CurrentUnitedHealthcarePolicy CS085NM.D

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

UnitedHealthcare New Mexico medical policy on use of maternal plasma cell-free fetal DNA (cfDNA) testing for fetal genotyping and aneuploidy screening, defining medically necessary indications (notably RhD/alloimmunization) and listing technologies/tests considered unproven/unnecessary.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS085NM.D

Change TypeAdded proven indication for cfDNA fetal genotype in alloimmunized/at‑risk pregnancies; revised unproven indications and removed select codes

Effective DateAug 1, 2025

Next Review Date

Key ActionProvider must document paternal genotyping showing heterozygosity or unknown paternal RhD status and that indicated invasive diagnostic testing was offered and declined to meet coverage criteria.

SourceLink

POLICY UPDATE CHANGES

Removed prior language indicating DNA-based noninvasive prenatal tests of fetal aneuploidy are proven and medically necessary as screening tools for trisomies 21, 18, 13 (with/without sex chromosomes) for listed higher-risk circumstances (e.g., maternal age ≥35, abnormal ultrasound, prior affected pregnancy, positive prior screening, parental translocation, screening after counseling).

Replaced broad 'unproven and not medically necessary for all other indications' language with a clarified statement 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, and revised the list of unproven indications.

Vanadis® was removed from the policy as unproven and not medically necessary.

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

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

1Primary covered indication (alloimmunization/RhD genotyping)

4Explicitly listed unproven indications

7Representative procedure codes listed

1ACMG conditional recommendation for 22q11.2

3Common trisomies recommended for cfDNA screening (13,18,21)

manyRemoved CPT/ICD code changes

Coverage Summary

UnitedHealthcare New Mexico Medical Policy CS085NM.D (effective August 1, 2025) addresses use of maternal plasma cell‑free fetal DNA (cfDNA) testing for fetal genotyping and aneuploidy screening. The policy defines a primary medically necessary indication for cfDNA fetal genotype testing in the setting of alloimmunization or when the pregnant individual is at risk for alloimmunization (notably RhD-related) and specifies required documentation and conditions for coverage. The policy also clarifies that cfDNA tests are screening tools—not diagnostic—and limits covered uses while listing several expanded or genome‑wide applications and other indications as unproven and not medically necessary.

Key thresholds & quick facts

Fetal fraction (FF) threshold noteLow fetal fraction (FF) is the most common cause of no-call results; numeric FF thresholds vary by assay (examples include FF 2.8–6.5% used for limited evaluation in some protocols)

CNV size and PPV stratificationPPV higher for larger CNVs: in Xue et al. overall PPV 38.42% for clinically significant CNVs; PPV 46.5% for CNVs >10 Mb vs 28.57% for CNVs ≤10 Mb; select syndromes had higher PPVs (e.g., DiGeorge 75%)

Primary covered indication count1 proven covered primary indication: fetal genotype testing for alloimmunization/RhD genotyping (coverage when paternal heterozygosity or unknown and invasive testing offered and declined)

Explicitly listed unproven/removed indications count4 explicitly listed unproven indications (twin zygosity, genome/exome-wide screening, expanded cfDNA panels beyond common trisomies, fetal antigen testing other than RhD)

Representative removed/updated codes notePolicy removed certain CPT codes and updated applicable code lists (e.g., Removed CPT codes 0327U, 81420, 81507 and reduced ICD-10 lists) per policy revisions

Medical Necessity and Coverage Criteria

Medically Necessary Indication — cfDNA for fetal genotype in alloimmunized or at-risk pregnancies

Covered when ALL of the following are met:

ALL of the following

Pregnancy in an individual who is alloimmunized or at risk for alloimmunization due to maternal RhD negative status or presence of maternal red cell antigen antibodies.
Paternal genotyping demonstrates heterozygosity for the antigen of interest (e.g., RhD) or paternal antigen status is unknown.
Indicated invasive diagnostic testing (e.g., amniocentesis or chorionic villus sampling) for fetal genotyping has been offered and the pregnant person has declined.
Testing considered proven and medically necessary only when invasive testing is offered and declined.

Unproven and Not Medically Necessary Indications

Guidance, Evidence Summary, and Limitations

cfDNA/NIPT for common autosomal aneuploidies (trisomies 21, 18, 13)

Professional society recommendations summarized:

ACMG and ACOG/SMFM recommend cfDNA as the most sensitive and specific screening test for trisomies 13, 18, and 21 in singleton pregnancies and recommend offering it to all pregnant individuals regardless of age/risk.

Positive cfDNA screening results are screening only and should be confirmed by diagnostic testing (CVS or amniocentesis) prior to any definitive clinical action.

