ModifiedPremera BluecrossPolicy ROUTINE TEST MANAGEMENT POLICY - 15.01.024

Folate testing (serum, RBC, and folate receptor autoantibody)

Policy governing reimbursement and medical necessity for serum folate, red blood cell (RBC) folate, and folate receptor autoantibody testing for Premera Blue Cross members; describes covered indications and non-reimbursable situations.

Policy Summary

PayerPremera Bluecross

PolicyFolate testing (serum, RBC, and folate receptor autoantibody)

Policy CodePolicy ROUTINE TEST MANAGEMENT POLICY - 15.01.024

Change TypeAdded coverage allowance for serum folate in specified post-treatment anemia

Effective DateFeb. 6, 2026

Next Review Date

Key ActionOrder serum folate only for patients with megaloblastic or macrocytic anemia that does not resolve after folic acid treatment and document failure to respond.

SourceLink

POLICY UPDATE CHANGES

New policy approved October 14, 2025 and effective for dates of service on or after February 6, 2026 following 90-day provider notification.

Measurement of serum folate concentration may be considered reimbursable for certain individuals when criteria are met.

serum folate reimbursable only in specific anemiascoverage restriction

RBC folate not reimbursablecoverage exclusion

folate receptor autoantibody not reimbursablecoverage exclusion

2026-02-06

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90-dayprovider notification

2025-10-14approval date

Coverage Criteria

Serum folate (initial/diagnostic)

Covered when ALL of the following are met

Serum folate coverage: Serum folate testing is reimbursable for individuals diagnosed with megaloblastic or macrocytic anemia and for whom the megaloblastic anemia and/or macrocytosis does not resolve after folic acid treatment.

Provider must document the diagnosis of megaloblastic or macrocytic anemia and lack of resolution after an adequate trial of folic acid therapy.

RBC folate and folate receptor autoantibody testing

Not covered (explicit)

RBC folate and other tests: Measurement of red blood cell (RBC) folate is not reimbursable for any indications. Folate receptor autoantibody testing (e.g., FRAT®) is not reimbursable for all situations due to lack of published evidence demonstrating clinical benefit.

CPT 82747 (RBC folate) and proprietary test 0399U (FRAT®) are non-reimbursable.

Recommended testing contexts

Guidance-based indications where RBC folate or serum folate testing is recommended or preferred

CKD with anemia: In patients with chronic kidney disease and anemia include serum vitamin B12 and folate levels in the initial evaluation; measure RBC folate when serum folate is equivocal or when recent dietary intake may obscure underlying folate deficiency.

KDIGO guidance supports including B12 and folate in initial anemia workup and measuring RBC folate selectively.

Myelodysplastic syndromes initial evaluation: For initial evaluation of suspected myelodysplastic syndromes, RBC folate is preferred as a measure of folate stores; serum folate may be considered as an alternative but is not preferable.

NCCN recommends RBC folate preferred for MDS evaluation.

Pre-operative bariatric assessment and pregnancy surveillance after bariatric surgery: Pre-operative nutrient screening for bariatric surgery should include iron studies, B12 and folic acid (with RBC folate and homocysteine optional); after bariatric procedures, trimester surveillance for folate deficiency is recommended.

Mechanick et al. recommend preoperative screening and trimester surveillance post-bariatric surgery.

RBC folate testing (CPT 82747) and folate receptor autoantibody testing (proprietary FRAT®, CPT 0399U) are explicitly excluded from reimbursement for all indications. The policy states that measurement of red blood cell folate is not reimbursable for any indications and that folate receptor autoantibody testing is not reimbursable due to lack of published evidence supporting clinical benefit.

The British Committee for Standards in Haematology (BCSH) guidance notes that routine red cell (RBC) folate testing is not necessary because serum folate alone is sufficient in most cases. BCSH does acknowledge select situations where RBC folate may be measured when there is a strong clinical suspicion of deficiency despite normal serum folate after ruling out cobalamin deficiency.

This medical policy is not applicable to Medicare Advantage members. Providers should verify plan-specific rules and prior authorization requirements with the member’s benefit plan or customer service for Medicare Advantage enrollees.

Serum folate testing is reimbursable only when all coverage conditions are met: an individual has been diagnosed with megaloblastic or macrocytic anemia and the anemia and/or macrocytosis does not resolve after a trial of folic acid treatment. For indications outside this scenario, serum folate testing is not reimbursable.

Routine or indiscriminate ordering of RBC folate is discouraged in the post-fortification era and when national guidance indicates serum folate provides equivalent information. The National Pathology Alliance (2003) recommended serum folate measurements can be equivalent to RBC folate, and BCSH states serum folate is sufficient in most cases, reserving RBC folate for select circumstances with strong clinical suspicion.

