ModifiedUnitedHealthcarePolicy CS085KY.13

Cell‑Free Fetal DNA Testing (for Kentucky Only)

Defines medical necessity and coverage stance for cell-free fetal DNA (cfDNA) testing in Kentucky Medicaid members, including indications such as RhD genotyping and screening for common trisomies, and exclusions for expanded/experimental uses.

Policy Summary

PayerUnitedHealthcare

PolicyCell‑Free Fetal DNA Testing (for Kentucky Only)

Policy CodePolicy CS085KY.13

Change TypeMaterial coverage revisions and coding removals

Effective DateAug 1, 2025

Next Review Date

Key ActionDocument that invasive diagnostic testing was offered and declined and include genetic counseling when requesting cfDNA fetal genotyping for alloimmunized or at‑risk pregnancies.

SourceLink

POLICY UPDATE CHANGES

Added language that cfDNA 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 presence of red cell antigen antibodies and specific conditions are met.

Removed language indicating DNA-based noninvasive prenatal tests of fetal Aneuploidy are proven and medically necessary as screening tools for trisomy 21, 18, or 13 and sex chromosomes for certain high-risk circumstances (advanced maternal age, ultrasound findings, prior trisomy, positive serum screen, parental translocation, SDM after counseling).

Replaced broad 'unproven and not medically necessary for all other indications' language with a more specific statement that cfDNA using maternal plasma is unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy.

Added 'Cell-Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome Aneuploidy)' to the 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 applicable ICD-10 diagnosis codes from the policy.

10+ wk

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earliest gestational age

Trisomies 21/18/13 + SCAestablished targets

manyICD-10 codes removed

no-callno-call risk emphasis

Coverage Criteria

inv-01: cfDNA testing for fetal RhD in alloimmunized or at-risk pregnancies

Covered when ALL of the following are met:

Primary coverage criteria: Individual undergoing testing is alloimmunized or at risk for alloimmunization due to maternal RhD status or presence of red cell antigen antibodies.

Paternal genotype requirement: Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown.

Prior offer of invasive diagnostic testing: Indicated invasive diagnostic testing (e.g., amniocentesis or chorionic villus sampling) for fetal genotyping has been offered and declined.

Document that invasive diagnostic testing was offered and declined as required for coverage.

inv-02: Coverage by indication

Coverage considerations by indication:

Common trisomies and SCAs: Standard cfDNA/NIPT has high sensitivity and specificity for trisomy 21, 18, 13 and sex chromosome aneuploidies and is effective as a screening test for these conditions.

Supported by cohort and systematic review data reporting sensitivity ~100% and specificity >0.99 in many studies.

Rare autosomal aneuploidies (RAAs): Evidence shows low pooled positive predictive values for RAAs with high heterogeneity; many cfDNA-detected RAAs are not confirmed in the fetus, commonly due to placental mosaicism.

Systematic reviews report pooled PPVs as low as ~0.07 (confirmed cases) to ~0.13 (extended method), indicating limited clinical utility.

Genome-wide CNVs and microdeletions: Performance for CNV detection is variable across studies; PPVs and detection depend on CNV size, sequencing depth, and assay/algorithm, with higher detection for larger CNVs and some well-characterized syndromes.

Prospective and cohort studies report overall PPVs ranging from low/moderate (eg ~38%) with improved performance for larger CNVs or specific syndromes.

22q11.2 microdeletion screening:

inv-03: Coverage considerations and evidence synthesis

Guidance and evidence summary for expanded cfDNA screening:

Professional society recommendations: ACMG strongly recommends cfDNA screening for trisomies 13, 18, and 21 over traditional screening in singleton and twin pregnancies and suggests offering cfDNA screening for 22q11.2 (conditional); insufficient evidence to recommend routine screening for CNVs other than 22q11.2 or for RAAs.

ACMG guidance emphasizes cfDNA as screening and the need for confirmatory diagnostic testing.

