DraftUnitedHealthcarePolicy CS085TN.Y

Cell-Free Fetal DNA Testing (for Tennessee Only)

Medical policy governing use and coverage of cell-free fetal DNA testing (noninvasive prenatal screening) for Medicaid and CoverKids in Tennessee, including indications considered medically necessary and those considered unproven/not medically necessary.

Policy Summary

PayerUnitedHealthcare

PolicyCell-Free Fetal DNA Testing (for Tennessee Only)

Policy CodePolicy CS085TN.Y

Change TypeMaterial coverage revision (added proven RhD/alloimmunization indicationclarified unproven expanded panelscode removals)

Effective DateAugust 1, 2025

Next Review Date

Key ActionWhen ordering fetal genotype (RhD) cfDNA for an alloimmunized or at‑risk individual, document that invasive diagnostic testing was offered and declined and that paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown.

SourceLink

POLICY UPDATE CHANGES

Cell-Free Fetal DNA testing using maternal plasma to determine fetal genotype is proven and medically necessary when the individual undergoing testing is alloimmunized or at risk for alloimmunization due to maternal RhD status or the presence of red cell antigen antibodies, and all of the following: paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown; indicated invasive diagnostic testing for fetal genotyping has been offered and declined.

Previous language stating DNA-based noninvasive prenatal tests of fetal aneuploidy are proven and medically necessary as screening tools for trisomy 21, 18, or 13 (with/without sex chromosomes) for individuals meeting listed risk criteria was removed.

Replaced broad statement that DNA-based noninvasive prenatal tests are unproven and not medically necessary for all other indications with wording that cfDNA testing using maternal plasma is unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy, including but not limited to the listed examples.

Added 'Cell-Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome aneuploidy)' to the revised list of unproven and not medically necessary indications.

Removed CPT codes 0327U, 81420, and 81507 from the applicable codes list.

Removed a long list of specific ICD-10 diagnosis codes from the applicable diagnosis code list.

No material clinical or coverage changes in this revision.

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1new proven clinical indication added (alloimmunization/RhD fetal genotype)

3CPT codes removed

~150ICD-10 diagnosis codes removed

Tennesseegeographic/benefit scope

Trisomies 21/18/13 + SCAsprimary cfDNA screening indications considered proven

expanded panels, CNVs, single-geneexplicitly listed not medically necessary uses

Coverage Criteria for Cell‑Free Fetal DNA Testing

Expanded cfDNA screening — general coverage stance

Covered when ALL of the following are met:

ALL of the following

Prenatal cfDNA screening is limited to detection of fetal trisomies 21, 18, 13, and sex chromosome aneuploidy (SCA) as the primary, routinely supported screening indications.
Expanded cfDNA screening (including but not limited to genome-wide CNV screening, routine microdeletion/microduplication screening, routine single-gene disorder screening, and routine prenatal exome or genome sequencing) is considered investigational/unproven and not medically necessary for population-based or routine screening due to insufficient evidence of clinical validity and clinical utility.
Screening for rare autosomal aneuploidies (RAAs) or expanded panels in average-risk singleton and twin pregnancies is not routinely recommended because of limited evidence, high false-positive rates, and uncertain positive predictive value; such testing may result in unnecessary invasive diagnostic procedures and should be reserved for contexts with clear, validated clinical indications and appropriate pretest counseling.
Testing for specific targeted conditions (e.g., 22q11.2) may be considered when there is supporting evidence and validated assay performance; however, routine population-based screening for CNVs other than 22q11.2 is not recommended at this time.
cfDNA assays marketed as expanded panels that include targets beyond trisomies 21, 18, 13, and SCA are not covered as routine screening unless there is documented, specific clinical rationale and supporting validation evidence for the indication.

