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Human and Clinical Nutrition
Abbreviations: MTHFR, methylenetetrahydrofolate reductase; SNP, single nucleotide polymorphism
Small size at birth continues to be a problem even in populations with adequate energy and protein intakes. Many factors may account for small birth size, and it has been shown that low folate status or intake(1-4) and excess Pb burden(5-8) are independently associated with reduced birth weight and length. As discussed by Andrews et al.(9) the magnitude of the association between Pb and size at birth varied among studies and could not be explained by study design or confounding. Similarly, in some studies, folate intake or status explained only a small proportion of variability in outcome(4), suggesting that other factors may play a role.
Links between Pb exposure and folate intake have not been well studied, although there is evidence that folate metabolism may be related to Pb toxicity. In one study, serum folate levels were inversely associated with blood Pb concentrations among women of reproductive age(10). A comparison of women who did and did not have fetuses with neural tube defects revealed higher Pb but lower folate levels in amniotic fluid at 15-20 weeks gestation(11). In addition, Pb levels were inversely correlated with both folate and vitamin B12 concentrations. More recently, higher erythrocyte folate concentration appeared to attenuate the adverse relationship between Pb exposure and cognitive performance of children from the Philippines(12). Further evidence of a connection is found in studies of plasma homocysteine. Both reduced folate intake and increased Pb exposure are associated with higher plasma homocysteine(13,14), which in turn is linked with adverse pregnancy outcomes(15,16).
Variation in genes coding for folate-metabolising enzymes may be relevant because some polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, such as the C677T or A1298C, are common(17) and produce enzymes with lower metabolic activity(18). Other variants, such as the G1793A, are less frequent and their functional significance is unclear(19,20). However,...