The evidence that folates reduce the risk of neural tube defects (NTDs) is so compelling that supplementation has been recommended by every relevant authority. The Cochrane Database of Systematic Reviews has determined that folate supplementation should be rated as a Grade 1 recommendation. United States Preventive Health Services Task Force, the US Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) have all produced clear guidelines for such

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... tion. Unfortunately, despite food fortification and targeted public health campaigns promoting folic acid supplementation, periconceptional utilization of folic acid supplements has decreased in the US in recent years. Worldwide, over 300,000 newborns are affected with NTDs every year. NTDs account for 10% of all neonatal mortality. This article will review the risk factors for NTDs and the evidence supporting folate supplementation. It will also describe the remaining problems and outline current ideas to solve them. Finally, new evidence of the effectiveness of adding metafolin to drospirenone-containing oral contraceptives in raising serum and red blood cell folate levels, the rationale for making such an addition, and an estimate of the magnitude of the contribution use of such pills might have on reducing NTDs will be discussed.