- Click here for explanation of classification scheme.

 

 

 

To examine the evidence for an association between water fluoride level and Down's Syndrome.

 

All study designs which compared the incidence of Down's Syndrome in populations with different levels of fluoride, either artificially added or naturally occurring, in their water supplies were included in this review.

Not applicable

Recruitment

 

25 specialist databases were searched by a qualified librarian, including Medline, Embase, Toxline and the Current Contents (Science Citation Index) from database inception to February 2000. In addition, hand searching of Index Medicus (1945–1959) and Excerpta Medica (1955–1973) was undertaken. Additional references were sought from individuals and organizations through a dedicated web site for this review [http:// www.york.ac.uk/inst/crd/fluoride.htm] and through members of a specifically designated advisory panel. Published and unpublished studies in any language were included.

Design

Systematic Review

 

Blinding used 

Not applicable

 

Intervention

Not applicable

 

Statistical Analysis

The study results are based on narrative synthesis and no raw data is available to make adjustments of the measures. Relative risk was calculated with 95% confidence intervals. 

Timing of Measurements

Not applicable

Dependent Variables

Incidence of Down's Syndrome

Independent Variables

Water Fluoride

Control Variables

• Maternal age
• Race
• Minerals in water.

• Initial N: 25
• Attrition (final N): Six
• Age: Not applicable
• Ethnicity: Not applicable
• Other relevant demographics: Not applicable
• Anthropometrics: Not applicable
• Location: Five studies of US populations, one of UK population.

 

• 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
• Other factors which could have led to misleading study results include selection of study areas, ascertainment of cases, population selected for the denominator, migration,classification of exposure and blinding of investigators to the fluoridation status of cases. If study areas are not selected at random there is a possibility that selection may be biased, for example, a fluoridated area with a relatively high incidence of Down's Syndrome (possibly for reasons other than fluoride concentration of the water) and a non-fluoridated area with a relative low incidence may be selected which would result in biased results.

Association of Down's Syndrome with water fluoride level

Author (Year)	Crude relative risk	Confounding factors discussed in study	Controlled for	Validity score
Erickson (1976)	1.16(P>0.05) 0.96 (P>0.05)	Maternal age, race	Yes	3.5
Erickson (1980)	0.93 (0.7, 1.2)	Maternal age, race	Yes	3.5
Needleman (1974)	1.14	Maternal age	No	2.0
Rapaport (1957)	2.3 (P<0.01) 2.9 (P<0.01) 2.4 (P<0.05)	Maternal age	No	2.0
Rapaport (1963)	3.0 (P<0.001)	Maternal age, minerals in water	No	2.0
Berry (1958)	0.84-1.48	None	No	1.0

• The evidence of an association between water fluoride level and Down's Syndrome incidence is inconclusive. However, the quality of the studies included in the review was relatively low and further high-quality research is needed.
• Future studies investigating the association of Down's Syndrome with water fluoride levels should measure individual exposure to water fluoride and control appropriately for confounding factors, especially maternal age, incidence of termination of pregnancies in which the child is diagnosed with Down's Syndrome and exposure to other sources of fluoride
• Study areas should be chosen at random and investigators should be blinded to the fluoridation status of mothers when identifying cases
• The denominator selected to measure the risk of a Down's Syndrome birth should relate to the total number of births, not to the overall population of the study area
• Case ascertainment should be as complete as possible and should be identical in all populations studies
• The major weakness of these studies was the failure to control sufficiently for confounding factors. All six studies used study designs that measured population rather than individual exposure to fluoridated water and because of this are particularly susceptible to confounding.

 

University/Hospital:

NHS Centre for Reviews and Dissemination, University of York, York, Y010 5DD, England

• This review is based on qualitative narrative research
• This systematic review includes both published and unpublished results and it includes 20-year-old studies and the results may not be relevant to the present context
• A systematic review should also include number of subjects involved in each study and the exposure time of mother to fluoride levels and other outcomes along with the number of births and abnormalities
• There is no analysis relevant to the fluoride levels and urine levels of the subjects and its association with Down's Syndrome
• It is not clear whether the studies are distributed based on the high fluoride areas geographically vs. low levels of fluoride
• Also search terms are very important to do systematic reviews 
• No significant analysis was reported and confounding factors and other factors influencing the outcomes were not adjusted to the relative risk
• Further strong research reviews with appropriate methodology is required.