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From the Townsend Letter
April 2016

Prenatal Fluoride and Autism
by John D. MacArthur
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Page 1, 2, 3, 4

51.    Zhang M, Wang AG, He WH, et al. Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons. Toxicology. 2007 Jul 17;236(3):208–216.
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55.    Qian W, Miao K, Li T, Zhang Z. Effect of selenium on fluoride-induced changes in synaptic plasticity in rat hippocampus. Biol Trace Elem Res. 2013 Nov;155(2):253–260.
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58.    Mundy WR, Padilla SJ, Shafer TJ, et al. Building a database of developmental neurotoxicants: evidence from human and animal studies. Society of Toxicology Annual Meeting. Baltimore, MD; March 15–19, 2009. Available at
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59.    National Scientific Council on the Developing Child. Early exposure to toxic substances damages brain architecture: Working Paper No. 4. 2006. Available at Accessed April 22, 2016.
60.    Institute of Medicine. Op cit., 309.
61.    Ibid., 26.
62.    Ibid., 60.
63.    Ibid., 26.
64.    Ibid., 309.
65.    Aminabadi NA, Oskouei SG, Pouralibaba F, Jamali Z, Pakdel F. Enamel defects of human primary dentition as virtual memory of early developmental events. J Dent Res Dent Clin Dent Prospects. 2009 Autumn;3(4):110–116.
66.    Bhat M, Nelson KB. Developmental enamel defects in primary teeth in children with cerebral palsy, mental retardation, or hearing defects: a review. Adv Dent Res. 1989 Sep;3(2):132–142.
67.    Ekanayake L, van der Hoek W. Dental caries and developmental defects of enamel in relation to fluoride levels in drinking water in an arid area of Sri Lanka. Caries Res. 2002 Nov–Dec;36(6):398–404.
68.    Nunn JH, Rugg-Gunn AJ, Ekanayake L, Saparamadu KD. Prevalence of developmental defects of enamel in areas with differing water fluoride levels and socio-economic groups in Sri Lanka and England. Int Dent J. 1994 Apr;44(2):165–173.
69.    Weeks KJ, Milsom KM, Lennon MA. Enamel defects in 4- to 5-year-old children in fluoridated and non-fluoridated parts of Cheshire, UK. Caries Res. 1993;27(4):317–320.
70.    Wong HM, McGrath C, Lo EC, King NM. Association between developmental defects of enamel and different concentrations of fluoride in the public water supply. Caries Res. 2006;40(6):481–486.
71.    Hiller KA, Wilfart G, Schmalz G. Developmental enamel defects in children with different fluoride supplementation – a follow-up study. Caries Res. 1998;32(6):405–411.
72.    European Food Safety Authority. Scientific opinion on Dietary Reference Values for fluoride. EFSA J. 2013;11(8):3332:11. Available at Accessed April 22, 2016.
73.    Shi J, Dai G, Zhang Z. Relationship between bone fluoride content, pathological change in bone of aborted fetuses and maternal fluoride level. Zhonghua Yu Fang Yi Xue Za Zhi. 1995 Mar;29(2):103–105.
74.    British Fluoridation Society. Dental fluorosis. In: One in a Million [online report]. March 2012. Accessed April 22, 2016.
75.    Choi AL, Zhang Y, Sun G, et al. Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study. Neurotoxicol Teratol. 2015 Jan–Feb;47:96–101.
76.    Grandjean P. Mottled fluoride debate [online article]. Chemical Brain Drain. December 17, 2014. Accessed April 22, 2016.
77.    Everett ET. Fluoride's effects on the formation of teeth and bones, and the influence of genetics. J Dent Res. 2011 May;90(5):552–560.
78.    Zhang S, Zhang X, Liu H, et al. Modifying effect of COMT gene polymorphism and a predictive role for proteomics analysis in children's intelligence in endemic fluorosis area in Tianjin, China. Toxicol Sci. 2015 Apr;144(2):238–245.
79.    Kaushik G, Thomas MA, Aho KA. Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network. BMC Bioinformatics. 2015;16 Suppl 7:S3.
80.    Harrington RA, Lee LC, Crum RM, Zimmerman AW, Hertz-Picciotto I. Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy. Autism Res. 2013 Jun;6(3):149–168.
81.    McGinnis WR, Audhya T, Edelson SM. Proposed toxic and hypoxic impairment of a brainstem locus in autism. Int J Environ Res Public Health. 2013 Dec; 10(12):6955–7000.
82.    Kupelian D. Top Doc: media bias on antidepressants astounding [online article]. WND. August 1, 2014. Accessed April 22, 2016.
83.    Raillant-Clark W. Taking antidepressants during pregnancy increases risk of autism by 87% [online article]. Université de Montréal. December 14, 2005. Accessed April 22, 2016; Boukhris T, Sheehy O, Mottron L, Bérard A. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatrics. 2015 Dec 14:1–8.
84.    Whyte MP, Totty WG, Lim VT, Whitford GM. Skeletal fluorosis from instant tea. J Bone Miner Res. 2008 May;23(5):759–769.