General prenatal cfDNA screening

Covered when ALL of the following are met:

ALL of the following

Patient counseling documented that includes discussion of screening intent, limitations of cfDNA (screening, not diagnostic), potential for false-positive and false-negative results, and options for diagnostic testing (CVS or amniocentesis).
Test indication is for routine prenatal screening for fetal trisomies 21, 18, 13, and/or sex chromosome aneuploidy in a singleton or multifetal gestation as part of prenatal care, and not for expanded-panel or genome-wide screening beyond these targets.
Only one prenatal screening approach is being used per pregnancy episode (i.e., cfDNA should not be performed concomitantly with another aneuploidy screening test unless part of an agreed clinical pathway documented in the medical record).
For multifetal gestations, pretest counseling documents limitations of cfDNA performance in twins and higher-order multiples and, when indicated, alternative diagnostic testing options are discussed.

Indications Considered Covered / Proven

Screening for trisomies 21, 18, 13 and sex chromosome aneuploidy.

Considered proven for standard cfDNA screening:

Standard cfDNA screening indications: Screening for fetal trisomies 21, 18, and 13 and for sex chromosome aneuploidies (SCA) in singleton pregnancies is an established indication for cfDNA screening and may be offered to pregnant individuals with appropriate counseling; cfDNA is preferred over traditional screening methods per professional guidance.

ACMG, ACOG and ISPD guidance support cfDNA for common aneuploidies; SCA screening is recommended to be offered in singleton pregnancies.

Screening for common fetal trisomies (13, 18, 21) in singleton and twin gestations

ACMG and ACOG recommend cfDNA over traditional screening for these indications:

Trisomy screening in singleton and twin gestations: Prenatal cfDNA screening for trisomies 13, 18, and 21 is recommended over traditional screening methods for pregnant individuals with singleton and twin gestations; cfDNA should be offered with counseling and diagnostic testing options for positive results.

Not Covered / Unproven Indications

Genome-wide or exome-wide cfDNA screening (for example, tests such as MaterniT Genome), expanded cfDNA panels beyond trisomies and sex chromosome aneuploidies, microdeletions/CNV screening, and single-gene cfDNA testing are designated not covered as routine services.

Routine, population-based cfDNA screening for RAAs, CNVs, microdeletions, or prenatal exome/genome sequencing is not supported by current evidence and therefore is not recommended for routine screening.

Routine cfDNA screening for rare autosomal trisomies (RATs) and most CNVs beyond 22q11.2 is not supported due to insufficient evidence; the clinical utility in average-risk populations is unclear and not established.

Routine screening for microdeletions, genome-wide cfDNA for large deletions/duplications, and single-gene cfDNA screening are not covered for general population screening because clinical validation and performance characteristics are inadequate.

Expanded cfDNA panel testing and cfDNA indications beyond trisomies 21, 18, 13, and sex chromosome aneuploidy are considered unproven and not medically necessary due to insufficient evidence of efficacy.

For clarity, the policy reiterates that twin zygosity testing when performed solely to determine zygosity is excluded from medical necessity coverage.

Applicable Codes and Billing

Applicable CPT/PLA Codes (part 1)mixed

0060U	Twin zygosity, genomic targeted sequence analysis of chromosome 2, using circulating cell-free fetal DNA in maternal blood.
0488U	Obstetrics (fetal antigen noninvasive prenatal test), cell-free DNA sequence analysis for detection of fetal presence or absence of 1 or more of the Rh, C, c, D, E, Duffy (Fya), or Kell (K) antigen in alloimmunized pregnancies, reported as selected antigen(s) detected or not detected.
0489U	Obstetrics (single-gene noninvasive prenatal test), cell-free DNA sequence analysis of 1 or more targets (e.g., CFTR, SMN1, HBB, HBA1, HBA2) to identify paternally inherited pathogenic variants, and relative mutation-dosage analysis based on molecular counts to determine fetal inheritance of maternal mutation, algorithm reported as a fetal risk score for the condition (e.g., cystic fibrosis, spinal muscular atrophy, beta hemoglobinopathies [including sickle cell disease], alpha thalassemia).
0494U	Red blood cell antigen (fetal RhD gene analysis), next-generation sequencing of circulating cell-free DNA (cfDNA) of blood in pregnant individuals known to be RhD negative, reported as positive or negative

