Blue Cross Blue Shield RI prenatal testing Coverage

Coverage Criteria for Invasive Prenatal Genetic Testing

Medical necessity criteria for single-gene invasive prenatal testing

Invasive diagnostic prenatal molecular testing for single-gene disorders may be considered medically necessary when the pregnancy has been identified as high risk and ALL of the following criteria are met:

Inheritance and risk requirements: For autosomal dominant conditions: at least one parent has a known pathogenic variant; OR For autosomal recessive conditions: both parents are suspected or known carriers OR one parent is clinically affected and the other is suspected to be or is a known carrier; OR For X-linked conditions: a parent is suspected to be or is a known carrier.

Disease natural history and penetrance: The natural history of the disease is well-understood and there is a reasonable likelihood that the disease confers high morbidity in the homozygous or compound heterozygous state; any variants considered have high penetrance.

Test performance and marker association: The genetic test has adequate sensitivity and specificity to guide clinical decision making and residual risk is understood; an association of the marker with the disorder has been established.

NGS coverage determination

Policy stance on next-generation sequencing (NGS) in the setting of invasive prenatal testing:

NGS coverage stance: Use of next-generation sequencing in invasive prenatal diagnostic testing is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products because the evidence is insufficient to determine the effects of the technology on health outcomes; interpretation and clinical relevance concerns exist.insufficient evidence

Prior authorization required for named proprietary tests (see coding/authorization).

Clinical validity and coverage stance

Covered when the following distinctions are met:

Molecular single-gene testing (invasive prenatal diagnostic specimens): When testing targets a known familial pathogenic variant, clinical validity is high (expected very high sensitivity and specificity) and testing can improve net health outcome by informing reproductive decision-making and perinatal management.presence of known familial pathogenic variant

Evidence includes case series supporting test validity and impact on decisions.

Next-generation sequencing (invasive prenatal diagnostic specimens): Clinical validity of NGS in the prenatal invasive diagnostic setting is unknown; evidence is insufficient to determine that NGS improves net health outcome and interpretive concerns limit clinical utility.insufficient evidence

NGS is not supported by adequate evidence in this setting; proprietary whole-genome/NGS assays (eg, IriSight) have specific coding but remain subject to medical criteria.

Laboratories and their representatives are not permitted to obtain prior authorization or to participate in the authorization, appeal, or other administrative processes on behalf of the ordering physician. Only the ordering physician may be involved in requests for prior authorization or appeals. If a laboratory or third party is found to have supported any portion of the authorization process, BCBSRI considers this a violation and may take severe action, up to termination from the BCBSRI provider network. Services provided by a laboratory that were not authorized will be denied and the financial liability for those services will rest with the participating laboratory; such services may not be billed to the member.

The evidence for next-generation sequencing (NGS) performed on invasive prenatal diagnostic specimens is inadequate to establish clinical validity in this setting. There are specific concerns about interpretation of sequence data and uncertain clinical relevance of many findings in the prenatal context, and available studies do not provide sufficient evidence that NGS improves test validity or patient health outcomes for invasive fetal testing.

Policy determination: Next-generation sequencing (NGS) performed on invasive prenatal (fetal) diagnostic specimens is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products. Coverage for invasive molecular testing is limited to single-gene testing when the medical criteria in this policy are met and prior authorization requirements are satisfied.

Because the clinical validity is unknown for NGS in the invasive prenatal context, use of NGS for fetal diagnostic testing lacks the necessary evidence to support its routine clinical use. The insufficiency of evidence centers on uncertain interpretation of results and unclear impact on reproductive decision-making and net health outcomes.

Covered Indications

Pregnancy high risk for monogenic disorder

Pregnancy identified as high risk for a monogenic disorder based on parental carrier status or known familial pathogenic variant. Coverage requires ALL of the following be met:

High-risk pregnancy definition: Pregnancy identified as high risk because of parental known or suspected carrier status or presence of a known familial pathogenic variant.

Disease characteristics: The natural history of the disorder is well-understood with reasonable likelihood of high morbidity in homozygous/compound heterozygous state; variants have high penetrance.

Test performance: The molecular test demonstrates adequate sensitivity and specificity for the familial variant and residual risk is understood.

Clinical validity expected to be very high when familial pathogenic variant is known (case-series evidence).

