correlation (r = 0.55) was found between water fluoride levels and the mother’s urinary fluoride levels during pregnancy, though it is unclear whether fluoride levels in the drinking water remained stable over the 10-year follow-up period.

Singh et al conducted several sensitivity analyses, adjusting for key neurotoxicants, such as cadmium, arsenic, and lead, and found that the association between fluoride and lower IQ remained significant. They also examined whether ‘above requirement’ iodine intake during pregnancy might modify this association. Since 1989, Bangladesh has implemented a salt iodization program. Excessive or deficient iodine levels can lead to thyroid dysfunction in pregnant women and negatively affect offspring neurodevelopment, particularly when combined with high fluoride exposure.16,17 Importantly, median urinary iodine concentrations (UIC) in the MINIMat cohort were ‘above requirements’ as based on the World Health Organization’s (WHO) recommended levels for pregnant women.18 However, a previous study from the MINIMat cohort found no significant association between high maternal UIC and child IQ19, which may explain why controlling for UIC in this study did not alter the fluoride-IQ findings.

In 2006, the National Research Council concluded that exposure to fluoride at the Environmental Protection Agency’s maximum allowable level of 4 mg/L was associated with severe enamel fluorosis and risk of bone fracture.20 While previous risk assessments were focused on dental fluorosis, the NTP’s meta-analysis highlighted that children’s intellectual ability may be a more sensitive and consequential endpoint at fluoride levels below 1.5 mg/L (i.e. the WHO Guidelines for Drinking-Water Quality).5 The study by Singh et al provides additional evidence in a low-exposed cohort.

Given the significant implications for public health and the ubiquity of fluoride exposure, ongoing assessment of potential risks and benefits of fluoride exposure is of critical importance. While multiple studies show an association at lower levels of fluoride, determining causality remains complex, and additional research is needed to fully understand the impact of cumulative fluoride exposure from various sources across the lifespan. Prospective cohort studies are particularly valuable, as they can establish a temporal relationship between exposure and outcome, an essential component for causality. As scientific understanding evolves, it is crucial to evaluate the totality of evidence and rely on the most rigorous studies to guide decision making and ensure public health guidelines are health-protective for all.

References

  1. Centers for Disease Control and Prevention (CDC). CDC Scientific Statement on Community Water Fluoridation. CDC Scientific Statement on Community Water Fluoridation. 2024. https://www.cdc.gov/fluoridation/about/statement-on-the-evidence-supporting-the-safety-and-effectiveness-of-community-water-fluoridation.htmls://www.cdc.gov/fluoridation/statistics/index.htm
  2. Guth S, Hüser S, Roth A, et al. Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses. Arch Toxicol. 2020;94(5):1375-1415. doi:10.1007/s00204-020-02725-2
  3. Taher MK, Momoli F, Go J, et al. Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water. Crit Rev Toxicol. 2024;54(1):2-34. doi:10.1080/10408444.2023.2295338
  4. National Toxicology Program (NTP). NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review. Published online 2024.
  5. Taylor KW, Eftim SE, Sibrizzi CA, et al. Fluoride Exposure and Children’s Intelligence: A Systematic Review and Meta-analysis. JAMA Pediatr. 2024;179(3):1-12.
  6. Green R, Lanphear B, Hornung R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019;173(10):940-948. doi:10.1001/jamapediatrics.2019.1729
  7. Goodman CV, Bashash M, Green R, et al. Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6–12 years in the ELEMENT cohort. Environ Res. 2022;211:112993. doi:10.1016/j.envres.2022.112993
  8. Cantoral A, Téllez-Rojo MM, Malin AJ, et al. Dietary fluoride intake during pregnancy and neurodevelopment in toddlers: A prospective study in the progress cohort. Neurotoxicology. 2021;87:86-93. doi:10.1016/j.neuro.2021.08.015
  9. Valdez Jiménez L, López Guzmán OD, Cervantes Flores M, et al. In utero exposure to fluoride and cognitive development delay in infants. NeuroToxicology. 2017;59:65-70. doi:10.1016/j.neuro.2016.12.011
  10. Ibarluzea J, Gallastegi M, Santa-Marina L, et al. Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children. Environ Res. 2022;207:112181. doi:10.1016/j.envres.2021.112181
  11. Grandjean P, Meddis A, Nielsen F, et al. Dose dependence of prenatal fluoride exposure associations with cognitive performance at school age in three prospective studies. Eur J Public Health. 2023;34(1):143-149. doi:10.1093/eurpub/ckad170
  12. Kampouri M, Zander E, Gustin K, et al. Associations of gestational and childhood exposure to lead, cadmium, and fluoride with cognitive abilities, behavior, and social communication at 4
    years of age: NICE birth cohort study. Environ Res. 2024;263:120123. doi:10.1016/j.envres.2024.120123
  13. Singh, T., Glustin, K, Moshfiqur Rahman, S., Shiraji, S., Tofail, F., Vahter, M., Kampouri, M., Kippler, M. Prenatal and childhood exposure to fluoride and cognitive development: findings from thelongitudinal MINIMat cohort in rural Bangladesh. Env Health Perspect.
  14. Malin AJ, Eckel SP, Hu H, et al. Maternal urinary fluoride and child neurobehavior at age 36 months. JAMA Netw Open. 2024;7(5):e2411987. doi:10.1001/jamanetworkopen.2024.11987
  15. Hefferon R, Goin DE, Sarnat JA, Nigra AE. Regional and racial/ethnic inequalities in public drinking water fluoride concentrations across the US. J Expo Sci Environ Epidemiol. 2024;34(1):68-76. doi:10.1038/s41370-023-00570-w
  16. Liu S, Yu X, Xing Z, Ding P, Cui Y, Liu H. The Impact of Exposure to Iodine and Fluorine in Drinking Water on Thyroid Health and Intelligence in School-Age Children: A Cross-Sectional Investigation. Nutrients. 2024;16(17):2913. doi:10.3390/nu16172913
  17. Goodman CV, Hall M, Green R, et al. Iodine status modifies the association between fluoride exposure in pregnancy and preschool boys’ intelligence. Nutrients. 2022;14(14):2920. doi:10.3390/nu14142920
  18. World Health Organization (WHO)/United Nations Children’s Fund/International Council for the Control of Iodine Deficiency Disorders. Assessment of the Iodine Deficiency Disorders and  Monitoring Their Elimination. A Guide for Programme Managers. 2007.
  19. Kampouri M, Tofail F, Rahman SM, Gustin K, Vahter M, Kippler M. Gestational and childhood urinary iodine concentrations and children’s cognitive function in a longitudinal mother-child cohort in rural Bangladesh. Int J Epidemiol. 2023;52(1):144-155. doi:10.1093/ije/dyac110
  20. National Research Council (NRC). Fluoride in Drinking Water: A Scientific Review of EPA’s Standards.; 2006:467.

This Preprint is online line in the PDF at https://ehp.niehs.nih.gov/doi/10.1289/EHP16269