Background: Folic acid supplement use during pregnancy might affect childhood respiratory health, potentially mediated by methylenetetrahydrofolate reductase polymorphism C677T (MTHFR-C677T) carriership. Objectives: We examined the associations of maternal folic acid supplement use and folate, vitamin B12 and homocysteine concentrations during pregnancy with childhood lung function and asthma. Methods: This study was embedded in a population-based prospective cohort study among 5653 children. Folic acid supplement use was assessed by questionnaires. Folate, vitamin B12 and homocysteine plasma concentrations were measured in early pregnancy and at birth. At age 10 years, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow between 25% and 75% (FEF25-75), at 75% of FVC (FEF75), and asthma were examined. Results: Maternal folic acid supplement use during pregnancy was associated with higher childhood FEV1 and FVC and with a lower FEV1/FVC, compared with no folic acid supplement use. Among mothers carrying MTHFR-C677T variants, preconceptional start of folic acid supplement use was associated with lower FEV1/FVC (-0.17 [-0.32, -0.02]) and FEF25-75 (-0.24 [-0.40, -0.07]). Among children carrying MTHFR-C677T wild-type, a higher vitamin B12 level at birth was associated with a lower FEV1 (-0.07 [-0.12, -0.01]) and FVC (-0.09 [-0.15, -0.04]). Folate and homocysteine concentrations were not consistently associated with lower childhood lung function or asthma. Conclusions: Preconceptional start of maternal folic acid supplement use and higher vitamin B12 concentrations at birth might adversely affect childhood lung function depending on MTHFR-C677T carriership. The clinical implications need to be evaluated.

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Keywords Asthma, Epidemiology, Genetics, Pediatrics
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Journal Clinical and Experimental Allergy
den Dekker, H.T, Jaddoe, V.W.V, Reiss, I.K.M, de Jongste, J.C, & Duijts, L. (L.). (2017). Maternal folic acid use during pregnancy, methylenetetrahydrofolate reductase gene polymorphism, and child's lung function and asthma. Clinical and Experimental Allergy. doi:10.1111/cea.13056