Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
oral folic acid + multivitamin supplementation
There is conclusive evidence that use of folic acid supplementation pre-conceptually and during pregnancy reduces the incidence of fetal neural tube defects (NTDs).[15][31][43]
Population-based studies suggest that female fetuses/infants may derive greater benefit (rate of decrease in NTDs) from maternal folic acid supplementation than males.[72][73] Continued folic acid supplementation beyond the first trimester until the end of pregnancy may confer neurodevelopmental benefits.[74] Further randomised trials are needed.
Guidelines recommend pre-conception folic acid supplementation at a dose of 400-800 micrograms/day for the prevention of fetal NTDs in women who are planning to conceive or who are capable of becoming pregnant.[32][33][34] Higher doses (up to 4 mg/day) are recommended for certain risk groups. The UK National Institute for Health and Care Excellence recommends 5 mg/day in certain risk groups.[35][36] Canadian guidelines use the following stratification for women at risk for fetal NTD, or other folic acid-sensitive congenital anomaly:[32]
Low risk: no personal or family history of fetal NTD or folate-related congenital abnormalities.
Medium risk: family history of fetal NTD; personal history in the patient or male partner of folate-related congenital abnormality; or diabetes, teratogenic medication, or malabsorption in the patient.
High risk: personal history of fetal NTD in the patient or her male partner; or previous fetal NTD birth by the patient.
In the US, the recommended dietary allowance for folate during pregnancy and lactation varies from 400-800 micrograms/day depending upon factors such as diet, inclusion of food fortified with folic acid, socio-economic status, and individual medical history. US Department of Agriculture and US Department of Health and Human Services: dietary guidelines for Americans, 2020-2025 Opens in new window NIH: dietary supplement fact sheet - folate Opens in new window
The World Health Organization recommends a red blood cell (RBC) folate level >906 nanomol/L (400 nanograms/mL) in women of reproductive age.[44]
Randomised clinical trial data suggest that a plasma folate level of 25.5 nanomol/L (11 nanograms/mL) corresponds to the recommended RBC folate level (≥906 nanomol/L [≥400 nanograms/mL]) in most situations.[45]
For maximal protection against fetal NTDs, the optimal calculated RBC folate level is 1000-1300 nanomol/L (442-574 nanograms/mL) at the end of the first 4 weeks of pregnancy, when neural tube closure is achieved.[46]
The US Preventive Services Task Force advises that the critical period for beginning supplementation is at least 1 month before conception.[33] Reproductive-age women (without folate fortification) randomised to 800 micrograms/day folate supplementation were more likely to achieve desirable RBC-folate concentrations (≥906 nanomol/L [≥400 nanograms/mL]) at 4 weeks than women receiving 400 micrograms/day.[47] Similar results were reported at an 8-week timepoint.
Evidence suggests that folic acid supplementation during pregnancy reduces megaloblastic anaemia in mothers. While there is no conclusive evidence that supplementation prevents preterm birth, stillbirth, neonatal mortality, or miscarriage, data from the Screening for Pregnancy Endpoints (SCOPE) study indicate that folic acid supplementation during pregnancy is associated with a lower risk of small for gestational age infants without increasing the risk for large for gestational age infants.[48][49][50]
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In low- and middle-income countries, maternal multiple micronutrient supplementation with iron and folic acid reduces the number of infants born at low birth weight.[51]
Primary options
folic acid: low risk: 0.4 to 0.8 mg orally once daily starting 1-3 months before pregnancy and continuing until 6 weeks postnatally or the end of lactation; medium risk: 1 mg orally once daily starting 1-3 months before pregnancy and continuing through the first 12 weeks of pregnancy, followed by 0.4 to 1 mg once daily from week 13 of pregnancy and continuing until 6 weeks postnatally or the end of lactation; high risk: 4-5 mg orally once daily starting 1-3 months before pregnancy and continuing through the first 12 weeks of pregnancy, followed by 0.4 to 1 mg once daily from week 13 of pregnancy and continuing until 6 weeks postnatally or the end of lactation
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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