CurrentUnitedHealthcarePolicy CS085NE.E

Cell Free Fetal Dna Testing Ne Cs

UnitedHealthcare medical policy CS085NE.E governing use of maternal plasma cell-free fetal DNA testing in Nebraska, including coverage rationale, limitations, genetic counseling recommendation, definitions, supporting evidence summaries, and applicable procedure codes.

Policy Summary

PayerUnitedHealthcare

PolicyCell Free Fetal Dna Testing Ne Cs

Policy CodePolicy CS085NE.E

Change TypeMaterial revision (added proven RhD/genotype indicationremoved prior proven trisomy screening languagerevised unproven listremoved codes)

Effective DateAug 1, 2025

Next Review Date

Key ActionProviders must document paternal RhD genotype (heterozygosity or unknown) and that indicated invasive diagnostic testing was offered and declined before cfDNA RhD/fetal genotype testing will be covered.

SourceLink

POLICY UPDATE CHANGES

Added proven coverage indication for cfDNA fetal genotype testing in alloimmunized or at-risk-for-alloimmunization pregnancies with specified conditions.

Removed prior proven/medically necessary wording for DNA-based NIPT for common trisomies in specified risk situations.

Replaced broad 'unproven and not medically necessary for all other indications' language with focused language: unproven/not medically necessary beyond screening for trisomies 21,18,13 and sex chromosome aneuploidy; revised list of unproven indications including expanded panels and genome-wide tests.

Removed specific CPT codes from applicable codes list.

Removed a large set of ICD-10 diagnosis codes from the applicable codes list.

Clarified/updated background, evidence, and reference sections; archived previous policy version CS085NE.D.

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1State-specific policy (Nebraska)

1New proven indication added (alloimmunization fetal genotype)

3CPT/ICD code groups removed

7Procedure codes listed

38%Overall PPV for CNV detection (Xue et al. 2022)

Coverage Summary

This document summarizes UnitedHealthcare Medical Policy CS085NE.E (effective August 1, 2025) that applies only to Nebraska and addresses use of maternal plasma cell-free fetal DNA (cfDNA) testing for prenatal applications, including coverage rationale, limitations, recommended counseling, definitions, evidence summaries, and applicable procedure codes.

The policy adds a proven and medically necessary indication for cfDNA testing to determine fetal genotype when the pregnant individual is alloimmunized or at risk for alloimmunization (due to maternal RhD status or red cell antigen antibodies) and ALL of the following are met: paternal genotyping shows RhD heterozygosity or paternal RhD is unknown, and indicated invasive diagnostic testing (e.g., amniocentesis or CVS) was offered and declined.

For all other indications beyond screening for the common aneuploidies (trisomies 21, 18, 13 and sex chromosome aneuploidy), cfDNA testing using maternal plasma is considered unproven and not medically necessary. The policy explicitly lists unproven applications such as twin zygosity testing, genome- or exome-wide screening (e.g., MaterniT Genome), expanded cfDNA panels beyond the common trisomies, CNV/microdeletion screening, single-gene disorder screening (e.g., Vistara, PreSeek), and fetal antigen testing other than RhD.

The policy revision also documents state-specific applicability (Nebraska), updates to listed applicable procedure codes, and removal of certain previously listed proven indications and code groups in the August 1, 2025 update.

Policy metadata and key thresholds

refb0_1

policy_numberCS085NE.E

effective_date2025-08-01

state_noteThis Medical Policy only applies to the State of Nebraska.

key_threshold_122q11.2 deletion syndrome prevalence reported as 1 in 1,524 (Dar et al. 2022).

key_threshold_2Fetal fraction (FF) range where altered analysis applied: 2.8-6.5%.

Medical-Necessity Criteria

Medically Necessary Indication (RhD/alloinmunization risk)

Covered when ALL of the following are met:

ALL of the following

Individual undergoing testing is alloimmunized or at risk for alloimmunization due to maternal RhD status or presence of red cell antigen antibodies
Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown
Indicated invasive diagnostic testing (e.g., amniocentesis, chorionic villus sampling [CVS]) for fetal genotyping has been offered and declined

Medically Necessary: cfDNA testing for fetal genotype in alloimmunized or at-risk for alloimmunization pregnancies

Covered when ALL of the following are met:

Provider Actions & Requirements

Documentation Required

Document paternal genotyping status and offer of invasive testing

Document paternal genotyping status (heterozygous for RhD or paternal RhD unknown) and explicitly document that indicated invasive diagnostic testing (e.g., amniocentesis or CVS) was offered and declined prior to coverage for cfDNA RhD/fetal genotype testing.

Prior Authorization

Prior authorization implied for Nebraska policy

This policy applies to Nebraska; providers should obtain any applicable preauthorization per the member's UnitedHealthcare plan/process when requesting coverage for cfDNA testing for RhD/genotyping under the stated criteria.

