Maternal folate nutrition and offspring health: evidence and current controversies

Abstract

Periconceptional folic acid (FA) is known to have a protective effect in the prevention of neural tube defects (NTD), leading to global recommendations for FA supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate is essential for C1 metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair and methylation reactions. The evidence reviewed here shows a conclusive role for offspring health of maternal folate nutrition in early pregnancy and probable benefits in later pregnancy. Folate-mediated epigenetic changes in genes related to brain development and function offer a plausible biological basis to link maternal folate with effects in offspring brain, albeit this research is in its infancy. Mandatory FA fortification of food has proven to be highly effective in decreasing NTD cases in populations where it has been implemented, but this policy is controversial owing to concerns related to potential adverse effects of over-exposure to FA. In the absence of population-wide fortification, and given the generally poor compliance with current FA recommendations, optimising folate status of mothers in very early pregnancy for protection against NTD remains challenging. Thus, current policy in the UK, Ireland and elsewhere in Europe for the prevention of NTD (based on periconceptional FA supplementation only), has proven to be largely ineffective. This review addresses the evidence and the controversies that surround this area, as well as identifying the challenges in translating policy into practice.

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

“…Neural tube defect was reported in correlation with gene imprinting (Bai et al, 2014; Wang et al, 2017; Wu et al, 2013). Supplemental intake of formate during pregnancy was suggested as a method of preventing some neural tube defects owing to its function as methyl donor (Caffrey, McNulty, Irwin, Walsh, & Pentieva, 2018; Rochtus, Jansen, Van Geet, & Freson, 2015). Abnormal DNA methylation status in imprinting genes is related to diseases such as Beckwith‐Wiedemann Syndrome (Brzezinski et al, 2017; Chen, 2007; Cui et al, 2001; Sparago et al, 2004).…”

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

“…Low folate status (as defined by various measures including blood folate concentrations, folate intake, and/or FA intake) has been associated with an increased risk of cardiovascular disease, cancers, CAs, CHD, and NTD [5,6,[89][90][91][92][93][94]. Also, this deficiency is clearly detrimental to the embryo and shows possible longer-term risks of diabetes or other health outcomes and health problems associated with child mortality and morbidity [95]. Periconceptional supplementation of FA also reduces the risk of congenital heart diseases (previous ref) and preterm birth and low birth weight [96,97].…”

Plant Kingdom as Source of Vitamins

“…For these reasons, folic acid, a very minor form of natural vitamin B9 which is fully oxidized on the pyrazine ring, has long been considered the best form of administration: it is a single chemical entity, the simplest form (without one-carbon unit and monoglutamoylated), chemically stable, and used as a synthetic derivative without the risk of matrix effect. The Institute od Medicine (1998) has suggested the use of dietary folate equivalents (DFE), where foof folates are considered to be considerably less bioavailable than folic acid: μg DFE ¼ μg food folates + μg folic acid  1,7 1 μg DFE ¼ 1 μg food folate ¼ 0.6 μg folic acid from fortified food or as a supplement consumed with food ¼ 0.5 μg of a folic acid supplement taken on an empty stomach Yet, this assumption is still debated, with numerous papers suggesting higher bioavailability for food folates, while the effectiveness of food fortification with folic acid, which is mandatory in some countries and has been described as "highly effective in decreasing NTD cases in populations where it has been implemented" (Caffrey et al 2018), has recently been more cautiously addressed in a meta-analysis (Centeno Tablante et al 2019).…”