Covered Indications

Megaloblastic or macrocytic anemia not resolved after folic acid treatment

Covered when ALL of the following are met

Megaloblastic or macrocytic anemia not resolved after folic acid treatment: Measurement of serum folate concentration may be considered reimbursable for individuals diagnosed with megaloblastic or macrocytic anemia that does not resolve after folic acid treatment.

Documentation must show the diagnosis and failure to respond to folic acid therapy prior to reimbursement consideration.

Monitoring for patients with IBD or celiac disease

Covered when criteria met for monitoring

IBD monitoring: In patients with inflammatory bowel disease, measure serum vitamin B12 and folic acid at least annually or sooner if macrocytosis is present.at least annually

ECCO guidance: measure at least annually or when macrocytosis present.

Provider Actions & Billing Guidance

Documentation Required
Anemia in CKD — include serum B12/folate; consider RBC folate when serum is equivocal
For individuals with chronic kidney disease (CKD) and anemia, include serum vitamin B12 and folate levels as part of the initial anemia evaluation. If serum folate is equivocal or there is concern that recent dietary intake may obscure deficiency, measure RBC folate. Documentation should indicate CKD diagnosis and the clinical rationale for folate testing.
Initial CKD anemia workup: CBC, absolute reticulocyte count, ferritin, TSAT, serum B12 and folate
Measure RBC folate when serum folate is equivocal or dietary intake may obscure deficiency
Document CKD stage, anemia findings, and rationale for ordering folate tests

Note
AAFP: prefer RBC folate; serum folate may be misleading
AAFP guidance recommends obtaining RBC folate when other etiologies are not found because serum folate fluctuates with dietary intake and may be misleading. Reserve serum folate testing for situations where RBC folate is not available or when other guideline-directed steps have been taken.

Codes and Billing

Folate-related CPT / Proprietary test codesCPT

82746	Folic acid; serum
82747	Folic acid; RBC
0399U	Neurology (cerebral folate deficiency), serum, detection of anti-human folate receptor IgG-binding antibody and blocking autoantibodies by enzyme-linked immunoassay (ELISA), qualitative, and blocking autoantibodies, using a functional blocking assay for IgG or IgM, quantitative, reported as positive or not detected Proprietary test: FRAT® (Folate Receptor Antibody Test) Lab/Manufacturer: Religen Inc.

Ordering Requirements

Billing Rule
Ordering requirement — align orders with coverage criteria
Order serum folate only when consistent with coverage criteria: for patients with megaloblastic or macrocytic anemia that does not resolve after folic acid treatment; do not order serum folate for other indications expecting reimbursement.
Ensure clinical documentation demonstrates prior folic acid therapy and lack of response before ordering/ billing.

Note
Ordering requirement — follow specialty evaluation pathways
Follow specialty-specific evaluation pathways when selecting serum vs RBC folate: e.g., AAFP and KDIGO recommend RBC folate in certain diagnostic sequences or initial CKD anemia evaluations; choose the test based on clinical context and guidelines.
Use RBC folate when recommended by specialty guidance (AAFP for macrocytic anemia, KDIGO for CKD-related anemia scenarios).

Frequency Limits and Surveillance

Frequency limits — general

Frequency limits statedNone specified in this section of the document.

Policy noteFrequency limits are addressed elsewhere for specific populations (see annual or trimester guidance in other entries).

Action for providersWhen in doubt, document clinical indication and verify member benefits for coverage frequency rules.

Frequency limits — B12 and folate (serum or RBC as indicated)

Test and intervalB12 and folate (serum or RBC as indicated): annual.

Applicable contextsRecommended for monitoring after radical cystectomy (NICE) and for at-risk patients with IBD or celiac disease (ECCO) as part of annual surveillance.

Not Covered

Measurement of red blood cell folate and folate receptor autoantibody testing (FRAT®) are listed as not covered for any situations. The policy explicitly states that RBC folate testing is not reimbursable for all indications and that folate receptor autoantibody testing is not reimbursable due to insufficient published scientific literature demonstrating benefit.

Routine RBC folate testing is discouraged: BCSH guidance indicates that in most situations serum folate alone is sufficient, and RBC folate should be reserved for select cases where serum levels are normal but clinical suspicion remains after excluding cobalamin deficiency.

This policy does not apply to Medicare Advantage. Coverage and reimbursement determinations for Medicare Advantage members should be made according to the member’s specific plan benefits and related authorization processes.

