Primary prevention of neural-tube defects and some other major congenital abnormalities: recommendations for the appropriate use of folic acid during pregnancy

A E Czeizel
Paediatric Drugs 2000, 2 (6): 437-49
Neural-tube defects (NTDs) are common and serious congenital abnormalities of the central nervous system. Although some cases of NTDs are induced by hyperhomocysteinaemia, resulting from genetic polymorphism of a thermolabile enzyme, in the majority of cases the cause is unknown. Diet supplementation with a folic acid-containing multivitamin or high dose of folic acid alone in the periconception period reduced the recurrence of NTDs by 83 to 91% and 71%, respectively. Two Hungarian intervention studies demonstrated a high efficacy for periconception multivitamin supplementation (containing a physiological dose: 0.8mg of folic acid) in the primary prevention of the first occurrence of an NTD (approximately 92% reduction in the incidence of NTDs). However, a high dose of folic acid (approximately 6mg) alone during the periconception period was less efficient. Periconception folic acid-containing multivitamin supplementation reduces the occurrence of urinary tract and cardiovascular congenital abnormalities, and congenital limb deficiencies. The occurrence of orofacial cleftings may also be reduced by a high dose of folic acid. This preventive effect may be the result of other mechanisms of action (e.g. compensation of impaired mitosis caused by a folate deficiency). There are 3 options for ensuring appropriate multivitamin/folic acid consumption for women of childbearing age. First, providing a folate- and other vitamin-rich diet, which unfortunately may not be appropriate for this purpose. Second, and perhaps the best choice, the unique opportunity for multivitamin/folic acid supplementation during the periconception period. However, a major proportion of pregnancies are unplanned and, even in planned pregnancies, this type of primary prevention has not been widely used. Furthermore, it would require changes to the previous recommendations since a multivitamin containing a physiological dose of folic acid (0.5 to 0.8mg) seems to be more effective in reducing the occurrence of the first NTD and other congenital abnormalities than folic acid alone. Periconception multivitamin supplementation may also reduce the occurrence of recurrent NTDs. Thirdly, food (e.g. flour, bread) may be fortified with folic acid or 3 B vitamins (folic acid, B 12 and B6). This provides a practical means to ensure all women, especially those from lower socioeconomic backgrounds and/or with a low level of education who are more likely to have unplanned pregnancies, have an adequate folic acid intake.

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