What about screening for folate (folic acid) deficiency?

From the Guidelines

Screening for folate (folic acid) deficiency is not routinely recommended for the general population, but rather for women of childbearing age who are planning or capable of pregnancy, as folic acid supplementation has been shown to reduce the risk of neural tube defects in offspring 1.

Key Points

• The USPSTF recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 μg) of folic acid to reduce the risk of neural tube defects 1.
• Folic acid supplementation should commence at least 1 month before conception and continue through the first trimester for maximal protection 1.
• For high-risk women, a higher dose of 4,000 μg (4 mg) daily is recommended, starting at least 3 months prior to conception and continuing until 12 weeks gestation 1.
• Universal prophylaxis with daily folic acid of 400 μg (0.4 mg) is recommended for all women of childbearing age, in addition to a folate-rich diet 1.
• The evidence supports the hypothesis that supplementation with 0.4 to 0.8 mg (400 to 800 μg) of folic acid in the periconceptional period reduces the risk for neural tube defects in offspring 1.

From the FDA Drug Label

Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e. g. folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin False low serum and red cell folate levels may occur if the patient has been taking antibiotics, such as tetracycline, which suppress the growth of Lactobacillus casei.

The FDA drug label suggests that folate deficiency screening may be necessary in certain situations, such as:

• Renal dialysis
• Interference with metabolism (e.g. due to folic acid antagonists like methotrexate)
• Administration of certain anticonvulsants (e.g. diphenylhydantoin, primidone, and barbiturates)
• Alcohol consumption and alcoholic cirrhosis
• Administration of certain medications (e.g. pyrimethamine and nitrofurantoin) However, the label does not provide explicit guidance on screening for folate deficiency in general, and it is not clear how to screen for it based on the provided information 2.

From the Research

Screening for Folate Deficiency

• Folate deficiency can be screened using laboratory tests, including measurement of folate in serum or plasma, as well as folate in red blood cells 3, 4
• The analysis of folate in red cells is indicative of folate status over the preceding ~4 months, making it a useful marker for assessing long-term folate status 4
• Point-of-care diagnostic tests, such as fluorescence lateral flow assays, can also be used to quantify levels of folate in human serum, making them suitable for use in resource-limited settings 5

Importance of Screening

• Screening for folate deficiency is important, particularly in women of reproductive age, as maternal folate supplementation around the time of conception can decrease the risk of neural tube defects (NTDs) 5
• Folate deficiency can also be associated with other health problems, such as megaloblastic anemia, cognitive decline, depression, and neuropathy, making screening and diagnosis important for preventing and managing these conditions 4

Challenges and Limitations

• Laboratory tests for folate status have limitations, including technical and biological issues, which can affect their sensitivity, specificity, and predictive value 3
• The interpretation of homocysteine results, which can be used as a marker of folate and vitamin B12 status, requires consideration of age, sex, and pregnancy, as well as specific reference ranges 4
• The use of folic acid supplementation and fortification can also affect folate status, and excessive exposure to folic acid has been linked to adverse health effects, highlighting the need for careful management of folate status 6, 4

Target Populations

• Women of reproductive age, particularly those who may become pregnant, are a key target population for folate deficiency screening 5
• Other populations at risk of folate deficiency, such as those with malnutrition, alcohol use disorder, or certain medical conditions, may also benefit from screening 7
• Urban safety net populations, which may have limited access to healthcare and nutrition, may also be at risk of folate deficiency and could benefit from targeted screening and intervention efforts 7