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Indeed, FA has a weak capacity to be metabolized to the physiologic, soluble and active methylated form because requiring a double reduction by DHFR (see Figure 1) and results in the occurrence in circulation of unmetabolized folic acid (UMFA: UMFA syndrome) ( The Rotterdam Periconception Cohort ( Statements Data availability statement The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author