Fetal antigen testing (non-RhD): Analytical and limited clinical validation studies report high sensitivity and specificity for some NGS-based fetal antigen cfDNA assays, but high-quality outcome studies demonstrating clinical impact are needed before routine adoption.

Peer-reviewed cohort/validation studies show promising accuracy but additional outcome-focused research is required.

22q11.2 and other microdeletions/CNVs: Multiple studies report variable sensitivity, specificity, and PPV for 22q11.2 and other CNVs; evidence is evolving and depends on assay and ascertainment, with ACMG giving a conditional suggestion for 22q11.2 only.

inv-04: Fetal genotype testing — alloimmunization

Covered when ALL of the following are met:

Fetal genotype testing in alloimmunized pregnancies: 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 presence of red cell antigen antibodies and all of the following are met:

Paternal genotype status: Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown.

Document paternal genotyping results where available.

Offer of invasive diagnostic testing: Indicated invasive diagnostic testing (eg amniocentesis, CVS) for fetal genotyping has been offered and declined.

Documentation that invasive testing was offered and declined is required for coverage.

inv-05: Unproven / Not Medically Necessary Indications

Not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy, including but not limited to:

Expanded panel testing: Cell-Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome aneuploidy).

Listed as unproven and not medically necessary.

Genome-/exome-wide screening: Genome-wide or exome-wide cfDNA screening (eg MaterniT Genome).

Considered investigational or insufficient evidence for clinical utility.

Twin zygosity: Testing solely to determine twin zygosity.

Listed among indications considered unproven and not medically necessary.

Microdeletions/CNVs:

Use of cell-free fetal DNA (cfDNA) testing for indications beyond screening for the common aneuploidies (trisomies 21, 18, 13 and sex chromosome aneuploidy) is considered unproven and not medically necessary. The policy explicitly lists examples of such non-covered uses, including testing solely to determine twin zygosity, genome-/exome-wide screening (e.g., MaterniT® Genome), and expanded cfDNA panel testing that includes targets beyond the core trisomies and sex chromosomes.

Prenatal exome- or genome-wide sequencing approaches that analyze maternal plasma cfDNA are investigational/insufficient for routine prenatal screening. The evidence base is limited and validation data on sensitivity, specificity, and positive predictive value for cfDNA-based prenatal whole-exome or whole-genome applications are lacking, and the policy therefore considers these applications not established for clinical use.

There is currently a lack of peer-reviewed evidence to support routine use of cfDNA testing to determine fetal antigen status other than RhD in alloimmunized pregnancies. While some analytical validations exist for non‑RhD antigens, additional high-quality outcome studies demonstrating clinical impact are needed before coverage can be supported.

Professional societies (ACOG, SMFM, ISPD, and ACMG) caution against unvalidated uses of cfDNA and emphasize that cfDNA is a screening, not diagnostic, test. Society guidance advises providers to offer pretest counseling, to refer positive or unusual results for genetic counseling and diagnostic confirmation, and does not support routine use of unvalidated genome-wide CNV or microdeletion screening, rare autosomal aneuploidy screening, or single-gene cfDNA screening for general population use without additional evidence.

UnitedHealthcare considers cfDNA testing using maternal plasma to determine fetal genotype proven and medically necessary only for specified, evidence-supported indications (for example, fetal RhD genotyping in alloimmunized or at‑risk pregnancies when stated conditions are met). For indications beyond screening for trisomies 21, 18, 13 and sex chromosome aneuploidy, cfDNA testing is regarded as unproven and not medically necessary.

Expanded uses of cfDNA — including genome-wide or exome-wide approaches, and expanded panels that include microdeletions, copy number variants, or single‑gene targets beyond the core trisomies and sex chromosome aneuploidies — are considered not medically necessary / unproven because current evidence does not demonstrate sufficient clinical validity or utility.

