Folate deficiency

A primary strategy for prevention is with national mandatory folic acid fortification. In the US, the US Food and Drug Administration (FDA) mandates the addition of 140 micrograms folic acid/100 g to breads, cereals, flours, corn meals, pastas, rice, and other grain products.[33]

Folate deficiency may also be prevented through folic acid supplementation during states of increased demand (e.g., pregnancy and lactation) and in patients with conditions associated with folate malabsorption (e.g., coeliac disease) or loss (e.g., chronic haemolytic anaemias).

Folic acid supplementation in pregnancy and lactation

There is conclusive evidence that folic acid supplementation pre-conceptually and during pregnancy reduces the incidence of fetal neural tube defects (NTDs).[19][20][21]

Guidelines recommend pre-conception folic acid supplementation at a dose of 400-800 micrograms/day for the prevention of NTDs in women who are planning to conceive or who are capable of becoming pregnant.[34][35][36]

US recommended dietary allowance for folate during pregnancy and lactation

Varies from 400 to 800 micrograms/day depending upon factors such as diet, inclusion of food fortified with folic acid, socio-economic status, and individual medical history.[37] NIH: dietary supplement fact sheet - folate Opens in new window

The US Preventive Services Task Force advises that the critical period for beginning supplementation is at least 1 month before conception.[35] Persons planning pregnancy, or who could become pregnant, should begin daily folic acid supplementation at least 1 month prior to anticipated conception and continue through the first 2-3 months of pregnancy.[35]

The National Institutes of Health recommends a dietary folate equivalent of 500 micrograms/day for breastfeeding women. NIH: dietary supplement fact sheet - folate Opens in new window

World Health Organization (WHO) guideline recommendations

To achieve the greatest reduction of NTDs, WHO recommends a red blood cell folate level >906 nanomol/L (>400 nanograms/mL) in women of reproductive age.[38]

Risk stratification for women at higher risk for fetal NTD

Higher doses (up to 5 mg/day) may be recommended for certain at-risk groups pre-conceptually and during the first 12 weeks of pregnancy.[34][39]

Features associated with increased risk for folate deficiency and /or having a fetus with an NTD include:

Personal or family history of fetal NTD or congenital malformation in the patient or her male partner
Previous fetal NTD or congenital malformation birth by the patient
Personal history of type 1 or type 2 diabetes or a haematological condition requiring folic acid supplementation
Personal use of drugs affecting folic acid absorption or metabolism, or any teratogenic drug

Folic acid supplementation may reduce risk for low birth weight

Supplementary folic acid during pregnancy is associated with a lower risk of small for gestational age infants, without increasing risk for large for gestational age infants.[40]

There is no conclusive evidence that supplementation prevents preterm birth, stillbirth, neonatal mortality, or miscarriage.[41][42][43] [ ]

Folate malabsorption and loss

Correction of the underlying cause and/or folic acid supplementation can prevent folate deficiency in patients with malabsorptive disorders, such as tropical sprue and coeliac disease.

Increased folate loss occurs in patients with exfoliative dermatitis, chronic haemolytic anaemias, and in those undergoing chronic peritoneal dialysis (due to loss of folate in dialysis fluid).[14][15] Daily folic acid supplementation may be required in these patients to prevent folate deficiency.

Patients taking drugs that interfere with folate absorption and metabolism may require supplementation with oral or parenteral folinic acid to prevent folate deficiency.

Intervention

Goal

Intervention

Goal

Continued folic acid supplementation is necessary in certain conditions with poor folate absorption or ongoing losses (e.g., coeliac disease, chronic haemolytic anaemia) and states of increased demand (e.g., pregnancy, lactation, prematurity).

National food fortification can prevent folate deficiency on a large scale.[73] This can positively affect the folate status of the population at large, and specifically that of certain vulnerable populations, such as pregnant and lactating women and older people.

Primary prevention

Intervention

Goal

Secondary prevention