High Circulating Folate and Vitamin B-12 Concentrations in Women During Pregnancy Are Associated with Increased Prevalence of Atopic Dermatitis in Their Offspring

Abstract

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.

Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort

“…Our findings that moderate folate levels in early pregnancy are associated with higher birth weight regardless of race/ethnicity are consistent with previous studies, [14][15][16][17][18][19][20][21][22][23][24]50 although an equally large number of studies from Europe, Asia and the US [25][26][27][28][29][30][31] have not confirmed these associations. Reasons for discordant findings are unclear.…”

“…13 In humans, evidence of associations between maternal folate concentrations and fetal growth is conflicting, as high levels have been linked to both low and high birth weight, [14][15][16][17][18][19][20][21][22][23][24] while other studies found no associations. [25][26][27][28][29][30][31] Extremes of the birth weight distribution have been associated with a wide range of childhood and adultonset chronic diseases and conditions including obesity, impaired glucose tolerance, type 2 diabetes, coronary artery disease, congestive heart failure and some cancers.…”

Folate and Asthma

“…In contrast to the negative findings for asthma in the Dutch studies, a case-control study of 1,962 Norwegian children (nested within a birth cohort) found a significant linear association between maternal plasma folate in the second trimester of pregnancy and asthma at age 3 years (38). Due to short duration of follow-up, both the second Dutch study (37) and the Norwegian study (38) are limited by potential misclassification of asthma.…”

“…Although the overall results were consistent, and the phenotypic assessment of asthma was adequate, this study was limited by potential selection bias and nonassessment of folate status in the first or second trimester of pregnancy (36). A second, larger birth cohort study of Dutch children (n ¼ 8,742) found that nonfasting maternal plasma levels of folate or vitamin B 12 during the first trimester of pregnancy were significantly associated with increased odds of atopic dermatitis but not with asthma at age 4 years (37). In contrast to the negative findings for asthma in the Dutch studies, a case-control study of 1,962 Norwegian children (nested within a birth cohort) found a significant linear association between maternal plasma folate in the second trimester of pregnancy and asthma at age 3 years (38).…”

“…Three birth cohort studies have examined circulating or intracellular (using RBC folate) maternal folate status during pregnancy and asthma in offspring (36)(37)(38). In a study of 2,834 Dutch children, maternal intracellular folate status (measured in the third trimester of pregnancy in 837 [29.5%] participants) was not significantly associated with allergic sensitization at age 2 years or asthma or lung function at age 6 to 7 years (36).…”