Centene Prenatal cfDNA Coverage Update

Coverage Criteria

Prenatal Cell-free DNA Testing for Chromosome 13, 18, 21, X and Y Aneuploidies

Covered when ALL of the following are met:

Aneuploidy cfDNA coverage: Member has a singleton or twin pregnancy AND member has not previously had cell-free DNA screening in the current pregnancy

Applies to testing for chromosomes 13, 18, 21, X and Y (0327U, 81420, 81507).

Investigational Indications

The following uses are considered investigational (not medically necessary):

Investigational cfDNA indications: Prenatal cfDNA to predict twin zygosity; cfDNA for microdeletions/microduplications; cfDNA for single-gene disorders; cfDNA for all other aneuploidies beyond T13/T18/T21; cfDNA for multiple gestation pregnancies of triplets or higher; cfDNA performed simultaneously with maternal serum screening; cfDNA use in singleton pregnancy with a known vanishing twin; cfDNA for sole purpose of fetal sex determination; fetal RhD genotyping is investigational except where specific criteria met

Specific CPTs listed as investigational include 0060U, 81422, and single-gene disorder codes (81302, 81404-81408, 81442).

Maternal Serum Screening (MSS)

Covered when ALL of the following are met:

MSS coverage: Maternal serum screening using no more than one of the listed MSS options one time per pregnancy

Covered MSS options include first trimester screening (81508); second trimester screening or related panels (81509, 81510, 81511, 81512); integrated/stepwise/contingent sequential screening (81508/81509/81510/81511/81512); and Penta screen (81512).

Prenatal Cell-Free DNA Testing for Fetal RhD Genotyping

Covered when ALL of the following are met:

Fetal RhD genotyping coverage: Member is pregnant AND member is confirmed RhD negative AND member is not planning to undergo amniocentesis AND member's practice setting is experiencing RhIg shortages

Applies to CPTs 81403 and 81479; prenatal cfDNA for fetal RhD genotyping is investigational for other indications.

Policy-aligned coverage considerations

Coverage considerations and clinical recommendations summarized from cited professional society guidance:

Aneuploidy screening: cfDNA screening for common fetal aneuploidies should be offered to all pregnant patients and discussed alongside other screening and diagnostic options; avoid performing multiple independent screening approaches because this can increase false positives and conflicting results.

Based on ACOG Practice Bulletin No. 226 recommending offering prenatal genetic screening to all pregnant women and advising against unlinked multiple screening tests (chunk 23).

Microdeletions: Screening for microdeletions via cfDNA is available but has not been clinically validated broadly and is not recommended due to very low prevalence and low positive predictive value.

ACOG/SMFM highlight low PPV for microdeletions (chunk 19); Concert notes insufficient evidence for improved outcomes (chunk 21).

22q11.2 (DiGeorge) screening: ACMG issues a conditional recommendation to offer screening for 22q11.2 deletion syndrome after counseling about benefits and limitations; shared decision-making is emphasized.

This policy explicitly excludes a number of prenatal cfDNA applications from coverage. cfDNA testing for microdeletions/microduplications (CPT 81422), cfDNA screening for single-gene disorders (CPTs 81302, 81404–81408, 81442), and cfDNA to predict twin zygosity (0060U) are considered investigational. The policy also excludes cfDNA testing for aneuploidies beyond trisomy 13, 18, and 21, cfDNA use in multiple gestation pregnancies of triplets or higher, cfDNA performed simultaneously with maternal serum screening, cfDNA applied to a singleton pregnancy with a known vanishing twin, and cfDNA ordered solely for fetal sex determination

Fetal RhD genotyping by cfDNA is not broadly excluded but is covered only when specific criteria are met (see RhD genotyping criteria); outside those criteria it is treated as investigational.

Professional society guidance cautions about routine expansion of cfDNA beyond common aneuploidies. ACOG/SMFM state that screening for a limited number of microdeletions is available but not clinically validated and not recommended because the paneled deletions are rare and have much lower positive predictive value than common trisomies. ACOG practice advisories similarly note that cfDNA screening for single-gene disorders lacks sufficient data on accuracy and predictive value in the general population and is therefore not recommended at this time.

