Down syndrome (DS) birth rates (BR) as a function of maternal age exhibit a relatively flat linear regression line for younger mothers and a fairly steep one for older mothers with the second line intersecting the first line a little above maternal age 30. Consequently, overall DS- BR for all maternal ages are not a very reliable parameter for detecting environmental influences, since they may be strongly affected by the ratio of the number of younger to older mothers. For this reason, data for mothers under age 30 were selected to detect an association between water fluoridation and DS for which the lower maternal age regression would be a much smaller contributing factor.

The early research of I Rappaport indicating a link between fluoride in drinking water and Down syndrome was followed by studies claiming there was no such association. Application of sound methodology to the data in those later investigations shows that none of the criticisms against Rapaport's work are valid. For example, in the data of JD Erickson on maternal age-specific DS births in Metropolitan Atlanta, Georgia, when the three youngest maternal age subgroups are reasonably combined into single groups for areas with and without water fluoridation, a highly significant association (P <0.005) os revealed between fluoridated water and DS births.

It also appears that the dose-response line(DRL) DS-BR for daily fuoride intake may have no allowable level that does not induce fluoride-linked DS births. Therefore fluoride may be one of the major causes of DS other than aging of mothers. The number of excess DS births due to water fluoridation is estimated to be several thousand cases annually throughout the world.