Applicable CPT/PLA/CPT Unlisted (part 2)mixed

0536U	Red blood cell antigen (fetal RhD), PCR analysis of exon 4 of RHD gene and housekeeping control gene GAPDH from whole blood in pregnant individuals at 10+ weeks gestation known to be RhD negative, reported as fetal RhD status.
81422	Fetal chromosomal microdeletion(s) genomic sequence analysis (e.g., DiGeorge syndrome, Cri-du-chat syndrome), circulating cell-free fetal DNA in maternal blood.
81479	Unlisted molecular pathology procedure

Removed CPT CodesCPT

0327U	CPT code removed
81420	CPT code removed
81507	CPT code removed

Removed ICD-10 Diagnosis Codes (partial list shown)ICD-10

O09.00	Diagnosis code removed
O09.01	Diagnosis code removed
O09.02	Diagnosis code removed
O09.03	Diagnosis code removed

inv-26: Earliest gestational age for screening — As early as 10 weeks gestation.

Earliest gestational ageAs early as 10 weeks gestation

Clinical implicationcfDNA may be performed starting at 10 weeks but is a screening test and cannot definitively diagnose fetal conditions

Follow-up requirementPositive or unreportable results should prompt counseling and offer of diagnostic testing (CVS or amniocentesis)

inv-27: Nuchal translucency threshold for offering diagnostic testing — ≥ 3.5 mm.

Nuchal translucency threshold≥ 3.5 mm — fetuses with NT ≥ 3.5 mm should be offered diagnostic testing

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Prior Authorization / Applicable Codes

Certain cfDNA/NIPT procedure codes are listed for reference. Inclusion of a code does not imply coverage; benefit determination follows federal, state, and contractual requirements. Prior authorization may be required consistent with UnitedHealthcare standard procedures and applicable Medicaid/CoverKids rules.

Prior authorization may be required; check UnitedHealthcare prior authorization procedures before ordering.
Listing of codes is for reference only and is not a guarantee of coverage or payment.

Prior Authorization

Prior Authorization — Expanded / Genome‑Wide cfDNA

Expanded, genome-wide, or 'NIPT-plus' cfDNA screening that includes screening beyond common trisomies and sex chromosome aneuploidy (for example, genome-wide CNV panels, exome/genome sequencing, or expanded microdeletion panels) lacks sufficient evidence of clinical utility and may be considered unproven. Such testing may require prior authorization and is at increased risk for denial.

Requests for expanded/genome‑wide cfDNA screening may require prior authorization.

Definitions and Background

Background: Cell-free fetal DNA (cfDNA) is derived from placental trophoblasts and circulates in maternal plasma; it can be analyzed noninvasively as early as 10 weeks gestation to screen for fetal aneuploidies. cfDNA screening identifies increased risk but is not diagnostic; invasive testing (CVS or amniocentesis) is required to confirm results.

inv-50: Aneuploidy definition.

DefinitionAneuploidy: an abnormal number of chromosomes in a human cell (includes trisomy and monosomy).

ExamplesIncludes trisomy 21 (Down syndrome), trisomy 13 (Patau), and trisomy 18 (Edwards).

ScopeAneuploidy can affect autosomes or sex chromosomes and may impact fetal development and pregnancy outcomes.

inv-51: Cell Free Fetal DNA (cffDNA/cfDNA) definition.

Definition

Eligibility and Preconditions

Eligibility requirements: None specified at the top level of this section in the policy text.

For certain single‑gene NIPD/RHDO approaches, the policy notes that a known family history and a confirmed molecular diagnosis in the family are typically required for reliable testing, and that diagnostic confirmation (eg, amniocentesis with chromosomal microarray or karyotype) is expected following positive expanded cfDNA or targeted screening results.

Multiple studies and reviews emphasized that when cfDNA screening yields a positive result for aneuploidy or CNV, providers should offer and document invasive diagnostic confirmation such as amniocentesis with chromosomal microarray or karyotype.

Guidance for Providers

Note

Genetic counseling strongly recommended prior to screening or diagnosis

Genetic counseling is strongly recommended prior to fetal screening or prenatal diagnosis to inform persons being tested about the advantages and limitations of the test.

