ModifiedUnitedHealthcarePolicy CS085NM.D

Cell‑Free Fetal DNA Testing (for New Mexico Only)

Policy governing use and coverage of maternal plasma cell‑free fetal DNA testing for prenatal screening and specific fetal genotyping in New Mexico; affects pregnant individuals, ordering providers, and payers in NM.

Policy Summary

PayerUnitedHealthcare

PolicyCell‑Free Fetal DNA Testing (for New Mexico Only)

Policy CodePolicy CS085NM.D

Change TypeMaterial coverage revisions

Effective Date08/01/2025

Next Review Date

Key ActionDocument alloimmunization risk, paternal RhD genotype (or unknown/heterozygous), and that invasive diagnostic testing was offered and declined when requesting fetal genotype testing coverage.

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; and indicated invasive diagnostic testing for fetal genotyping has been offered and declined.

Language indicating DNA-based noninvasive prenatal tests of fetal Aneuploidy are proven and medically necessary as screening tools for trisomy 21, 18, or 13, with or without fetal sex chromosomes, for individuals with a singleton or twin pregnancy under specified risk conditions (maternal age ≥35, ultrasound findings, prior affected pregnancy, positive prior screen, parental translocation, or after counseling).

Replaced broad 'unproven and not medically necessary for all other indications' language with 'Cell-Free Fetal DNA testing using maternal plasma is considered unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome Aneuploidy; this includes but is not limited to the listed indications due to insufficient evidence of efficacy.'

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 'screening for fetal RhD' from the unproven/not medically necessary list (i.e., fetal RhD previously listed as unproven was removed).

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

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.

08/01/2025policy revision effective date

3CPT codes removed

~100%RhD genotyping sensitivity

99.3%RhD genotyping specificity

0.07/0.13RAT pooled PPV

Coverage Criteria for Cell-Free Fetal DNA Testing

RhD fetal genotyping - Medically necessary indications

Covered when ALL of the following are met:

RhD genotyping coverage criteria: 1) The individual undergoing testing is alloimmunized or at risk for alloimmunization due to maternal RhD-negative status or presence of red cell antigen antibodies; 2) Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown; 3) Indicated invasive diagnostic testing (e.g., amniocentesis or chorionic villus sampling) for fetal genotyping has been offered and declined.

From Coverage Rationale (policy)

Not medically necessary / Unproven indications

Not covered / considered unproven when used for the following indications:

Unproven or not medically necessary uses: Cell‑Free Fetal DNA testing using maternal plasma for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy. Examples include: testing for the sole purpose of determining twin zygosity; genome‑wide or exome‑wide screening; expanded cfDNA panels beyond common trisomies and sex chromosome aneuploidy; screening for microdeletions/microduplications/CNVs; single‑gene disorder screening (e.g., Vistara, PreSeek); and fetal antigen status other than RhD.

Policy states these are considered unproven and not medically necessary due to insufficient evidence of efficacy.

General coverage guidance for expanded cfDNA testing

Coverage consideration based on current evidence:

General coverage logic: Routine cfDNA screening is supported for common trisomies (13, 18, 21) and sex chromosome aneuploidies; expanded genome‑wide cfDNA for rare autosomal trisomies (RAAs), CNVs, and microdeletions has limited and variable clinical utility and should be considered only in specific clinical contexts (for example, abnormal ultrasound findings) with informed pretest counseling and a plan for diagnostic confirmation.

Derived from evidence summaries indicating low/variable PPV and insufficient clinical utility for routine population screening.

Acceptable indications for expanded cfDNA testing

Potential medically reasonable uses when criteria met:

When expanded cfDNA/CNV screening may be considered: Presence of fetal structural ultrasound anomalies or ultrasound soft markers associated with CNVs (e.g., aberrant right subclavian artery), or when invasive diagnostic testing (CVS/amniocentesis) is declined or unavailable; in these situations expanded cfDNA testing may be offered with explicit counseling regarding limitations and requirement for confirmatory diagnostic testing.

Supported by retrospective and prospective studies evaluating CNV detection in ultrasound‑abnormal cohorts.

