Maternal Folic Acid Supplementation during Pregnancy and Childhood Allergic Disease Outcomes: A Question of Timing?

Abstract

Abstract:Since the early 1990s, maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy, to reduce the risk of infant neural tube defects. In addition, many countries have also implemented the folic acid fortification of staple foods, in order to promote sufficient intakes amongst women of a childbearing age, based on concerns surrounding variable dietary and supplementation practices. As many women continue to take folic acid supplements beyond the recommended first trimester, there has been an overall increase in folate intakes, particularly in countries with mandatory fortification. This has raised questions on the consequences for the developing fetus, given that folic acid, a methyl donor, has the potential to epigenetically modify gene expression. In animal studies, folic acid has been shown to promote an allergic phenotype in the offspring, through changes in DNA methylation. Human population studies have also described associations between folate status in pregnancy and the risk of subsequent childhood allergic disease. In this review, we address the question of whether ongoing maternal folic acid supplementation after neural tube closure, could be contributing to the rise in early life allergic diseases.

Dietary Folate Intake and Folic Acid Supplements among Pregnant Women from Southern Italy: Evidence from the “Mamma & Bambino” Cohort

“…It has been clearly demonstrated that low maternal folate intake during the periconceptional period increases the risk for neural tube defect (e.g., spina bifida, anencephaly) and perhaps for other congenital anomalies (e.g., congenital heart defects, oral cleft lip and plate) and adverse outcomes [17]. In our study, for instance, we reported higher proportions of SGA and LGA births among women with inadequate folate intake compared with those who met dietary recommendation.…”

“…Beyond folate intake, supplementation of folic acid during the periconceptional period represents one of the best strategies to tackle pregnancy adverse outcomes, as suggested by the WHO in 2006 [17]. However, the prevalence of folic acid supplementation remains often inadequate in several countries [20,68].…”

“…Subsequently, several countries promoted policies for folate fortification [16]. Nowadays, developed countries proposed folic acid supplementation as a strategy to ensure the correct fetal growth [17]. However, several lines of evidence showed that folic acid supplementation was often insufficient in the preconception period, with several negative effects on pregnancy and neonatal outcomes [18].…”

Impact of Micronutrient Status during Pregnancy on Early Nutrition Programming

“…While this is likely to be multifactorial, there has been interest in the role of specific nutrients, such as the changes in vitamin D, folate and n-3 PUFA status based on the documented immunomodulatory properties of these nutrients, as discussed in detail elsewhere [59,60]. Although there are no specific recommendations for allergy prevention with regard to specific nutrients at this stage, there is the need for a better understanding of nutritional programming of immune health, nutritional epigenetics and other biological processes sensitive to nutritional ex- posures in early life.…”

Vitamin and mineral supplementation during pregnancy: is more necessarily better?

“…Such disappointing findings have not prevented omega‐3 fatty acids from finding their way into many pregnancy multivitamins on the premise of improving fetal neurodevelopment. Finally, high prenatal folic acid exposure, particularly beyond the first trimester, has been associated with an increased risk of childhood atopic disease …”