Note

Evidence Summary and Background

740,076tests pooled in Konya et al. meta-analysis

0.07pooled PPV for RATs (confirmed method)

100%PPV for 22q11.2 in Hammer et al. (confirmed cases)

100%/99.3%RhD cfDNA sensitivity/specificity (Gilstrop et al.)

Background narrative: cfDNA originates from the placenta and is present in maternal blood; assays use various sequencing or targeted molecular methods and performance varies by method, fetal fraction, and condition prevalence.

Revision History and Policy Changes

2025-08-01addedLatest

Added a proven/medically necessary indication: cell-free fetal DNA testing using maternal plasma to determine fetal genotype for individuals who are alloimmunized or at risk for alloimmunization when paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown and indicated invasive diagnostic testing has been offered and declined.

2025-08-01removed

Removed prior language that broadly characterized DNA-based noninvasive prenatal tests for aneuploidy (trisomy 21, 18, 13 with/without sex chromosomes) as proven and medically necessary under specified risk criteria.

Policy Summary

PayerUnitedHealthcare

PolicyCell-Free Fetal DNA Testing (for Tennessee Only)

Policy CodePolicy CS085TN.Y

Change TypeMaterial coverage revision (added proven RhD/alloimmunization indicationclarified unproven expanded panelscode removals)

Effective DateAugust 1, 2025

Next Review Date

SourceLink

On This Page

For cases with a no-call or uninterpretable cfDNA result, documentation that the patient was informed of increased aneuploidy risk associated with no-call results and offered further evaluation including repeat cfDNA, comprehensive ultrasound, or diagnostic testing.

ACMG gives a strong recommendation for both singleton and twin gestations; ACOG/SMFM practice bulletins align with offering cfDNA to all pregnant individuals.

Screening for sex chromosome aneuploidies (SCA) in singleton pregnancies

ACMG recommends offering cfDNA to assess for fetal SCA in singleton pregnancies:

SCA screening in singleton pregnancies: cfDNA may be offered to assess for fetal sex chromosome aneuploidies in singleton pregnancies with appropriate pretest counseling regarding limitations and implications.

Recommendation based on ACMG guidance.

Optional screening for 22q11.2 deletion syndrome

ACMG suggests offering 22q11.2 screening (conditional):

Optional 22q11.2 screening: Prenatal cfDNA screening for 22q11.2 deletion syndrome may be offered (conditional recommendation) recognizing variable performance across studies and the need for counseling and confirmatory diagnostic testing for positive results.

Performance metrics vary; some studies report improved PPV with specific platforms/algorithms.

Fetal RhD genotyping in RhD-negative or alloimmunized pregnancies when criteria met

Evidence supports high accuracy and potential to reduce unnecessary RhIG prophylaxis when criteria met:

Fetal RhD genotyping to guide anti-D prophylaxis: Noninvasive cfDNA testing for fetal RhD genotype in RhD-negative pregnant individuals or in alloimmunized pregnancies may be used to guide antenatal anti-D prophylaxis and management decisions, contingent on validated diagnostic accuracy and cost-effectiveness considerations.

NICE recommends high-throughput cfDNA testing for RhD genotype dependent on cost thresholds; clinical validation studies report high sensitivity and specificity.

Fetal antigen genotyping (RhD and non-RhD antigens) in alloimmunized pregnancies and RhD-negative individuals

Multiple validations report high concordance:

Fetal antigen genotyping in alloimmunized pregnancies: Fetal antigen genotyping (RhD and selected non-RhD antigens) using cfDNA has shown high concordance with neonatal genotyping/serology in validation studies and may reduce the need for invasive testing when used in appropriate clinical contexts.

Rego et al. and Alford et al. report high sensitivity/specificity and concordance.

Screening for common autosomal aneuploidies (trisomy 21, 18, 13)

Most accurate screening test for common autosomal aneuploidies:

Screening for common autosomal aneuploidies: cfDNA is the most accurate screening test for trisomy 21, 18, and 13 in singleton pregnancies and should be offered to all pregnant individuals regardless of baseline risk, with counseling about limitations and diagnostic confirmation for positives.

