Fig 1 Relation between folic acid intake, blood folate concentration, and risk of neural tube defects. a: Many studies have shown that folic acid intake from multivitamin and folic acid only supplements (common doses between 200 and 5000 µg/day) in the periconceptional period (before neural tube closure at day 28) reduces risk of neural tube defects in those pregnancies. b: Controlled folic acid intake studies show that folic acid increases blood folate concentrations; these studies have shown that absolute concentration after folic acid intake is dependent on dose of folic acid supplements, length of time supplement is consumed, baseline folate concentration, and genetic variation in folate metabolism (notably MTHFR677). c: Single study of blood folate concentration (red blood cell (RBC) and plasma) during pregnancy (mean gestational age 15 weeks) showed inverse dose-response with risk of neural tube defects in offspring. Study reported here used information from existing data sources to build a statistical model to predict association between RBC folate concentration at time of neural tube closure (embryologic day 28) and risk of neural tube defects