recent epidemiological studies state that a high dose of folic acid status during pregnancy increases the risk of asthma, wheezing, and respiratory disease in childhood. As potential biological mechanism, folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated the association between maternal folate levels during pregnancy with childhood wheeze, and whether DNA methylation differentiation of

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... children in genes is related to wheezing or not. Methods: the cohort comprised 6651 mother-child pairs who were evaluated for an association between maternal folate level during pregnancy and childhood wheeze at 1, 2, 4, and 7 years age, which were assessed by the International Study of Asthma and Allergies in Childhood questionnaire. Results: the median of maternal serum was 16.76 nmol/l, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheeze at 2 years age according to maternal folate levels, compared with lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second; 1.27 [1.05, 1.55]), however, no changes were observed at 1, 4, and 7 years age. In a case-control study of childhood wheeze due to DNA methylation at 7 years age, no association of maternal folate levels with DNA methylation was observed. Conclusion: our result proposes that the negative effect of maternal folate on an infant's wheeze did not remain until 7 years of age and no association with maternal folate levels and DNA methylation (at the same age) was observed.