In multifetal gestations and twin pregnancies cfDNA may be used but performance is less certain; counseling should note lower accuracy and offer diagnostic testing where indicated.

cfDNA screening for CNVs and genome-wide CNV detection

Guidance and evidence notes on CNV / genome-wide screening:

Coding

Listed relevant procedure and molecular codes in policymixed

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.
0489U	Obstetrics (single-gene noninvasive prenatal test), cell-free DNA sequence analysis of 1 or more targets to identify paternally inherited pathogenic variants and relative mutation-dosage analysis.
0494U	Red blood cell antigen (fetal RhD gene analysis), next-generation sequencing of circulating 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.
81422	Fetal chromosomal microdeletion(s) genomic sequence analysis, circulating cell-free fetal DNA in maternal blood.
81479	Unlisted molecular pathology procedure

Removed CPT codesCPT

0327U
81420
81507

Removed ICD-10 diagnosis codes (long list)ICD-10

O09.00
O09.01
O09.02
O09.03
O09.10
O09.11
O09.12
O09.13
O09.211
O09.212

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Provider Actions and Operational Requirements

Documentation Required

Document paternal genotyping and offer of invasive testing

Document paternal genotyping status and that invasive diagnostic testing was offered and declined. For alloimmunized pregnancies, paternal genotype must be recorded (heterozygous or unknown) and there must be documentation that indicated invasive diagnostic testing (e.g., CVS or amniocentesis) was offered and the patient declined prior to considering cfDNA testing medically necessary.

Paternal genotype status (heterozygous or unknown)
Documentation that invasive diagnostic testing (CVS/amniocentesis) was offered and declined

Prior Authorization

Prior authorization likely required per payer policy

Obtain prior authorization consistent with UnitedHealthcare New Mexico procedures before performing covered cfDNA tests when required by the member's benefit plan. Failure to obtain prior authorization may result in claim denial or out-of-pocket liability.

Definitions

Definitions:

Aneuploidy — An abnormal number of chromosomes in a human cell (includes trisomy and monosomy, e.g., trisomy 21, 18, 13).

Cell Free Fetal DNA (cffDNA or cfDNA) — Small fragments of fetal DNA from the placenta circulating in maternal blood that can be analyzed by noninvasive prenatal screening.

NIPT / NIPS — Non‑Invasive Prenatal Testing/Screening; common term for cfDNA‑based screening approaches.

CNV (Copy Number Variant) — A subchromosomal deletion or duplication (microdeletion/microduplication).

Fetal fraction — The proportion of fetal cfDNA in maternal plasma; an important quality control metric linked to 'no‑call' results and assay performance.

SDM (Shared Decision‑Making) — A collaborative process by which clinicians and patients make health decisions together, referenced in prior policy language.

Additional terms referenced in the policy: Comparative Genomic Hybridization (CGH), Twin Zygosity, Whole Genome Sequencing (WGS), and cfDNA / NIPT as a screening test.

Revision History

2025-08-01addedLatest

Added language that 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 red cell antigen antibodies and all listed conditions are met. Detail: Requires paternal genotyping heterozygosity or unknown paternal RhD status and that invasive diagnostic testing was offered and declined.

2025-08-01removedLatest

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS085NM.D

Change TypeAdded proven indication for cfDNA fetal genotype in alloimmunized/at‑risk pregnancies; revised unproven indications and removed select codes

Effective DateAug 1, 2025

Next Review Date

SourceLink

On This Page

Proven and medically necessary when ALL of the following are met:

ALL of the following

Pregnant individual is alloimmunized or at-risk for alloimmunization (maternal alloantibodies detected or maternal RhD negative with potential exposure).
cfDNA testing is used specifically to determine fetal antigen status for management of alloimmunization (e.g., guiding anti-D prophylaxis or monitoring for hemolytic disease of the fetus and newborn).
Paternal genotyping is heterozygous for the relevant antigen or paternal status is unknown.
Indicated invasive diagnostic testing (e.g., amniocentesis or CVS) for fetal genotyping has been offered and declined.
Testing considered proven and medically necessary only when invasive testing is offered and declined.
Operational considerations
- cfDNA RhD testing in RhD-negative, non-alloimmunized pregnancies may be used to direct administration of anti-D prophylaxis per clinical practice and available evidence supporting reduction in unnecessary prophylaxis (see policy discussion).
- For monozygotic twin pregnancies, cfDNA RhD testing may be considered if zygosity is known and both fetuses are monozygotic; performance in dizygotic twins is limited and generally not reliable.