Expanded cfDNA screening — evidence-based coverage considerations

Summary of evidence-based coverage considerations for cfDNA beyond common aneuploidies:

{\"operator\":\"any\",\"n\":1,\"label\":\"22q11.2 microdeletion screening\",\"text\":\"Emerging evidence shows detection of many 22q11.2 deletions with moderate sensitivity and high specificity in enriched/high‑risk cohorts, but positive predictive value (PPV) is variable and case numbers are small; positive results require diagnostic confirmation and counseling.\",\"threshold\":\"sensitivity reported 75%–90%; specificity ~99.7%–99.84%; PPV variable (19.6%–52.6%)\",\"note\":\"From Dar et al. and guideline summaries; confirmatory testing required.\"}

{\"operator\":\"any\",\"n\":1,\"label\":\"Other CNV/subchromosomal screening\",\"text\":\"Some large‑cohort algorithms can identify subchromosomal events with true positives in high‑risk populations, but sensitivity and false‑negative rates are not well established and evidence is insufficient to support routine population screening for CNVs beyond 22q11.2.\",\"threshold\":\"subchromosomal events reported ~1.4%–1.6% in certain cohorts\",\"note\":\"Generalizability limited when cohorts enriched by anomalies; see Hayes evaluation.\"}

{\"operator\":\"any\",\"n\":1,\"label\":\"Fetal antigen genotyping (RhD and selected RBC antigens)\",\"text\":\"NGS‑based cfDNA fetal antigen testing demonstrates high analytic sensitivity and specificity in validation studies and prospective cohorts, with some reports of near‑perfect concordance in limited samples; additional high‑quality outcome studies are needed before broad routine adoption.\",\"threshold\":\"validated as early as 10 weeks gestation in some cohorts; analytic sensitivity/specificity reported near 100% in validations\",\"note\":\"Useful for management of alloimmunized pregnancies when paternal genotype is heterozygous/unknown.\"}

Coverage-aligned clinical criteria

Covered when clinical use aligns with professional society guidance and documented counseling:

General prenatal screening: cfDNA may be offered as a prenatal screening option to all pregnant individuals after counseling about alternatives (serum +/- nuchal translucency) and that cfDNA is a screening — not diagnostic — test.

ACOG/ACMG/ISPD guidance recommends offering screening with counseling.

Multifetal gestations: In twin or higher‑order gestations, document counseling that cfDNA and serum‑based screening are less accurate and have higher failure rates; offer diagnostic testing when fetal demise, vanishing twin, or anomaly is present.

ACOG/SMFM caution regarding reduced accuracy and higher no‑call rates in multifetal pregnancies.

Expanded/genome‑wide testing and microdeletions: Routine population‑based screening for microdeletions, genome‑wide CNVs, rare autosomal trisomies, and other expanded analyses is not recommended due to insufficient validation and uncertain clinical utility; if offered, platform‑specific counseling and protocols for high‑risk results must be in place.

ISPD/ACMG/ACOG/SMFM advise caution and require protocols for management of high‑risk results.

Fetal genotype testing in alloimmunized or at-risk pregnancies

Covered when ALL of the following are met:

Fetal genotype determination for alloimmunized or at‑risk 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: paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown; and indicated invasive diagnostic testing (e.g., amniocentesis or CVS) for fetal genotyping has been offered and declined.

Policy History added this covered indication; supports management decisions including targeted RhIG administration.

Unproven/Not Medically Necessary

Not medically necessary for indications beyond core trisomy/sex chromosome screening:

Unproven expanded indications: Cell‑Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome aneuploidy), routine genome‑wide/exome‑wide screening, screening for rare autosomal trisomies (RAAs), copy number variants (CNVs), microdeletions, single‑gene disorders, and fetal antigen status other than RhD are considered unproven and not medically necessary for routine use.

Policy explicitly lists expanded panel testing as unproven and clarifies scope of unproven indications.

Cell‑Free Fetal DNA testing using maternal plasma is considered unproven and not medically necessary when performed solely to determine twin zygosity or when offered as broad genome‑wide or exome‑wide screening (for example, platforms marketed as whole‑genome maternal plasma assays). The policy explicitly lists genome‑wide/exome‑wide approaches and tests described as expanded panels that go beyond the core aneuploidies as examples of indications lacking sufficient evidence for routine coverage.

