The Role of Folic Acid Fortification in Neural Tube Defects: A Review

Abstract

The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past 30 years, but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a significant portion of NTDs still persists. Population data suggest that women of childbearing age may not yet be adequately targeted, while the general population may be overfortified with folic acid. While an excessive folate intake may be associated with adverse effects, there remains uncertainty about the minimum effective folate intake and status required for NTD prevention, and the safe upper folate level. Besides folate, several other lifestyle and environmental factors as well as genetic variations may influence NTD development, possibly by affecting one-carbon metabolism and thus epigenetic events. In conclusion, mandatory folic acid fortification plays a significant part in the reduction of NTD prevalence, but possibly at a cost and with a portion of NTDs remaining. More effective preventive strategies require better understanding of the etiology of this group of birth defects.

Solar activity at birth predicted infant survival and women's fertility in historical Norway

“…Folate is needed for DNA synthesis and for the maintenance of the epigenome [39] and is thus essential for the development of healthy and fecund individuals during gestation [13]. Folate deficiency during pregnancy is associated with higher morbidity and mortality (reviewed in [40]), and hence, increased folate degradation in solar maximum periods could result in folate deficiency in pregnant women and, consequently, fetal loss [19,20] as well as reduced subsequent survival of children [13]. Another candidate explanation may be the selection for specific genotypes associated with folate loss and vitamin D biosynthesis at the time of conception or early pregnancy in relation to solar activity.…”

Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography

“…Although introduction of folic acid fortification has led to a significant reduction of NTDs, this inborn disease still persists and the etiology is largely unknown [3]. Despite numerous studies on neurulation in various animal models, the developmental perturbations that induce mammalian NTDs remain poorly defined [4,5], limiting progress in formulating strategies to prevent human NTDs [6].…”

Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus

“…Maternal deficiencies in folate and choline during pregnancy have been associated with increased risk for neural tube defects (NTDs) [17–19]. Likewise, folate supplementation of maternal diet, via the fortification of foods or prenatal vitamins, has been associated with nearly a 30% decreased risk for NTDs [20–23].…”