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USE OF FOLIC ACID IN PREGNANCY

Date of issue: February 2018
Version: 2

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on folic acid use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

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.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.