Routine cfDNA screening for rare autosomal aneuploidies (RAAs) and for copy number variant (CNV) screening in twin pregnancies is not supported by current evidence. Published evaluations report high false-positive proportions and insufficient high‑quality data in multifetal gestations, so routine use in twins for RAAs/CNVs is not recommended.

ACMG guidance indicates there is insufficient evidence to support routine prenatal cfDNA screening for CNVs other than optional consideration of 22q11.2 deletion. The policy aligns with this position and does not support routine CNV screening beyond 22q11.2.

ACOG does not recommend routine single‑gene cfDNA screening for the general obstetric population due to insufficient evidence of analytic and clinical validity and of predictive values; single‑gene NIPD approaches are currently applicable mainly in specific at‑risk families with appropriate diagnostic follow‑up.

Cell‑Free Fetal DNA expanded panel testing — defined as panels that include targets beyond trisomies 21, 18, 13 and sex chromosome aneuploidy — is explicitly listed in the policy as not covered / unproven and should not be ordered as routine screening.

Covered Indications

inv-53: cfDNA testing for fetal RhD genotyping in alloimmunized or at-risk-for-alloimmunization pregnancies when paternal genotyping is heterozygous or unknown and invasive testing offered and declined

Covered when ALL of the following are met:

Eligibility for cfDNA RhD genotyping (alloimmunized or at-risk): Individual is alloimmunized or at risk for alloimmunization due to maternal RhD status or presence of red cell antigen antibodies.

Paternal genotype heterozygous or unknown: Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown.

Invasive testing offered and declined: Indicated invasive diagnostic testing (eg amniocentesis or CVS) for fetal genotyping was offered and declined by the patient.

Documentation of the offer and declination of invasive diagnostic testing is required for coverage consideration.

Not Covered / Investigational Indications

Not covered indications include testing for twin zygosity, genome‑ or exome‑wide screening (e.g., MaterniT® Genome), genome‑wide CNV/microdeletion panels, single‑gene or expanded panels beyond the core trisomies and SCAs, and routine fetal antigen testing other than RhD. These uses are listed as not covered due to insufficient evidence of clinical utility.

Prenatal exome and genome sequencing performed on maternal plasma cfDNA and other non‑validated cfDNA applications are considered investigational/insufficient and therefore not covered pending further validation and evidence of clinical utility.

Routine CNV screening other than targeted 22q11.2 testing and routine cfDNA fetal antigen testing (other than RhD) lack sufficient evidence to support coverage. Professional guidance and existing studies highlight variable performance and the need for confirmatory diagnostic testing for CNV findings.

Cell‑Free Fetal DNA expanded panel testing that goes beyond screening for the common trisomies and sex chromosome aneuploidies is explicitly listed as not covered; claims for such expanded panel testing may be denied as not medically necessary.

Placeholder: No additional summary provided in this inventory slot; refer to the policy exclusions and not‑medically‑necessary sections for the full list of non‑covered cfDNA applications.

Eligibility Requirements

Eligibility header: Coverage and medical necessity determinations for cfDNA testing depend on the specific indication, available evidence, and the conditions specified in the policy (for example, requirements surrounding alloimmunization and offer of invasive diagnostic testing). Refer to the detailed criteria for covered and not‑covered indications.

A documented family history is not specifically required for routine cfDNA aneuploidy screening; however, pretest counseling is emphasized so that individuals understand the test's scope, alternatives, and limitations and that results requiring action will prompt diagnostic confirmation.

For coverage of cfDNA RhD genotyping, the policy requires documentation that invasive diagnostic testing for fetal genotyping (eg, amniocentesis or CVS) was offered and declined. Coverage also requires that paternal genotyping shows heterozygosity for RhD or that paternal RhD status is unknown, and that the pregnant individual is alloimmunized or at risk for alloimmunization.

This requirement for offering and documenting that invasive diagnostic testing was offered and declined is reiterated in the RhD genotyping coverage criteria to ensure confirmatory diagnostic options were discussed and made available.

