CurrentPremera BluecrossPolicy 2.04.152

Maternal serum biomarker testing for preeclampsia and spontaneous preterm birth

Governs coverage stance for maternal serum biomarker tests (with or without algorithmic analysis) used to predict pre-eclampsia and spontaneous preterm birth for pregnant individuals; intended for providers and payers evaluating medical necessity and coding. Applies to Premera Bluecross policy documentation in this window.

Policy Summary

PayerPremera Bluecross

PolicyMaternal serum biomarker testing for preeclampsia and spontaneous preterm birth

Policy CodePolicy 2.04.152

Change TypeAnnual reviewcoding updates

Effective DateMay 1, 2025

Next Review Date

Key ActionDo not request prior authorization for maternal serum biomarker tests expecting coverage; these tests are considered investigational and prior authorization is expected to be denied.

SourceLink

POLICY UPDATE CHANGES

Added new CPT code 0390U (new code effective 7/1/2023).

Policy updated with literature review through January 2, 2024; references added. Policy statements unchanged.

Added new CPT code 0482U.

Added new CPT code 0524U.

Updated code descriptor on HCPCS code 0524U.

Annual Review: Policy updated with literature review through December 9, 2024; references added. Policy statements unchanged.

InvestigationalCoverage stance

0243U,0247U,0482U,0524UListed CPT codes

May 2023FDA De Novo clearance

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Most recent approval

Coverage Criteria

Preeclampsia — Investigational

Covered when ALL of the following are met

Investigational stance: The use of maternal serum biomarker tests with or without additional algorithmic analysis for prediction of pre-eclampsia is considered investigational.

From Policy Coverage Criteria.

Spontaneous Preterm Birth — Investigational

Covered when ALL of the following are met

Investigational stance: The use of maternal serum biomarker tests with or without additional algorithmic analysis for prediction of spontaneous preterm birth is considered investigational.

From Policy Coverage Criteria.

Clinical guidance and regulatory context

Summary of policy-relevant clinical guidance and regulatory status (no new coverage criteria in this section):

Guideline positions: ACOG and ACOG-SMFM describe maternal serum biomarker screening as investigational and do not recommend using these biomarkers for routine risk assessment for preeclampsia or spontaneous preterm birth; FIGO endorses first-trimester combined testing including biomarkers; ISSHP recommends adding angiogenic imbalance assessment when available for suspected pre-eclampsia before 37 weeks; NICE recommends specified PLGF-based tests for suspected preterm pre-eclampsia (20 to 36+6 weeks) and does not recommend certain ratios for routine use.

guideline heterogeneity noted

Regulatory status: FDA cleared BRAHMS sFlt-1/PlGF KRYPTOR Test System (De Novo DEN220027, May 2023) for prognostic use along with other laboratory tests and clinical assessments to aid risk assessment in hospitalized singleton pregnancies between 23+0 and 34+6/7 weeks for progression to preeclampsia with severe features within 2 weeks; other commercially produced PLGF/sFlt-1 assays are described but may not be available in the United States; laboratory-developed tests are offered under CLIA high-complexity laboratory regulations.

Specific FDA clearance specifies intended population and use

Proteomic test for preterm birth (PreTRM): PreTRM test is intended by the manufacturer for asymptomatic pregnant individuals aged 18 years or older with a singleton pregnancy, performed via a single blood draw during the 19th week of gestation to assess risk of spontaneous preterm birth; this provides regulatory/availability context but does not establish coverage criteria.

Maternal serum biomarker tests — with or without algorithmic analysis — used to predict pre-eclampsia are classified as investigational under this policy. The use of these tests for prediction of pre-eclampsia does not meet criteria for coverage.

The National Institute for Health and Care Excellence (NICE) guidance (2022) recommends specified PLGF-based tests to assist diagnosis in people with suspected preterm pre-eclampsia between 20+0 and 36+6 weeks, but explicitly states that the BRAHMS sFlt-1 KRYPTOR/BRAHMS PLGF plus KRYPTOR PE ratio is not recommended for routine use in the NHS and that further research is needed to show accuracy when using specified thresholds.

The evidence is insufficient to demonstrate that maternal serum biomarker testing, either alone or as part of an algorithmic risk score, improves net health outcomes for pregnant individuals. Studies include observational clinical‑validity work and randomized trials, but clinical decision thresholds varied, many tests evaluated are not cleared in the U.S., and randomized trials (including those of the commercially produced PreTRM test) have not shown improvement in preterm birth or neonatal outcomes. Therefore these tests remain investigational.

This policy’s investigational stance is concordant with major U.S. guideline groups: ACOG and the joint ACOG–SMFM guidance describe maternal serum biomarker screening as investigational and do not recommend using these biomarkers for routine risk assessment for preeclampsia or spontaneous preterm birth. The policy history and guideline review were considered in reaching the not‑covered designation.

