Folic acid levels and the impact on the newborn epigenome and childhood asthma risk



Folic acid supplementation in pregnancy is recommended worldwide to prevent neural tube defects, despite the fact that the mechanism underlying this protection is largely unknown. Recently, concerns have been raised about the possible adverse effects of increasing folate levels across the population as whole, including impacts on the developing epigenome of newborns, and a possible increase in asthma risk.


IRP researchers led by Stephanie J. London, M.D., Dr.P.H., and collaborators in Norway, set out to validate their initial findings that showed that an increased risk of early childhood respiratory illness and asthma is associated with higher maternal folate levels during pregnancy. By conducting a study across a large prospective population-based cohort, the team found that pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reached a total folate level associated with a slightly elevated risk of their children developing asthma. By examining possible epigenetic impacts, these researchers, along with colleagues in the Netherlands also found that maternal folate, measured in plasma, had widespread impacts on methylation across the genome of a fetus.


The discovery that maternal folate levels can impact the genome-wide methylation of a fetus, may shed light on the mechanisms by which this essential vitamin acts to prevent the development of neural tube defects. While the discovery that children of mothers with very high levels of folate intake have a slightly higher risk of developing asthma is important, this association does not negate the public health recommendation for the use of folic acid supplementation for the prevention of neural tube defects. However, in the future this information may prove useful to countries looking to adjust the fortification of their food supply.


Parr CL, Magnus MC, Karlstad Ø, Haugen M, Refsum H, Ueland PM, McCann A, Nafstad P, Håberg SE, Nystad W, London SJ. (2017). Maternal folate intake during pregnancy and childhood asthma in a population-based cohort. Am J Respir Crit Care Med. 195(2):221 28.

Joubert BR, den Dekker HT, Felix JF, Bohlin J, Ligthart S, Beckett E, Tiemeier H, van Meurs JB, Uitterlinden AG, Hofman A, Håberg SE, Reese SE, Peters MJ, Andreassen BK, Steegers EA, Nilsen RM, Vollset SE, Midttun Ø, Ueland PM, Franco OH, Dehghan A, de Jongste JC, Wu MC, Wang T, Peddada SD, Jaddoe VW, Nystad W, Duijts L, London SJ. (2016). Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns. Nat Commun. 7:10577.