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  • Title: Elevated midtrimester serum methylmalonic acid levels as a risk factor for neural tube defects.
    Author: Adams MJ, Khoury MJ, Scanlon KS, Stevenson RE, Knight GJ, Haddow JE, Sylvester GC, Cheek JE, Henry JP, Stabler SP.
    Journal: Teratology; 1995 May; 51(5):311-7. PubMed ID: 7482352.
    Abstract:
    The role of folic acid in the primary prevention of neural tube defects (NTDs) is well established. However, questions related to the protective mechanism remain unanswered. To help answer these questions, we designed a case-control study to assess the role of folate- and cobalamin-related metabolites in the pathogenesis of NTDs. Concentrations of folate, cobalamin, and 14 other related metabolites were measured by gas chromatography/mass spectrometry in midtrimester serum specimens from 32 women with an NTD-affected pregnancy and from 132 control women, and in serum specimens from 46 nonpregnant women who had a history of NTD-affected pregnancy and from 43 nonpregnant control women. Log-transformed means of metabolites were compared between case and control women for both the midtrimester and nonpregnant groups. In the pregnant group, serum methylmalonic acid (MMA) concentrations were higher among case women than among control women (130 vs 105 nM). There was a strong dose-response relationship between midtrimester serum MMA level and the risk for an NTD-affected pregnancy, with the relative risk increasing 13-fold for women with MMA levels > 90th percentile. In the nonpregnant group, there was no difference in serum MMA levels between case and control women (140 vs 140 nM). Thus, the serum MMA levels of women in the midtrimester of pregnancies unaffected by NTDs were significantly lower than the levels of nonpregnant women, whereas the levels of women whose pregnancies were affected by NTDs were similar to those of nonpregnant women. The finding of elevated MMA serum concentrations among women in the midtrimester of NTD-affected pregnancies suggests that cobalamin may be involved in the etiology of NTDs. The possible role of cobalamin in relation to the protective effect of folic acid needs further evaluation.
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