Biological Role of Folic Acid in Pregnancy and Possible Therapeutic Application for the Prevention of Preeclampsia

The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal-placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.