Recent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism,
folic acid supplementation, and circulating
folate and
vitamin B-12 concentrations during pregnancy were associated with
wheezing,
shortness of breath, and
atopic dermatitis in offspring. The study was a population-based birth cohort from fetal life until 48 mo (n = 8742). The use of
folic acid supplementation during pregnancy was assessed by questionnaire. Plasma
folate and serum
vitamin B-12 concentrations and the MTHFR C677T polymorphism were available from blood collected in early pregnancy.
Atopic dermatitis,
wheezing, and
shortness of breath in the offspring were assessed by parental-derived questionnaires at 12, 24, 36, and 48 mo. Maternal
folate >16.2 nmol/L and
vitamin B-12 >178 pmol/L were positively associated with the development of
atopic dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI: 1.06-1.60) for the highest quartiles of
folate and
vitamin B-12 concentrations, respectively] but not with
wheezing and
shortness of breath. Maternal MTHFR C677T polymorphism and
folic acid supplementation were not associated with
wheezing,
shortness of breath, and
atopic dermatitis. No interactions were found by age, family history of atopy,
folic acid supplementation, MTHFR C677T polymorphism, or maternal smoking (P-interaction > 0.10). High
folate and
vitamin B-12 levels during pregnancy are associated with increased prevalence of
atopic dermatitis in the offspring. Potential risks of high
folate and
vitamin B-12 concentrations on allergic outcomes should be evaluated when discussing mandatory fortification programs.