Use of cfDNA for prenatal exome or genome sequencing or for routine screening of microdeletions/CNVs in unselected twin pregnancies is not supported by current evidence and therefore is excluded from routine coverage. Existing reviews and evaluations conclude that additional validation studies are needed to determine sensitivity, specificity, and positive predictive value for these expanded applications before they can be recommended for population‑based screening.

There is insufficient evidence to recommend routine cfDNA screening for copy number variants (CNVs) other than the 22q11.2 microdeletion and for routine screening for rare autosomal trisomies (RATs). Published evaluations report low quality evidence, high false positive rates in many series, and limited demonstration of clinical utility for these indications.

Routine use of genome‑wide cfDNA to screen for copy number variants, microdeletions, or for population screening of rare autosomal trisomies is not recommended for unselected pregnancies. Professional society statements emphasize lack of clinical validation and advise that if such testing is offered locally, detailed, platform‑specific counseling and management protocols must be in place.

Expanded cfDNA panel testing that includes targets beyond trisomies 21, 18, 13 and sex chromosome aneuploidy is considered unproven and not medically necessary. Routine coverage is limited to established screening indications for the common autosomal trisomies and sex chromosomes; expanded panels lack sufficient evidence of clinical utility.

Use of maternal plasma cfDNA testing for indications outside the core trisomies and sex chromosome screening — including single‑gene disorders, microdeletion panels, genome‑wide analyses, or fetal antigen testing other than RhD — is considered unproven. The policy therefore treats these indications as not medically necessary for routine coverage absent stronger validation and clear evidence of clinical benefit.

Screening for rare autosomal aneuploidies (RAAs) and for copy number variants in unselected singleton or twin pregnancies is supported by only low‑quality evidence and frequently yields high false positive rates; consequently, routine population screening for RAAs and broad CNV panels is not recommended except in specific clinical contexts where further diagnostic evaluation is planned.

The routine use of cfDNA testing to determine fetal antigen status other than RhD lacks peer‑reviewed evidence demonstrating clinical utility. Additional high‑quality outcome studies are needed before these applications can be recommended for routine management of alloimmunized pregnancies.

Single‑gene cfDNA screening approaches (sgNIPT/sgNIPS‑SGD) and unvalidated expanded genome‑wide NIPT assays for CNVs, microdeletions, and rare autosomal trisomies are considered insufficiently validated for routine clinical use. While some studies report promising analytic performance in selected cohorts, evidence remains preliminary and diagnostic testing remains the preferred method when single‑gene disorders are suspected.

Unproven expanded uses include, but are not limited to: expanded panel testing beyond trisomies 21/18/13 and sex chromosomes, genome‑wide or exome‑wide prenatal sequencing, routine microdeletion/CNV population screening, single‑gene disorder screening, and fetal antigen screening other than RhD. These uses are listed as examples of indications for which routine coverage is not supported due to insufficient evidence.

Applicable Codes and Coding Notes

Applicable cfDNA CPT/PLA Codes (excerpt)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

Additional Applicable Codesmixed

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	Removed from applicable codes
81420	Removed from applicable codes
81507	Removed from applicable codes

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

O09.00	Removed from applicable ICD-10 codes list (example)
O26.20	Removed from applicable ICD-10 codes list (example)
Z34.00	Removed from applicable ICD-10 codes list (example)
Z36.0	Removed from applicable ICD-10 codes list (example)
Z3A.09	Removed from applicable ICD-10 codes list (example)

Gestational age for testing — common windows

Typical earliest gestational age for RhD genotypingAs early as 9–10 weeks gestation (NGS-based RhD assays reported performance beginning at 9 weeks).

Typical earliest gestational age for routine cfDNA aneuploidy screeningApproximately 10+ weeks gestation for standard cfDNA aneuploidy screening.

Later-gestation sampling reported in some studiesSome validation studies collected samples at 24–28 weeks (e.g., Manfroi et al. for RhD genotyping).

