Homocysteine and Folate in Pregnancy (Editorial‪)‬

The importance of folate during pregnancy was addressed 40 years ago by Bryan Hibbard (1) in his study of folate status in 1484 low-income obstetric patients from Liverpool. He assessed folate status as urinary excretion of formiminoglutamic acid. Abnormal formiminoglutamic acid excretion was related not only to placental abruption and spontaneous abortion but also to adverse outcomes in previous pregnancies, including prematurity, congenital defects, and perinatal mortality. Shortly thereafter, Hibbard and Smithells (2) suggested that folate deficiency in pregnancy may be related to central nervous system malformations, and Smithells started a series of observational and intervention studies demonstrating that adequate folate status reduced the risk of neural tube defects (NTDs), observations that eventually in the early 1990s were confirmed in large, randomized intervention trials (3, 4). It is now established that periconceptional folate supplementation reduces the occurrence and recurrence of NTDs (3,4). The results obtained in many observational studies suggest that low folate intake or low circulating folate increases the risk of preterm delivery and low birth weight (5). However, a recent Dutch study on several B vitamins measured before and during pregnancy in healthy, well-nourished women demonstrated no association between the vitamin concentrations and birth weight or risk of early pregnancy loss (6). The results from randomized intervention trials with folic acid have been equivocal (5). Thus, the link between maternal folate status and birth weight is uncertain.