Placeholder: no additional eligibility content in this inventory slot; see policy body for specific eligibility requirements tied to each covered indication.

The policy repeatedly states that invasive diagnostic testing (amniocentesis or CVS) must have been offered and declined when cfDNA testing is used for fetal genotyping in the alloimmunization context; documentation of this offer/decline and associated counseling should be maintained.

Provider Actions and Documentation

Prior Authorization

Prior Authorization for Expanded/Targeted cfDNA

Prior authorization may be required for expanded or targeted cfDNA tests (beyond core aneuploidy screening) and for certain molecular procedure codes. Verify prior authorization requirements with UnitedHealthcare before ordering expanded panels, genome‑wide tests, RAAs/CNV panels, or fetal antigen/genotype assays.

Check payer prior authorization policies for tests that include CNV/microdeletion, single-gene, genome-wide, or antigen panels.
Removed CPT codes (see policy Applicable Codes) may affect billing — confirm current CPT/HCPCS requirements and PA rules.

Documentation Required

Counseling and Diagnostic Follow-up Requirements

Document that pretest genetic counseling was provided and that counseling explained cfDNA is a screening test (not diagnostic), its limitations (false positives/negatives, no-call risk), and available follow-up options. For positive or no‑call results, document that genetic counseling and offer of diagnostic testing (CVS or amniocentesis) and comprehensive ultrasound were provided.

Coding

Applicable procedure codes referencedmixed

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 (eg, 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.
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.

Covered CPT Codesmixed

No codes listed

Removed CPT CodesCPTNot Covered

0327U	Removed CPT code (previously listed)
81420	Removed CPT code (previously listed)
81507	Removed CPT code (previously listed)

Removed ICD-10 Diagnosis CodesICD-10Not Covered

O09.00	Removed ICD-10 diagnosis codes (list truncated in policy)
Z3A.49	Removed ICD-10 diagnosis codes (list truncated in policy)

Gestational age for testing

Earliest gestational ageAs early as 10 weeks gestation (tests offered beginning ~9–11 weeks in some RhD assay validations)

Typical reporting windowMany cfDNA assays report performance starting around 9–11 weeks gestation

Diagnostic confirmation notecfDNA is screening only; definitive diagnosis requires invasive testing (CVS or amniocentesis)

CNV size thresholds

Common CNV size strataStudies often stratify detection by CNV size (eg, >10 Mb vs ≤10 Mb)

PPV varies by sizePPV for clinically significant CNVs higher for larger CNVs (eg, PPV 46.5% for CNVs >10 Mb vs 28.6% for ≤10 Mb in Xue et al.)

Background and Definitions

Background: Cell‑free fetal DNA (cfDNA) derived from the placenta circulates in maternal blood and can be analyzed noninvasively (NIPT/NIPS) as early as 10 weeks gestation. cfDNA screening identifies increased risk for targeted aneuploidies but is not diagnostic; confirmatory invasive testing (CVS or amniocentesis with karyotype/CMA) is required to confirm positive screening results.

Aneuploidy

DefinitionAn abnormal number of chromosomes in a human cell (eg, trisomy = extra chromosome; monosomy = missing chromosome)

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

ScopeAneuploidy can affect autosomes or sex chromosomes

Cell Free Fetal DNA (cffDNA or cfDNA)

DefinitionSmall fragments of fetal DNA from the placenta circulating in maternal blood that can be analyzed by noninvasive prenatal screening (cfDNA or cffDNA)

Revision History

2025-08-01coverage_revisionLatest

Added language: cfDNA testing using maternal plasma to determine fetal genotype is proven and medically necessary when the individual is alloimmunized or at risk for alloimmunization due to maternal RhD status or presence of red cell antigen antibodies, with paternal heterozygosity/unknown status and invasive diagnostic testing offered and declined.

