Neural tube defects and disturbed maternal folate- and homocysteine-mediated one-carbon metabolism

Disturbances in maternal folate and homocysteine metabolism are associated with neural tube defects (NTDs). However, the role played by specific components in the one-carbon metabolic pathways leading to NTDs remains unclear. Here, we conducted a case-control study to investigate the relationship between the disturbed one-carbon metabolism and the risk of NTD-affected pregnancies. Major components were examined in population-based samples of women who had NTD-affected pregnancies (case subjects, n = 46) or unaffected by any birth defects (control subjects, n = 44). We used the newly developed high-performance liquid chromatography tandem mass spectrometry along with a routine chemiluminescent assay, to measure serum concentrations of 5-methyltetrahydrofolate (5-MeTHF), 5-formyltetrahydrofolate (5-FoTHF), folic acid, serine, histidine, homocysteine, cystathionine, methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total folate and vitamin B12 in both groups adjusting for lifestyle and sociodemographic variables. We found significantly lower serum concentrations of 5-MeTHF (P < 0.001), 5-FoTHF (P = 0.004), total folate (P < 0.001) and vitamin B12 (P = 0.005) and remarkably higher concentrations of SAH (P = 0.016) in cases than in controls. Therefore, these compounds could be identified as potential risk factors for NTD's early diagnosis. Further analysis of relevant genetic and epidemiologic investigations may provide more insights into the pathogenesis of NTDs and enhance current nutritional intervention strategies to reduce the risk of NTD-affected pregnancies.