A new study published in The Journal of Nutrition concluded maternal folic acid status (the synthetic form of folate) during pregnancy is not a contributing factor to allergic disease in infants with a family history of allergy.

To reduce the incidence of neural tube defects, > 80 countries worldwide have introduced fortification of staple foods with folic acid. Women are also advised to take folic acid containing supplements prior to and during early pregnancy. A high intake of folic acid can overwhelm the liver and end up in the circulation as unmetabolized folic acid, an indicator of excessive folic acid intake. Australia has among the highest prevalence of allergic disorders in the world in addition to high prenatal folic acid exposures from food fortification and prenatal supplementation and is therefore an ideal setting to examine associations between folic acid in pregnancy and allergic disease outcomes in offspring.

To determine if maternal folic acid concentrations in late pregnancy predicted infant allergic disease outcomes at 1 y of age, Karen Best (South Australian Health and Medical Research Institute) and colleagues conducted a prospective study consisting of 561 mother-infant pairs.  To be eligible for the study, the cohort of pregnant women had to have at least 1 immediate family member with a history of allergic disease. Folic acid status was measured between 36 and 40 wk of gestation. Infant allergic disease outcomes of eczema and medically diagnosed wheeze were assessed at 1 y of age. Skin-prick tests were used to detect allergen sensitization to common Australian food and environmental allergens.

In late gestation, the presence of unmetabolized folic acid in circulation was detectable in 93% of maternal serum samples. Of the infants, 34.6% had medically diagnosed eczema and 26.7% had eczema requiring steroid treatment during the first year of life. No associations were found between unmetabolized folic acid in women and infant allergic disease outcomes.

This is the first prospective cohort study to examining the association between maternal late pregnancy unmetabolized folic acid status and multiple allergic disease outcomes in a high-risk infant population. A corresponding editorial by Anne Molloy and James Mills discuss the rigor in which this study was conducted and also conclude that folic acid exposure in pregnancy is not an important factor contributing the increase in allergies seen in Australia.


Best KP, Green TJ, Sulistyoningrum DC, Sullivan TR, Aufreiter W, Prescott SL, Makrides, M, Skubisz M, O’Connor DL, Palmer D. Maternal Late-Pregnancy Serum Unmetabolized Folic Acid Concentrations Are Not Associated with Infant Allergic Disease: A Prospective Cohort Study. The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1553–1560, https://doi.org/10.1093/jn/nxab040.

Molloy AM, Mills JL. Folic Acid and Infant Allergy: Avoiding Rash Judgments. The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1367–1368, https://doi.org/10.1093/jn/nxab084.

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