Supported by ACOG and ISPD guidance.

Fetal RhD genotyping to guide anti-D prophylaxis

Supported by guideline and diagnostic accuracy studies; consider cost-effectiveness:

RhD genotype to guide prophylaxis: High-throughput cfDNA testing for fetal RhD genotype can be used to guide antenatal anti-D prophylaxis decisions depending on cost-effectiveness thresholds and diagnostic accuracy evidence.

NICE recommends use contingent on cost thresholds; policy revision added fetal genotype indication for alloimmunized/at-risk pregnancies.

Newly added proven indication — fetal RhD/fetal genotype by cfDNA

Newly added proven indication:

New proven indication - fetal genotype (RhD) by cfDNA: Fetal RhD or fetal genotype determination using maternal plasma cfDNA is proven and medically necessary when the pregnant individual is alloimmunized or at risk for alloimmunization, paternal genotyping is heterozygous for RhD or paternal RhD status is unknown, and invasive diagnostic testing has been offered and declined.all listed conditions required

Added to policy effective 08/01/2025 as a material change to coverage rationale.

Evidence from cohort and prospective studies shows higher yield for CNV detection when cfDNA is used in the context of abnormal fetal ultrasound findings or strong clinical suspicion; in these circumstances, providers should offer invasive diagnostic testing (eg, amniocentesis with chromosomal microarray or karyotype) rather than rely on cfDNA alone.

NT ≥ 3.5 mm is cited as an ultrasound finding that warrants offering diagnostic testing (eg, CVS or amniocentesis)

Relationship to cfDNAWhen NT is ≥ 3.5 mm, cfDNA screening may be insufficient and invasive diagnostic testing should be discussed/offered

Expanded cfDNA indications are subject to denial due to insufficient evidence (see denial risk).

Documentation Required

Confirmatory Diagnostic Testing Recommended

When cfDNA screening yields a positive (high‑risk) result for aneuploidy, copy number variant (CNV), rare autosomal trisomy (RAT), or other abnormality, confirmatory diagnostic testing (e.g., chorionic villus sampling or amniocentesis with karyotype and/or chromosomal microarray analysis [CMA]) should be offered and documented.

Offer and document invasive diagnostic testing (amniocentesis with karyotype/CMA) following a positive expanded cfDNA or other high‑risk result.
Confirmatory testing results and counseling must be included in the medical record.

Note

Regulatory and Laboratory Requirements (Informational)

FDA clearance or approval is informational only and is not sufficient alone to establish coverage. Laboratories performing cfDNA tests are subject to CLIA and other regulatory oversight; coverage decisions consider lab accreditation and the clinical evidence demonstrating utility.

Verify laboratory CLIA/CAP status and validation of fetal fraction thresholds and 'no‑call' criteria where relevant.
FDA-cleared/approved status does not guarantee coverage.

Documentation Required

cfDNA as Contingent / Follow‑Up Testing — Counseling Requirement

When cfDNA is used as a follow-up (contingent) screen after a positive serum analyte screening test, the ordering provider must counsel the individual regarding limitations: cfDNA is a screening—not diagnostic—test, may delay definitive diagnosis, and a negative cfDNA screen does not provide absolute reassurance.

Document that counseling was provided about cfDNA limitations and the option for immediate invasive diagnostic testing.
If cfDNA is selected as contingent testing, record the rationale and the counseling discussion in the medical record.

Documentation Required

Paternal Genotyping and Documentation for Fetal RhD Testing

Before ordering noninvasive fetal genotyping for fetal RhD status in alloimmunized or at‑risk individuals, consider and document paternal genotyping. Coverage for fetal RhD cfDNA testing is contingent on demonstration that paternal RhD is heterozygous or unknown and that invasive diagnostic testing was offered and declined.

Document paternal genotyping status (heterozygous for RhD or unknown) when ordering fetal RhD cfDNA testing.
Document that invasive diagnostic testing was offered and declined by the individual.

