title: Developmental fluoride neurotoxicity: a systematic review and meta-analysis.
abstract: BACKGROUND
  Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children's neurodevelopment.
  
  
  OBJECTIVE
  We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.
  
  
  METHODS
  We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg's funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.
  
  
  RESULTS
  The standardized weighted mean difference in IQ score between exposed and reference populations was -0.45 (95% confidence interval: -0.56, -0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.
  
  
  CONCLUSIONS
  The results support the possibility of an adverse effect of high fluoride exposure on children's neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.
authors: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA. achoi@hsph.harvard.edu
authors: Anna L
authors: AL
authors: Choi
authors: Guifan
authors: G
authors: Sun
authors: Ying
authors: Y
authors: Zhang
authors: Philippe
authors: P
authors: Grandjean
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000453:epidemiology; D060766:Drinking Water / Q000737:chemistry*; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005459:Fluorides / Q000633:toxicity*; D006801:Humans; D007361:Intelligence Tests; D008954:Models, Biological; D020258:Neurotoxicity Syndromes / Q000453:epidemiology / Q000209:etiology*
chemical_list: D060766:Drinking Water; D005459:Fluorides