Methylmalonic acid in amniotic fluid and maternal urine as a marker for neural tube defects

Abstract

To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatographymass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B₁₂ levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4±0.9 μmol/L, and 22.1±12.6 nmol/μmol creatinine) were significantly higher than that of normal pregnancies (1.0±0.4μmol/L, and 2.5±1.1 nmol/μmol creatinine). There was no significant differences between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B₁₂ levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B₁₂ is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B₁₂ deficiency. This study suggests that it is necessary to monitor the vitamin B₁₂ deficiency and advocates vitamin B₁₂ supplementation with folate prevention program.

Keywords

neural tube defects / methymalonic acid / vitamin B₁₂ / folic acid

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