Christine L Parr1,2, Maria C Magnus1,3,4, Øystein Karlstad1, Margaretha Haugen5, Helga Refsum6, Per M Ueland7,8, Adrian McCann9, Per Nafstad1,10, Siri E Håberg1, Wenche Nystad1, Stephanie J London2. 1. 1 Department of Mental and Physical Health and. 2. 2 Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina. 3. 3 Medical Research Council Integrative Epidemiology Unit and. 4. 4 School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. 5. 5 Department of Exposure and Risk Assessment, Norwegian Institute of Public Health, Oslo, Norway. 6. 6 Institute of Basic Medical Sciences, Department of Nutrition, and. 7. 7 Department of Clinical Science, University of Bergen, Bergen, Norway. 8. 8 Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway; and. 9. 9 Bevital AS, Bergen, Norway. 10. 10 Department of Community Medicine, University of Oslo, Oslo, Norway.
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 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based 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 μg/d) and nearly all took at least 400 μg/d of supplemental folic acid (median, 500; interquartile range, 400-600 μg/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.
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 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based 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 μg/d) and nearly all took at least 400 μg/d of supplemental folic acid (median, 500; interquartile range, 400-600 μg/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.
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