The Association Between Folate/Folic Acid Metabolites and the Development of Food Allergy (FA) in Children

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Rationale

Although folic acid exposure is a potential risk factor for the development of allergic disease, the association between total folate, 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA) concentrations at birth/early life and the development of FA is unknown.

Methods

A nested case control study was performed in the Boston Birth Cohort (BBC). Total folate and 5-MTHF/UMFA were measured at birth and in early life by a chemiluminescent assay and LC-MS/MS, respectively. Diet, clinical history, and specific-IgE (sIgE) to common food allergens were assessed in early life. Based on sIgE and clinical history, children were classified as FA or not. Folate levels were divided into quartiles, and multiple logistic regression was used to estimate ORs and 95% CIs.

Results

1,394 children were included in this study: 507(36%) had food sensitization (sIgE≥0.35 ku/L) and 78(5.6%) were FA. A subset had 5-MTHF and UMFA measured at birth (n=502) and early life (n=362). While mean total folate levels at birth were lower among those who developed FA (30.2v.35.3 nmol/L; p=0.02), mean levels of the synthetic folic acid derivative, UMFA, were higher (1.7v1.3 nmol/L, p=0.001). Higher quartiles of UMFA were associated more strongly with FA (OR 9.4; 95%CI 1.9-47.2; p=0.007;

Conclusions

Among children in the BBC, higher levels of UMFA at birth was associated with the development of FA, which may be due to increased exposure to synthetic folic acid in utero or underlying genetic differences.

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