Maternal Folate Intake during Pregnancy and Childhood Asthma in a Population-based Cohort

Abstract

Rationale: A potential adverse effect of high folate intake during pregnancy on children's asthma development remains controversial.Objectives: To prospectively investigate folate intake from both food and supplements during pregnancy and asthma at age 7 years when the diagnosis is more reliable than at preschool age.Methods: This study included eligible children born [2002][2003][2004][2005][2006] from the Norwegian Mother and Child Cohort Study, a populationbased pregnancy cohort, linked to the Norwegian Prescription Database. Current asthma at age 7 was defined by asthma medications dispensed at least twice in the year (1,901 cases; n = 39,846) or by maternal questionnaire report (1,624 cases; n = 28,872). Maternal folate intake was assessed with a food frequency questionnaire validated against plasma folate. We used log-binomial and multinomial regression to calculate adjusted relative risks with 95% confidence intervals.Measurements and Main Results: Risk of asthma was increased in the highest versus lowest quintile of total folate intake with an adjusted relative risk of 1.23 (95% confidence interval, 1.06-1.44) that was similar for maternally reported asthma. Mothers in the highest quintile had a relatively high intake of food folate (median, 308; interquartile range, 241-366 mg/d) and nearly all took at least 400 mg/d of supplemental folic acid (median, 500; interquartile range, 400-600 mg/d). Conclusions:In this large prospective population-based cohort with essentially complete follow-up, pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reach a total folate intake level associated with a slightly increased risk of asthma in children.

Association of prenatal folate status with early childhood wheeze and atopic dermatitis

“…In our cohort, over half of the women had high prenatal folate levels (above 20 ng/mL). This is in contrast with other studies with much lower prenatal folate levels . Despite concerns that high folate exposure may be associated with adverse health effects, we observed that these higher 2nd trimester folate levels were associated with a modest decrease in relative odds of child wheeze in the 3rd year of life.…”

“…A recent MoBa study reported a modest but increased risk of asthma at age 7 years with higher maternal total folate intake . However, 2nd trimester maternal plasma folate levels (median 8.7 nmol/L or ~3.8 ng/mL) were not associated with asthma in a subset of 2681 children …”

“…In contrast, the Norwegian Mother and Child Cohort Study (MoBa) reported an increased risk of asthma at 3 years in children born to mothers in the highest plasma folate levels (>17.8 nmol/L or ~8 ng/mL) relative to children with mothers in the lowest levels (folate <5.5 nmol/L or ~2.5 ng/mL) . A recent MoBa study reported a modest but increased risk of asthma at age 7 years with higher maternal total folate intake . However, 2nd trimester maternal plasma folate levels (median 8.7 nmol/L or ~3.8 ng/mL) were not associated with asthma in a subset of 2681 children …”

“…High prenatal folic acid exposure has been studied as a risk factor for childhood atopic diseases, due in part to its recognized capacity to epigenetically modify DNA . Some observational studies have suggested that higher folic acid during pregnancy may be associated with increased risk of allergic and respiratory phenotypes in offspring, while other studies found null or inverse associations …”

Maternal folic acid use during pregnancy, methylenetetrahydrofolate reductase gene polymorphism, and child's lung function and asthma

“…Folic acid supplement use during pregnancy is recommended to prevent neural tube defects, 1 but high dosages have been associated with increased risks of asthma and allergic diseases in animal studies. Besides folic acid use and related folate blood concentrations, vitamin B 12 and homocysteine are involved in the one-carbon metabolism, which is important for DNAmethylation. [3][4][5][6][7][8][9][10][11][12] This could be due to different methods used to assess folic acid supplement use, including food frequency questionnaires, diet records and self-administered questionnaires, and differences in techniques and ages at which folate concentrations were measured.…”