Folate Metabolism in Pregnancy

Abstract

Folate plays a crucial and indispensible role in cell division so it is not surprising that it is important in pregnancy. This importance was first highlighted by the historical observation made by Lucy Wills in India¹ that the latter stages of pregnancy are frequently associated with a megaloblastic anaemia that is folate responsive, i.e. in pregnancy not only is extra folate needed but it is frequently lacking. Subsequent studies over the years have found that folate deficiency in the second and particularly the third trimester is common in some countries and quite rare in others. The determining feature was found to be adequate folate nutrition for the mother not only during pregnancy but before the pregnancy began². The most often suggested mechanism for folate deficiency in pregnancy is increased requirement for the rapidly growing fetus and placenta. However the mechanism is unclear and certainly cannot be accounted for by transfer of the vitamin to the fetus. One possible explanation is that the events of fetal/placental growth cause an increase in the rate of catabolism of the vitamin. Early studies in our laboratory demonstrated that the mechanism of folate catabolism in the rat was cleavage of the C9-N10 bond with excretion of a mixture of pteridines and p-aminobenzoylglutamate (pABGlu) with the latter being largely acetylated to acetamidobenzoylglutamate (apABGlu)³. Subsequent studies by us in the rat⁴ and by Krumdieck⁵ in man confirmed this mechanism. These studies used radioactive tracers. They had the disadvantage that they assumed that the exogenous tracer would equilibrate with the endogenous pool given sufficient time. In addition while they could be used to compare rates of catabolism in specific circumstances between animals, say treated with convulsant drugs and controls⁶, they did not measure true endogenous rates of catabolism. Furthermore, since they used radioactive tracers they were unsuitable for routine studies on humans.