Documentation Required

No‑Call Results — Validation and Follow‑Up Documentation

Laboratories and providers should have validated fetal fraction thresholds and clear clinical pathways for handling 'no‑call' results. Providers must document counseling, recommended follow‑up (repeat testing, ultrasound, or offer of diagnostic testing), and any decision to proceed or decline further testing.

Document counseling and follow-up plan after a no‑call cfDNA result, including offer of repeat cfDNA, comprehensive ultrasound, or diagnostic testing.
Labs should report their no‑call thresholds and validated procedures.

Denial Risk

Denial Risk for Expanded or Unsupported Indications

Requests for cfDNA testing for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy (including expanded panels, genome/exome sequencing, and many CNV/RAT screens) may be denied due to insufficient evidence. Document clinical indication and counseling to reduce denial risk.

Include clear clinical justification and documentation when ordering cfDNA for non‑standard indications; anticipate possible denial.
Denials are more likely for expanded or unproven indications (see policy list).

Documentation Required

Genetic Counseling and Follow‑Up Documentation

Providers should ensure documentation of pre‑test genetic counseling (strongly recommended) and of post‑test counseling and follow‑up plans for high‑risk cfDNA results. Offer and document referral to genetic counseling when appropriate.

Document that genetic counseling was offered or provided prior to testing and after any high‑risk or uncertain result.
Document any diagnostic testing offers, patient decisions, and outcomes in the medical record.

Cell Free Fetal DNA (cffDNA/cfDNA): small fragments of fetal DNA from the placenta circulating in maternal blood used for noninvasive prenatal screening.

UseAnalyzed via NIPT/NIPS to screen for fetal aneuploidies and some other genomic abnormalities

LimitationsDetects increased risk but cannot definitively diagnose fetal genetic conditions; diagnostic testing (CVS or amniocentesis) is required for confirmation.

inv-52: Twin Zygosity definition.

DefinitionTwin Zygosity: classification of twin conception as dizygotic (fraternal) or monozygotic (identical).

DizygoticResult from fertilization of two separate ova; twins share ~50% of genes (like siblings).

MonozygoticResult from division of a single zygote; twins are genetically identical (originating from one fertilized ovum).

inv-53: NIPT/NIPS definition.

DefinitionNIPT/NIPS: Non-Invasive Prenatal Testing/Screening — umbrella term for analyses of cfDNA to screen for fetal chromosomal abnormalities.

PurposeOffered as a screening option to assess risk for common aneuploidies (eg, trisomies 21, 18, 13) and sex chromosome aneuploidies

NatureScreening test (not diagnostic); positive results warrant counseling and offer of diagnostic testing

inv-54: Placental mosaicism definition.

DefinitionPlacental mosaicism: discordance between placental and fetal karyotype that can cause cfDNA to reflect placental, not fetal, chromosomal status and lead to false-positive NIPT results.

Clinical significancePlacental mosaicism is a common explanation for positive cfDNA results that are not confirmed in the fetus and may be associated with adverse pregnancy outcomes.

ImplicationPositive cfDNA findings possibly due to placental mosaicism should prompt diagnostic testing and increased prenatal monitoring.

inv-55: PPV - confirmed vs extended definitions.

Confirmed PPVConfirmed PPV: counts only cases verified by diagnostic genetic testing as true positives (eg, Konya et al. confirmed-method PPV for RATs = 0.07).

Extended PPVExtended PPV: also counts likely true positives such as intrauterine fetal death or termination for ultrasound-confirmed abnormality when diagnostic confirmation was not obtained (Konya extended PPV = 0.13).

Use in studiesBoth metrics are reported in systematic reviews and affect interpretation of cfDNA performance for rare aneuploidies and RAAs.

inv-56: No-call / uninterpretable result definition.

DefinitionNo-call / uninterpretable result: a laboratory result not reported due to insufficient fetal fraction or other assay failure; associated with increased risk of aneuploidy.

Most frequent causeInsufficient fetal fraction is the most common reason for a no-call result (ACMG notes low FF as frequent explanation).