Documentation Required

Genetic counseling recommendation

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

Coding

Listed Applicable Procedure Codesmixed

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 (e.g., CFTR, SMN1, HBB, HBA1, HBA2) 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 cell-free DNA of blood in pregnant individuals known to be RhD 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 (large 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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Background & Evidence Summary

Cell-free fetal DNA (cfDNA) are small fetal-derived DNA fragments from the placenta that circulate in maternal blood and can be analyzed noninvasively as early as about 10 weeks gestation. cfDNA assays can screen for common chromosomal aneuploidies and, depending on the assay, may provide information about microdeletions, CNVs, fetal antigen status, or single-gene variants. These tests identify pregnancies at increased risk but are screening tools and cannot definitively diagnose fetal genetic conditions; invasive diagnostic procedures (CVS or amniocentesis) remain required to confirm a diagnosis.

The policy focuses coverage on cfDNA RhD genotyping in the context of alloimmunized or at-risk pregnancies because evidence supports high analytic and clinical performance in that indication. By contrast, expanded applications — including genome-wide/exome-wide screening, expanded panels, CNV/microdeletion screening, and routine single-gene cfDNA screening — are considered unproven due to limited, heterogeneous, or low-quality evidence and variable positive predictive values, and therefore are not covered as medically necessary outside the specified RhD/alloinmunization criteria.

Citation	Key finding / metric
Rego et al. (2025)	Multicenter prospective cohort (156 alloimmunized pregnancies; 465 antigen calls): sensitivity, specificity, accuracy 100% for fetal antigen genotyping (including D) as early as 10 weeks; no paternal testing needed; limited by racial overrepresentation and vendor affiliation.
Gilstrop et al. (2025)	Clinical validation 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.
Yang et al. (2019) 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.
Hayes Clinical Utility Evaluations (2021/2024)	Hayes evaluations: low-quality evidence for clinical utility of cfDNA RhD testing reducing unnecessary anti‑D prophylaxis (utility score = 3/probable); evidence insufficient for clinical utility of RAA/RAT and CNV cfDNA screening (high false positives).
Xue et al. (2022)	Prospective NIPT-plus cohort (31,260 singleton pregnancies): 221 high‑risk CNV calls (0.71%); 203 underwent invasive testing with 78 true positives → overall PPV 38.42%; false positive rate 0.40%; DiGeorge (22q11.2) PPV 75%.
Dar et al. (2022)	Multicenter prospective SNP‑based cfDNA for 22q11.2 (20,887 enrolled; outcome for 18,289): sensitivity 75%, specificity 99.84%, PPV 23.7% (updated algorithm PPV 52.6%); prevalence ~1 in 1,524.
Wynn et al. (2023)	Largest sgNIPT carrier‑reflex cohort (42,067 screened; 7,538 reflexed; outcomes for 528): sgNIPT sensitivity ~96% (subset), specificity 95.2%; average PPV ~50%; overall panel sensitivity 92.4%, specificity 99.9%.
Hoskovec et al. (2023)	Unselected population (9,151 screened; 1,669 reflexed): informative sgNIPT results in 98.7%; average PPV 48.3%; NPV 99.4%; study limited by small outcome capture and some no‑call results.

Key definitions

cfDNASmall fragments of fetal DNA from the placenta circulating in maternal blood used for noninvasive prenatal screening.

NIPT/NIPSNon-invasive prenatal testing/screening, a common term for analysis of cfDNA.

Revision History

2025-08-01material_revision_addedLatest

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 and all the following are met: paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown, and indicated invasive diagnostic testing (e.g., amniocentesis, CVS) for fetal genotyping has been offered and declined.

2025-08-01material_revision_removedLatest

Removed language that DNA-based noninvasive prenatal tests of fetal aneuploidy are proven and medically necessary as screening tools for trisomy 21, 18, 13 (with or without sex chromosomes) for specified risk circumstances (advanced maternal age, ultrasound findings, prior trisomy, positive screening, Robertsonian translocation, post-counseling).

Policy Summary

PayerUnitedHealthcare

PolicyCell Free Fetal Dna Testing Ne Cs

Policy CodePolicy CS085NE.E

Change TypeMaterial revision (added proven RhD/genotype indicationremoved prior proven trisomy screening languagerevised unproven listremoved codes)

Effective DateAug 1, 2025

Next Review Date

SourceLink

On This Page

ALL of the following

Individual undergoing testing is alloimmunized or at risk for alloimmunization due to maternal RhD status or presence of red cell antigen antibodies
Paternal genotyping shows heterozygosity for RhD or paternal RhD status is unknown
paternal RhD heterozygosity or unknown paternal RhD required
Indicated invasive diagnostic testing (e.g., amniocentesis, chorionic villus sampling (CVS)) for fetal genotyping has been offered and declined
invasive testing must have been offered and declined

Unproven / Not Medically Necessary

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; including but not limited to the listed indications due to insufficient evidence of efficacy.

