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Folic Acid in Utero Tied to Food Allergy Risk

— But total folate at birth not associated with later food allergies

MedpageToday

ORLANDO -- Newborns with high levels of unmetabolized folic acid had a higher risk for food allergy later in childhood than newborns with lower circulating folic acid levels -- suggesting that increased exposure to synthetic folic acid in utero could be a risk factor for food allergy.

In a nested case-control study performed using data from the , mean folate levels at birth were found to be lower among children who went on to develop food allergies, while mean levels of unmetabolized folic acid were higher.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The research was presented here at the joint meeting of the American Academy of Allergy, Asthma & Infectious Disease (AAAAI) and the World Allergy Organization (WAO).

"Food allergy prevalence seems to be increasing, and it has been hypothesized that increased [in utero] folic acid exposure may be a central contributor to this," said study co-author Corinne Keet, MD, PhD, of Johns Hopkins Hospital in Baltimore.

In a press conference at the meeting Keet said early research suggests that unmetabolized folic acid could have a negative impact on health. In the early 1990s folic acid was found to be protective of neural tube birth defects, and in 1998 the U.S. mandated the fortification of flour and other grain products with folic acid. Supplementation with 400 micrograms of folic acid is also recommended for women in their childbearing years.

"When the synthetic form of folate is metabolized, only a certain amount is able to be processed through the normal pathways, and the excess circulates as unmetabolized folic acid," Keet said.

Keet, lead researcher Emily McGowan, MD, of the University of Virginia Health System, and colleagues studied the association between total folate, 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA) concentrations at birth/early life and the development of food allergies.

Total folate and 5-MTHF/UMFA were measured at birth and in early life by a chemiluminescence assay and liquid chromatography-tandem mass spectrometry, respectively, in 1,394 Boston Birth Cohort participants.

Diet, clinical history, and specific-IgE (sIgE) to common food allergens were assessed in early life, and based on sIgE and clinical history, the children were classified as either having or not having a food allergy. Folate levels were divided into quartiles, and multiple logistic regression was used.

A total of 507 (36%) children in the analysis had had food sensitization, and 78 (5.6%) had a diagnosed food allergy.

While mean total folate levels at birth were lower among those who developed food allergies (30.2 versus 35.3 nmol/L), mean levels of the synthetic folic acid derivative, UMFA, were higher (1.7 versus 1.3 nmol/L).

Higher quartiles of UMFA were associated more strongly with food allergy (OR 9.4; 95% CI, 1.9-47.2).

No association was seen between early life total folate, 5-MTHF, or UMFA levels and the development of food allergies.

Keet said the findings should be considered preliminary, but they do suggest that there may be different effects from different forms of folate.

"At this point we are definitely not recommending that anyone change their diet or supplementation given that folic acid is very clearly associated with protection from neural tube defects," she said. "There are still a lot of things that we need to understand to figure out how this may relate. The fact that we saw a different relationship for total folate and for unmetabolized folic acid suggests that either the dietary source is important or that there are other things we haven't measured yet that might be influencing this association."

Primary Source

American Academy of Allergy, Asthma & Infectious Disease and the World Allergy Organization

McGowan EC, et al "The association between folate/folic acid metabolites and the development of food allergy in children" AAAAI/WAO annual meeting. Abstract 275.