Epigenetic mechanisms of fetal programming in excessive intake of synthetic folates at the preconception stage

Abstract

To date, there is no doubt that taking folic acid at the perigravid stage in an adequate dosage has a positive effect on fetal development and the course and outcome of pregnancy. There is extensive evidence that during pregnancy, folate deficiency is associated with spontaneous miscarriages, premature birth, and premature detachment of the normally positioned placenta, and it can cause intrauterine malformations of the nervous and cardiovascular systems of the fetus. Understanding the need to reduce such severe complications, which have both medical and social significance, has contributed in a number of countries to the introduction of programs for food fortification and routine prescribing of folic acid preparations to pregnant women. The measures taken significantly reduced the incidence of fetal congenital malformations, but at the same time, this strategy had a negative effect, resulting in a chronic overdose of synthetic folic acid. Recent studies have shown that the accumulation of non-metabolized folic acid in a pregnant woman may be associated with obstetric pathology and impaired development of fetuses and newborns. There is growing evidence that prolonged folic acid overdose during pregnancy, especially in the presence of altered levels of other vitamins, may lead to such diseases in children as autism and multiple amyotrophic sclerosis. Thus, this issue requires in-depth study in order to move from the routine prescription of folic acid preparations to personalized nutritional support for women at the preconception stage and during pregnancy.