Fetal fraction ranges reported — study data

Study-specific early-sample exclusionSamples < 9 weeks gestation were excluded in Ravi et al.'s study of 22q11.2 (and related validations).

Provider Actions, Prior Authorization, and Documentation

Documentation Required

Pretest Counseling and Documentation

Document pretest counseling discussing screening options, limitations, and specific considerations. Genetic counseling is strongly recommended prior to fetal screening or prenatal diagnosis to ensure the person being tested understands the advantages, limitations, and potential outcomes (including false positives, false negatives, and no-call results) and the need for confirmatory diagnostic testing for screen-positive results. Counseling should cover: the single-screening approach recommendation; implications of sequential or concurrent screening; limitations of expanded cfDNA panels, microdeletion/CNV screening, and single-gene cfDNA tests; the possibility that a no-call result is associated with increased aneuploidy risk; and the availability of diagnostic testing (amniocentesis, CVS) if indicated.

Discuss all available prenatal screening options (serum screening ± nuchal translucency, cfDNA screening) and diagnostic testing (CVS, amniocentesis).
Explain that cfDNA is a screening, not diagnostic, test and that positive or no-call results should prompt genetic counseling, comprehensive ultrasound, and offer of diagnostic testing.
Explain limitations and low evidence for expanded cfDNA uses (microdeletions/CNVs, genome/exome-wide testing, single-gene screening) and potential for increased false positives and unnecessary invasive testing.
Document that counseling occurred in the medical record, including the chosen screening approach and that informed consent was obtained.

Background and Rationale

Cell‑free fetal DNA (cfDNA) refers to small fragments of placental DNA circulating in maternal blood that can be detected and analyzed as early as 9–10 weeks' gestation. cfDNA screening assesses risk for fetal chromosomal abnormalities but is a screening test, not diagnostic; positive or suspicious results require confirmatory invasive diagnostic testing (chorionic villus sampling or amniocentesis) for definitive diagnosis.

Definitions

Cell Free Fetal DNA (cffDNA / cfDNA) — definition

DefinitionAn abnormal number of chromosomes in a human cell (includes trisomy—an extra chromosome—or monosomy—missing chromosome).

Common examplesTrisomy 21 (Down syndrome), Trisomy 13 (Patau syndrome), Trisomy 18 (Edwards syndrome).

Twin Zygosity — definition

DefinitionZygosity classification for twin conception: dizygotic (fraternal) twins arise from two ova and two sperm and share ~50% of genes; monozygotic (identical) twins arise from division of a single zygote.

Implication for testingZygosity affects interpretation of cfDNA results in multifetal gestations and can influence test accuracy.

TerminologyAlso described as dizygotic vs monozygotic based on origin of embryos.

Policy Revision History

08/01/2025material_change_addedLatest

Added covered indication: cfDNA testing of maternal plasma to determine fetal genotype in alloimmunized or at‑risk pregnancies when paternal RhD is heterozygous/unknown and invasive diagnostic testing was offered and declined.

08/01/2025material_change_removed

Removed prior enumerated proven screening indications that had listed DNA‑based NIPT for trisomies 21, 18, 13 (with or without sex chromosomes) under specific risk conditions (age ≥35, ultrasound findings, prior affected pregnancy, positive prior screen, parental translocation, or after counseling).

08/01/2025material_change_revised

Policy Summary

PayerUnitedHealthcare

PolicyCell‑Free Fetal DNA Testing (for New Mexico Only)

Policy CodePolicy CS085NM.D

Change TypeMaterial coverage revisions

Effective Date08/01/2025

Next Review Date

SourceLink

On This Page

{\"operator\":\"any\",\"n\":1,\"label\":\"Single‑gene disorder cfDNA testing (sgNIPT)\",\"text\":\"Carrier screening with reflex to sgNIPT and targeted single‑gene cfDNA approaches show promising high sensitivity and specificity in selected studies, but many are preliminary with limited outcome ascertainment; diagnostic testing remains preferred when clinically indicated.\",\"threshold\":\"reported sensitivity ~92%–96% and specificity up to 99.9% in selected validations\",\"note\":\"Evidence stronger in enriched/high‑risk cohorts or when family history known.\"}

