title: Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study.
abstract: 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-IV) 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-IV 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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. Electronic address: achoi@hsph.harvard.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Choi
authors.affiliation: School of Stomatology, China Medical University, Shenyang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Public Health, China Medical University, Shenyang, China.
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Department of Neurology, Children's Hospital, Boston, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Bellinger
authors.affiliation: Mianning Center for Disease Control and Prevention, Xichang, Sichuan, China.
authors.forename: Kanglin
authors.initials: K
authors.lastname: Wang
authors.affiliation: Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, China.
authors.forename: Xiao Jing
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, China.
authors.forename: Jin Shu
authors.initials: JS
authors.lastname: Li
authors.affiliation: School of Public Health, China Medical University, Shenyang, China.
authors.forename: Quanmei
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Center for Disease Control and Prevention of Liangshan Perfecture, Xichang, Sichuan, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
mesh_terms: D002648:Child; D002681:China / Q000453:epidemiology; D003072:Cognition Disorders / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005458:Fluoride Poisoning / Q000150:complications* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D012044:Regression Analysis; D012189:Retrospective Studies
keywords: Children; Confounding; Fluoride; Fluorosis; Neuropsychological measures; Prenatal exposure delayed effects