2025-08-01coverage_revision

Removed prior proven coverage language for DNA-based noninvasive prenatal tests as screening tools for trisomy 21, 18, 13 and sex chromosomes in specified high-risk circumstances.

Policy Summary

PayerUnitedHealthcare

PolicyCell‑Free Fetal DNA Testing (for Kentucky Only)

Policy CodePolicy CS085KY.13

Change TypeMaterial coverage revisions and coding removals

Effective DateAug 1, 2025

Next Review Date

Key ActionDocument that invasive diagnostic testing was offered and declined and include genetic counseling when requesting cfDNA fetal genotyping for alloimmunized or at‑risk pregnancies.

SourceLink

On This Page

Evidence is mixed: some large WGS-based cohorts report high PPV among cases with diagnostic follow-up, while prospective multicenter studies report more modest sensitivity and PPV that vary by algorithm; overall utility depends on assay and ascertainment.

Study-level PPVs and sensitivities vary, and algorithm improvements can increase PPV.

Twin pregnancies and CNV/RAA screening: Current evidence is insufficient to support routine cfDNA screening for RAAs or CNVs in twin pregnancies; peer-reviewed data demonstrating clinical utility in twins are lacking.

Clinical utility evaluations found no adequate twin pregnancy data and high false positive rates in available studies.

Screen-positive follow-up: All screen-positive results for RAAs, CNVs, and microdeletions should prompt genetic counseling and be followed by offer of confirmatory diagnostic testing (eg amniocentesis with karyotype/CMA) before making pregnancy-management decisions.

Multiple evaluations emphasize need for confirmatory testing due to false positives and placental causes of discordance.

Some large cohorts report high PPV in selected cases, but prospective multicenter data show more modest performance.

Single-gene disorder cfDNA testing: Feasibility and validation studies (eg sgNIPT, reflex carrier screening approaches) demonstrate promising sensitivity and specificity in selected populations, but broader clinical utility and general population use are not established.

Large clinical validation cohorts for sgNIPT report high sensitivity/specificity, but outcome ascertainment limitations and need for further study remain.

Routine screening for microdeletions, microduplications, or other copy number variations (CNVs) beyond 22q11.2.

Evidence is limited and routine use is not supported.

Single-gene disorders: Single-gene cfDNA screening (eg Vistara™, PreSeek™) for general population use.

ACOG and other bodies do not recommend routine single-gene cfDNA screening due to insufficient evidence.

Fetal antigen status other than RhD: Determination of fetal antigen status other than RhD for routine clinical management.

Peer-reviewed evidence is limited; fetal antigen testing other than RhD is not established for routine coverage.

inv-54: Screening for common autosomal trisomies (21, 18, 13) and sex chromosome aneuploidies as established cfDNA screening indications

Established cfDNA screening indications: Screening for common autosomal trisomies (trisomy 21, 18, 13) and sex chromosome aneuploidies is an established cfDNA screening indication and should be offered to pregnant individuals; cfDNA is more accurate than traditional serum/ultrasound screening.

Offer screening options and counseling; cfDNA screening may be offered as early as 10 weeks gestation.

inv-55: Screening for common trisomies (21, 18, 13) and SCAs — well-supported by high sensitivity/specificity

Performance for common trisomies and SCAs: Standard cfDNA screening demonstrates high sensitivity and specificity for trisomies 21, 18, 13 and sex chromosome aneuploidies across multiple studies and meta-analyses, supporting its effectiveness for these indications.

Multiple studies report near-perfect sensitivity and specificity in selected cohorts.

inv-56: Screening for common fetal trisomies and sex chromosome aneuploidies in singleton and twin pregnancies — ACMG recommendation

ACMG recommendation for singleton and twin pregnancies: ACMG recommends prenatal cfDNA screening for trisomies 13, 18, and 21 over traditional screening methods for singleton and twin pregnancies and recommends offering cfDNA screening for SCAs.

