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

Summary 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 B 12 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 B 12 and homocysteine plasma concentrations were measured in early pregnancy and at birth. At age 10 years, forced expiratory volume in 1 second ( FEV 1 ), forced vital capacity ( FVC ), FEV 1 / FVC , forced expiratory flow between 25% and 75% ( FEF 25‐75 ), at 75% of FVC ( FEF 75 ), and asthma were examined. Results Maternal folic acid supplement use during pregnancy was associated with higher childhood FEV 1 and FVC and with a lower FEV 1 / 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 FEV 1 / FVC (−0.17 [−0.32, −0.02]) and FEF 25‐75 (−0.24 [−0.40, −0.07]). Among children carrying MTHFR ‐C677T wild‐type, a higher vitamin B 12 level at birth was associated with a lower FEV 1 (−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 B 12 concentrations at birth might adversely affect childhood lung function depending on MTHFR ‐ C677T carriership. The clinical implications need to be evaluated.