Recommended follow-upIndividuals with no-call results should receive genetic counseling, comprehensive ultrasound, and be offered diagnostic testing or repeat testing per lab protocols.

inv-57: PPV/NPV/DR (sensitivity/specificity) definition.

PPV/NPV/DR definitionsPPV (positive predictive value), NPV (negative predictive value), and DR (detection rate/sensitivity) measure cfDNA screening performance; values vary by condition prevalence and population studied.

Dependence on prevalencePPV is influenced by condition prevalence—rare conditions yield low PPV even with high specificity (e.g., RATs).

InterpretationThese metrics guide counseling: high NPV reduces but does not eliminate risk; positive screens require confirmatory diagnostic testing.

inv-58: Fetal fraction (FF) definition.

DefinitionFetal fraction (FF): the proportion of circulating cell-free DNA in maternal blood that is fetal in origin; low FF is the most frequent reason for no-call results.

Quality metricFF is an important assay quality control metric; laboratories should validate FF thresholds for reporting and no-call determinations.

Clinical implicationLow FF is associated with increased risk of aneuploidy and may necessitate repeat sampling, ultrasound, or diagnostic testing.

inv-59: Genome-wide cfDNA screening definition.

DefinitionGenome-wide cfDNA screening: cfDNA approaches that analyze the whole genome to detect large deletions and duplications beyond targeted microdeletions; currently not recommended by ACOG/SMFM due to lack of clinical validation.

CapabilitiesMay detect large CNVs and rare autosomal aneuploidies using whole-genome low-coverage sequencing, but performance and false-positive rates vary across studies.

Policy stanceRoutine population-based genome-wide cfDNA screening for RAAs/CNVs is not supported by sufficient evidence and is considered unproven/not medically necessary in many contexts.

inv-60: Misc. defined terms list (Trisomy 21, 18, 13; Mosaicism; NGS; SNPs; SDM).

TrisomiesTrisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome)

MosaicismMosaicism: presence of two or more cell lines with different karyotypes; can underlie discordant cfDNA results (eg, confined placental mosaicism).

NGS and SNPsNGS (Next-Generation Sequencing) and SNP-based assays are technologies used in cfDNA testing; performance varies by platform and algorithm.

SDMSDM (Shared Decision-Making): an approach recommended in counseling around prenatal screening options.

Documentation Required

Documentation and follow-up should accompany testing

Providers must document counseling, results communication, and follow-up plans when testing is performed; ensure appropriate clinical follow-up is arranged for positive or unreportable results.

Documentation Required

Documentation and follow-up should accompany testing

Providers should document counseling, results communication, and follow-up plans when testing is performed; ensure appropriate clinical follow-up is arranged for positive or unreportable results.

Documentation Required

Documentation and follow-up should accompany testing

Providers must document counseling, results communication, and follow-up plans when testing is performed; arrange genetic counseling referral for positive or unclear results.

Replaced prior categorical wording about unproven indications with clarified scope: cfDNA using maternal plasma is unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy, and explicitly added expanded panel testing to the unproven list.

2025-08-01added

Added explicit notation that 'Cell‑Free Fetal DNA expanded panel testing' (panels including tests beyond trisomies 21, 18, 13, and sex chromosomes) is considered unproven and not medically necessary.

2025-08-01removed

Removed Vanadis® from the policy (previously listed as unproven/not medically necessary).

2025-08-01removed

Removed CPT codes 0327U, 81420, and 81507 from the applicable codes list.

2025-08-01removed

Removed an extensive list of ICD‑10 diagnosis codes from the applicable diagnosis code list as part of code updates.

Policy summary: This policy governs use and coverage of cfDNA (noninvasive prenatal testing) for Tennessee Medicaid and CoverKids. It specifies covered indications (eg, standard screening for trisomies 21/18/13 and sex chromosome aneuploidies, and fetal RhD/genotype testing in alloimmunized or at‑risk pregnancies when criteria are met) and lists numerous expanded or investigational cfDNA applications that are considered unproven and not medically necessary. Effective date: 2025-08-01.