The policy also references Concert’s review that studies validating microdeletion analysis via cfDNA have shown low PPV and higher false-positive rates, supporting the cautious stance against routine use.

The policy lists specific CPTs for cfDNA applications that are considered investigational and therefore not medically necessary when billed for those indications: 81422 for microdeletion/microduplication panels, and 81302, 81404, 81405, 81406, 81407, 81408, 81442 for single-gene disorder screening. It also identifies 0060U for twin zygosity prediction as investigational.

When these CPTs are submitted for the listed investigational indications, the policy indicates such claims may be denied as not medically necessary.

The policy concludes there is currently to support routine cfDNA screening for many expanded uses. Concert notes that microdeletion panels (including 22q11.2) have low positive predictive value and insufficient evidence of improved outcomes. ACOG/SMFM and ACOG practice advisories similarly state that microdeletion and single-gene cfDNA screening are not clinically validated for routine use due to limited data on accuracy and predictive values.

As a result, cfDNA for these expanded indications is classified as investigational or not recommended for general population screening until stronger validation and outcome data are available.

Covered Indications

Screening for fetal aneuploidy for chromosomes 13, 18, and 21 and sex chromosomes (13, 18, 21, X and Y) in singleton or twin pregnancies where cfDNA has not previously been performed in the current pregnancy.

Covered when ALL of the following are met:

Screening for common fetal aneuploidies: Member has a singleton or twin pregnancy AND cfDNA has not previously been performed in the current pregnancy

Applies to CPTs 0327U, 81420, 81507 per policy.

Fetal RhD genotyping for RhD-negative pregnant members when not planning amniocentesis and when practice setting is experiencing RhIg shortages.

Covered when ALL of the following are met:

Fetal RhD genotyping coverage (shortages/alloimmunized): Member is pregnant AND member is confirmed RhD negative AND member is not planning to undergo amniocentesis AND member's practice setting is experiencing RhIg shortages

Applies to CPTs 81403 and 81479; ACOG also supports use as alternative in alloimmunized patients who decline amniocentesis (chunk 24).

Coding

Aneuploidy cfDNA CPTsCPTCovered

0327U	Prenatal cell-free DNA testing for chromosome 13, 18, 21, X and Y (example)
81420	Noninvasive prenatal testing (NIPT) for aneuploidy (listed)
81507	Prenatal cfDNA test (example - Harmony)
0060U	Test to predict twin zygosity (listed as investigational)

Microdeletion cfDNACPTNot Covered

81422

cfDNA testing for microdeletions/microduplications

Single-gene cfDNA CPTsCPTNot Covered

81302	cfDNA single-gene disorders (example codes listed)
81404	cfDNA single-gene disorders (example)
81405	cfDNA single-gene disorders (example)
81406	cfDNA single-gene disorders (example)
81407	cfDNA single-gene disorders (example)
81408	cfDNA single-gene disorders (example)
81442	cfDNA single-gene disorders (example)
0488U	UNITY Fetal Antigen NIPT (example)
0489U	UNITY Fetal Risk Screen (example)

Maternal Serum Screening (MSS) CPTsCPTCovered

81508	First trimester maternal serum screen
81509	Second trimester maternal serum screen (hCG, msAFP, uE3, DIA)
81510	Second trimester maternal serum screen
81511	Serum integrated screen, part 2
81512	Penta screen

Fetal RhD genotyping CPTsCPTCovered

81403	UNITY Fetal RhD NIPT (add on) example
81479	Fetal RhD NIPT (example)

Common ICD-10 codes referencedICD-10

O09	Pregnancy related ICD example group
O28	Encounter for supervision of high-risk pregnancy
O30	Multiple gestation
O35	Maternal care for known or suspected fetal abnormality
Q90-Q99	Congenital malformations, deformations and chromosomal abnormalities
Z34	Encounter for supervision of normal pregnancy
Z36.0	Encounter for antenatal screening for chromosomal anomalies
Z36.04	Encounter for antenatal screening for single-gene disorders

Referenced CPT codesCPT

81405

Example code referenced in policy text (listed for RhD/genotyping)

inv-17: Maternal Serum Screening frequency — No more than one of the listed MSS options one time per pregnancy

Limit per pregnancyNo more than one of the listed maternal serum screening (MSS) options may be performed one time per pregnancy