Coding

Listed CPT CodesCPT

0243U	Obstetrics (preeclampsia), biochemical assay of placental-growth factor, time-resolved fluorescence immunoassay, maternal serum, predictive algorithm reported as a risk score for preeclampsia (use to report: PGIF Preeclampsia Screen by PerkinElmer Genetics, Inc., Brahms sFlt-1/ PlGF KRYPTOR Test System).
0247U	Obstetrics (preterm birth), insulin-like growth factor-binding protein 4 (IBP4), sex hormone-binding globulin (SHBG), quantitative measurement by LC-MS/MS, utilizing maternal serum, combined with clinical data, reported as predictive-risk stratification for spontaneous preterm birth (use to report: PreTRM test by Sera Prognostics, Inc.).
0482U	Obstetrics (preeclampsia), biochemical assay of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), serum, ratio reported for sFlt-1/PlGF, with risk of progression for preeclampsia with severe features within 2 weeks.
0524U	Obstetrics (preeclampsia), sFlt-1/PlGF ratio, immunoassay, utilizing serum or plasma, reported as a value.

Policy-related CPT/HCPCS codes (history log)mixed

0390U	CPT code added 07/01/2023 (later removed from HCPCS list per 05/01/24 history note)
0482U	CPT code added 10/01/24
0524U	CPT/HCPCS code added 01/01/25; descriptor updated 01/01/26

sFlt-1/PlGF ratio cutoff

Reported cutoffsVarious cutoffs reported in literature; the PRAECIS study proposed an sFlt-1/PlGF ratio cutoff of 40

Variation across studiesOther publications have proposed different sFlt-1/PlGF ratio thresholds (no single universally accepted cutoff)

Test system examplePRAECIS evaluated the KRYPTOR test system and suggested cutoff of 40 in a U.S. cohort

BRAHMS sFlt-1/PlGF indicated use window

FDA-cleared intended populationHospitalized singleton pregnancies between gestational age 23+0 to 34+6/7 weeks

Intended useAid in risk assessment for progression to preeclampsia with severe features within 2 weeks when used along with other laboratory tests and clinical assessments

Provider Actions and Billing Guidance

Prior Authorization

Prior Authorization — verify with payer

Prior authorization is not typically required specifically for investigational maternal serum biomarker tests; however, providers should verify member benefit coverage and obtain any required prior authorization for laboratory services per the member's plan before ordering tests. If a test is billed using one of the listed CPT codes, confirm benefit eligibility and prior authorization rules with the payer to avoid unexpected denials.

Verify member-specific prior authorization requirements before ordering laboratory-developed tests
Confirm benefit coverage for the specific CPT/HCPCS code billed

Denial Risk

Investigational — potential claim denial

Maternal serum biomarker tests for prediction of preeclampsia or spontaneous preterm birth are designated investigational in this policy and are subject to denial when billed for these indications. Claims for these services will be reviewed against the policy coverage criteria; lack of documented medical necessity consistent with the policy may result in claim denial.

Background

Preeclampsia is new‑onset hypertension occurring after 20 weeks’ gestation that may be accompanied by proteinuria or end‑organ dysfunction and can progress to severe disease (eclampsia or HELLP syndrome). It is a potentially life‑threatening hypertensive disorder of pregnancy and can result in significant maternal and perinatal morbidity. Standard evaluation relies on clinical history, blood pressure monitoring, and laboratory assessment; maternal serum biomarker tests have been studied as adjuncts to risk stratification but have not been shown to improve health outcomes.

Definitions

Preeclampsia definition

Core definitionNew-onset maternal hypertension and proteinuria, or new-onset hypertension with significant end-organ dysfunction, occurring after 20 weeks of gestation

Possible progressionMay progress to eclampsia or HELLP syndrome and can cause maternal and fetal morbidity and mortality

Epidemiology noteHypertensive disorders affected approximately 1 in 7 delivery hospitalizations (2017–2019); higher prevalence in certain groups

Spontaneous preterm birth definition

DefinitionBirth occurring between the 20th and 37th week of pregnancy due to spontaneous labor or rupture of membranes (distinct from iatrogenic preterm birth)

EpidemiologyU.S. preterm birth rate ~10.1% in 2020

Policy Summary

PayerPremera Bluecross

PolicyMaternal serum biomarker testing for preeclampsia and spontaneous preterm birth

Policy CodePolicy 2.04.152

Change TypeAnnual reviewcoding updates

Effective DateMay 1, 2025

Next Review Date

Key ActionDo not request prior authorization for maternal serum biomarker tests expecting coverage; these tests are considered investigational and prior authorization is expected to be denied.

