title: Association of Down's syndrome and water fluoride level: a systematic review of the evidence.
abstract: BACKGROUND
  A review of the safety and efficacy of drinking water fluoridation was commissioned by the UK Department of Health to investigate whether the evidence supported a beneficial effect of water fluoridation and whether there was any evidence of adverse effects. Down's syndrome was one of the adverse effects reported. The aim of this review is to examine the evidence for an association between water fluoride level and Down's syndrome.
  
  
  METHODS
  A systematic review of research. Studies were identified through a comprehensive literature search, scanning citations and online requests for papers. Studies in all languages which investigated the incidence of Down's syndrome in areas with different levels of fluoride in their water supplies were included. Study inclusion and quality was assessed independently by 2 reviewers. A qualitative analysis was conducted.
  
  
  RESULTS
  Six studies were included. All were ecological in design and scored poorly on the validity assessment. The estimates of the crude relative risk ranged from 0.84 to 3.0. Four studies showed no significant associations between the incidence of Down's syndrome and water fluoride level and two studies by the same author found a significant (p < 0.05) positive association (increased Down's syndrome incidence with increased water fluoride level). Only two of the studies controlled for confounding factors and only one of these presented summary outcome measures.
  
  
  CONCLUSIONS
  The evidence of an association between water fluoride level and Down's syndrome incidence is inconclusive.
authors.affiliation: NHS Centre for Reviews and Dissemination, University of York, York, Y010 5DD, England.
authors.forename: P
authors.initials: P
authors.lastname: Whiting
authors.forename: M
authors.initials: M
authors.lastname: MacDonagh
authors.forename: J
authors.initials: J
authors.lastname: Kleijnen
mesh_terms: D003257:Consumer Product Safety; D004314:Down Syndrome / Q000139:chemically induced / Q000453:epidemiology*; D005457:Fluoridation / Q000009:adverse effects*; D006801:Humans; D011635:Public Health Administration; D015203:Reproducibility of Results; D012307:Risk Factors; D014881:Water Supply / Q000592:standards