{\"operator\":\"any\",\"n\":1,\"label\":\"No‑call/uninterpretable results\",\"text\":\"No‑call results, often due to low fetal fraction, are associated with increased aneuploidy risk; follow‑up with genetic counseling, targeted ultrasound, and offer of diagnostic testing is recommended.\",\"threshold\":\"no‑call rates vary by assay; linked to adverse outcomes\",\"note\":\"Consistent with ACMG/ACOG/ISPD guidance.\"}

Fetal RhD and selected antigen testing: cfDNA for fetal RhD genotype and selected non‑RhD red blood cell antigens may be used to guide management in alloimmunized pregnancies or when invasive testing is declined; consider cost, access, and local validation before routine use.

ACOG update and NICE support targeted RhD cfDNA use to reduce unnecessary anti‑D prophylaxis where validated.

Reason for exclusionVery early gestational samples may have insufficient fetal fraction or be otherwise unsuitable for specific algorithmic analyses.

Note

Single Screening Approach — Offer and Document

Consider offering a single chosen screening approach and document the patient’s informed selection. If screening is accepted, providers should recommend that patients undergo one prenatal screening approach rather than multiple simultaneous screening tests. When patients choose sequential or follow-up testing (for example, cfDNA after a positive serum screen), counsel them that this may delay definitive diagnosis and may still miss some chromosomal abnormalities.

Offer and document a single screening strategy; note any patient preference for sequential testing and the counseling provided about delays and limitations.
If cfDNA is used as follow-up to a positive serum screen, document that the patient was counseled about the option to avoid invasive testing and the potential for delayed or missed diagnosis.
For multiple gestations, vanishing twin, or fetal demise, document counseling that screening performance differs from singleton pregnancies and discuss diagnostic options.

Prior Authorization

Prior Authorization and Affected Codes

Prior authorization may be required for certain cfDNA tests and specific coding should be verified with the plan. For fetal RhD and other antigen testing, and for requests involving expanded or genome-wide cfDNA testing, prior authorization or review is recommended given limited evidence and potential for claim denial when used for unproven indications.

When requesting fetal RhD or other fetal antigen testing, document paternal genotype and maternal alloimmunization status in the request.
Expanded cfDNA panels, genome-wide CNV testing, microdeletion panels, and single-gene cfDNA tests are low-evidence indications and may require prior authorization or be denied.
Removed/obsolete CPT codes should not be submitted; verify current CPT/HCPCS codes and plan prior authorization rules before billing.

Denial Risk

Denial Risks and Documentation Requirements

Failure to offer or document counseling, diagnostic options, or to record rationale/confirmation of invasive testing when indicated may affect coverage determinations. Claims for expanded panel testing and other unproven indications may be denied if documentation does not support medical necessity.

Document pretest counseling, the chosen screening approach, and informed consent. Document any offer of invasive diagnostic testing and the patient’s decision if declined.
For alloimmunized or at-risk pregnancies requesting cfDNA fetal genotype testing, support coverage by documenting paternal genotype (heterozygous or unknown) and that invasive diagnostic testing was offered and declined.
After positive or no-call results, document that patients were offered genetic counseling, comprehensive ultrasound, and diagnostic testing options; lack of documentation may lead to denial.

Confined placental mosaicism — definition and relevance

DefinitionA biological cause of discordant cfDNA-positive but fetal‑negative results where the placenta and fetus have different chromosomal constitutions (placental mosaicism).

Clinical relevanceConfined placental mosaicism can produce false‑positive cfDNA results and is associated with increased risk of adverse pregnancy outcomes, warranting follow-up.

ConfirmationPlacental testing or invasive fetal diagnostic testing (amniocentesis/CMA) may be required to resolve discordant results.

22q11.2 deletion syndrome screening — assay context and variability

cfDNA assay context22q11.2 deletion screening is performed using WGS or SNP‑based cfDNA assays targeting the 22q11.2 microdeletion; study sensitivity, specificity, and PPV vary by platform and cohort.

Performance variabilityStudies report variable sensitivity and PPV and emphasize dependence on fetal fraction and cohort enrichment; positive results require diagnostic confirmation.

