Fluoride Action Network

Abstract

Background

Previous studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California.

Methods

Archived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n = 48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women’s addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection.

Results

Fluoride concentrations in the community water supplies ranged from 0.02 to 1.00 mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7 mg/L), as compared with communities with less than 0.7 mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1 mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B = 0.052, 95% CI:0.019,0.085), MUFSG (B = 0.028, 95% CI: -0.006, 0.062), MSF (B = 0.001, 95% CI: 0.000, 0.003) and AFF (B = 0.001, 95% CI: 0.000, 0.002).

Conclusions

We found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.

Peer Review reports

 

Excerpt:

Introduction

In the United States (US), water and water-based beverages contribute to approximately 75% of the total fluoride intake among adults living in communities that fluoridate their water supply [1]. The most recent estimates posted by the US Centers for Disease Control and Prevention (CDC), are that nearly three-fourths of the U.S. population with access to community water systems receive water adjusted to the federally recommended concentration of 0.7 mg/L fluoride (https://www.cdc.gov/fluoridation/statistics/2016stats.htm). This concentration of community water fluoridation in the US is higher than in Canada, where approximately one-third of Canadian communities fluoridate their water supply, and Europe, where only 3% of Europeans have fluoridated water [2, 3]. Recent studies of the potential effects of fluoride on neurodevelopment from prenatal exposures [4,5,6,7,8], and the onset of puberty in boys [6], suggest the need to evaluate fluoride concentrations in communities in the US and their relationship to fluoride concentrations in pregnant women.

Enamel fluorosis, which is a bioindicator for systemic fluoride exposure during times of tooth enamel formation, has been increasing in the US. In 1986–1987, 22.6% of adolescents aged 12–15 were reported to have dental fluorosis, and this increased to 40.7% in 1999–2004 [9]. In adolescents aged 16 and 17 years, fluorosis prevalence was reported to have again increased by 31.6% in 2012–2011, as compared with concentrations in 2002–2001 [10]. The purported increase in enamel fluorosis has led to concerns that overall systemic fluoride exposure is increasing, and in 2015 the CDC recommended concentrations for fluoride in drinking water be reduced from 1 mg/L fluoride to 0.7 mg/L fluoride [11]. However, the US Environmental Protection Agency has continued to allow fluoride concentrations of up to 4 mg/L in drinking water (https://www.epa.gov/ground-water-and-drinking-water/national-primary-drinking-water-regulations).

There are no contemporary measurements of systemic fluoride in adult humans in the United States, and no evaluation of their relationship to water fluoridation. Additionally, there are no contemporary studies of fluoride concentrations in pregnant women in fluoridated communities in the US, nor in fetal related tissues, despite recent concerns about effects on neurodevelopment.

To address this, we measured fluoride concentrations in urine, serum and amniotic fluid of second trimester pregnant women in Northern California. We used publicly available information on fluoride concentrations in their water systems to evaluate the relationship between reported fluoride concentrations and biomonitoring measurements, to assess the contribution of water fluoridation to measured fluoride concentrations in biological samples.

… Fig. 1

figure1

Map of the location of pregnant women participants and the community water fluoridation concentrations. Note: One participant lived in Montana at the time of sample collection but was excluded from this map for clarity

References

  1. U.S. EPA. Fluoride: relative source contribution analysis: US Environmental Protection Agency; 2010. 820-R-10-015. https://www.epa.gov/sites/production/files/2019-03/documents/fluoride-exposure-relative-report.pdf..

  2. Canada PHAo: The State of Community Water Fluoridation across Canada. In.; 2017.
    Google Scholar

  3. Till C, Green R, Grundy JG, Hornung R, Neufeld R, Martinez-Mier EA, Ayotte P, Muckle G, Lanphear B. Community water fluoridation and urinary fluoride concentrations in a National Sample of pregnant women in Canada. Environ Health Perspect. 2018;126(10):107001.

  4. Bashash M, Marchand M, Hu H, Till C, Martinez-Mier EA, Sanchez BN, Basu N, Peterson KE, Green R, Schnaas L, et al. Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12years of age in Mexico City. Environ Int. 2018;121(Pt 1):658–66.

  5. Bashash M, Thomas D, Hu H, Martinez-Mier EA, Sanchez BN, Basu N, Peterson KE, Ettinger AS, Wright R, Zhang Z, et al. Prenatal fluoride exposure and cognitive outcomes in children at 4 and 6-12 years of age in Mexico. Environ Health Perspect. 2017;125(9):097017.

  6. Liu Y, Tellez-Rojo M, Hu H, Sanchez BN, Martinez-Mier EA, Basu N, Mercado-Garcia A, Solano-Gonzalez M, Peterson KE. Fluoride exposure and pubertal development in children living in Mexico City. Environ Health. 2019;18(1):26.

  7. Ding Y. YanhuiGao, sun H, Han H, Wang W, Ji X, Liu X, Sun D: The relationships between low levels of urine fluoride on children’s intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China. J Hazard Mater. 2011;186(2–3):1942–6.

  8. Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, Ayotte P, Muckle G, Till C. Association between maternal fluoride exposure during pregnancy and IQ scores in offspring in Canada. JAMA Pediatr. 2019;173:940.

  9. Beltran-Aguilar ED, Barker L, Dye BA. Prevalence and severity of dental fluorosis in the United States, 1999-2004. NCHS Data Brief. 2010;(53):1–8.

  10. Wiener RC, Shen C, Findley P, Tan X, Sambamoorthi U. Dental fluorosis over time: a comparison of National Health and nutrition examination survey data from 2001-2002 and 2011-2012. J Dent Hyg. 2018;92(1):23–9.

