Short interpregnancy intervals and unfavourable pregnancy outcome: role of folate depletion

There is no generally accepted explanation for the excess risk of adverse pregnancy outcome after short interpregnancy intervals. In this paper, we present a hypothesis that is both biologically plausible, empirically testable, and able to explain many observations. Maternal serum and erythrocyte concentrations of folate decrease from the fifth month of pregnancy onwards and remain low for a fairly long time after delivery. Women who become pregnant before folate restoration is complete have a raised risk of folate insufficiency at the time of conception and during pregnancy. As a consequence, their offspring have higher risks of neural tube defects, intrauterine growth retardation, and preterm birth. We make several predictions based on our hypothesis and suggest ways of testing them empirically. The proposed mechanism implies, among other things, that postpartum supplementation with folic acid might prevent excess risk of unfavourable pregnancy outcome in women with short interpregnancy intervals.