Clinical implicationOffering 22q11.2 screening requires platform‑specific counseling and plans for confirmatory testing.

22q11.2 deletion syndrome (DiGeorge) — brief description

Clinical description22q11.2 deletion syndrome (DiGeorge/velocardiofacial) is a microdeletion syndrome with variable manifestations including congenital heart defects, immune dysfunction, hypocalcemia, learning disabilities, and increased risk of mental health disorders.

IncidenceReported incidence approximately 1 in 3,000–6,000 births.

Screening implicationGiven variable presentation, positive cfDNA screen for 22q11.2 requires diagnostic confirmation and specialized counseling.

No‑call / insufficient fetal fraction (FF) — definition and implications

DefinitionA cfDNA result that is not reported or is uninterpretable most commonly due to low fetal fraction (FF); often called 'no‑call' for insufficient FF.

Associated risksNo‑call/insufficient FF is associated with increased risk of fetal aneuploidy and adverse pregnancy outcomes; additional evaluation is recommended.

Recommended follow‑upCounseling, targeted ultrasound, offer of repeat sampling or invasive diagnostic testing should be offered per society guidance.

No‑call / uninterpretable result — definition

DefinitionA laboratory result that is not reported or is uninterpretable (no‑call) often due to assay limitations or low fetal fraction.

Clinical consequenceNo‑call/uninterpretable results are linked to increased aneuploidy risk and should prompt genetic counseling and offer of diagnostic testing.

Laboratory roleLabs should have pathways for managing no‑call results, including options for redraw, alternative testing, or diagnostic referral.

Fetal fraction (FF) — quality metric definition

DefinitionProportion of cell‑free fetal DNA in the maternal plasma sample; used as a quality control metric for cfDNA assays.

Impact on testingLow fetal fraction is a common cause of no‑call results and can reduce assay sensitivity and specificity.

Operational noteFetal fraction thresholds and limits of detection vary by laboratory and assay methodology.

Shared Decision‑Making (SDM) — definition

DefinitionShared Decision‑Making (SDM) is a collaborative process between clinician and patient to make healthcare decisions that align with patient values and preferences.

RelevanceSDM is recommended when offering expanded or optional cfDNA screening tests due to variable utility and possible downstream consequences.

DocumentationDocumenting counseling and patient preference supports appropriate use and informed consent.

Single Nucleotide Polymorphisms (SNPs) — definition

DefinitionSingle nucleotide polymorphisms (SNPs) are single‑base genetic variants used as markers in cfDNA assays (SNP‑based methods) to infer fetal genotype and detect chromosomal abnormalities.

Use in assaysSNP panels are used in specialized algorithms for zygosity, microdeletion, and aneuploidy detection.

LimitationsPerformance depends on assay design, fetal fraction, and population allele frequencies.

Next Generation Sequencing (NGS) — definition

DefinitionNext Generation Sequencing (NGS) is a high‑throughput DNA sequencing technology used to analyze cfDNA for fetal aneuploidy, RhD genotype, and other targeted genomic regions.

ApplicationsNGS platforms are applied to RhD genotyping, WGS‑based cfDNA assays, and targeted panels.

Operational noteSequencing depth and bioinformatic algorithms influence assay sensitivity, specificity, and ability to detect subchromosomal events.

Mosaicism — definition

DefinitionMosaicism: presence of two or more genetically distinct cell lines within the same individual or tissue (e.g., fetal or placental mosaicism).

Types relevant to cfDNAConfined placental mosaicism (placenta differs from fetus) can cause discordant cfDNA results; fetal mosaicism affects fetal phenotype and diagnostic interpretation.

Clinical implicationMosaicism complicates interpretation of cfDNA screening and often necessitates invasive diagnostic testing for clarification.

Revised unproven/not medically necessary language to clarify cfDNA is unproven for indications beyond screening for trisomies 21, 18, 13 and sex chromosome aneuploidy, and explicitly added 'expanded panel testing' to the unproven list while removing fetal RhD from that list to allow separate coverage for RhD genotype in alloimmunized/at‑risk cases.