  11. Health USDo. Human Services Federal Panel on Community Water F: U.S. Public Health Service Recommendation for Fluoride Concentration in Drinking Water for the Prevention of Dental Caries. Public Health Rep (Washington, DC : 1974). 2015;130(4):318–31.

  12. Taves DR. Determination of submicromolar concentrations of fluoride in biological samples. Talanta. 1968;15(10):1015–23.

  13. Cone EJ, Caplan YH, Moser F, Robert T, Shelby MK, Black DL. Normalization of urinary drug concentrations with specific gravity and creatinine. J Anal Toxicol. 2009;33(1):1–7.

  14. Husdan H, Vogl R, Oreopoulos D, Gryfe C, Rapoport A. Serum ionic fluoride: normal range and relationship to age and sex. Clin Chem. 1976;22(11):1884–8.

  15. Torra M, Rodamilans M, Corbella J. Serum and urine ionic fluoride: normal range in a nonexposed population. Biol Trace Elem Res. 1998;63(1):67–71.

  16. Yadav AK, Kaushik CP, Haritash AK, Singh B, Raghuvanshi SP, Kansal A. Determination of exposure and probable ingestion of fluoride through tea, toothpaste, tobacco and pan masala. J Hazard Mater. 2007;142(1–2):77–80.

  17. Going RE, Hsu SC, Pollack RL, Haugh LD. Sugar and fluoride content of various forms of tobacco. J Am Dent Assoc. 1980;100(1):27–33.

  18. Del Carmen AF, Javier FH, Aline CC. Dental fluorosis, fluoride in urine, and nutritional status in adolescent students living in the rural areas of Guanajuato, Mexico. J Int Soc Prev Community Dent. 2016;6(6):517–22.

  19. Jain RB. Observed differentials in the levels of selected environmental contaminants among Mexican and other Hispanic American children, adolescents, adults, and senior citizens. Environ Sci Pollut Res Int. 2018;25(5):4524–43.

  20. Zipkin I, Likins RC, McClure FJ, Steere AC. Urinary fluoride levels associated with use of fluoridated waters. Public Health Rep. 1956;71(8):767–72.

  21. Sorahan T, Pang D, Esmen N, Sadhra S. Urinary concentrations of toxic substances: an assessment of alternative approaches to adjusting for specific gravity. J Occup Environ Hyg. 2008;5(11):721–3.

  22. Vij HS, Howell S. Improving the specific gravity adjustment method for assessing urinary concentrations of toxic substances. Am Ind Hyg Assoc J. 1998;59(6):375–80.

  23. Smith FA, Gardner DE, Hodge HC. Investigations on the metabolism of fluoride. II. Fluoride content of blood and urine as a function of the fluorine in drinking water. J Dent Res. 1950;29(5):596–600.

  24. Lewis DW, Banting DW. Water fluoridation: current effectiveness and dental fluorosis. Community Dent Oral Epidemiol. 1994;22(3):153–8.

  25. Whitford GM. Intake and metabolism of fluoride. Adv Dent Res. 1994;8(1):5–14.

  26. Malin AJ, Lesseur C, Busgang SA, Curtin P, Wright RO, Sanders AP. Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013-2016. Environ Int. 2019;132:105012.

  27. Spak CJ, Berg U, Ekstrand J. Renal clearance of fluoride in children and adolescents. Pediatrics. 1985;75(3):575–9.

  28. Taves DR. Normal human serum fluoride concentrations. Nature. 1966;211(5045):192–3.

  29. Ron M, Singer L, Menczel J, Kidroni G. Fluoride concentration in amniotic fluid and fetal cord and maternal plasma. Eur J Obstet Gynecol Reprod Biol. 1986;21(4):213–8.

  30. Armstrong WD, Singer L, Makowski EL. Placental transfer of fluoride and calcium. Am J Obstet Gynecol. 1970;107(3):432–4.

  31. Shen YW, Taves DR. Fluoride concentrations in the human placenta and maternal and cord blood. Am J Obstet Gynecol. 1974;119(2):205–7.

  32. Gedalia I, Brzezinski A, Zukerman H, Mayersdorf A. Placental transfer of fluoride in the human fetus at low and high F-intake. J Dent Res. 1964;43:669–71.

  33. Gedalia I, Shapira L. Effect of prenatal and postnatal fluoride on the human deciduous dentition. A literature review. Adv Dent Res. 1989;3(2):168–76.

  34. Gupta S, Seth AK, Gupta A, Gavane AG. Transplacental passage of fluorides. J Pediatr. 1993;123(1):139–41.

  35. Gessner BD, Beller M, Middaugh JP, Whitford GM. Acute fluoride poisoning from a public water system. N Engl J Med. 1994;330(2):95–9.

  36. Wilde JJ, Petersen JR, Niswander L. Genetic, epigenetic, and environmental contributions to neural tube closure. Annu Rev Genet. 2014;48(1):583–611.

  37. Chau KF, Springel MW, Broadbelt KG, Park HY, Topal S, Lun MP, Mullan H, Maynard T, Steen H, LaMantia AS, et al. Progressive differentiation and instructive capacities of amniotic fluid and cerebrospinal fluid proteomes following neural tube closure. Dev Cell. 2015;35(6):789–802.

  38. Fini JB, Mughal BB, Le Mevel S, Leemans M, Lettmann M, Spirhanzlova P, Affaticati P, Jenett A, Demeneix BA. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos. Sci Rep. 2017;7:43786.

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Acknowledgements

Not applicable.

Funding

This work was supported by NIH P01ES022841, US EPA RD 83543301, and the Center for Children’s Oral Health Research (UCSF).