ANY of the following

Cell-Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome Aneuploidy)
Screening for fetal antigen status other than RhD
Other indications beyond screening for trisomies 21, 18, 13, and sex chromosome Aneuploidy (not an exhaustive list)
policy states this includes but is not limited to listed indications

Not Medically Necessary / Unproven Indications (Expanded cfDNA and other uses)

Considered unproven and not medically necessary due to insufficient evidence for indications beyond screening for trisomies 21, 18, 13, and sex chromosome aneuploidy, including but not limited to:

ANY of the following

Testing for the sole purpose of determining Twin Zygosity
Genome-wide or exome-wide screening (e.g., MaterniT® Genome)
Cell-Free Fetal DNA expanded panel testing (panels that include testing beyond trisomies 21, 18, 13, and sex chromosome aneuploidy)
Screening for microdeletions/microduplications/copy number variations (CNVs)
Screening for single gene disorders (e.g., Vistara™, PreSeek™)
Screening for fetal antigen status other than RhD

Removed Previously Proven Indications (no longer in policy as proven/medically necessary)

These were removed from proven/medically necessary language in the 08/01/2025 revision:

ANY of the following

DNA-based noninvasive prenatal tests of fetal aneuploidy as screening tools for trisomy 21, trisomy 18 or trisomy 13 (with or without fetal sex chromosomes) for individuals with singleton or twin pregnancy in any of the following circumstances: birthing person aged 35 years or older at delivery and/or donor oocyte aged 35 years or older
Fetal ultrasound findings indicating an increased risk of aneuploidy
History of a prior pregnancy with a trisomy due to translocation
Positive first- or second-trimester screening test results for aneuploidy
Parental balanced Robertsonian translocation with an increased risk of fetal trisomy 13 or trisomy 21
Screening after pre-test counseling from a board-certified genetic counselor or from the prenatal care physician or healthcare professional using shared decision-making (SDM)

Documentation Required

Counseling and diagnostic confirmation after positive cfDNA

For positive cfDNA screening results, offer genetic counseling, perform a comprehensive ultrasound evaluation, and discuss/offer diagnostic testing (CVS or amniocentesis) to confirm results prior to using the result for management decisions; cfDNA is a screening test and not diagnostic.

Documentation Required

Manage no-call/failed cfDNA results

For no-call or uninterpretable cfDNA results (often due to low fetal fraction), counsel the patient about the increased risk of aneuploidy, offer comprehensive ultrasound evaluation, and offer diagnostic testing (or repeat testing per laboratory protocols) as appropriate.

Documentation Required

Single screening approach

If prenatal screening is accepted, perform only one screening approach; do not perform multiple screening tests simultaneously.

Documentation Required

Twin/multifetal counseling

Counsel patients with multifetal gestations that cfDNA and serum-based screening are less accurate than in singletons and that factors such as a vanishing twin, fetal demise, or fetal anomalies can reduce accuracy; consider offering diagnostic testing in these situations.

Prior Authorization

Confirmatory diagnostic testing requirement

Diagnostic confirmation (CVS or amniocentesis with chromosomal microarray or karyotype) is required before irreversible management decisions are made based on a positive cfDNA screen; note that screening for some CNVs and rare autosomal trisomies has high false-positive rates and requires confirmatory testing.

Documentation Required

Offer invasive diagnostic testing before noninvasive cfDNA for alloimmunized cases

For alloimmunized or at-risk pregnancies, invasive diagnostic testing (e.g., amniocentesis or CVS) for fetal genotyping must be offered and documented as declined prior to covering cfDNA fetal genotype testing; this requirement should be documented in the medical record.

An abnormal number of chromosomes in a human cell, including trisomy and monosomy.

FFFetal fraction — proportion of cell-free fetal DNA in the maternal plasma sample.

Twin ZygosityType of conception: dizygotic (fraternal) vs monozygotic (identical) twins.

WGSWhole Genome Sequencing: determines the sequence of the entire DNA, including coding and non-coding regions.

CGHComparative Genomic Hybridization: technology to detect genomic copy number variations using labeled DNA hybridized on an array.

2025-08-01material_revision_revisedLatest

Replaced broad 'unproven and not medically necessary for all other indications' language with 'unproven and not medically necessary for indications beyond screening for trisomies 21, 18, 13, and sex chromosome Aneuploidy' and revised the list of unproven/not medically necessary indications (added expanded panel testing; removed several previously listed unproven items including fetal RhD, repeat testing for low fetal fraction, certain pregnancy scenarios, Vanadis).

2025-08-01material_revision_removed_codesLatest

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

2025-08-01material_revision_removed_codesLatest

Removed an extensive list of ICD-10 diagnosis codes from the applicable codes list.

2025-08-01clarificationLatest

Updated Description of Services, Clinical Evidence, FDA, and References sections to reflect the most current information.

administrativeLatest

Archived previous policy version CS085NE.D.