CurrentPremera BluecrossPolicy 2.04.152

Maternal Serum Biomarkers for Prediction of Adverse Obstetric Outcomes

Defines coverage stance for maternal serum biomarker testing (with or without algorithmic analysis) to predict pre-eclampsia or spontaneous preterm birth for Premera Bluecross members and providers.

Policy Summary

PayerPremera Bluecross

PolicyMaternal Serum Biomarkers for Prediction of Adverse Obstetric Outcomes

Policy CodePolicy 2.04.152

Change TypeNo material change

Effective DateMay 1, 2025

Next Review DateJan 1, 2026

Key ActionVerify benefit and prior authorization requirements before ordering or billing maternal serum biomarker tests, as they are designated investigational and may be denied.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

InvestigationalCoverage stance

4 codesCPT codes listed

1 De NovoRegulatory clearance noted

ACOG differsGuideline variance

Coverage Criteria

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FDA-cleared prognostic use (described)

Tests with regulatory clearance have limited specified clinical contexts

FDA-cleared assay context: The BRAHMS sFlt-1/PlGF KRYPTOR Test System is FDA De Novo cleared for use along with other laboratory tests and clinical assessments to aid in the risk assessment of hospitalized pregnant individuals (singleton pregnancies between gestational age 23+0 to 34+6/7 weeks) for progression to preeclampsia with severe features within 2 weeks of presentation.gestational age 23+0 to 34+6/7 weeks

Clearance specifies hospitalized individuals and use with other clinical assessment.

The evidence is insufficient to demonstrate that maternal serum biomarker testing, either alone or combined with algorithmic analysis, improves net health outcomes. Systematic reviews, observational clinical validity studies, and randomized trials have limitations: many studies used assays not cleared in the US, proposed varying biomarker cutoffs (for example for PlGF or sFlt-1/PlGF ratio), and randomized trials (including those of the PreTRM test) did not show improvements in clinically important maternal or neonatal outcomes. Consequently, available data do not establish that biomarker testing leads to better clinical outcomes or management decisions.

Coding

Listed CPT codes for maternal serum biomarker testsCPT

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-tracked CPT/HCPCS codesmixed

0390U	CPT/HCPCS code added July 1, 2023 (descriptor not restated in this excerpt)
0482U	CPT code added October 1, 2024 (descriptor not restated in this excerpt)
0524U	CPT code added January 1, 2025; HCPCS code descriptor updated January 1, 2026

Provider Actions / Billing

Prior Authorization

Prior Authorization Expected

Prior authorization may be required for the maternal serum biomarker CPT codes listed in this policy. Providers should obtain prior authorization according to the member's benefit plan before performing or submitting claims for these tests.

Affected CPT codes include, but may not be limited to: 0243U, 0247U, 0482U, 0524U.

Note

Verify Coverage / Prior Authorization

Verify coverage and prior authorization requirements with the member’s benefit plan and payer before ordering or billing maternal serum biomarker tests. Member contracts and benefit designs vary; coverage is not guaranteed by this policy statement.

Denial Risk

Investigational — Clinical Use

The use of maternal serum biomarker tests (with or without additional algorithmic analysis) for prediction of preeclampsia or prediction of spontaneous preterm birth is considered investigational under this policy.

Billing Rule

Billing Guidance — CPT Reporting

When billed, providers may report one of the listed CPT codes that most accurately describes the test performed. Ensure coding matches the test methodology and vendor (for example, PGIF Preeclampsia Screen, PreTRM, sFlt-1/PlGF ratio assays) and that supporting documentation is available.

Common CPT codes: 0243U, 0247U, 0482U, 0524U.

Documentation Required

Required Documentation for Laboratory Biomarker Testing

Maintain documentation supporting the medical necessity and the specific test performed, including clinical indication, gestational age when applicable, laboratory report, and any algorithmic or vendor test name. Laboratories must be CLIA-certified for high-complexity testing when offering these assays.

Denial Risk

Investigational Status May Lead to Denial

Because these maternal serum biomarker tests are considered investigational by this policy, claims may be denied as not medically necessary. Providers should verify prior authorization and coverage before ordering; lack of prior authorization or investigational status may result in claim denial.

Definitions

Preeclampsia definition and key points

DefinitionNew-onset maternal hypertension with proteinuria or new-onset hypertension with significant end-organ dysfunction occurring after 20 weeks of gestation (may progress to eclampsia or HELLP).

Clinical significanceCan cause maternal organ damage, fetal growth restriction, and increased maternal and neonatal mortality; often detected late requiring premature delivery in severe cases.

Typical onset timingAfter 20 weeks of gestation.

Related complicationsEclampsia, placental abruption, HELLP syndrome, fetal growth restriction, intrauterine death.

Policy relevanceMaternal serum biomarker tests to predict preeclampsia are considered investigational and not covered by this policy.

Spontaneous preterm birth definition

DefinitionBirth occurring between the 20th and 37th week of pregnancy that is spontaneous (following preterm labor or rupture of membranes), not iatrogenic.

Timing20+0 to 36+6 weeks of gestation (preterm period).

Risk factorsPrior preterm birth, cervical shortening/dilation, vaginal bleeding or infection, maternal age <18 or >35, smoking, short interpregnancy interval, maternal stress.

Clinical impactLeading cause of neonatal morbidity and mortality; increased infant mortality up to 5 years and long-term morbidity into adulthood.

Policy relevanceMaternal serum biomarker tests to predict spontaneous preterm birth are considered investigational and not covered by this policy.

sFlt-1/PlGF ratio definition

DefinitionLaboratory measurement comparing soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) reported as a ratio to assess angiogenic imbalance associated with preeclampsia.

FDA-cleared system exampleThe B·R·A·H·M·S sFlt-1/PlGF KRYPTOR Test System (Thermo Fisher) was FDA De Novo cleared (DEN220027) for use with other clinical assessments in hospitalized singleton pregnancies 23+0 to 34+6/7 weeks to aid risk assessment for progression to preeclampsia with severe features within 2 weeks.

Reported formatsReported as a ratio value (sFlt-1/PlGF) from serum or plasma via immunoassay or combined assays identified by CPT/HCPCS codes in the policy.

Clinical context per clearanceClearance specifies use in hospitalized pregnant individuals for hypertensive disorders of pregnancy and to be used alongside other laboratory tests and clinical assessment.

PreTRM test definition

DefinitionA proteomic biomarker test that measures insulin-like growth factor‑binding protein 4 (IBP4) and sex hormone‑binding globulin (SHBG) in maternal serum and combines biomarker data with clinical variables to generate a risk score for spontaneous preterm birth.

Intended populationAs described by the manufacturer: asymptomatic pregnant individuals aged ≥18 years with a singleton pregnancy and no signs or symptoms of preterm labor, performed at 19 weeks' gestation.

Assay reportingReported as a predictive‑risk stratification (risk score) for spontaneous preterm birth; historically associated with the commercial PreTRM test (Sera Prognostics) and CPT code reporting in the policy.

Regulatory/operational notePerformed via a single blood draw during the 19th week of gestation; marketed as a laboratory service and subject to CLIA high‑complexity requirements for labs offering laboratory‑developed tests.

OpenPayer

Maternal Serum Biomarkers for Prediction of Adverse Obstetric Outcomes

Coverage Criteria

Coding

Provider Actions / Billing

Background

Definitions