Definitions

Definition — Folate (vitamin B9)

DefinitionFolate (vitamin B9): a water-soluble vitamin involved in one-carbon metabolism, nucleic acid biosynthesis, and methionine/homocysteine metabolism.

Clinical relevanceFolate deficiency can cause megaloblastic/macrocytic anemia and increase risk of neural tube defects; usually corrected with diet or folic acid supplementation.

Relationship to B12Folate metabolism is closely linked to vitamin B12 (cobalamin); both required for key steps in methylation pathways.

Definition — Megaloblastic anemia

DefinitionMegaloblastic anemia: a macrocytic anemia due to nucleic acid metabolic defects causing nuclear-cytoplasmic dyssynchrony, caused by folate and/or B12 deficiency.

Key features

Background

Folate (vitamin B9) is essential for one‑carbon metabolism, nucleic acid synthesis, and methionine/homocysteine metabolism, and it is closely linked with vitamin B12. Folate deficiency can cause megaloblastic/macrocytic anemia and increases risk for neural tube defects; dietary intake or supplementation corrects deficiency in most cases, and population folic acid fortification has reduced the prevalence of deficiency.

Supporting references

Guideline and evidence sourcesKey references include IOM (1998), Mechanick et al. 2019 (bariatric guidelines), NICE (2015), NCCN (2024), ECCO (2015), KDIGO (2012), and multiple systematic and observational studies relevant to folate testing.

Population/public healthNIH and CDC recommendations on folic acid supplementation have reduced folate deficiency prevalence in fortified countries; consult public health guidance for reproductive-age individuals.

Clinical utility studiesShojania & von Kuster (2010) and other studies report low incidence of folate-deficiency anemia in fortified countries, informing recommendations to limit routine testing.

Revision History

2025-10-14approval

Policy approved by Premera Blue Cross.

2025-11-01revision_history_entry

New policy added to Routine Test Management Policy section and documented in policy history (entry dated 11/01/2025).

2026-02-06effective_dateLatest

Policy effective for dates of service on or after February 6, 2026 following a 90-day provider notification period.

Policy Summary

PayerPremera Bluecross

PolicyFolate testing (serum, RBC, and folate receptor autoantibody)

Policy CodePolicy ROUTINE TEST MANAGEMENT POLICY - 15.01.024

Change TypeAdded coverage allowance for serum folate in specified post-treatment anemia

Effective DateFeb. 6, 2026

Next Review Date

Key ActionOrder serum folate only for patients with megaloblastic or macrocytic anemia that does not resolve after folic acid treatment and document failure to respond.

SourceLink

On This Page

Strong clinical suspicion despite normal serum folate: When there is strong clinical suspicion of folate deficiency despite a normal serum folate level (after ruling out cobalamin deficiency), perform RBC folate testing to evaluate folate stores.

BCSH acknowledges RBC folate testing may be undertaken in selected cases with discrepant clinical picture.

IBD or celiac disease monitoring: In patients with inflammatory bowel disease or newly diagnosed celiac disease, measure serum B12 and folic acid at least annually or if macrocytosis is present; test and treat micronutrient deficiencies including folic acid as indicated.at least annually

ECCO and ACG guidance support at least annual measurement or testing at baseline for celiac disease.

Oncology patients with suspected nutritional anemia: Include folate (serum or as indicated) in a nutritional anemia profile alongside hemoglobin, hematocrit, B12, and iron when evaluating oncology patients for nutritional anemia.

Academy of Nutrition and Dietetics recommends folate as part of the nutritional anemia profile.

Celiac disease monitoring: People with newly diagnosed celiac disease should undergo testing for micronutrient deficiencies including folic acid at baseline and individualized follow-up to verify correction of abnormalities.

ACG recommends testing for folic acid among other micronutrients at diagnosis and individualized follow-up.

Post-radical cystectomy and bariatric surgery patients

Covered when routine surveillance is indicated

Post-radical cystectomy surveillance: After radical cystectomy, monitor for vitamin B12 and folate deficiency at least annually.at least annually

NICE recommends annual monitoring after radical cystectomy.

Bariatric surgery perioperative and pregnancy surveillance: Preoperative bariatric assessment should include iron studies, B12 and folic acid (RBC folate optional); for patients who become pregnant after bariatric surgery, perform trimester surveillance for folate deficiency.each trimester for pregnancy surveillance after bariatric surgery

Mechanick et al. recommend preoperative screening and trimester surveillance post-bariatric surgery.

Oncology patients with suspected nutritional anemia

Covered when part of nutritional anemia evaluation

Oncology nutritional anemia assessment: In oncology patients with suspected nutritional anemia, include folate measurement as part of the nutritional anemia profile (hemoglobin, hematocrit, folate, B12, iron).

