Macrocytic anemia primary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]
Overview
Folic acid supplementation can prevent folate deficiency in states of increased demand (e.g., pregnancy and lactation) and in conditions with folate malabsorption (e.g., celiac disease) or loss (e.g., chronic hemolytic disorder). Preconception folic acid supplementation in women can also prevent fetal neural tube defects (NTDs).
Pregnancy and lactation
Evidence suggests that folic acid supplementation during pregnancy reduces megaloblastic anemia in mothers, but there is no conclusive evidence it has any beneficial effect on pregnancy outcomes, such as preventing premature birth, stillbirth, neonatal mortality, or miscarriage. [35] [36]
There is conclusive evidence that use of folic acid supplementation preconceptually and during pregnancy can prevent fetal NTDs. [26] [37] [38] Therefore, preconception folic acid supplementation is recommended at a dose of 400-800 micrograms/day for women who are planning to or are capable of becoming pregnant, with higher doses (up to 4 mg/day) recommended for certain risk groups. [27] [28] [29] For maximal protection against fetal NTDs, the optimal calculated red blood cell folate level is 442-574 nanograms/mL at the end of the first 4 weeks of pregnancy, when neural tube closure is achieved. [39] The oral intake of folate to achieve these folate levels will vary significantly depending upon diet, folic acid fortification, socioeconomic status, and individual medical history. [US Dept of Agriculture/US Dept of Health and Human Services: dietary guidelines for Americans] [NIH: dietary supplement fact sheet - folate]
A review of European guidelines found large variations in recommendations for periconceptional folic acid supplementation, including when to begin supplementation. [40] However, there were no recommendations that supplementation should begin at 3 months prior to conception, which is recommended by some guidelines outside of Europe (e.g., Canada and Australia). [27] [41] The US Preventive Services Task Force advises that the critical period for beginning supplementation is at least 1 month before conception. [28]
Canadian guidelines use the following risk stratification for women at risk for a fetal NTD or other folic acid-sensitive congenital anomaly: [27]
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.
The recommended dietary allowance (RDA) for folate during pregnancy and lactation varies from 400-600 micrograms/day depending upon factors such as diet, folic acid fortification, socioeconomic status, and individual medical history. [US Dept of Agriculture/US Dept of Health and Human Services: dietary guidelines for Americans] [NIH: dietary supplement fact sheet - folate]
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 celiac disease (nontropical sprue).
Increased folate loss occurs in patients with chronic hemolytic disorder (due to increased cell turnover), and in those undergoing chronic dialysis (due to loss of folate in dialysis fluid). Daily folic acid supplementation is required in these patients to prevent folate deficiency.
Patients taking drugs that interfere with folate absorption and metabolism (e.g., methotrexate, pyrimethamine, and trimethoprim) may require supplementation with oral or parenteral leucovorin to prevent folate deficiency. In some cases, where a drug has reduced efficacy when administered with leucovorin, a change to another drug may be required.==References==