ACMG characterizes these as strong recommendations based on high certainty evidence.

inv-57: Optional offering of prenatal cfDNA screening for 22q11.2 deletion syndrome — ACMG conditional recommendation

22q11.2 screening optional offering: ACMG suggests offering prenatal cfDNA screening for 22q11.2 deletion syndrome (conditional recommendation); some large WGS-based cohort studies report high PPV in selected populations but overall evidence is assay-dependent.

Offer may be considered with counseling about variable performance and need for confirmatory testing.

inv-58: Fetal antigen genotyping (RhD and other antigens) in alloimmunized pregnancies or to inform management — validation studies supportive

Fetal antigen genotyping evidence: Validation studies of NGS-based fetal antigen cfDNA assays (including RhD and other red cell antigens such as C, c, K, Fy a, E) report high sensitivity and specificity in cohort and analytical validations, supporting potential clinical use to inform management in alloimmunized pregnancies.

Additional high-quality outcome studies measuring clinical impact are needed despite high analytical concordance reported.

inv-59: Carrier screening with reflex to sgNIPT when partner sample unavailable — cohort studies report high sensitivity/specificity

Carrier screening with reflex to sgNIPT: Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) in situations where partner sample is unavailable has been evaluated in large cohorts and shows high sensitivity and specificity, though broader clinical utility remains under study.

Large validation cohorts report sensitivity ~96% for sgNIPT in selected conditions.

inv-60: Screening for common autosomal aneuploidies (trisomy 21, 18, 13) in singleton pregnancies — to be offered to all pregnant individuals

Offer to all pregnant individuals: Screening for common autosomal aneuploidies (trisomy 21, 18, 13) in singleton pregnancies should be offered to all pregnant individuals as the most sensitive and specific screening option.

Providers should discuss screening options and counsel patients per ACOG/ISPD guidance.

inv-61: Fetal RhD genotyping in alloimmunized pregnancies or where paternal genotype is heterozygous/unknown — NICE and ACOG notes

RhD genotyping guidance: NICE and ACOG note that cfDNA fetal RhD genotyping can guide antenatal anti-D prophylaxis decisions; ACOG recognizes cfDNA testing as a reasonable alternative for fetal RhD determination among alloimmunized patients who decline amniocentesis.

NICE recommends high-throughput cfDNA testing for fetal RhD genotype to guide anti-D prophylaxis decisions depending on cost-effectiveness.

inv-62: cfDNA testing to determine fetal genotype in alloimmunized or at-risk-for-alloimmunization pregnancies when paternal genotyping shows heterozygosity or paternal status unknown and invasive testing was offered and declined

Covered scenario for fetal genotype testing: cfDNA testing to determine fetal genotype is covered when the pregnant individual is alloimmunized or at risk for alloimmunization, paternal genotyping shows heterozygosity or is unknown, and indicated invasive testing was offered and declined.

Documentation of paternal genotype (if available) and that invasive testing was offered and declined must be included in the medical record.

Placeholder: no top‑level eligibility nodes in this inventory slot; refer to the policy criteria for specific eligibility details.

Pretest counseling should include discussion of targeted aneuploidies, potential for false results, and whether expanded screening is being offered.
For positive or no‑call results document counseling, offer of diagnostic testing (CMA/karyotype), and plan for ultrasound and clinical follow-up.
If cfDNA is used after a positive serum screen to avoid invasive testing, document that patient was informed about limitations and potential delay to definitive diagnosis.

Documentation Required

Regulatory and Laboratory Validation Considerations

Document laboratory regulatory status and validation details when ordering or interpreting cfDNA assays. Ensure the performing laboratory is CLIA‑certified and has published or available validation for the specific assay and claim (e.g., sensitivity/specificity, fetal fraction limits, no‑call thresholds). Provide lab validation or technical documentation upon request.