SourceLink

On This Page

Regulatory/availability context provided

Test system referencedB·R·A·H·M·S sFlt-1/PlGF KRYPTOR Test System (Thermo Fisher Scientific) cleared via De Novo (May 2023)

PreTRM intended use gestational age

Gestational age for testSingle blood draw during the 19th week of gestation

Intended patient populationPregnant individuals aged 18 years or older, asymptomatic, with a singleton pregnancy

Test componentsUses maternal serum biomarkers (IBP4 and SHBG) combined with biometric measures

Services considered investigational include maternal serum biomarker tests with or without algorithmic analysis for prediction of preeclampsia or spontaneous preterm birth
Denials may occur when billed for predictive/screening indications rather than for supported diagnostic uses

Denial Risk

Investigational designation — denial likelihood

When a specific test or code has been evaluated and designated investigational by the payer (per this policy), anticipate denials unless there is clear documentation that the service falls outside the investigational indication (e.g., use consistent with an FDA-cleared indication or guideline-supported diagnostic use). Providers may request medical review or peer-to-peer discussion if clinical circumstances suggest a different determination.

Investigational designation applies to maternal serum biomarker tests for prediction of preeclampsia or spontaneous preterm birth
Consider appeal or provider inquiry if the service aligns with an FDA-cleared indication or other guideline-supported diagnostic use

Documentation Required

Documentation expectations (background)

Document the clinical indication, relevant medical and obstetric history, gestational age at testing, prior screening or diagnostic results (for example, blood pressure measurements, cervical length measurements, prior preterm birth history), and rationale for ordering the serum biomarker test. Include laboratory reports, test method, and whether the test is a laboratory-developed test or an FDA-cleared system in the clinical record to support medical necessity.

Record gestational age and specific clinical question being addressed
Include prior clinical assessments (blood pressure, cervical length, prior preterm birth) and contraceptive/medication history if relevant
Specify laboratory name, CLIA status, and whether test is FDA-cleared or a laboratory-developed test (LDT)

Documentation Required

Laboratory and regulatory context

Indicate the laboratory context (CLIA certification, LDT status) and regulatory status of the assay when available. For tests performed using FDA-cleared systems (for example, the B·R·A·H·M·S sFlt-1/PlGF KRYPTOR Test System with its specified inpatient prognostic indication), document how the use aligns with the cleared indication. For laboratory-developed tests, include CLIA high-complexity laboratory information.

Document CLIA certification and whether the test is an LDT or FDA-cleared
If using an FDA-cleared test, document how clinical use matches the cleared indication and gestational age window

Note

Preferred standard evaluations before experimental testing

Before ordering investigational maternal serum biomarker testing for prediction of preeclampsia or preterm birth, complete preferred standard evaluations first: review obstetric and medical history, measure and document blood pressure at prenatal visits, perform indicated ultrasonographic cervical length measurement per ACOG guidance, and assess other established clinical risk factors. Use guideline-recommended interventions (for example, cervical length–based surveillance and progesterone where indicated) based on those standard assessments.

Perform and document standard risk assessments (history, blood pressure monitoring) prior to experimental testing
Obtain cervical length assessment per ACOG when indicated before relying on biomarker testing

Step Therapy

Guideline-aligned step considerations

If considering use of a biomarker test as an adjunct, follow guideline-aligned step considerations: ensure the test would change management beyond standard care, confirm appropriate gestational timing (per test instructions or FDA clearance), and prefer tests with external validation or guideline support. Tests without demonstrated added predictive value over standard assessments are not supported by this policy.

Confirm that test timing and population match the intended/cleared use (e.g., gestational age windows)
Use tests only when results would meaningfully alter surveillance or interventions
Prefer externally validated tests or those recommended by professional guidelines

Key risk factorsPrior preterm birth, shortened cervical length, vaginal bleeding or infection, extremes of maternal age; most preterm births occur without clear maternal risk factors

Angiogenic imbalance definition

Angiogenic imbalance definedReduced PlGF (<5th centile for gestational age) or increased sFlt-1/PlGF ratio

Guideline recommendationISSHP recommends adding evaluation of angiogenic imbalance when available for assessment of suspected preeclampsia (<37 weeks)

Clinical roleConsidered an adjunct marker of uteroplacental dysfunction to be used with other clinical tests

PreTRM test definition/description

Test descriptionA proteomic risk assessment using IBP4 and SHBG combined with biometric measures to assess risk of spontaneous preterm birth

Intended populationAsymptomatic pregnant individuals aged 18 years or older with a singleton pregnancy

Timing of specimenPerformed via a single blood draw during the 19th week of gestation