[Folic acid and prevention of neural tube closure defects: the question is not solved yet]

Abstract

Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.