Confirm CLIA certification and that the assay’s analytic/clinical validation applies to the requested indication and gestational age.
Document assay-specific limits (minimum fetal fraction, no‑call criteria) and any laboratory protocols for suspected maternal malignancy or discordant results.

Denial Risk

Tests Performed for Indications Beyond Core Aneuploidy

Tests ordered for indications beyond the core trisomies (21, 18, 13) and sex chromosome aneuploidy — including twin zygosity, genome‑wide/exome panels, microdeletions/CNV screening, single‑gene NIPT, or other expanded panels — are considered unproven for many indications and may be denied. Order only indications supported by clinical evidence and document medical necessity.

Claims for genome-wide cfDNA, expanded microdeletion/CNV panels, single‑gene NIPT for indications beyond documented paternal risk, or fetal antigen screening other than RhD may be denied.
For twin pregnancies, evidence for RAAs/CNV screening is insufficient; document rationale if such testing is requested.

Documentation Required

Confirmatory Testing and Documentation

Confirmatory diagnostic testing must be documented for any positive expanded cfDNA result (RAAs, CNVs, microdeletions, single‑gene findings). Document that diagnostic confirmation (karyotype, CMA, or targeted molecular testing) was offered and whether it was accepted or declined. Medical records should include diagnostic test type, results, and any impact on pregnancy management.

For screen‑positive RAAs or CNVs, indicate offer and outcome of invasive testing (amniocentesis/CVS) and CMA/karyotype confirmation.
If diagnostic testing was offered and declined, document the counseling provided and the patient’s informed refusal.

Documentation Required

Pretest Counseling Documentation

Document pretest counseling that addresses the limitations of cfDNA screening (false positives/negatives, potential no‑call results, and that cfDNA is not diagnostic). Record the counseling provider, topics covered, and the patient’s informed decision regarding testing.

Include discussion of alternative screening options (serum screening, ultrasound) and the recommendation that only one screening strategy be used at a time.
Document that patients with no‑call results were advised of increased aneuploidy risk and offered repeat testing, detailed ultrasound, and diagnostic testing.

Documentation Required

Documentation for Fetal Genotype Testing in Alloimmunized Pregnancies

For alloimmunized or RhD‑negative pregnancies where fetal genotype testing is ordered, document paternal genotyping results (if available), offer of invasive diagnostic testing, and that invasive testing was offered and declined when applicable. Record the testing rationale, gestational age, and how results will inform anti‑D prophylaxis management.

If paternal genotyping shows heterozygosity or is unknown, document the indication for fetal RhD genotyping.
Provide documentation that invasive testing for definitive fetal genotype was offered and declined when noninvasive cfDNA was used to guide management.

Documentation Required

Preference for Diagnostic CMA After Abnormal Ultrasound

When fetal structural abnormalities are identified on ultrasound, document that diagnostic testing with chromosomal microarray analysis (CMA) via invasive sampling (amniocentesis/CVS) was recommended and preferred over cfDNA screening due to greater diagnostic yield; if CMA was declined and cfDNA screening performed, document counseling and rationale.

CMA is the preferred diagnostic test after abnormal ultrasound findings (including NT ≥ 3.5 mm).
If cfDNA was chosen despite abnormal ultrasound, document informed refusal of invasive diagnostic testing and detailed counseling.

Detection thresholds varySensitivity and specificity depend on assay, sequencing depth, and size threshold; smaller CNVs have lower detection performance

Invasive diagnostic testing offer

Offer and decline requirementInvasive diagnostic testing (eg, amniocentesis or CVS) must have been offered and declined for cfDNA fetal genotyping coverage in alloimmunized or at-risk pregnancies

Documentation requiredDocumentation should include that invasive testing was offered and declined and evidence of maternal alloimmunization or red cell antigen antibodies

Paternal genotype contextThis requirement applies when paternal genotyping is heterozygous for RhD or paternal RhD status is unknown

Clinical useAnalyzed to assess risk for fetal aneuploidies and certain genomic abnormalities; offered as early as 10 weeks gestation

