Maternal-fetal red blood cell folate concentrations and 5,10-methylenetetrahydrofolate reductase (mthfr) 677c→ t mutation in pregnancies with neural tube defects

OBJECTIVE: To study paired maternal and fetal red blood cell (RBC) folate concentration and the prevalence of the 677C-T mutation in the MTHFR gene in pregnancies complicated hv neural tube defects (NTDs). STUDY DESIGN: Parental and fetal blood samples were prospectivelv ohtained from 22 pregnancies complicated by a NTD, including 21 fetuses with spina bifida and 1 with encephalocele. The median gestational age was 20 weeks (range 10-30). RBC. folale concentration was measured using specific radioimmunoassay. Genoinic DNA samples were analyzed b\ mutation specific restriction analysis of a 198bp DNA fragment amplified by the polymerase chain reaction method. The 077C-T mutation was identified after digestion with endonuciease Itnij I. the digested products being separated by agarose gel electrophoresis and visuali/ed bv UY-transillumination of the erhidium bromide stained gel. RESULTS: Fetal concentrations of RBC folate were greater than maternal levels in all cases (median 653 (Jig/L [range 385-1030j versus median 353(jLg/I. [range 164-632]. lespectiveh; t = 7.8, P 1 and T - 0.46 ) frequency in the UK. control population 0.7 and 0.3, respectively}. In 75% of the fetal samples (n = 8), hetero/vgositv for the 677C-T mutation was demonstrated: in two of these pregnancies the mothei had a folate level below the normal range. CONCLUSIONS: Maternal-fetal gradient suggest intact placental transfer of foilc acid in pregnancies with N'TDs. However, the high pre\alence of 677C→ T hetero/ygositv in affected fetuses supports a role of genetic abnormalities in folate metabolism as a risk factor for NTDs.