Academy of Nutrition and Dietetics recommends including folate in the nutritional anemia profile.

Certain individuals may have measurement of serum folate concentration reimbursed when criteria are met.

Selective reimbursement: Measurement of serum folate concentration may be reimbursable for certain individuals when the applicable clinical criteria are met and appropriately documented; specific additional criteria are not detailed in this document segment.

Policy history notes measurement may be considered reimbursable when criteria are met; verify member benefits and document clinical indications.

Obtain RBC folate if folate deficiency is suspected and other causes have been excluded
Serum folate may be misleading due to rapid dietary fluctuations; use RBC folate preferentially

Prior Authorization
Prior authorization / Reimbursement summary and documentation requirements
For individuals diagnosed with megaloblastic or macrocytic anemia that does not resolve after folic acid treatment, measurement of serum folate concentration may be considered reimbursable. Documentation must support the diagnosis and prior folic acid treatment and failure to resolve. For other indications, serum folate testing is not reimbursable; RBC folate is generally not reimbursable except as noted by specialty guidance (e.g., NCCN for MDS) and plan-specific benefit rules.
Reimbursable CPT: 82746 (serum folic acid) only when megaloblastic/macrocytic anemia persists after folic acid treatment
RBC folate (CPT 82747) discouraged routinely; preferred in certain specialty evaluations per NCCN
Ensure documentation shows prior folic acid therapy, clinical response, and rationale for testing

Denial Risk
Denial triggers and plan verification
Claims for serum folate testing will be denied except when used for individuals diagnosed with megaloblastic or macrocytic anemia that do not resolve after folic acid treatment. Verify member benefits and prior authorization rules; this policy does not apply to Medicare Advantage.
Denial trigger: serum folate billed for indications outside persistent megaloblastic/macrocytic anemia post-treatment
Verify plan-specific coverage and prior authorization with the member's benefit booklet or member services
This policy does not apply to Medicare Advantage

Note
Ordering requirement — verify coverage when unspecified
Consult the member benefit booklet or contact member services to determine coverage for a specific folate test request when the policy or clinical scenario does not clearly specify coverage.
If coverage is uncertain for a requested test, verify benefits and prior authorization requirements before performing the test.

Ordering guidanceUse serum or RBC folate based on clinical context; document indication when billing for annual testing.

Frequency limits — folate (surveillance laboratories)

Test and intervalFolate (surveillance laboratories) for patients post-bariatric surgery who become pregnant: each trimester.

Guideline sourceMechanick et al. 2019 (perioperative bariatric guidelines) recommend trimester surveillance after bariatric surgery.

Clinical noteInclude folate with other prenatal nutrient surveillance (iron, B12, vitamin D) in trimester checks for post-bariatric patients.

Frequency limits — serum folate concentration

Frequency limits statedSerum folate concentration: frequency limits not specified in this section of the document.

Policy history noteMeasurement of serum folate concentration may be considered reimbursable for certain individuals when criteria are met (policy addition, effective Feb 6, 2026).

Provider actionDocument clinical indication when ordering; verify member benefits for any plan-specific frequency limitations.

Characterized by large RBCs (elevated mean corpuscular volume) and marrow nuclear abnormalities in erythroid and myeloid precursors.

SymptomsMay include weakness, fatigue, difficulty concentrating, irritability, headache, palpitations, and shortness of breath.

Definition — Folate receptor autoantibody testing (FRAT®)

Test nameFolate receptor autoantibody testing (FRAT®): blood test detecting autoantibodies to folate receptor alpha (proprietary FRAT®).

Clinical claimsFRAT® has been described in literature in association with cerebral folate deficiency and certain neurodevelopmental disorders, but this policy states it is not reimbursable due to lack of published evidence supporting routine use.

Proprietary statusFRAT® is a proprietary assay (autoantibody detection to folate receptor alpha).

Definition — RBC folate versus serum folate

RBC vs serum folate—stores vs intakeRBC folate reflects folate stores (less affected by recent intake) and is preferred in some settings; serum folate fluctuates with recent dietary intake and may be less reliable for chronic deficiency assessment.

Guideline contextGalloway & Rushworth (National Pathology Alliance) concluded serum folate often provides equivalent information to RBC folate for initial screening, while NCCN prefers RBC folate for MDS evaluation.

When to choose RBC folateConsider RBC folate when strong clinical suspicion exists despite normal serum folate, in malabsorptive states, or when assessing long-term folate status (e.g., MDS evaluation or certain bariatric surgery contexts).