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Unproven and Not Medically Necessary Indications

Cell‑free fetal DNA testing using maternal plasma is considered unproven and not medically necessary for ANY of the following indications:

ANY of the following

Testing for the sole purpose of determining twin zygosity (including use of cfDNA to determine zygosity in multifetal gestations).
Cell‑free DNA expanded panel testing that includes targets beyond trisomies 21, 18, 13, and sex chromosome aneuploidy (genome-wide or exome-wide screening).
Screening for microdeletions, microduplications, or copy number variations (CNVs) beyond established, guideline-supported indications.
Screening for single‑gene disorders via cfDNA (e.g., sgNIPT, NIPS‑SGD, NIPD using RHDO or other methods) — not proven for routine clinical use except as described in policy for detecting paternally inherited variants in specific contexts.
Fetal antigen testing other than RhD (e.g., C, c, E, Kell, Duffy) when used outside of validated, peer-reviewed protocols and without demonstrated clinical utility — considered not medically necessary for routine use.
Fetal sex determination for nonmedical reasons (including social or elective sex selection).
Use of cfDNA-based assays in twin or multifetal gestations to assess individual fetal genotypes (including fetal antigen status) except when validated for the specific indication and performance characteristics are available and adequate; in general, cfDNA performance is limited in dizygotic twin pregnancies and multifetal gestations.
Use of cfDNA tests that report expanded or commercial panels (e.g., Vistara™, PreSeek™, MaterniT® Genome) for indications beyond established aneuploidy screening.
Any cfDNA application with inadequate evidence of analytic validity, clinical validity, or clinical utility as determined by the medical policy committee.

ACMG: suggests offering cfDNA screening for 22q11.2 deletion syndrome (conditional); insufficient evidence to recommend routine screening for other CNVs.

ACOG/SMFM: microdeletion screening and genome-wide cfDNA for large deletions/duplications are not recommended due to lack of clinical validation and uncertain accuracy/false-positive rates.

Evidence findings: Studies show variable sensitivity/PPV for CNV detection; Xue et al. (2022) NIPT-plus: PPV overall 38.42% for clinically significant CNVs (FPR 0.40%); Dar et al. (2022) SNP-based cfDNA for 22q11.2: sensitivity 75%, specificity 99.84%, PPV 23.7% (updated algorithm PPV 52.6%); Hammer et al. (2024) reported high PPV for 22q11.2 with FF amplification but further validation needed.

Fetal antigen testing (RhD and non‑RhD) using cfDNA

Evidence and policy stance on fetal antigen testing (RhD and non‑RhD) using cfDNA:

ACOG (Practice Update 2024): fetal antigen genotyping is recommended when paternal genotype is heterozygous or unknown; cfDNA is a reasonable alternative to molecular testing for fetal RhD in alloimmunized patients who decline amniocentesis.

Recent cohort/validation studies report high sensitivity and specificity for NGS/qct-based assays for multiple antigens (e.g., Rego 2025; Alford 2023) but limitations include selected populations and potential conflicts of interest.

Policy statement: peer-reviewed evidence insufficient to broadly support cfDNA fetal antigen testing (other than RhD) for alloimmunized patients; additional high-quality outcome studies needed.

Cell‑free fetal DNA originates from the placenta and circulates in maternal blood and can be analyzed as early as 10 weeks gestation to screen for fetal aneuploidies and certain genetic targets; however, cfDNA testing is explicitly a screening method and cannot definitively diagnose genetic conditions—only invasive diagnostic testing (chorionic villus sampling or amniocentesis) can provide a definitive diagnosis. The policy requires that positive or high‑risk cfDNA screening results be followed by genetic counseling, a comprehensive ultrasound, and offer of diagnostic testing prior to definitive clinical decisions. In multifetal (including twin) gestations the policy and professional society guidance note that performance is less certain, test‑failure rates are higher, and accuracy can be reduced (for example when there is a vanishing twin or fetal demise), so diagnostic testing should be offered and counseling provided about these limitations.

