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Folate deficiency

Background

Overview

Definition
Folate deficiency is dietary folate equivalents < 400 mcg/day in adults and < 600 mcg/day in pregnant women characterized by megaloblastic anemia, and risk of neural tube defects and congenital anomalies.
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Pathophysiology
Folate deficiency is mostly caused by inadequate folate intake, pregnancy and lactation, alcoholism, gene polymorphism (C1561T), and certain medications (methotrexate, anticonvulsants, sufasalazine, pyrimethamine).
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Epidemiology
The prevalence of folate deficiency anemia in the US adults is estimated at < 0.1%.
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Disease course
Clinical manifestations include megaloblastic anemia and increased incidence of various cancers (colorectal, prostate, and breast cancer). Pregnancy-related complications include neural tube defects) spina bifida, anencephaly), and other congenital anomalies (congenital heart defects, oral cleft lip and palate) in neonates, maternal megaloblastic anemia, low infant birth weight, stillbirth, and premature delivery.
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Prognosis and risk of recurrence
Folate deficiency is associated with increased all-cause mortality with a hazard ratio of 1.33 (95% CI 1.01-1.76).
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of folate deficiency are prepared by our editorial team based on guidelines from the U.S. Preventive Services Task Force (USPSTF 2023), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2021), the American College of Obstetricians and Gynecologists (ACOG 2017), and the British Society for Haematology (BSH 2014).
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Screening and diagnosis

Indications for testing: as per BSH 2014 guidelines, test for folate deficiency in clinical situations similar to those in which testing for cobalamin deficiency is obtained.
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  • Diagnostic criteria

Diagnostic investigations

Serum folate and cobalamin: as per BSH 2014 guidelines, obtain cobalamin and folate assays concurrently, given the close relationship in their metabolism.
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  • CBC and peripheral blood smear

  • RBC folate

  • Serum homocysteine

  • Evaluation for medication-associated folate deficiency

Medical management

Folic acid
As per BSH 2014 guidelines:
Initiate folic acid 5 mg PO daily for 4 months in patients with folate-deficient megaloblastic anemia (due to dietary insufficiency, pregnancy, or antiepileptics). Continue treatment in pregnant patients until term. Consider initiating 15 mg daily for 4 months in malabsorptive states.
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Consider initiating prophylactic folic acid 5 mg PO daily to weekly in patients with chronic hemolytic states and renal dialysis, depending on the diet and rate of hemolysis.
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Specific circumstances

Pregnant patients: as per USPSTF 2023 guidelines, offer folic acid supplementation of 400-800 mcg/day in all individuals planning to or who could become pregnant, to prevent fetal neural tube defects.
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  • Patients with pernicious anemia