LimitationscfDNA screening is not diagnostic; positive results require invasive diagnostic confirmation

Twin zygosity

DefinitionRefers to dizygotic (fraternal) or monozygotic (identical) twin conception based on origin of embryos

Policy stanceTesting for twin zygosity using cfDNA is listed among indications considered unproven/not medically necessary

Genetic relationDizygotic twins share ~50% of genes; monozygotic twins arise from one zygote dividing

Confined placental mosaicism

DefinitionA placental-only chromosomal mosaicism causing discordant cfDNA results (positive in maternal plasma but not present in fetus)

Clinical impactConfined placental mosaicism can produce false-positive cfDNA results and is associated with increased risk of adverse pregnancy outcomes

ImplicationMay warrant invasive diagnostic confirmation and increased prenatal monitoring

PPV (positive predictive value)

DefinitionPositive predictive value (PPV) is the proportion of screen-positive cfDNA results that are true fetal positives confirmed by diagnostic testing

VariationPPVs for rare findings and CNVs vary widely across studies depending on prevalence, assay, and follow-up confirmation rates

Clinical relevanceLow PPV for rare autosomal aneuploidies and some CNVs necessitates counseling and confirmatory diagnostic testing

22q11.2 deletion (DiGeorge) syndrome

Definition22q11.2 deletion (DiGeorge) syndrome is a common microdeletion syndrome (incidence ~1 in 3,000–6,000 births) associated with congenital heart defects, immune dysfunction, hypocalcemia, and developmental/neuropsychiatric features

Screening evidenceSome cfDNA studies report relatively high PPV for 22q11.2 in selected cohorts, but overall evidence is mixed and assay-dependent

Confirmatory testingPositive cfDNA screens for 22q11.2 require diagnostic confirmation (eg, CMA) before clinical management decisions

Subchromosomal abnormalities

DefinitionSubchromosomal abnormalities are regional deletions or duplications (microdeletions/microduplications) detectable by targeted cfDNA algorithms

FrequencyReported overall frequency of subchromosomal abnormalities is approximately 1.6% of pregnancies

Detection limitsDetection performance varies by CNV size, assay method, sequencing depth, and study ascertainment

No-call (uninterpretable) result

DefinitionA 'no-call' (uninterpretable) cfDNA result is a test not reported by the laboratory, commonly due to insufficient fetal fraction

Associated riskNo-call results are associated with increased risk of aneuploidy and should prompt genetic counseling, ultrasound evaluation, and offer of diagnostic testing

Laboratory practiceLaboratories may have redraw or follow-up protocols; persistent no-call often requires further clinical evaluation

cfDNA screening

DefinitioncfDNA screening is a noninvasive test analyzing cell-free fetal DNA in maternal blood to assess risk for common fetal chromosomal aneuploidies

RoleIt is a screening, not diagnostic, test; positive or no-call results should prompt counseling and offered diagnostic testing

IndicationsEstablished indications include screening for trisomies 21, 18, 13 and sex chromosome aneuploidies; can be offered in singleton and twin pregnancies

Expanded cfDNA panel

DefinitionExpanded cfDNA panel testing includes panels that test beyond trisomies 21, 18, 13 and sex chromosome aneuploidy (eg, genome-wide CNVs, microdeletions, RAAs, single-gene targets)

Policy stanceExpanded cfDNA panels are listed as unproven and not medically necessary for routine coverage beyond core aneuploidies

Performance noteEvidence for expanded panels (CNVs, microdeletions, RAAs, single-gene tests) is variable and often limited by low prevalence and low PPV

Replaced broader 'unproven for all other indications' wording with a specific statement that cfDNA using maternal plasma is unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy.

2025-08-01coverage_revision

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

2025-08-01coding_change

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

2025-08-01coding_change

Removed a long list of applicable ICD-10 diagnosis codes from the policy's applicable codes list.