ABSTRACT
I. Introduction .................................................................................................. 180 II. Recommendations to Prevent Neural Tube Defects ..................................... 181
A. United States ............................................................................................ 181 1. Centers for Disease Control and Prevention...... .................................. 181 2. United States Public Health Service .................................................... 181 3. Institute of Medicine......... .................................................................... 181
B. Canada, Central America, and Chile ....................................................... 182 C. Australia, New Zealand, United Kingdom, Ireland,
and the Netherlands.............................................................................................182 III. Forti cation .................................................................................................. 182
A. Food Vehicles That Can Be Forti ed ...................................................... 183 B. Recommendations to Determine the Level
of Folic Acid Added to Flour ................................................................... 183 C. Cost and Cost-Effectiveness of Establishing a Program ......................... 183 D. Establishment of New Programs ............................................................. 184
IV. Current Forti cation Policies and Forti cation Levels ................................ 184 A. Mandatory Forti cation Policies ............................................................. 184
1. United States ........................................................................................ 184 2. Canada ................................................................................................. 185 3. Chile...................................................................................................... 185 4. Other Countries ................................................................................... 185
B. Voluntary Forti cation Policies ............................................................... 185 V. The Effect of Forti cation Programs ........................................................... 186
A. Reduction of Birth Prevalence Rates of Neural Tube Defects ................. 186 1. United States ........................................................................................ 186 2. Canada ................................................................................................ 187
3. Chile...................................................................................................... 187 4. Summary ............................................................................................. 188
B. Increased Blood Folate Concentrations Postforti cation ........................ 188 1. United States ........................................................................................ 188 2. Canada, Chile, and Costa Rica ............................................................ 193 3. Summary ............................................................................................. 195
C. Increased Dietary Intake of Folic Acid from Forti cation ...................... 195 D. Limitations of Studies of the Effects of Folic Acid Forti cation ........... 195
VI. Minimum Effective Blood Folate Concentration for Neural Tube Defect Prevention ......................................................................................... 197
VII. Other Potential Effects Associated with Folic Acid Forti cation ................ 197 VIII. Summary ..................................................................................................... 198 Acknowledgments ......................................................................................... 199
References ..................................................................................................... 199
It became widely accepted in the early 1990s that adequate maternal consumption of folic acid before pregnancy and during the early weeks of gestation could prevent most, but not all, neural tube defects (NTDs). This acceptance resulted from the early stopping of both the British Medical Research Council (MRC) [1] and Hungarian [2] randomized controlled trials (RCTs) of vitamins to prevent NTDs in 1991 and 1992, respectively (see Section II, Recommendations to Prevent NTDs). In 1991, the Centers for Disease Control and Prevention (CDC) recommended that all women with a history of a previous NTD-affected pregnancy should consume 4,000 µg of folic acid daily to prevent the recurrence of an NTD-affected pregnancy [3]. In 1992, the US Public Health Service (USPHS) recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent the rst occurrence of an NTD-affected pregnancy [4]. In 1998, a similar recommendation from the Institute of Medicine (IOM) stated that women capable of becoming pregnant should consume 400 µg of folic acid daily from forti ed foods, supplements, or both, in addition to consuming food folate from a varied diet [5].