Coding and Billing Codes

Covered CPT-like Codes (Proband)CPTCovered

0335U

Rare diseases (constitutional/heritable disorders), whole genome sequence analysis, including small sequence changes, copy number variants, deletions, duplications, mobile element insertions, uniparental disomy (UPD), inversions, aneuploidy, mitochondrial genome sequence analysis with heteroplasmy and large deletions, short tandem repeat (STR) gene expansions, fetal sample, identification and categorization of genetic variants

Covered CPT-like Codes (Comparator)CPTCovered

0336U

Rare diseases (constitutional/heritable disorders), whole genome sequence analysis, including small sequence changes, copy number variants, deletions, duplications, mobile element insertions, uniparental disomy (UPD), inversions, aneuploidy, mitochondrial genome sequence analysis with heteroplasmy and large deletions, short tandem repeat (STR) gene expansions, blood or saliva, identification and categorization of genetic variants, each comparator genome (eg, parent)

Covered CPT/PLA CodesCPTCovered

0335U

0336U

Rare diseases (constitutional/heritable disorders), whole genome sequence analysis, including small sequence changes, copy number variants, deletions, duplications, mobile element insertions, uniparental disomy (UPD), inversions, aneuploidy, mitochondrial genome sequence analysis with heteroplasmy and large deletions, short tandem repeat (STR) gene expansions, blood or saliva, identification and categorization of genetic variants, each comparator genome (eg, parent). (IriSight™ Prenatal Analysis - Comparator)

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for IriSight™ Prenatal Analysis - Proband (CPT 0335U) and IriSight™ Prenatal Analysis - Comparator (CPT 0336U). Laboratories are not permitted to obtain authorization or participate in the authorization process on behalf of the ordering physician. Only the ordering physician may initiate, participate in, or appeal prior authorization/medical necessity decisions. If a laboratory provides a service that has not been authorized, the service will be denied as the financial liability of the participating laboratory and may not be billed to the member.

Prior authorization required for CPT 0335U and 0336U.
Only the ordering physician may engage in authorization, appeal, or related administrative processes.
Unauthorized lab-provided services will be denied and are the financial liability of the participating laboratory.

Note

Coverage Contingent on Medical Criteria

Claims for the PLA CPT codes (0335U, 0336U) will be covered only when the medical criteria specified in this policy are documented in the medical record and available to BCBSRI upon request.

Services Not Covered

Not covered / not medically necessary: Next-generation sequencing (NGS) for invasive prenatal diagnostic testing is not covered under Medicare Advantage Plans and is considered not medically necessary for Commercial Products due to insufficient evidence supporting clinical validity and improvement in health outcomes.

Rationale for noncoverage: NGS applied to invasive prenatal diagnosis has insufficient evidence of clinical validity and uncertain clinical relevance of many findings. These limitations prevent determination that NGS improves net health outcomes in the prenatal invasive diagnostic setting.

Definitions

Invasive prenatal testing (CVS or amniocentesis)

DefinitionDirect testing of fetal tissue obtained by chorionic villus sampling (CVS) or amniocentesis to collect fetal cells for genetic evaluation; both procedures carry an increased risk of miscarriage and are typically used when the fetus is at increased risk for a chromosomal abnormality or single-gene disorder.

Typical specimen typesCVS obtains placental chorionic villi; amniocentesis samples amniotic fluid containing fetal cells.

Clinical purposeTo diagnose chromosomal abnormalities, single-gene disorders, or other genetic conditions to inform pregnancy management (eg, prenatal treatment, delivery planning, or pregnancy termination).

Chromosomal microarray (CMA)

DefinitionA genome-wide assay that detects copy number variants (gains and losses of DNA) across the genome by comparative hybridization to a reference and analysis of hybridization signal intensities.

Eligibility Requirements

Eligibility requirements for invasive prenatal molecular testing are specified elsewhere in this policy and include clinical criteria tied to known familial pathogenic variants, inheritance pattern, disease natural history, and test performance characteristics.

This section contains placeholder text for eligibility requirements. No additional top-level eligibility nodes are specified in this portion of the policy.

Additional eligibility details (for example, required documentation of familial variants or carrier status) are addressed in the policy's coverage criteria and provider documentation sections.

Where indicated, prior authorization and demonstration of the specific medical criteria must be submitted by the ordering physician to establish eligibility for coverage of invasive prenatal molecular testing.

Background

Invasive prenatal diagnostic testing—typically chorionic villus sampling (CVS) or amniocentesis—obtains fetal tissue or cells for genetic analysis to identify inherited conditions that can inform pregnancy management. These procedures enable molecular testing for single-gene (Mendelian) disorders, chromosomal microarray to detect copy number variants, and, in some settings, next-generation sequencing. For single-gene disorders, prenatal testing is most informative when the familial pathogenic variant is known because most Mendelian disorders are caused by single-nucleotide variants or very small insertions/deletions, and test sensitivity and specificity are high when targeting a known variant. Findings from invasive testing can affect reproductive decision-making, timing and location of delivery, and immediate postnatal care.

OpenPayer

Invasive Prenatal (Fetal) Diagnostic Testing — Coverage Criteria (Molecular/Genetic Testing)