Folate dose and form during pregnancy may program maternal and fetal health and disease risk.

The role of folate, in its synthetic and bioactive form, as an in utero modifier of metabolic outcomes in mothers and offspring is examined in this review. During pregnancy, a continuum of adaptive changes occurs to support maternal and fetal requirements. However, an unfavorable in utero environment may lead to permanent changes in cellular and physiological functions, adversely affecting the development of the child and postpartum health of the mother. In North American countries, synthetic folic acid (FA) is overconsumed by pregnant women, and uncertainty exists about its potential unintended health effects. Because the metabolism of FA is different than that of other folate forms, it may modulate disease risk differently. The bioactive form of folate, 5-methyltetrahydrofolic acid, has emerged as a popular alternative to FA, but clinical studies comparing their effects during pregnancy are limited. Current evidence points to the need for caution when maternal intake of either folate form exceed recommended amounts. Research directed toward defining an optimal folate dose and form for healthy pregnancy and long-term metabolic outcomes in mothers and children is urgently needed.