85.    Toh S, Mitchell AA, Louik C, Werler MM, Chambers CD, Hernández-Díaz S. Selective serotonin reuptake inhibitor use and risk of gestational hypertension. Am J Psychiatry. 2009 Mar; 166(3):320–328.
86.    Mann JR, McDermott S, Bao H, Hardin J, Gregg A. Pre-eclampsia, birth weight, and autism spectrum disorders. J Autism Dev Disord. 2010 May;40(5):548–554.
87.    Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr. 2015 Feb;169(2):154–162.
88.    MacArthur JD. Placental fluorosis: fluoride and preeclampsia. Townsend Lett. 2015;382:74–79.
89.    Fujita E, Dai H, Tanabe Y, et al. Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1. Cell Death Dis. 2010 Jun;1(6):e47.
90.    Fujita-Jimbo E, Tanabe Y, Yu Z, et al. The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis. Mol Autism. 2015;6:17.
91.    MacArthur JD. Fluoride and preterm birth. Townsend Lett. 2013;364:84-94. Available at: Accessed April 22, 2016.
92.    Hwang YS, Weng SF, Cho CY, Tsai WH. Higher prevalence of autism in Taiwanese children born prematurely: a nationwide population-based study. Res Dev Disabil. 2013 Sep;34(9):2462–2468.
93.    Singh GK, Kenney MK, Ghandour RM, Kogan MD, Lu MC. Mental health outcomes in US children and adolescents born prematurely or with low birthweight. Depress Res Treat. 2013;2013:570743.
94.    Neergaard L. Study: bacteria live even in healthy placentas [online article]. WTOP. May 24, 2014. Accessed April 22, 2016; Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra265.
95.    Dunlop AL, Mulle JG, Ferranti EP, Edwards S, Dunn AB, Corwin EJ. Maternal microbiome and pregnancy outcomes that impact infant health: a review. Adv Neonatal Care. 2015 Dec;15(6):377–385.
96.    Parents of Fluoride-Poisoned Children (PFPC). Fluoride and developmental neurotoxicity. Comments submitted to the National Toxicology Program Board of Scientific Counselors. January 8, 2016. Available at Accessed April 22, 2016.
97.    Andersen SL, Olsen J, Laurberg P. Fetal programming by maternal thyroid disease. Clin Endocrinol (Oxf). 2015;83(6):751–758.
98.    Klein RZ, Sargent JD, Larsen PR, Waisbren SE, Haddow JE, Mitchell ML. Relation of severity of maternal hypothyroidism to cognitive development of offspring. J Med Screen. 2001;8:18–20.
99.    Peckham S, Lowery D, Spencer S. Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water. J Epidemiol Community Health. 2015;0:1–6.
100.  National Research Council. Op cit., 236.
101.  Malin AJ, Till C. Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association. Environ Health. 2015;14:17.
102.  Sauerheber R. Physiologic conditions affect toxicity of ingested industrial fluoride. J Environ Public Health. 2013;2013:439490; Overview of Fluoride Poisoning. Merck Manual. December 2013. Available at Accessed April 22, 2016.
103.  MacArthur JD. Overdosed: fluoride, copper, and Alzheimer's disease. Townsend Lett. 2013;363:63–70. Available at Accessed April 22, 2016.
104.  Bjorklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp (Wars). 2013;73(2):225–236.
105.  Vela G, Stark P, Socha M, Sauer AK, Hagmeyer S, Grabrucker AM. Zinc in gut-brain interaction in autism and neurological disorders. Neural Plast. 2015;2015:972791.
106.  US Food and Drug Administration. Summary of proposed rule on pregnancy and lactation labeling. Federal Register. 2008 May29;73(104):30834. Available at Accessed April 22, 2016.
107.  Institute of Medicine. Op cit., 304.
108.  US Centers for Disease Control and Prevention. Recommendations for using fluoride to prevent and control dental caries in the United States. Morbid Mortal Rep. August 17, 2001;50(14);3. Table 4 (footnote). Available at Accessed April 22, 2016.
109.  Iheozor-Ejiofor Z, Worthington HV, Walsh T, et al. Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev. 2015;6. Art. No.: CD010856. Available at Accessed April 22, 2016.
110.  National Research Council. Op cit., 203, 222.
111.  Brambilla E, Felloni A, Gagliani M, Malerba A, García-Godoy F, Strohmenger L. Caries prevention during pregnancy: results of a 30-month study. J Am Dent Assoc. 1998 Jul;129(7):871–877.
112.  National Toxicology Program. Proposed NTP evaluation on fluoride exposure and potential for developmental neurobehavioral effects. Office of Health Assessment and Translation (OHAT). November 19, 2015. Available at Accessed April 22, 2016.

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The Townsend Letter has published five other reports by John D. MacArthur: "Placental Fluorosis: Fluoride and Preeclampsia" (May 2015); "Fluoride and Preterm Birth" (November 2013); "Too Much Copper, Too Little Zinc, and Cognitive Deterioration in Alzheimer's Disease" (with George J. Brewer, MD) and "Overdosed: Fluoride, Copper, and Alzheimer's Disease" (October 2013); "Cell Phones and the Brain" (July 2002). 

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