Covered MSS optionsFirst trimester screening (81508); second trimester screening (81509, 81510, 81511, 81512); integrated/stepwise/contingent sequential screening (81508, 81509, 81510, 81511, 81512); Penta screen (81512)

Examples of componentsFirst trimester: free or total beta-hCG and PAPP-A; Second trimester: hCG, msAFP, uE3, DIA; Penta adds ITA

inv-18: Positive predictive value (PPV) — Lower PPV for microdeletions compared to common trisomies

PPV comparison

Provider Actions & Documentation Requirements

Billing Rule
Coverage tied to specific CPTs — prior auth/verification may be required
Coverage for prenatal cfDNA tests is tied to specific CPT/HCPCS codes. Prior authorization or verification may be required for tests billed with the listed codes; confirm plan-specific operational PA requirements before ordering.
Covered/considered medically necessary only when billed with the approved codes for the indicated indications (e.g., 0327U, 81420, 81507 for common aneuploidy panels).
Tests billed with codes for investigational indications (e.g., 81422 for microdeletions; 81302, 81404–81408, 81442 for single-gene disorders) are subject to denial.
Confirm operational prior authorization/coding guidance when ordering RhD/genotyping tests (81403, 81479, and in some operational references 81405).

Denial Risk

Eligibility Requirements

No specific top-level eligibility requirement nodes are defined in this policy window.

Not Covered / Exclusions

Not covered under this policy are cfDNA tests used to screen for microdeletions (CPT 81422) and single-gene disorders (CPTs 81302, 81404–81408, 81442). cfDNA testing to predict twin zygosity (0060U) and cfDNA for aneuploidies beyond trisomy 13, 18, and 21 are also not covered. Additionally, cfDNA in multiple gestations of triplets or higher, cfDNA ordered simultaneously with maternal serum screening, use in a singleton pregnancy with a known vanishing twin, and testing solely for fetal sex determination are considered not covered/investigational.

Fetal RhD genotyping is only covered when the policy’s specific criteria are met; otherwise it is considered investigational.

Routine cfDNA screening for microdeletions and for single-gene disorders is not supported by current evidence and therefore is considered not covered for general population screening. ACOG/SMFM and ACOG advisories emphasize that limited microdeletion panels are not clinically validated and have low positive predictive value, and that single-gene cfDNA screening lacks sufficient accuracy data to recommend routine use.

Providers should recognize that these expanded cfDNA applications may be denied as investigational and document appropriate counseling when these options are discussed with patients.

Background

Prenatal cell-free DNA testing (also referred to as NIPT in some literature) analyzes placental-derived cell-free DNA fragments circulating in maternal blood to estimate the risk of fetal chromosomal abnormalities. The technology is most commonly used to screen for trisomy 21, trisomy 18, and trisomy 13, and can also report sex chromosome composition (X and Y).

Important clinical points: cfDNA is a screening test, not diagnostic; positive or high-risk results should be confirmed by diagnostic testing (karyotype, FISH, or chromosomal microarray). Performance may be affected by factors such as placental mosaicism, vanishing twin, maternal genetic conditions, or maternal malignancy, and these limitations should be discussed during pretest counseling.

Definitions

inv-28: Prenatal Cell-free DNA Testing — definition of the screening test

DefinitionA screening test that analyzes traces of cell-free DNA (cfDNA) in a pregnant woman's blood to determine risk for specific fetal genetic disorders

Common targetsMost commonly used to screen for fetal aneuploidies such as trisomy 21, 18, and 13 and sex chromosome aneuploidies

Not diagnosticcfDNA is a screening test with potential for false-positive and false-negative results; positive results should be confirmed with diagnostic testing

inv-29: Singleton pregnancy — definition

DefinitionA pregnancy with one fetus

Coverage relevancePolicy coverage for cfDNA aneuploidy testing explicitly applies to singleton pregnancies (and certain twin scenarios)

OpenPayer

Prenatal Cell-free DNA Testing (cfDNA) — Coverage Criteria and Medical Necessity

Coverage Criteria

Covered Indications

Coding

Provider Actions & Documentation Requirements

Eligibility Requirements

Not Covered / Exclusions

Background

Definitions