Study / Source	Key Findings
Gilstrop et al. (2025)	Clinical validation of NGS-based cfDNA test for fetal RhD in 655 RhD‑negative pregnant individuals: sensitivity 100% (95% CI 98.9–100%), specificity 99.3% (95% CI 97.6–99.8%), PPV 98.4%, NPV ~100% beginning at 9 weeks gestation; authors note manufacturer involvement as potential bias.
Yang et al. (meta-analysis)	Meta-analysis of high‑throughput NIPT for fetal RhD: false‑negative rate 0.34% (95% CI 0.15–0.76%), false‑positive rate 3.86% (95% CI 2.54–5.82%); accuracy varies by gestational age.
Rego et al. (2025)	Multicenter prospective cohort of NGS‑based quantitative cfDNA fetal antigen genotyping in alloimmunized pregnancies (465 antigen calls): reported 100% sensitivity, specificity, and accuracy for evaluated antigens; study limitations include overrepresentation of White individuals and manufacturer affiliations.
Alford et al. (2023)	Analytical validation of QCT‑NGS fetal antigen assay: analytical sensitivity/specificity 100% (95% CI 99–100%) in preclinical samples; clinical validation showed 100% concordance in limited clinical samples; authors note need for larger outcome studies.
Xue et al. (2022)	Prospective study of NIPT‑plus in 31,260 singletons: 221 high‑risk CNVs (0.71%); overall PPV 38.42%, false positive rate 0.40%; higher PPV for certain syndromes (e.g., DiGeorge 75%); PPV greater for CNVs >10 Mb (46.5%) vs ≤10 Mb (28.57%).
Dar et al. (2022)	SNP‑based cfDNA screening for 22q11.2 in 20,887 individuals: sensitivity 75%, specificity 99.84%, PPV 23.7% (updated algorithm PPV 52.6%); limited confirmed cases restrict precision of estimates.
Wynn et al. (2023)	Carrier screening with reflex to sgNIPT in 42,067 pregnancies: sgNIPT subset sensitivity 96% (subset), specificity 95.2%; overall carrier reflex sensitivity 92.4%, specificity 99.9%; outcome data limited (528 outcomes, 25 affected pregnancies).
Cui et al. (2019)	Study in pregnancies with ultrasound anomalies: for CNVs >1 Mb, sensitivity 83.33% and specificity 99.34%; limited generalizability to average‑risk screening populations.
Hayes, Inc. evaluations (2021–2025)	Clinical utility assessments summarized: evidence for RhD testing infers utility (reduced unnecessary anti‑D prophylaxis) though quality rated low; evidence for CNVs, RATs, and expanded screening judged low/insufficient to support routine clinical utility.
Systematic reviews/meta‑analyses for RATs/CNVs (e.g., Konya 2024, Acreman 2023)	Meta‑analyses report low pooled PPVs for rare autosomal trisomies and high heterogeneity: confirmed‑method pooled PPV ~0.07–0.13 (RATs) or pooled PPV ~11.5% (Acreman); overall high false‑positive rates and limited clinical utility.

Follow UnitedHealthcare New Mexico prior authorization processes for covered cfDNA testing
Confirm benefit coverage and authorization requirements before testing

Documentation Required

Confirmatory diagnostic testing for positive cfDNA results

Counsel patients that positive cfDNA results are screening findings and require confirmatory diagnostic testing. Offer and document counseling about the need for CVS or amniocentesis to confirm positive cfDNA results before making irreversible clinical decisions.

Positive cfDNA results are screening, not diagnostic
Offer confirmatory diagnostic testing (CVS or amniocentesis) and document counseling

Documentation Required

Counseling and ultrasound for no-call/low FF

For no-call or low fetal fraction results, provide genetic counseling and perform a comprehensive ultrasound. Offer diagnostic testing (CVS or amniocentesis) as appropriate and document the counseling, ultrasound findings, and patient decisions.

Provide genetic counseling for no-call/low fetal fraction results
Perform and document a comprehensive ultrasound
Offer and document diagnostic testing (CVS/amniocentesis)

Denial Risk

Use of genome-wide CNV screening

Genome-wide or expanded cfDNA panels (e.g., screening for CNVs, microdeletions, or other expanded targets) lack sufficient clinical validation for routine use and may result in claim denials or unexpected out-of-pocket costs for members. Exercise caution and counsel patients about the higher likelihood of uncertain results and potential noncoverage.

Genome-wide/expanded panels (CNVs, microdeletions, exome-wide) may not be validated
Testing may lead to payer denials or member cost-sharing for noncovered indications

Prior Authorization

Consideration of cfDNA test scope

Counsel patients that cfDNA tests have limited validation for CNVs, microdeletions, fetal antigen genotyping beyond RhD, and single-gene disorders. When these tests are ordered, obtain prior authorization if required and document counseling about the need for follow-up diagnostic testing for any abnormal or actionable findings.

Limited clinical validation for CNVs, microdeletions, fetal antigen genotyping (other than RhD), and single-gene disorders
Obtain prior authorization per UnitedHealthcare New Mexico when required
Document counseling about need for diagnostic confirmation of abnormal/positive results

Documentation Required

Offer invasive diagnostic testing before cfDNA for alloimmunization

Offer invasive diagnostic testing (CVS or amniocentesis) before cfDNA testing is considered medically necessary for alloimmunization cases. Document that invasive diagnostic testing was offered and declined; cfDNA testing may be covered only when invasive testing was offered and the patient declined.

Offer of invasive diagnostic testing required prior to considering cfDNA medically necessary in alloimmunization
Document offer and patient declination of invasive testing

2025-08-01revisedLatest

Replaced broad 'unproven and not medically necessary for all other indications' language with clarified statement 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, and revised the list of unproven indications (added expanded panel testing; replaced 'fetal antigen status' with 'fetal antigen status other than RhD'; removed several prior specific exclusions such as fetal RhD and repeat testing for low fetal fraction).

2025-08-01removedLatest

Vanadis® was removed from the policy as unproven and not medically necessary.

2025-08-01removedLatest

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

2025-08-01removedLatest

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