USE OF FOLIC ACID IN PREGNANCY

Folic acid (pteroylglutamic acid/PGA) is a synthetic derivative of the water-soluble form of vitamin B9 (also known as folate).  It requires metabolism to dihydrofolic acid and then to its biologically active form tetrahydrofolate.  Folate is necessary for the production of blood cells and DNA.  Folic acid is used in the treatment of nutritional megaloblastic anaemias and prophylactically in individuals at risk of deficiency e.g. due to chronic haemolysis or renal dialysis. 

During pregnancy folate requirements are increased 5- to 10-fold and pregnant women are therefore at risk of folate deficiency.  Maternal folate deficiency is an established risk factor for neural tube defects.

There is good evidence that supplementation with folic acid (when used prior to conception and before closure of the neural tube at doses ≥360mcg) reduces the risk of primary and recurrent NTDs.  Some studies have also suggested a reduced risk of spontaneous abortion and congenital heart defects with folic acid supplementation peri-conceptually, however there is no conclusive evidence of a protective effect, or whether any possible benefit may be restricted to women at increased risks of these outcomes.  There is conflicting evidence regarding whether gestational folic acid supplementation reduces the risk of preterm delivery and low infant birth weight.  Studies have suggested that neurodevelopmental outcomes may be improved in children exposed in utero to folic acid, however data confounding cannot be ruled out.

Peri-conceptual folic acid supplementation is universally advised.  In certain countries basic food products such as flour and/or bread are routinely fortified with folic acid.  This is not the case in the UK, and current UK guidelines recommend 400mcg/day of folic acid pre-conceptually and until at least 12 weeks of gestation.  In women considered to be at increased risk of folate deficiency, e.g. those with a family history of neural tube defect, concurrent treatment with drugs which interfere with folate metabolism or maternal obesity, higher dose folic acid (5mg) is recommended peri-conceptually.  However, it is unclear whether there is increased benefit of a higher dose.  As maternal requirements for folate peak at around five months gestation, folic acid supplementation throughout pregnancy is often advised, however there is no definitive evidence of benefit of supplementation beyond the point of fetal neural tube closure.