Abstract
This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participated in the study, respectively. Maternal folate intake from diet and supplements was assessed by food frequency questionnaire in early (<16 weeks) and late (30-34 weeks) pregnancy. The primary outcome was physician-diagnosed asthma, obtained by maternal-completed questionnaire. Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69). The effect sizes did not change with adjustment for potential confounders. The association was similar at 5.5 years but did not reach statistical significance (RR = 1.17, 95% CI: 0.96, 1.42) in univariable models. These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children.
Highlights
This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n 1⁄4 557) from 1998 to 2005
Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) 1⁄4 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR 1⁄4 1.32, 95% CI: 1.03, 1.69)
Mothers of children not participating at 5.5 years were younger, less likely to take a prepregnancy folic acid supplement, less educated, more likely to smoke during early and late pregnancy, and more likely to report a history of asthma than those who completed the pregnancy phase of the study (P < 0.05)
Summary
This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n 1⁄4 557) from 1998 to 2005. The association was similar at 5.5 years but did not reach statistical significance (RR 1⁄4 1.17, 95% CI: 0.96, 1.42) in univariable models These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children. (Th2) cytokines during fetal development, in turn altering the inflammatory response and risk of allergic airways disease in the offspring [5] Application of these findings to human studies has begun, with a large study of asthma symptoms in 32,077 children in Norway demonstrating that a history of folic acid supplementation in pregnancy was related to wheeze and lower respiratory tract infections [6]. The aim of this study is to examine data from a prospective pregnancy cohort study for any association between the dose and timing of maternal folic acid and folate intake during pregnancy and asthma status at the ages of 3.5 and 5.5 years
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